Summary Biological Psychology

Chapter 1: The Cells of the Nervous System

Mental experience is composed of pieces

Nervous system consists of two kinds of cells: neurons and glia
o 100 billion neurons in the brain
o The synaptic gap was discovered by Santiago Ramn y Cajal around 1800 with the
emergence of microscopy
o Insight that the brain consists of pieces

Structure of a neuron

General cell properties:

o Plasma membrane: separates the inside of the cell from the outside environment, only lets
through certain chemicals
o Nucleus
o Mitochondrion
o Ribosomes
 Neuron properties:
o Soma = the cell body, also covered with synapses
o Dendrites = branching fibers that receive information from other neurons
Dendritic spines = short outgrowths that increase the surface area available for
synapses
o Axon = a thin fiber of constant diameter that conveys a signal to other neurons, an organ,
or a muscle
Afferent and efferent axons: afferent axon brings information into a structure;
efferent axon carries it away

Axons can span through the whole body

Myelin sheath = fats and proteins isolating the axons
Nodes of Ranvier = gaps in myelin sheath
o Presynaptic terminal (or end bulb/bouton) = point where axon releases chemicals into
synaptic gap
 Kinds of neurons: Motor neurons, sensory neurons and interneurons
Variations in neurons: neurons vary greatly, depending on their function:

Glia (Eng. Glue) = white matter

Astrocytes: wrap around the presynaptic terminals of a group of functionally related axons, and
synchronize the activity of neurons, they remove waste materials
 o Microglia: act as part of the immune system
o Oligodendrocytes (brain and spinal cord) and Schwann cells (periphery): build myelin
sheath, supply axon with nutrition
o Radial glia: guide the migration of neurons and their axons and dendrites during
embryonic development

The Blood Brain Barrier = mechanism excluding most chemicals from the brain
Protects brain from harmful chemicals and viruses
Although the brain needs to receive nutrients from the blood, many chemicals cannot cross from
the blood to the brain
o Nearly all chemotherapy drugs fail to cross the bloodbrain barrier
Endothelial cells form the walls of the capillaries
o The barrier is very tight special mechanisms are needed to get certain chemicals (like
water) through
Able to pass are: oxygen, carbon dioxide, water, molecules that dissolve in fat
Actively transported into the brain are: glucose, amino acids, and more
Nourishment of neurons: Glucose; the supply of glucose need oxygen; glucose is used because it
can cross the blood brain barrier in large quantities
Thiamin = vitamin B1, which is needed to use glucose; lack of it leads to Korsakoffs syndrome

Module 1.2: The Nerve Impulse

 Instead of conducting an electrical impulse, the axon regenerates an impulse at each point
The properties of impulse conduction in an axon are well adapted to your needs for information
(compensating the distances of sensory neurons through faster/slower axons to achieve correctly
timed perceptions)

The Resting Potential of the Neuron

The membrane of a neuron: 8nm thick; composed of two layers; consists of phospholipid
molecules, with proteins which act as gates,
o Controls the flow of chemicals

Electrical gradient/polarization = a difference in electrical charge between the inside and outside
of the cell
o The neuron inside the cell has a slightly negative electric potential with respect to the
outside. This is called the resting potential, which typically is around -70 millivolts
The membrane is selectively permeable: some chemicals can pass through it more freely than
others
o Oxygen, carbon dioxide, urea, and water can pass easily
o Sodium, potassium, calcium, and chloride must go through channels/gates
At rest, the sodium and potassium channels are (almost) closed
The sodiumpotassium pump repeatedly transports three sodium ions out of the cell while
drawing two potassium ions into it
o It is an active transport that requires energy
 Sodium = NA+ (Natriumion); in the resting state, it must stay outside (remember: Na: Na, du
must raus.)
Potassium = K+ (Kaliumion); in the resting state, it must stay inside (remember: K: OK, du
darfst rein)
o Several forces influence these ions, as shown in the

The resting potential prepares the neuron to respond rapidly

The Action Potential

Messages sent by axons are called action potentials
Hyperpolarization = to further increase the negative electric polarization inside the neuron
o After hyperpolarization, the neuron simply returns to its resting state
Depolarization = reducing the neurons polarization towards zero
Threshold of excitation = only a depolarization that passes the threshold releases an action
potential
o Any stimulation/depolarization that does not exceed the threshold produces just a small
response which is no action potential
 No action potential (threshold not reached) action potential

Three molecular principles

1. At the start sodium ions are mostly outside, potassium ions are mostly inside.
2. When the membrane is depolarized, sodium and potassium channels open.
3. At the peak of the action potential, the sodium channels close.
The sodium and potassium channels are voltage-gated channels
o Voltage-gated channels = their permeability depends on the voltage difference across the
membrane
o Reminder: at the resting level, the sodium channels are closed and the potassium channels
are almost closed.
Process of an action potential
1. With the start of depolarization, both channels begin to open, allowing freer flow
This has nearly no influence on potassium ions, as they are in balance anyway
This has influence on sodium ions though, the electrical- and concentration gradient
drive them into the neuron
2. When the threshold is reached, sodium and potassium channels open wide
Because of the aforementioned gradients, sodium ions rapidly enter the neuron, this
leads to a reversed polarity, now the neuron has a slightly positive potential
3. When the action potential reaches it its peak, the sodium channels snap shut
4. Because of the positive polarization inside, the potassium ions are driven out of the neuron
5. Refractory period (explanation later)
6. The cell is balances itself out
 7. At the end of this process, the membrane has returned to its resting potential, but the inside
of the neuron has slightly more sodium ions and slightly fewer potassium ions than before

Local anesthetic drugs, such a Novocain, attach to the sodium channels of the membrane,
preventing sodium ions from entering, and thereby preventing action potentials
All-or-non law = The amplitude and velocity of an action potential are independent of the
intensity of the stimulus that initiated it, provided that the stimulus reaches the threshold.
1. But: Thicker axons convey action potentials at greater velocities. Thicker axons can also
convey more action potentials per second.
All an axon can change is timing and frequency of signals
The refractory period = period immediately after an action potential during which a cell does not
produce another one
First part: absolute refractory period = the membrane cannot produce another
potential regardless of stimulation; 1ms long
Second part: relative refractory period = a stronger than usual stimulus is
necessary to initiate an action potential; 2-4 ms long
Caused by (1) closed sodium channels and (2) by potassium flowing out

Propagation of the Action Potential

Propagation of an action potential = transmission of an action potential down the axon
An action potential in one part of the axon depolarizes the neighboring part beyond the threshold
of excitation, causing it to release its action potential
 It only propagates into one direction because of areas it just past are still in their refractory period

The Myelin Sheath and Saltatory Conduction

Myelinated axons are faster than unmyelinated ones
The action potential starts at the first node of Ranvier (which are about 1 micrometer wide)
o The action potential cannot regenerate along the membrane between nodes because sodium
channels are virtually absent between them (in the myelin)
A change of charge is pushed along the axon to the next node, where the action potential gets
regenerated
 This jumping conduction (like a relay race) is called saltatory conduction
o This is faster and needs less energy
Multiple sclerosis = the immune system destroys myelination sheaths of already myelinated
axons, which leaves them unable to send an action potential between the nodes (there are no
sodium channels)

Local Neurons
Local neurons = neurons without an axon that can only communicate with their close neighbors
Graded potential = a membrane potential that varies in magnitude in proportion with the stimulus
o Is only found in local neurons
o Defies the all-or-none law
The We only use 10% of our brain statement is false
Chapter 2: The concept of the synapse

Properties of Synapses
Reflexes = automatic muscular responses to stimuli
Reflex arc = circuit from sensory neuron to muscle neuron

Sherringtons observations:
o Reflexes are slower than conduction along an axon
Means that there must be something slowing down the conduction of the signal
synapses
o Several weak stimuli presented at nearby places or times produce a stronger reflex than one
stimulus alone does
o When one set of muscles becomes excited, a different set becomes relaxed
Presynaptic neuron = neuron that delivers transmission
Postsynaptic neuron = neuron that receives transmission
Temporal summation: repeated stimuli within a brief time have a cumulative effect on the electric
potential
o EPSP = excitatory postsynaptic potential; is a graded depolarization
o A quick sequence of EPSPs can combine to exceed the threshold and produce an action
potential
 Spatial Summation: Synaptic inputs from separate locations combine their effects on a neuron
o Is critical for brain functioning a single synapse might produce a weak effect, which is
not sufficient to produce an action potential, spatial summation ensures that synchronized
inputs excite a neuron enough to activate it
Temporal and spatial summation ordinarily occur together
Summation effects can depend on the order of stimuli

Inhibitory synapses
o Hyperpolarize the cell, moving it further from the threshold
o IPSP = inhibitory postsynaptic potential
o was a debated concept in Sherringtons time
Relationship between EPSP, IPSP, and Action Potentials
There are numerous possibilities for wiring between neurons, e.g. neuron X only fires if neuron A
and B fires and C does not fire
Most neurons have a spontaneous fire rate = a periodic production of action potentials even
without synaptic input
o EPSPs and IPSPs higher or lower the fire rate of such neurons

Module 2.2: Chemical Events at the Synapse

Contrary to Sherringtons beliefs, the processes at synapses are chemical

o Loewi was the first to prove this
The Sequence of Chemical at a Synapse
 Nitric oxide = a neurotransmitter released by local neurons; increases blood flow by dilating the
blood vessels
The neuron synthetize neurotransmitters from amino acids
o These amino acids are based on proteins taken in by the diet
o Drugs can act on the brain by altering the synthesis of transmitters
o Most transmitters are synthetized in the presynaptic terminal
The presynaptic terminal stores transmitters in vesicles, nearly spherical packets
MAO is an enzyme which breaks down transmitters
o MAO-inhibitors are used as antidepressants
The depolarization of an action potential opens voltage dependent calcium gates in the presynaptic
terminal
o Calcium ion rushing in causes exocytosis, bursts of release of transmitters
o Transmitters diffuse across the synaptic cleft (in 1 or 2 milliseconds)
Neurons can release more than one kind of neurotransmitter at a time, and are generally flexible
and experience dependent in which kind of neurotransmitter gets released
Ionotropic effects are brief and fast on/off effects, suited for e.g. vision
o Neurotransmitters control transmitter-gated or ligand-gated channels
o GABA and glutamate are the most common neurotransmitters for this effect
o e.g. GABA opens chloride channels, chloride ions have a negative charge --> GABA has
an inhibitory effect
Metabotropic effects and second messenger systems
o Slower and longer lasting (around two seconds), uses e.g. dopamine and serotonin; suited
for more enduring effects such as taste
o The transmitter attaches to a receptor, which makes the receptor release a G-protein inside
cell
o The protein is high in energy and increases the concentration of second messengers (e.g.
cyclic AMP) which can do many things, like opening channels or activate genes
 Neuropeptides (also called neuromodulators) have several properties that set them apart from
other neurotransmitters
o They are synthetized in the cell body (instead of presynaptic terminal)
o They are mainly released from dendrites (instead of axon terminal)
o They lead neighboring cells to release them too and diffuse into a relatively wide area
o They have an effect for several minutes (instead of less than a seconds or a few seconds)
o Suitable for e.g. thirst
Drugs that bind on receptors
o Hallucinogenic drugs attach to serotonin receptors, stimulating the brain overly
 o Nicotine attaches to nicotinic receptors which releases dopamine --> addictive
o Opiate drugs bind to the same receptors as endorphin
Inactivation and reuptake
o Some transmitters can be broke down into reusable parts after use
o Others get transported back to the presynaptic cell by transporters, special membrane
proteins; this is called reuptake
o Transmitters not getting a reuptake will be broken down by an enzyme called COMT
o Amphetamines and cocaine block the transporters
o Ritalin is basically slow cocaine
Negative feedback (stop sending transmitters, thanks)
o Autoreceptors = located in the presynaptic terminal; respond to the released transmitter by
inhibiting further synthesis and release
o Some postsynaptic send transmitters back to the presynaptic one, telling it to stop sending
Cannabinoids do that, decreasing excitatory as well as inhibitory messages

 Electrical synapses: do actually convey messages electrically; used when synchrony is important,
e.g. breathing
o Gap junction = direct contact of membranes of two neurons at a synapse
o Pores are aligned in a way that allows ions to pass freely between them
o The two neurons nearly act as one

Hormones
If a neurotransmitter is a phone signal, a hormone is like a radio signal; neuropeptides lie between
neurotransmitters and hormones
Secreted by endocrine glands
Used for long-lasting changes
Protein and peptide hormones activate second messengers in the brain
The pituitary gland is attached to the hypothalamus
o The hypothalamus releases releasing hormones which make the pituitary gland release
other hormones
Chapter 3: Anatomy and Research Methods

Module 3.1: The Vertebrate Nervous System

Terminology
Central nervous system (CNS) = brain and spinal cord
Peripheral nervous system (PNS) = the rest of the nervous system, connects the CNS to the rest
of the body
 To understand ventral/dorsal:
o They are directions
Dorsal = toward the back
Ventral = toward the stomach
o The dorsal side of a humans brain is its top and not its back. This is because the definition
of dorsal has been taken from other, four legged, animals whose dorsal side of the brain
would be indeed the top of it.
The Spinal Cord
The spinal cord = part of the CNS, communicates with all sense organs and muscles, except from
those in the head
Axon bundles entering the dorsal side carry sensory information, axon bundles exiting the ventral
side carry motor information
Dorsal root ganglia = cluster of cell bodies of sensory nerves, located outside the spinal cord
o the cell bodies of the motor neurons are inside the spinal cord
The spinal cord is segmented; if it is cut at a given point, the brain will lose all information and
motor control from that segment and below
The Automatic Nervous System
Nerves connected to the heart, intestines, and other organs
Sympathetic nervous system = fight and flight reactions
o Consists of chains of ganglia just left and right from the spines central regions
o Sympathetic ganglia are closely interconnected and often act as a single system
o Mainly releases norepinephrine
Parasympathetic nervous system = vegetative, nonemergency responses
o Often works opposite to the sympathetic nervous system
o Ganglia are not interconnected, therefore the individual parts of this system can work
independently
o Mainly releases acetylcholine
Because the two systems use different neurotransmitters, they can be targeted individually with
drugs

The Hindbrain
Posterior part of the brain
Consists of the medulla, the pons, and the cerebellum
Medulla (oblongata) = extension of the spinal cord into the skull; controls reflexes like breathing
o Many cranial nerves (nerves for sensation and muscles of the head) enter the brain at the
medulla
Pons = axons from the brain cross here, so that the right hemisphere controls the left arm: also
contains nuclei of cranial nerves
Cerebellum = control of movement, switching of attention, timing


The Midbrain
Pretty small in humans
The tectum is the roof of the midbrain
o It has two swellings on each side, the superior colliculus and the inferior colliculus
These are important for processing of sensory information
Inferior for hearing, superior for vision
Tegmentum exists too, as well as the substantia nigra, which facilitates readiness for movement

The Forebrain
Most prominent part, consists of two hemispheres
The outer portion is the cerebral cortex
Limbic system = subcortical structure that forms a border around the brainstem
o Important for motivations and emotions, such as eating, drinking, sexual activity
o Most sensory information goes first to the thalamus, which processes it and sends output
to the cerebral cortex (except olfactory information)
 o Cerebral cortex can send information back to the thalamus, e.g. ordering it to magnify
certain kinds of input

o The hypothalamus controls the pituitary gland and is important for motivation and
emotion
o The pituitary gland is the master gland, sending out hormones which trigger other glands
throughout the body
the nucleus basalis, receives input from the hypothalamus and basal ganglia and sends axons that
release acetylcholine to widespread areas in the cerebral cortex; controls overall wakefulness
the hippocampus is critical for certain types of memories, especially memories for individual
events
The Ventricles
the ventricles are four fluid filled cavities in the brain

Cells called the choroid plexus inside the four ventricles produce cerebrospinal fluid (CSF), a
clear fluid similar to blood plasma
 CSF fill narrow spaces between the brain and the thin meninges, membranes that surround the
brain and spinal cord
o Swollen blood vessels in the meninges are responsible for the pain of a migraine headache
o CSF protects the brain against mechanical shocks, helps support the weight of the brain

Module 3.2: The Cerebral Cortex

Organization of the Cerebral Cortex
Cerebral Cortex = on the surface are the cell bodies, inside are the axons
o The two hemispheres are connected through two bundles of axons, the corpus callosum
and the anterior commissure
o The cerebral cortex is very big in humans, compared to the rest of the brain
The cerebral cortex contains up to six laminae, layers of cell bodies, parallel to the surface of the
cortex
o The laminae vary in thickness, or can even be absent, depending on the part of the cortex
The cells of the cortex are also organized into columns of cells perpendicular to the laminae
o The cells within a column have similar properties

The Lobes
Occipital Lobe
o Main target for visual information
o Damage to this lobe will cause cortical blindness in the related part of the visual field
o The eyes provide the stimulus, the visual cortex provides the experience
Parietal Lobe
o Lies between the occipital lobe and the central sulcus
The central sulcus is a deep groove in the surface of the cortex
o Posterior to the central sulcus lies the primary somatosensory area (also called postcentral
gyrus)
 o The parietal lobe monitors head and body positions, which are needed to interpret sensory
information and to control body movements
Temporal Lobe
o Primary target for auditory information
Understanding language
o perception of complex visual aspects, such as movements and recognition of faces
o Also important for emotional and motivational behaviors
Kluever-Bucy Syndrome: loss of fear
Frontal Lobe
o Contains the precentral gyrus (primary motor area)
Specialized for fine movements
o The most anterior portion of this lobe is the prefrontal cortex
The prefrontal cortex takes up a larger portion of the brain than it does in other
animals
The dendrites here have up to 16 times as many dendritic as neurons in other
cortical areas
o Prefrontal lobotomy = surgical disconnection of the prefrontal cortex from the rest
led to apathy, cant make plans, attention problems, ignoring rules
 is shit and not done anymore
o Functions: direction of attention, working memory, planning and decision making
o People with damage to the prefrontal cortex are worse at delayed recall tasks

How do the parts work together?

The visual, auditory, and somatosensory areas of the cortex are in different locations, only weakly
connected with one another
Leads us to the binding problem or large scale integration problem
Binding happens when we perceive two stimuli at the same time and place

Module 3.3: Research Methods

Four categories: 1. Examine the effects of brain damage, 2. Examine the effects of stimulating a
brain area, 3. Record brain activity during behavior, 4. Correlate brain anatomy with behavior

Effects of Brain Damage

Broca one of the first, Brocas area: 1861
 Reports of behavioral impairments after brain damage
Human studies are too limited, therefore researchers use animals
An ablation is a removal of a brain area, generally with a surgical knife
Research sometimes make lesions, meaning damage, by means of a stereotaxic instrument
o Uses an electrical current
o Can cause very precise lesions

o To make sure that a behavioral change is caused just by the lesions, sham lesions are done
in a control group, where the procedure is the same but no current is passed
o Electrical currents are not often used today, because they also destroy passing axons;
instead chemicals or genes are used
Transcranial magnetic stimulation (TMS) = application of magnetic stimulation to a portion of
the scalp; inactivates neurons in a narrow area below the scalp producing a temporal virtual lesion
In general, brain damage tells us what brain are is connected to what behavior, but not much more
Effects of Brain Stimulation
Old-fashioned way: insert electrode; this is crude, stimulating many types of neurons and passing
axons
Now: optogenetics, using light to control a limited population of neurons
o First light-sensitive proteins are inserted into a given type of neuron using a virus
o Using these proteins, inhibition and excitation of certain neurons can be controlled
o The investigator injects an optical fiber into the brain
o This is a very precise procedure

Recording Brain Activity

Noninvasive for humans
Electroencephalograph (EEG) = records electrical activity of the brain through electrodes
attached to the scalp
o Can record spontaneous brain activity or activity to stimuli, these activities are called
evoked potential or evoked responses
A magnetoencephalograph (MEG) is similar to an EEG but uses the magnetic field of the brain
o Like the EEG the MEG can locate brain activity within one centimeter
o Enables general localization of brain activity
Positron-emission tomography (PET) provides a high resolution image of activity in a living
brain by recording the emission of radioactivity from injected chemicals
o First a radioactive substance (e.g. radioactive glucose) is injected, than we measure the
radioactive decay inside the brain; presumably the most radioactivity comes from the most
active neurons
o Because it is expensive and uses radioactivity fMRIs are preferred
Functional magnetic resonance imaging (fMRI) measures the influence of hemoglobin in the
brain on the brains magnetic field. Hemoglobin with oxygen influences the magnetic field
differently than hemoglobin without oxygen
o When a brain area become active
1. More blood flows to this area
2. It uses oxygen, decreasing the percentage of hemoglobin with oxygen
 o An fMRI reacts to both of these processes
o A control condition is necessary to establish a baseline of activity
o The knowledge acquired from fMRI scans is somewhat limited because it does not often
lead to predictions or causality

Correlating Brain Anatomy to Behavior

Galls phrenology was stupid
Now we use computerized axial tomography (CT or CAT scan), using dye injected into the
blood
o X-rays are passed through the brain and measurements are taken from many angles

We now also use magnetic resonance imaging (MRI), which uses a powerful magnetic field and
certain properties of molecules in our brain to construct an image
o Apparatus is noisy and confining, people patient must stay motionless
These studies give us an idea of the function of certain brain area

Brain Size and Intelligence

There is no reasonable relationship between them neither inside the human species nor across
species
Men and womens brains differ structurally but accomplish the same
Chapter 4: Development and Plasticity

Module 4.2: Development of the Brain

Maturation of the Vertebrate Brain

The nervous system begins to form when the embryo is two weeks old
o First the neural tube is formed, which then differentiates into the hindbrain, midbrain, and
forebrain
Processes in the development of neurons
o Proliferation
Early in development cells divide either into stem cells that continue to divide, or
into different kinds of neurons that migrate to other locations
Nearly all neuron form during the first 28 weeks of pregnancy
o Migration
 Movement of neurons; some move fast and some very slow (taking until
adulthood); certain chemicals guide neuron migration
o Differentiation
The neuron grows its axon first, sometimes already having it while migrating; the
dendrites form after migration
o Myelination
Production of a fatty sheath around an axon which accelerates transmission;
continues until early adulthood; is a vulnerable process which can be impaired by
e.g. social isolation
o Synaptogenesis
Forming of new synapses; start before birth and continues throughout life but slows
down towards the end
Not many new neurons are formed after early infancy

Pathfinding by Axons
Axons have specific targets which they find using chemical gradients
o Axons are marked with a certain concentration of a protein, their targets are marked with a
similar concentration of the same protein
The fact that Axons have specific targets has been demonstrated by Sperry, how cut a newts optic
nerves, rotated the eye by 180 degrees and saw that the nerves grew back to their original targets
 Competition between axons as a general principle neural Darwinism = In the development of
the nervous system, we start with more neurons and synapse than we can keep. Synapses form
with approximate accuracy, and then a selection process keeps some and rejects others. The most
successful axons and combinations survive, and the others fail.
Determinants of neural survival
o The sympathetic nervous system initially forms excessively more neurons than it needs;
these build synapses to muscle cells; normally the neurons would commit sudoku through a
process called apoptosis; the muscle cells can cancel apoptosis through a protein called
nerve growth factor (NGF); only the neurons chosen by the muscle will survive
o Maturing brain areas undergo massive cell death, it is part of normal development
o In general, chemicals that promote neuron survival and activity are called neurotrophins
o Neurons in the brain die by different mechanisms which are not understood yet. It seems
like stimulation is essential for neuron survival in the cortical areas
During development, the brain is very vulnerable. Examples are: mutations on genes which control
development (homeobox genes), teratogens (especially alcohol), bad influences from the mother
Differentiation of the Cortex
Immature neurons take on the function that is needed in there are
The slightly more mature neurons cannot fully adopt when placed in a new are, showing that
differentiation is a rather quick decision
To what extend neurons can be rewired has been shown with ferrets
o The optical nerve from one eye has been connected to one half of the auditory part of their
brain, while the auditory nerves on that side got destroyed. It now perceives vision in that
half of the originally auditory part of the brain
Fine-Tuning by Experience
Although the central branch of a dendrite becomes stable by adolescence, the peripheral branches
remain flexible throughout life

Rats in enriched environment developed a thicker cortex with more dendritic branches and better
learning
 BUT: we cannot exercise our brain to become overall better and more intelligent; instead physical
ability is the best way to keep intellectual vigor in high age
Effects of special Experiences
o Blind people are better at processing tactile information; they use their occipital lobe to
process auditory and tactile information
o Musicians have changes in their brain anatomy (some areas are bigger) as well as brain
activity (more of it for tones) caused by their extensive experience. They are better at
discriminating sounds
o It is debated to what extend the adult brain can have such effects
Musicians cramp (focal hand dystonia) = when the areas of different fingers in the somatosensory
cortex start to overlap, it can happen that these fingers start to act in unity, making it impossible to
make coordinated individual movements; this is an example of brain reorganization that has gone
too far

Brain Development and Behavioral Development

Adolescents are less able to restrain their impulses, as their prefrontal cortex is less mature and
they are very susceptible to social influence
Old peoples memory and reason begin to fade due to physical decline of the brain

Module 4.3: Plasticity after Brain Damage

Brain Damage and Short-Term Recovery

There are many reasons for brain damage, the most prominent one in young people is closed head
injury, a sharp blow to the head that does not puncture the brain. One cause of damage after closed
head injury is the rotational forces that drive brain tissue against the inside of the skull
A stroke, also known as cerebrovascular accident has two types
o The more common ischemia
Result of a blood clot or other obstruction in an artery (deprivation of blood)
Neurons die because glucose and oxygen are missing
o The less common hemorrhage
 Result of a raptured artery
There is an excess of glucose, oxygen, and other chemicals
o For both types, excess glutamate is released which kills neurons and synapses by
overstimulation
A drug called tissue plasminogen activator (tPA) can break blood knots in case of ischemia
o The same drug would make matters worse in case of a hemorrhage. Normally, it is hard to
distinguish between the two types of stroke, so that the tPA is given, because hemorrhage
is less common and people with it usually die anyway
Cooling the brain is a new way to reduce stimulation in the brain, thereby reducing the death of
neurons, and cannabinoids actually seem to help too

Later Mechanisms for Recovery

Diaschisis = decreased activity of surviving neurons after damage to other neurons, caused by lack
of input
o Raising the activity of surviving neurons is crucial for long term recovery. Stimulating
drugs seem promising. Amphetamines would work, but they are too risky
Axon regeneration is limited in mammals. Way to fix this and to allow proper regeneration have
not been found yet
Axon Sprouting
o A neuron wants to fill vacant synapses on its dendrites. Therefore, it secretes neurotrophins
that induce other axons to form branches, or collateral sprouts
o Collateral sprouts can be helpful or hindering depending on the new axons that fill the
synapses. If they carry similar information, recovery will be aided.
 Denervation Supersensitivity
o Neurons adjust maintain a nearly constant level of arousal. If a certain set of synapses
becomes inactive, the remaining ones become more sensitive and responsive
o This helps compensate for decreased input, but can also lead to chronic pain
Phantom Limb
o If we lose an arm, the axons of the nerves there will degenerate, leaving the corresponding
area of the somatosensory cortex with a lot of empty synapses
o Through collateral sprouting and denervation supersenitivity it can happen that axons from
other areas, for example the face, will take over the synapses of that part of the cortex.
Stimulation from these new areas is still perceived as a stimulation from the arm, leading
to the feeling of a phantom limb

The feeling of a phantom limb can be painful and short term as well as long term
o Amputees who use artificial arms or legs gradually lose the phantom pain. As they start
attributing sensations to the artificial arm, they displace the abnormal connections that
caused phantom sensations.
 Learned adjustments in behavior
o Much recovery from brain damage is based on learning
o It is effortful but worth it to push and use the impaired limbs for better recovery

Chapter 7: Movement

Module 7.1: The Control of Movement

Muscles and Their Movements
There are 3 categories of vertebral muscles
o Smooth muscles = control the digestive system and other organs
o Skeletal/striated muscles = control movement of the body in relation to the environment
o Cardiac muscles = control the heart

Each muscle fiber receives information from only one axon, but an axon can activate more than
one muscle fiber
o E.g. in the eye one axon activates about 3 fibers for high precision
o and in the biceps about a hundred
Neuromuscular junction = synapse between a motor neuron and a muscle fiber
In skeletal muscles, the axon releases acetylcholine at the neuromuscular junction
o Acetylcholine always excites the muscle to contract
Not enough acetylcholine impairs movement
Just contracting, no message for relaxation (relaxes on its own if no signal is there)
Opposite direction through antagonistic muscles
 o One flexor and one extensor

Some animals have different kinds of muscle fibers: red (slow, but dont fatigue fast) white (fast,
but also fatigue fast) pink (in between)
Humans have also different kinds of muscle fibers:
o Fast-twitch fibers = fast contraction, fast fatigue
e.g. if you run
anaerobic use reactions that do not require oxygen, but need oxygen to recover
using builds up oxygen debt
o Slow-twitch fibers = slow contraction, slow fatigue
e.g. if you talk or if you walk
aerobic using oxygen during their movement pay as you go
Imagine you are on a bike
o First aerobic activity, uses glucose
o After glucose gets down, gene activates that inhibits muscles to use glucose (to safe
glucose for the brain)
 o You rely more on fast-twitching fibers, that depend on fatty acids
o You get gradually more fatigue
Percentage between fast- and slow-twitching fibers depends on genes and training
o Marathon runner have lots of slow-twitching fibers
o Runner have lots of fast-twitching fibers

A proprioceptor helps you adjust your body

o Detects the position or movement of the body
o Detect the stretch and send messages that enable the spinal cord to adjust its signals
Then the spinal cord sends signal to contract muscle reflexively (stretch reflex)
o One kind of proprioceptor: muscle spindle
Receptor parallel to the muscle that responds to the stretch
If it is stretched it sends message to contract the muscles around to oppose the
stretch
Like the knee reflex
o Another: golgi tendon organs
Located at opposite end of the muscles
Respond to increases in muscle tension
Brake against excessive contraction
Units of Movement
Reflexes: Few things totally involuntary, few things totally voluntary
Balistic movement = e.g. a reflex, like a thrown ball, executed as a whole, once initiated it can not
be altered
o Opposite are behaviours that are subject to feedback correction
Central pattern generators = neural mechanisms in the spinal cord that generate rhythmic
pattern of motor output (e.g. playing an instrument, birds that use their wings)
o Even do it without brain, you just need your spine
Motor program = Fixed sequence of movements
o Once begun the sequence is fixed from beginning to end
o E.g. flapping with the wings if you drop a bird
o Or yawning in humans

Module 7.2: Brain Mechanisms of Movement

The Cerebral Cortex

Direct electrical stimulation to the primary motor cortex elicits movement
o Its axons extend to the brainstem and spinal cord, which then generate the impulses that
control the muscles
Some axons go directly to motor neurons, others to interneurons
Somatosensory cortex and primary motor cortex are very similar
o Primary motor cortex just anterior to somatosensory cortex
o E.g. Left leg is on the same position on both
If given brief electrical stimuli to the neurons in animals they exhibit short isolated twitches
If given longer stimuli (half a second) they make more complex movement patterns like grasping
o Even in monkeys that they put their hands to the mouth, always the same way with the
same stimuli to the same spot
o Stimuli results in a certain outcome not just a muscle movement
 One area that becomes first active in planning movement is the posterior parietal cortex
 o It monitors the position of the body relative to the world
o If stimulated patients report an intention to move
o More intense stimulation leads the patients to assume they did move their bodypart
o Theories suppose that we first assume what to do and then act on it, while posterior parietal
cortex is active stronger if we want to move
Prefrontal cortex and supplementary motor cortex also important for planning and organising
rapid sequences of movement
o If you have the habitual action, such as turning to the left, the supplementary motor cortex
inhibits this action if you need to do something else
Premotor cortex is most active immediately before a movement
o Receives information about the target to what the person is moving
o Information about the bodies current position and posture
Prefrontal cortex also active during a delay before a movement and stores sensory information
relevant to the movement
o Damage would lead to disorganized movements (e.g. showering with clothes)
o Inactive while sleeping (one explanation why we do illogical things in our sleep)

Saccade is a voluntary movement of the eye to a target (e.g. moving finger)

Antisaccade task = look in the opposite direction
o Before 5 to 7, almost impossible for children
o Improves over the time
o Needs prefrontal cortex and basal ganglia activity before recognizing the target
o ADHD people not very good at antisaccade tasks

Mirror neurons
o Active for preparation of a movement and while observing someone performing an action
o Not just seeing, also if you are reminded of an action
Some respond on hearing or reading about it
o Question: Are the mirror neurons to imitate others (social learning) or because we see our
own movement in others?
 Different for different movements
Some are imitated from babies and show activation
Some are, if they observe movements they havent done, trigger no
activation
Some motor neurons can learn to react on other stimuli
If you move your index finger, if someone moves their pinky, after
some time the pinky will activate the mirror neurons of the index
finger

Paths from the cerebral cortex to the spinal cord are called the corticospinal tracts
o Two tracts: lateral and medial corticospinal tracts
o Lateral corticospinal tract:
From primary motor cortex and surrounding areas
From red nucleus = midbrain area primarily responsible for controlling the
muscles in the arms
In bulges of the medulla called pyramids the lateral tract crosses to the
contralateral (opposite) side of the spinal cord (contralateral connection)
Controls movement in peripheral areas such as feet and foot
o Medial corticospinal tract:
From many parts of the cortex
Also axons from the midbrain tactum, reticular formation & the vestibular nucleus
= receives input from the vestibular system
Go to both sides of the spinal cord
Controls muscles of the neck, shoulders, trunk and therefore bilateral movements
like walking, turning, bending & sitting down
Lateral tract control muscles on the lateral parts of the body, medial tract control muscles on the
medial part of the body
The Cerebellum
o Contains more neurons than the rest of the brain combined
o Damage leads to trouble in clapping, pointing at moving objects and everything else that
needs aim and timing
Does not impair continuous motor activity, like drawing a cycle
Have problems with saccades, ballistic eye movement from one point to another
Resembles symptoms of alcohol intoxication: clumsiness, blurred speech,
inaccurate eye movement
Finger to nose test in 3 steps:
o Finger moves ballistically to a point just in front of the nose
Depends on cerebellar cortex (surface of the cerebellum) that sends messages to the
deep nuclei in the interior cerebellum
o Finger remains steady at the spot for a fraction of a second
Depends on the nuclei alone
o Moves slowly to the nose by slower movement
Does not depend on cerebellum
Cerebellum also active if:
o An object is rubbed over unmoving hand
o Violations of expected sensation (think you touch something but you dont, dont think you
touch something, but you do)
Masao Ito: Cerebellum establishes new motor programs that enable to execute a sequence of
action as a whole
Seems to be also important for attention and attention shift
 Cellular organisation of the cerebellum:
o From spinal cord from each sensory systems by way of the cranial nerve nuclei & from
cerebral cortex
Neurons arranged in geometrical pattern
The Purkinje cells are flat (two-dimensional) cells in sequential planes, parallel to
one another
The parallel fibers are axons parallel to one another and perpendicular to the
planes of the Purkinje cells.
Action potentials in parallel fibers excite one Purkinje cell after another.
Each Purkinje cell then transmits an inhibitory message to cells in the
nuclei of the cerebellum (clusters of cell bodies in the interior of the
cerebellum) and the vestibular nuclei in the brainstem, which in turn send
information to the midbrain and the thalamus.
Depending on which and how many parallel fibers are active, they might stimulate
only the first few Purkinje cells or a long series of them
Because the parallel fibers messages reach different Purkinje cells one after
another, the greater the number of excited Purkinje cells, the greater their
collective duration of resonse
If the parallel fibers stimulate only the first few Purkinje cells, the
result is a brief message to the target cells
If the parallel fibers stimulate more Purkinje cells, the message lasts
longer
The output of Purkinje cells controls the timing of a movement, including both its
onset and offset
The Basal Ganglia
Applies collectively to a set of large subcortical structures in the forebrain
o Includes caudate nucleus, the putamen (together known as striatum or dorsal striatum
o Globus pallidus
Striatum
o Input from: cerebral cortex and substantia nigra
o Output to: globus pallidus
Globus pallidus to thalamus
Thalamus to frontal cortex
Direct and indirect pathway
o Direct: striatum inhibits globus pallidus, inhibits part of thalamus
By inhibiting an inhibitor the net effect is excitation
 o Scientist believe direct pathway enhances directed movement and indirect inhibits
inappropriate competing movements
o Indirect is essential for learning
Basal ganglia is important for spontaneous, self-initiated behaviors
o Activity when participants drew a free line, but not if they traced a line that was already
there
o In general, self initiated behaviours are slower than those that a stimulus triggers
o You can win a gunfight if you draw second, because reaction to a stimulus is faster than
spontaneous movement
Cells in the primary motor cortex becomes active before those in the basal ganglia
o Basal ganglia therefore not responsible for selecting which movement to make, but to
regulate the vigor of the movement
Many cells in the basal ganglia react to the reward value of a possible action
o React more strongly to a larger or more certain reward
Brain Areas and Motor Learning
Neurons in the motor cortex adjust their responses as a person or animal learns a motor skill
At first, movements are slow and inconsistent
As movements become faster, relevant neurons in the motor cortex increase their firing rates
After training, the movement patterns become more consistent from trial to trial, and so do the
patterns of activity in the motor cortex
Basal ganglia are critical for learning new habits (motor habits)
o Hard for people with basal ganglia damage to learn new motor skills and at converting
new movements into smooth automatic responses

Conscious Decisions and Movement

Before we voluntarily move, the motor cortex produces a kind of activity called a readiness
potential
o At least 500 ms before the movement
o So someone monitoring your activity knows your decision before you do
o Still debated
Module 7.3: Movement Disorders

Parkinsons Disease
Main symptoms:
o rigidity,
o muscle tremors,
o slow movements,
o difficulty initiating physical and mental activity
1 to 2 per cent of over 65 years old
Many but not all have cognitive deficits, which may include problems with attention, language, or
memory
Cause is the gradual loss of neurons in the substantia nigra
o Therefore loss of dopamine-releasing axons to the striatum (part of basal ganglia)
o With loss of this input, the striatum decreases its inhibition of the globus pallidus
o Which therefore increases its inhibitory input to the thalamus
Results in less vigorous voluntary movements
Spontaneous movements are slow and weak
 Causes
o Genes
Having a monozygotic twin with early onset greatly increases your probability
But not having a twin with late onset
o Toxics
MPTP, a chemical the body converts to MPP+ which accumulates in, and then
destroys neurons that release dopamine, partly by impairing the transport of
mitochondria from the cell body to the synapse
Postsynaptic neurons react to the loss of input by increasing their number of
dopamine receptors
Studies show increase in people with much exposure to insecticides, herbicides, and
fungicides
Cigarette smoking and coffee drinking decreases the chance to develop Parkinson
(FUCK YEAH)

L-Dopa Treatment
o L-dopa, a precursor to dopamine that crosses the blood-brain barrier
 o Most common treatment for Parkinsons disease
o Increases dopamine release in all axons, in those that had deteriorated and those that were
still functioning normally
o Does not replace other transmitters that are depleted and does not slow the continuing loss
of neurons
o Sideffects: nausea, restlessness, sleep problems, low blodd pressure, repetitive movements,
and sometimes hallucinations and delusions

Experiments on rats: transplanted tissue from rat foetuses into the damaged brains, worked well
Stem cell transplantation
o Guide development, that they produce large quantities of L-dopa and then transplant
Neurotrophins, that are released by transplanted tissue showed behavioural recovery signs
o To apply it you need a surgery, as neurotrophins do not cross the blood-brain barrier

Huntingtons Disease
1 in 10.000 people in the US
Symptoms
o Tremors: Jerking and facial twitches
o Gradually the tremors spread over the body and develop into writhing
o They interfere more and more with walking, speech, and other voluntary movements
o Lose of ability to learn or improve motor skills
o Associated with gradual, extensive brain damage, especially in the basal ganglia but also
the cerebral cortex
Because output from the basal ganglia is inhibitory to the thalamus, damge leads to
increased activity in motor areas of the thalamus
That increase produces the involuntary jerky movements
o Also suffer psychological disorders: Depression, sleeplessnesss, memory impairment,
anxiety, hallucinations and delusions, poor judgment, alcoholism, drug abuse, and sexual
disorders
o People in early stages are occasionally misdiagnosed as having schizophrenia
o Most between the ages of 30 and 50
 Heridity
o Results from an autosomal dominant gene (dominant gene)
o Accurate test if you get it
o The critical area of the gene includes a sequence of bases (C-A-G, cytosine, adenine,
guanine) which is repeated
11 to 24 times in most people,
up to 35 are considered safe from Huntingtons
36 to 38 might or might not get it, but probably not before old age
39 or more repetitons are likely to get the disease, unless they diee of other causes
earlier
The more C-A-G repetitions someone has, the earlier the probable onset of the
disease
o History of drug or alchohol abuse increases the probability of early onset
o The gene codes the protein huntingtin
Occurs in the whole body but does only produce harm in the brain
In early stage increases neurotransmitter release, sometimes causing
overstimulation of the target cells
Later, protein forms cluster that impair the neurons mitochondria
It also impairs the transport of chemicals down the axon

Chapter 8: Wakefulness and Sleep

Module 8.1: Rhythms of Waking and Sleeping
Endogenous Rhythms
Endogenous circannual rhythm: Yearly rhythms that lead animals to do season specific acts, e.g.
birds to fly south
Endogenous circadian rhythms: Rhythms that last about a day, like the sleep rhythm
o We have circadian rhythms in our eating and drinking, urination, hormone secretion,
metabolism, sensitivity to drugs, and other variables
o Also for mood
o Humans generate 24-hour wake-sleep rhythms, that can be modified only a little
Setting and Resetting the Biological Clock
We readjust our internal workings daily to stay in phase with the world
Although circadian rhythms persist without light, light is critical for resetting them
The stimulus that resets the circadian rhythm is referred to by zeitgeber
o Light is the dominant zeitgeber for land animals
o Other zeitgebers are
Exercise
Arousal of any kind
Meals
Temperature of the environment
They modify the effects of light, but have only weak effects on their own
Humans sleep midpoint (point between going to bed and awaken) correlates with the time the sun
goes up
o sun in west Germany rises half an hour earlier as in eastern Germany and their midpoint
differs half an hour on the weekends
Half of all blind people report frequent sleep problems, because light as a zeitgeber is not available
Jetlag: mismatch between internal circadian clock and external time
o Most people find it easier to adjust to crossing time zones going west
West, we stay awake later at night and then awaken late the next morning
West, we phase-delay our circadian rhythms
East, we phase-advance to sleep earlier and awaken earlier
o Leads to highten levels of the adrenal hormone cortisol
Prolonged elevations of cortisol damage neurons in the hippocampus
Flight attendants who spent 5 years making flights have on average smaller
hippocampus and surrounding structures and showed memory impairments
Night workers can adjust best if they sleep in a dark room and work their shift in short-wavelength
(bluish) light, instead of long-wavelength light
o Takes sometimes years to adjust to it
There are individual differences in circadian rhythms
o Some people awaken early (larks)
Most impaired at night shifts
o Some late (owls)
 Most impaired at morning shifts
Circadian rhythms differ by age
o Children normally go to bed early and wake up early
o Adolescent stay up lat and wake up late
This happens in all cultures and other species
apparently results from increased levels of sex hormones

People in big cities, that are surrounded by bright lights, are more likely to stay up late than people
from rural areas
People that go to school and are strongly evening types tend to get lower than average grades
o They suffer from social jet lag
o They are also more likely to use alcohol, overeat, and engage in other risky behaviours
Beyond teenage years, morning people report being happier than evening people
o Possibly because they are better tuned with a 9-to-5 work schedule

Mechanisms of Biological Clock

Curt Richter came up with the idea of the biological clock: the brain generates its own rhythms
o Biological clock remains surprisingly steady despite irritations like most kinds of brain
damage, or removal of endocrine organs
 Main driver of rhythms for sleep and body temperature is the suprachiasmatic nucleus (SCN)
o It is a part of the hypothalamus
o Just above the optic chiasm
o Damage to it leads the bodys rhythms to become erratic
o The SCN neurons, even if removed from the body, continue to produce a circadian rhythm
of action potentials
Even a single cell can maintain a rhythm, but interactions among cells sharpen the
accuracy of the rhythm
o Transplanted tissue from hamsters with a 20-hour rhythm into 24-hour rhythm hamsters, in
which the SCN was removed, lead them to have a 20-hour rhythm and vice versa

A small branch of the optic nerve from the retina to the SCN, called the retinohypothalamic path
alters the SCNs settings
o Most input to that path does not come from normal retinal receptors
The retinohypothalamic path to the SCN comes from special population of retinal
ganglion cells that have their own photopigment, called melanopsin, unlike the
ones found in rods and cones
 These ganglion cells receivesome input from rods and cones, but even if not
respond directly to light
They are located mainly near the nose towards the periphery
They respond to light slowly and turn off slowly when the light ceases
They respond mainly to short-wavelength (blue) light
o Consequences are
Some blind people, despite have damage to rods and cones or damage to visual
cortex entrain their wakin and sleeping cycle to the pattern of sunlight
Bright light, that aggravates migraine headaches for many blind people are caused
when the melanopsin-containing ganglion cells send input to the posterior thalamus
Exposure to short-wavelength light from e.g. computers or cell phones reset the
circadian rhythm and phase-delaying it

How is the circadian rhythm produced? Research on the fruit fly (Drosophila)
o Two genes produce two proteins
The gene period (PER) produce the protein PER
The gene timeless (TIM) produce the protein TIM
o These two proteins promote sleep and inactivity and oscillates over a day, based on
feedback interactions among neurons
o Early in the morning, the messenger RNA levels responsible for producing PER and TIM
start at low concentrations
o They increase during the day, they increase synthesis of the proteins, but the process takes
time, and the protein concentrations lag hours behind
o As PER and TIM protein concentration increase, they feed back to inhibit the genes that
produce the messenger RNA molecules
o So, during the night, the PER and TIM concentrations are high, but the messenger RNA
concentrations are declining
o At the next morning, PER and TIM protein levels are low and the cycle starts again
 Light breaks down the TIM protein, thereby increasing wakefulness and synchronizing the internal
clock to the external world
Mammals have three versions of the PER protein and several proteins closely related to TIM
Mutations in the gene PER alters the sleep schedule
o People with PER mutation have a circadian rhythm shorter than 24 hours

SCN regulates waking and sleeping by controlling activity levels in other brain areas, including
the pineal gland, an endocrine gland located just posterior to the thalamus
The pineal gland releases the hormone melatonin, which influences both circadian and circannual
rhythms
o Mostly secretes melatonin at night, making us sleepy at that time
o In new time zones, you will keep feeling sleepy until the melatonin rhythm shifts
o People with pineal gland tumors sometimes stay awake for days at a time
o Secretion starts to increase about 2 or 3 hours before bedtime

Module 8.2: Stages of Sleep and Brain Mechanisms

Sleep and Other Interruptions of Consciousness

Sleep is a state that the brain actively produces, characterized by decreased response to stimuli
 Coma is an extended period of unconsciousness caused by head trauma, stroke, or disease
o Someone in a coma has a low level of brain activity and little to no response to stimuli
Vegetative state alternates between periods of sleep and moderate arousal
o During aroused state the person shows no awareness of surroundings and no purposeful
behavior
Breathing is more regular
Painful stimulus produces at least the autonomic responses of increased heart rate,
breathing and sweating
Minimally conscious state is one stage higher than vegetative state, with occasional, brief periods
of purposeful actions and limited speech comprehension
Brain death a condition with no sign of brain activity and no response to any stimulus
o When someone has not shown signs of brain activity for 25 hours he is pronounced brain
death

Stages of Sleep

A polysomnograph combination of EEG and eye-movement records

(a) Alpha waves are at a frequency of 8 to 12 per second and steady (Relaxed, awake)
 (b) Stage 1: Beginning of sleep, irregular, jagged, low-voltage waves
o Brain activity less than in wakefulness but higher than other sleep stages
(c) Stage 2: Most prominent characteristics are
o Sleep spindles 12- to 14-Hz waves during a burst that lasts at least half a second
Result from oscillating interactions between cells in the thalamus and the cortex
o K-complex sharp wave associated with temporary inhibition of neuronal firing
(d) & (e) Stages 3 and 4: Heart rate, breathing rate, and brain activity decrease, slow, large
amplitude waves become more common
o Differ only in prevalence of these slow waves, and some combine them, calling them the
slow-wave sleep (SWS)
o Slow waves indicate that neuronal activity is highly synchronized

Paradoxical or REM Sleep

Periods while asleep in which rapid eye movement occur have been termed this way (REM sleep)
Paradoxical sleep, because the recorded sleep is in some ways deep and light in others
o EEG shows irregular, low-voltage fast waves that indicate increased neuronal activity
o But postural muscles of the body, including those supporting the head are more relaxed
during REM than in other stages
o Associated with heart rate, blood pressure, and breathing rate are more variable in REM
than in stage 2 through 4
o Stages other than REM are known as non-REM (NREM) sleep
 o When you fall asleep you start in stage 1 and slowly progress from 2-4
o After an hour you begin to cycle back from 4-2 and then REM
o Cycle repeats with each cycle lasting about 90 minutes
o Early at night, stages 3 and 4 predominate
o Towards the morning REM occupies an increasing percentage
Amount of REM depends on time of day more than how long you have been asleep
People who were awakened during REM reported dreams 80 to 90 % of the time
o Also dreams in NREM
o REM are more likely to include visual imagery and complicated plots
o REM and dreams are not the same thing

Brain Mechanisms of Wakefulness, Arousal, and Sleep

After a cut through midbrain separating the forebrain and part of the midbrain from all the lower
structures
o Animal enters a prolonged state of sleep for the next few days
o Even after weeks of recovery, the wakeful periods are brief
Might conclude: cut isolated the brain from the sensory stimuli from the medulla
and spinal cord
But if each individual tract that enters the medulla and spinal cord is cut, the animal
still has normal periods of wakefulness
 So the midbrain does more than just relay sensory information = Mechanism to
promote wakefulness
Cut through midbrain decreases arousal by damaging the reticular formation
o A structure that extends the medulla into the forebrain
o Some neurons have axons descending into the spinal cord form part of the medial tract of
motor control
o Some guy proposed that those with ascending axons regulate arousal
o One part of the reticular formation that contributes to cortical arousal is the
pontomesencephalon:
These neurons receive input from many sensory systems and generate spontaneous
activity
Axon extend into the forebrain, releasing acetylcholine and glutamate, which excite
cells in the hypothalamus, thalamus and basal forebrain
It maintains arousal during wakefulness and increases it in response to new
challenging tasks
Stimulation wakes sleeping, and alerts awake people
EEG shifts from long, slow waves to short, high-frequency waves
The locus coeruleus, is a small structure in the pons
o Usually inactive, especially during sleep
o Emits bursts of impulses in response to meaningful events, especially to emotionally
arousal
o Axons from the locus release norepinephrine widely throughout the cortex
Output from locus increases gain increased activity of most active neurons,
decrease activity of less active
The hypothalamus also influence arousal
o One pathway releases the excitatory neurotransmitter histamine
It enhances arousal and alertness throughout the brain
Antihistamine drugs, used for allergies, counteract this transmitter and produce
drowsiness
o Another pathway (mainly from the lateral and posterior nuclei) releases a peptide
neurotransmitter called orexin or hypocretin (we call it orexin)
 Extends from hypothalamus to the basal forebrain and other areas, enhancing
wakefulness
Not for waking up, but for staying awake
Especially towards the end of the day
Mice without orexin alternate faster between awake and asleep, even while
doing activities
Drugs that block orexin receptors help people go to sleep
o Other pathways from the lateral hypothalamus regulate cells in the basal forebrain (just
anterior and dorsal the hypothalamus)
Basal forebrain cells provide axons that extend throughout the thalamus and
cerebral cortex
Some release acetylcholine, which is excitatory and tends to increase
arousal
Acetylcholine is released during wakefulness and REM sleep, but not
during slow-wave sleep
During wakefulness, it sharpens attention increases the accurate, reliable
detection of sensory stimuli
 Sleep depends partly on decreased sensory input to the cerebral cortex
During sleep, neurons in the thalamus become hyperpolarized
o Decreasing rediness to respond to stimuli and decreasing the information they transmit to
the cortex
o If they fire, they often fire synchronous bursts, yielding the high-amplitude waves
characterizing slow-wave sleep
To remain unconscious in spite of neuronal activity, during sleep, axons that release the inhibitory
neurotransmitter GABA increase their activity, interfering with the spread of information
o Sleep depends on GABA-mediated inhibition, therefore sleep can be local within the brain.
This explains
Dolphins and other aquatic mammals just sleep with one side of the brain to control
swimming and breathing
Also can explain sleepwalking (somnambulism) awake in the motor cortex and a
few other areas
Also lucid dreaming some brain area is more awake than usual during dreaming,
capable of monitoring dreams
Or if one wakes up but finding that it is not possible to move arms or legs
During REM sleep, cells in the pons and medulla send messages that inhibit
the spinal neurons that control bodys large muscles
Normally awakening from REM period, those cells in the pons shut off and
you regain muscle control, but sometimes pons remains in REM you
cannot move

During REM sleep,

o activity increased in the pons (triggers the onset of REM sleep)
o The limbic system (important for emotional responses)
o Parts of the parietal and temporal cortex

o Activity decreased in the primary visual cortex

o The motor cortex
o And the dorsolateral prefrontal cortex
 REM sleep is associated with a distinctive pattern of high-amplitude electrical potentials known as
PGO waves (ponsgeniculate-occipital waves)
Waves of neural activity are detected first in the pons,
Shortly afterward in the lateral geniculate nucleus of the thalamus
Then in the occipital cortex

REM sleep depends on a relationship between the neurotransmitters serotonin and acetylcholine
o Injections of the drug carbachol, which stimulates acetylcholine synapses, quickly move a
sleeper into REM sleep
o Acetylcholine is important for both wakefulness and REM sleep (states of brain arousal)
o Serotonin and norepinephrine interrupt REM sleep

Sleep Disorders
Most people need about 7,5 to 8 hours sleep, but some have been known to just need 3
Insomnia (inadequate sleep) depends on how you feel the following day
Causes for insomnia
o Noise, uncomfortable temperatures, stress, pain, diet, and medications
o Result from epilepsy, Parkinson, brain tumors, depression, anxiety
 o Some children due to their milk-intolerance
o Some due to shifts in circadian rhythms
People normally fall asleep while their temperature is declining and awaken while
it is rising

Sleep apnea impaired ability to breathe while sleeping

1. Breathless periods for a minute from which they awaking gasping for breath
2. May not remember all their awakening, but still sleepiness during the day, impaired
attention etc.
3. People with apnea show reduced neurons and deficiencies of learning, reasoning, attention,
and impulse control
 Its correlational but research suggests apnea leads to brain abnormalities
In mice that were subjected to periods of low oxygen lose some neurons and impair
others, especially in areas responsible for alertness
o Results from causes, including genetics, hormones, and old-age deterioration of the brain
mechanisms for breathing, obesity (narrower airways)

Narcolepsy a condition characterized by frequent periods of sleepiness during the day

Main symptoms:
1. Attacks of sleepiness during the day
2. Occasional cataplexy attack of muscle wakness while the person remains awake.
Triggered by strong emotions (anger or great excitement e.g. wedding ceremony)
3. Sleep paralysis inability to move while falling asleep or waking up
4. Hypnagogic hallucinations dreamlike experiences that the person has trouble
distinguishing from reality
Reason for Narcolepsy relates to the neurotransmitter orexin
o People lack the hypothalamic cells that produce and release orexin
Since orexin cannot cross the blood- brain barrier, people get methylphenidate
(Ritalin) which enhance dopamine and norepinephrine activity

Another sleep disorder is periodic limb movement disorder

o Characterized by repeated involuntary movement of the legs and sometime the arms during
sleep
o Mostly middle-aged and older
o Legs kick once every 20 to 30 seconds for minutes or hours, mostly during NREM sleep

People with REM behavior disorder move around vigorously during their REM periods,
apparently acting out their dreams
o Often injure themselves or other people and damage property
o Mice deficient in GABA and other inhibitory transmitters show running, jerking, and
chewing movements in sleep
 Therefore it is suggest that inadequate inhibitory transmission is responsible for
REM behavior disorder

Night terrors the experiences of intense anxiety from which a person awakens screaming in
terror
o More severe than a nightmare
o Occur during NREM sleep
o More common in children than adults
Sleepwalking
o Runs in families
o Occurs mostly in children
o Most have additional sleep difficulties such as chronic snoring, disordered sleep breathing,
bed-wetting, and night terrors
o More common when people are sleep deprived or under unsusual stress
o Most common during slow-wave sleep early in the night and not during REM sleep
o Parts of the brain are awake, others are not
o Sexsomnia sleeping people engage in sexual behavior with partner or by masturbation

Module 8.3: Why Sleep? Why REM? Why Dreams?

Functions of Sleep
During Sleep, we
o Rest our musles
o Decrease metabolism
o Perform cellular maintenance in neurons
o Reorganize synapses
o Strengthen memories
People without enough sleep
o react more severly than average to stressful events
o develop symptoms of mental illness or aggravate symptoms they already had
o are a major cause of accidents by workers and poor performance by college students
 o activate their immune system you react to sleep deprivation as if you were ill

One hypothesis why we sleep is to save energy

o Nearly every species is more efficient at some times of day than at others (good vision
more efficient in the day, those rely on other senses better at night)
o Mammals decrease 1 to 2 degree in body temperature, which safes lots of energy
o Animals increase their sleep duration during food shortages, when energy conservation is
important
o Squirrel that is prevented from hibernating show symptoms like a human prevented from
sleeping hibernation is simply to conserve energy

When hibernating
o animals decrease their body temperature to only slightly above that of the environment
o Heart rate drops to almost nothing
o Brain activity drops to almost nothing
o Neuron cell bodies shrink
o Dendrites lose almost a fourth of their branches, replacing them later when body
temperature increases
Some facts about hibernating
o If bears hibernate is a matter of definition: bears sleep most of the winter, lowering their
body temperature a few degrees and decreasing their metabolism and heart rate, but their
state is not as extreme as that of smaller hibernators
o Hibernating animals come out of hibernation for a few hours every few days, raising body
temperature
o Hibernation retards the aging process
Also decrease vulnerability to infection and trauma

Some species differences in sleep that support the view of sleeping in times of inefficiency and to
conserve energy
o Some fish in caves without day in night do almost never sleep
o Dolphins and whale give birth and mother and baby stay awake the whole day for the first
couple of weeks while the baby is vulnerable show no signs of sleep deprivation
o Birds decrease their need for sleep during migration
o Grazing animals that need to eat for many hours per day get less sleep than carnivores
 Another function of sleep is improved memory
o If people learn something and then go to sleep, their memory often becomes better than it
was before the sleep
Not just absence of forgetting but gain of memory
o Also helps people to reanalyze their memories and detect hidden rules
Patterns in the hippocampus while learning resemble the same patterns during sleep, except they
were more rapid while sleeping
o Amount of hippocampal activity during sleep correlated highly with the subsequent
improvement in performance
o Brain replays its daily experiences
Maybe long-term potentiation takes place and important connections get strengthened and
unimportant ones gets weakened or removed
Sleep spindles, the connections between thalamus and ecerebral cortex in stage 2 increase number
after new learning and their number correlates positively with improvements in certain types of
memory
Functions of REM Sleep
Avarage person spends a third of her life asleep and about a fifth of sleep in REM
Species with most hours of sleep have the highest percentage of REM sleep
o Also in humans
One hypothesis is that REM is important for memory storage, especially for weakening the
inappropriate connections
REM and NREM sleep may be important for consolidating different types of memories
o Depriving people of sleep early in the night (mostly NREM sleep) impairs verbal learning,
such as memorizing a list of words
o Depriving people of sleep during the second half of the night (more REM) impairs
consolidation of learned motor skills
o But people on antidepressants with decreased REM sleep do not show memory problems
Might be to get enough oxygen to the corneas of the eyes
o Makes sense because the fluid around the corneas gets more stagnant with the night you
have more REM late
o More hours of sleep, more REM, more shaking, better for the corneas
o But the antidepressant people do not suffer damage to the cornea argument kinda invalid

Biological Perspectives on Dreaming

The activation-synthesis hypothesis a dream represents the brains effort to make sense of
sparse and distorted information
o Dreams begin with spontaneous activity in the pons. The PGO waves, that activate some
parts of the cortex, but not others
o The cortex combines this haphazard input with whatever other activity was already
occurring and does its best to synthesize a story that makes sense of the information
o Sounds in the room, occasionally get incorporated into a dream, although usually not
o While asleep the brain in its partly aroused condition feels the vestibular sensation of your
position of laying and interprets it as flying or falling

The clinic anatomical hypothesis

o Also emphasize that dreams begin with arousing stimuli combined with recent memories
 o Less emphasis on the pons, PGO waves, or REM sleep
o Dreams are thinking that takes place under unusual conditions
Litte info from sense organs and the primary visual and auditory areas of the cortex
have lower than usual activity
Also the primary motor cortex is suppressed, as are the motor neurons of the spinal
cord, so arousal cannot lead to action
Activity is suppressed in the prefrontal cortex, which is important for working
memory
Consistently we not only forget most dreams, but also lose track of what has
been happening within a dream (e.g. sudden scene changes) and loss of
volition (planning)
Other brain areas are free to generate images without constraints of interference
Activity is relatively high in the inferior (lower) part of the parietal cortex,
important for visuospatial perception
Damage there leads to problems binding body sensations with vision and
report not having dreams
Also activity in areas of visual cortex important for cisual imagery that
accompanies most dreams
Activity high in the hypothalamus, amygdala, and other areas important for
emotions and motivations
o Idea: internal or external stimulation activates parts of the parietal, occipital, and temporal
cortex and develops into a hallucinatory perception without sensory input to override it
Chapter 11: Emotional Behaviors
Module 11.1 What Is emotion?
Emotions are difficult to define across species, so we use the term emotional behaviors instead
The components of an emotion are: cognition, feeling, action

Emotions and autonomic arousal

Fight and flight reaction by the parasympathetic nervous system (see chapter 3)
James- Lange theory (we all know it)

o People who cannot feel their physiological reaction report weaker emotions
Feeling a body change is important for feeling emotion
Having a strong reaction of the sympathetic nervous system without knowing why, can lead to
a panic attack
Bottom Line: Physiological reactions influence our experience of emotions, but not in a
defining way.
The limbic system traditionally is critical for emotions. BUT: new studies show that no part of
the brain is critical
o Conclusion: Emotions are a social construct
Do people have a limited number of basic emotions?
The evidence for distinct basic emotions is unconvincing
Two continues dimensions approach
o Behavioral activation system (BAS)
Low to moderate autonomic arousal
Tendency to approach, associated with happiness or anger
Left hemisphere
o Behavioral inhibition system (BIS)
Associated with fear and disgust, inhibits action, increases attention and arousal
Right hemisphere

The functions of emotions

Moral decision making: when we are deciding about right and wrong, we seldom work it out
rationally. One decision or the other just feels right. After we have already decided, we try to
think of a logical justification
o Any choice requires consideration of values and emotionshow we think one outcome or
another will make us feel
Failure to anticipate the unpleasantness of likely outcomes leads to bad decisions
Module 11.2 Attack and escape Behaviors
Most fight and flight/anger and fear are closely related behaviorally and physiologically

Attack behaviors
Readiness to attack can be heightened by aggravating stimuli
This is associated with activity in the amygdala

Men are more aggressive, as they have to compete for women and defend the young
The ration of testosterone (enhances aggression) and cortisol (inhibits aggression) is important for
aggressive behaviors
o The level of testosterone is not that important on its own, but it certainly has a significant
influence
Serotonin
o Low serotonin turnover is consistently correlated with high aggression in animals
o Serotonin turnover is measured by 5-hydroxyindoleacetic acid (5-HIAA) concentration in
the cerebrospinal fluid (positive correlation)
Animals survive best if they are not too aggressive (taking too much risk) but also
not too fearful (taking no risk)
o In humans, serotonin is a significant factor, but not important enough to allow us to make
predictions
Heredity and environment
o Both have an influence (surprise); there is no single gene that determines aggression
 o Gene-environment interaction can be seen on the (by this point well known) MAO
example, where low MAO gene only leads to increased aggression, if the child was
maltreated

o
To summarize the aggression part: biological explanations of aggression are not very well
developed yet

Fear and anxiety

Startle reflex = The auditory information reaches the pons very quickly which stiffens muscles,
especially the neck muscles
o Is used as a measurement for fear
The amygdala is critical to establish conditioned fears
The amygdala controls several independent fear responses, like safe places, freezing up, fear of
predators
 I think the figure-text explains the picture sufficiently
If the functionality of the amygdala is disabled in rats, they show no learning in fear responses,
and they show less fear overall
Bed nucleus of the stria terminals = responsible for long-term generalized arousal (generalizing
fear responses)

The amygdala reacts strongly to angry faces, but reacts the strongest to ambiguous facial
expression. It is working hard to interpret emotion-related information
 People with high amygdala responsivity also show more anxiety, which has a genetic basis but is
also influenced by the environment
Damage to the human amygdala
o People with this damage still have the cognitive component, but have an impaired
feeling component to unpleasant emotions
o Impairment at processing emotional information and learned fear
o Patient SM is completely fearless, does not even perceive it
!!Instead of being responsible for feeling fear or other emotions, perhaps the amygdala is
responsible for detecting emotional information and directing other brain areas to pay attention to
it in the proper way!!

Anxiety disorders
Panic disorder is characterized by frequent periods of anxiety and occasional attacks of rapid
breathing, increased heart rate, sweating, and tremblingthat is, extreme arousal of the
sympathetic nervous system
o Has a genetic disposition
o Associated with problems in the hypothalamus, GABA, and orexin (which is associated
with wakefulness)
Post-traumatic stress disorder (PTSD) = marked by frequent distressing recollections
(flashbacks) and nightmares about the traumatic event, avoidance of reminders of it, and vigorous
reactions to noises and other stimuli
o We presumably evolved mechanisms to adjust our anxiety level up or down depending on
the level of danger. The problem arises, if someone fails to readjust the anxiety level back
to a moderate level, long after returning to a safer environment
o Associated with smaller than average hippocampus (even before PTSD)
o Does not develop if amygdala is damaged

Relieve from anxiety

Drugs that increase the activity of the transmitter GABA, which inhibits anxiety
Benzodiazepines: bind to the GABA(a) receptor
 o At the center of the GABA(a) receptor is a chloride channel. When open, it permits
chloride ions (Cl) to cross the membrane into the neuron, hyperpolarizing the cell. (That
is, the synapse is inhibitory.)
o Benzos bind to the receptor and twist them open in a way that makes it easier for GABA to
attach
o Side-effects are still a problem
Alcohol works in a similar fashion. There actually is a drug that inhibits a lot of alcohols effect,
but it did not get on the market as that would be irresponsible
Drugs only work temporarily. We can use desensitization to erase anxiety
o This is best done before the memory is consolidated
o Reconsolidation (see cognitive psychology) can be used to erase anxiety
Propanolol could be used in combination with reconsolidation. If a memory is brought up during
the influence of porpanolol, it will be reconsolidated much weaker
Module 11.3 Stress and Health

Stress and the general adaption syndrome

Behavioral medicine: emphasizes the effects on health of diet, smoking, exercise, stressful
experiences, and other behaviors. We accept the idea that emotions and other experiences
influence peoples illnesses and patterns of recovery
Stress: nonspecific response of the body to any demand made upon it
General adaption syndrome: generalized response to stress
o Initial stage: alarm
Fight and flight reaction,
o Second stage: resistance
Fight and flight declines, but cortisol is still present to as well as other hormones
that increase alertness
o Third stage: exhaustion
Tired, inactive, vulnerable
In our modern society, stress is much more present than it was for our ancestors

Stress and the hypothalamus-pituitary-adrenal cortex axis

Stress activates two body systems
o 1. Sympathetic nervous system
o 2. HPA axis (hypothalamus-pituitary-adrenal)
H induces P to release ACTH (adrenocorticotropic hormone), which induces A to
secret cortisol, which enhances metabolic activity, increases alertness, etc.
 Immune system consists of cell that protect the body against intruders
Autoimmune disease: when the immune system is working to hard it starts to attack the bodies
normal cells
Leukocytes: white blood cells and most important part of the immune system
o Leukocytes include B cells, T cells, and natural killer cells
 o
Cytokines: small proteins that combat infections
o Stimulate the release of prostaglandins which in turn stimulate the hypothalamus to
produce fever, sleepiness, lack of energy, lack of appetite, and loss of sex drive
This bodily reaction is geared towards fighting the intruder
Psychoneuroimmunology: deals with the way experiences alter the immune system and how the
immune system in turn influences the central nervous system
o Brief stressful experiences activate the immune system which also triggers prostaglandins,
so that the body shows the typical symptoms of illness
o A prolonged stress response produces symptoms similar to depression and weakens the
immune system
The constant cortisol directs energy towards increasing the metabolism and
therefore decreases the energy used to synthesize the proteins needed for the
immune system
o Prolonged stress also damages the hippocampus
Stress control
Resistance to stress correlates with a strong connection between prefrontal cortex and amygdala
Resilience to stress is due to a mixture of genes and environment (what a surprise)

Chapter 12: The Biology of Learning and Memory

Module 12.1: Learning, Memory and Amnesia

Localized Representations of Memory

Two major categories of learning: classical & operational conditioning
 Lashley searched for the engram => physical representation of what has been learned (e.g.
connection between two brain areas)
o He made cuts in rat brains to produce interrupted connections and let them run mazes to
find engrams => no success
o In reaction, Lashley proposed two principles of the nervous system:

o Couldve been that running mazes is too complex (visual & tactile stimuli, position of its
head)
o His unnecessary assumptions;
Cerebral cortex is the best or only place to search for engram
Every kind of learning is basically the same

Thompson:
o Lateral interpositus nucleus (LIP) => Essential for learning, if cooled or drugged to not
send signal rabbits did not learn a CS, when recovered learned freshly
o Red nucleus, midbrain motor area receiving input from cerebellum=> if suppressed,
rabbits showed no reaction or learning of CS, when recovered, clearly they have been
better than before
Prevented response, but not learning
o Cerebellum plays an important role in learning
o Many instances of learning take place in different brain areas (like if something tastes
in the amygdala, etc.)
Types of Memory

Hebb: Distinction long-term (LTM) & short-term memory (STM)

o By storing something long enough in the STM makes it possible to consolidate it into
the LTM
Evidence points against Hebbs simplistic view
o E.g. at a soccer play you remember the score until it changes and an hour later => It
does not become automatically LTM, even after rehearsing it for an hour
 Emotionally significant information can be remembered more quickly
o This excitement leads to secretion of epinephrine and cortisol
o Cortisol activates the amygdala and hippocampus => There they enhance the storage
and consolidation of recent experiences
o Amygdala stimulates the hippocampus and cerebral cortex (both important for memory
storage)
o Prolonged stress (more cortisol) impairs memory
Consolidation can be fast or slow

Working memory: delayed response tasks (reacting to a stimulus delayed)

o Prefrontal cortex is an important location for this storage
o Cells in the prefrontal cortex and parietal cortex increase activity
Older people with declining memory show decline in activity in the prefrontal cortex
Older people with intact memory show greater activity in the prefrontal cortex
o Maybe prefrontal cortex has to work harder to compensate for impairments elsewhere
in the brain

Hippocampus is important to form memory and recall of memories

Patient HM: got his hippocampus removed
o No LTM, but WM
o Was able to form a few weak semantic memories (factual information, e.g. names of
famous people after his brain damage)
o Severe impairment of episodic memory (single, personal events)
o Retrograde amnesia for episodic memory strong (knows information, but not where he
got them from)
 Anterograde amnesia = Inability to form memories after the brain damage
Retrograde amnesia = Loss of memories of things occurred before the brain damage
People with damage to hippocampus and surrounding structure of the medial temporal lobe
o Both, antero- & retrograde amnesia
Retro, most severe for time leading up to the damage
 o People with anterograde amnesia where able to remember their own descriptions for the
shapes after some time
Recalling the past and imagining the future active mostly the same areas, including the
hippocampus
o People with amnesia as impaired at imagining the future as they are to describe the past
(no trouble with describing the present)

Patients with amnesia show better implicit, than explicit (deliberate recall, declarative
memory) memory
o Patient with amnesia became 3 helper, 1 friendly, 1 neutral, and 1 unfriendly helper
They had to choose from photos who they would like to take care from
They usually choose the friendly helper, and never the unfriendly, even if the
unfriendly was a cute girl smiling on the photo
Could not tell why he avoids her
Procedural memory => Kind of implicit memory for how to do motor skills
o Amnesia patients have it: HP was able to read books in the mirror (he learned it) and
was surprised of his skill
o When amnesia patients played Tetris, they improved slowly without remembering
playing it and they saw bricks coming down when they closed their eyes without
knowing how to interpret this
 1.: Hippocampus related to declarative and episodic memory
o Tested in animals with delayed matching-to-sample tasks & delayed nonmatching-to-
sample tasks:

2.: Hippocampus is involved in spatial memory

Taxi driver show greater activation in hippocampus when asked for a route (e.g. fastest way)
They also had a bigger posterior hippocampus => Actual growth of adult human hippocampus
in response to spatial learning experiences

3.: Hippocampus is important for contextual memory

Hippocampus, to create episodic memory, is a coordinator, a director of all the experiences,
like sound, colour, series of events and reconstructs the context
When people use their episodic memory, activity in and around the hippocampus synchronize
with several parts of the cortex => consistent with the idea of the hippocampus as providing
the connections
People remember better with detail and context (same room or something) for the short term,
becomes less important in the long term
o With passing time, memories are not as detailed and lose context. Then, activity in the
cortex is greater and hippocampus becomes less

Other Types of Amnesia

Korsakoffs syndrome/ Wernicke-Korsakoff syndrome
o Caused by prolonged thiamine (vitamin B1) deficiency
o Often happens with alcoholics
 o Thiamine important to metabolize glucose
o Thiamine deficiency leads to loss or shrinkage of neurons throughout the brain
o Most affected is the dorsomedial thalamus => main source of input to the prefrontal
cortex
o Similar symptoms like patients with prefrontal cortex damage:
Apathy, confusion, memory loss
Overlapping symptoms with hippocampal damage: impairment of episodic
memory, but spared implicit memory
Confabulation: Filling memory gaps with guesses
Not about semantic questions or nonsense questions
Mainly about episodic questions
Most answers are more pleasant than the actual present
Try to act according to their confabulations

Alzheimers disease
o Better procedural than declarative memory
o Gradually progresses to more serious memory loss, confusion, depression, restlessness,
hallucinations, delusions, sleeplessness, and loss of appetite
o Occasionally under 40, becomes more common (5% of 65y-74y, 50% over 85y)
o People with down-syndrome get it almost invariably (they have 3 copies of
chromosome 21)
o A gene on chromosome 21 is linked to early onset of Alzheimers (2 other genes are
also linked to it)
These cause the protein amyloid- to accumulate in- and outside neurons
They damage dendritic spines, decrease synaptic input & decrease plasticity
As amyloid damages axons and dendrites, the damaged structures form into a
cluster into structures names plaques
As plagues accumulate, cerebral cortex, hippocampus, and other areas
atrophy (waste away)
Amyloid- causes more phosphate groups to attach to tau-proteins (=
intracellular support structure of axons)
 The altered tau cannot bind to its usual targets within axons and starts
spreading into cell body and dendrites
Researches hypothesize that altered tau also increase the production of
amyloid-, leading to a cycle of reinforcement
Tau-proteins are responsible for tangles, structures formed from
degenerated neurons
o Another important gene that controls the chemical apolipoprotein E, that helps remove
amyloid-
o Half of the people with late onset does not have relatives with Alzheimers
o Most common treatment are drugs that stimulate acetylcholine receptors or prolong
acetylcholine release
o Most medicaments seem to be ineffective, because when the disease is recognized the
damage is already too extensive

Basal Ganglia

To make educated guesses (does it rain tomorrow, should I go out tonight, will my team win
the next game)
People with Parkinsons disease have impairments of the basal ganglia
o They do not acquire nonverbal habits
People learning under massive distraction get better, because their basal ganglia forms habits
Other Brain Areas and Memory

Amygdala important for fear memories

Patients with parietal lobe damage are not able to elaborate on a memory spontaneously, but
have an intact episodic memory
o The ability to associate things with one another is impaired
o This ability is important for memory, since the start of a story reminds us of how things
go on
People with damage to the anterior temporal lobe suffer semantic dementia
o They lost the ability to remember concepts (like the funny things on zebras, the concept
of stripes)
Functions of the prefrontal cortex:

o Contributes to learned behaviour and decision making in many ways

o Immaturity of the red areas could explain why children and adolescents often have trouble
inhibiting their impulses
o Blue areas (including the ventral prefrontal cortex) are important for learning about
rewards and punishments and making decisions based on them e.g. which of two bets gives
the better payoff
Basal ganglia also learns it, but more slowly and after a lot of repetition based on
the average reward
 Prefrontal more quickly on the most recent events
Confronted with an opportunity the ventromedial prefrontal cortex responds based
on the expected reward and sends this information to the orbitofrontal cortex
The orbitofrontal cortex responds based on how the reward relates to the other
possible choices

Module 12.2: Storing Information in the Nervous System

Blind Alleys and Abandoned Mines

Some examples where researcher were on the wrong course
o 1. Wilder Penfield (1955) applied brief, weak electrical stimulus to the brain
When the temporal cortex got stimulated patients saw vivid pictures
He suggested that each neuron stores a particular memory like a video tape
Instead of a memory it evoked more like a dream state
o 2. Horridge (1962) tested if captivated cockroaches learn via a test called yoked-control
design
They were given electrical shocks if their legs touched the water
He showed that captivated cockroaches can learn over the first 5 to 10 minutes
by tucking their legs to avoid the shock
But way more slowly and the results werent amazingly significant
o 3. In the 60s and early 70s researcher thought that memories are stored in the RNA or
protein
They injected extracted RNA of trained animals into other animals and thought
that they were better at the tasks the animals that got their RNA extracted were
good at
Inconsistent and couldnt be replicated

Learning and the Hebbian Synapse

Hebb suggested that, if a synapse is firing repeatedly or consistently some metabolic change or
growth process would take place in one or both cells
 A successful stimulation in the past would contribute to the success rate afterwards
This is strongly connected to the ideas of classical conditioning, since responses get stronger
(are conditioned)
This synapses are called Hebbian synapses
o An example for a Hebbian synapse are neurons in the eye when synapses in both eyes
fire at the same time the visual cortex increases response to both of them

Single-Cell Mechanisms of Invertebrate Behaviour Change

Invertibrate (without backbone) animals have some benefits to study, here the Aplysia (marine
invertebrate related to the slug
o Fewer and larger neurons than vertebrate
o Neurons are nearly identical from individual to individual
Often the withdrawal behaviour is studied: When something touches the Aplysia it withdraws
the irritated structure
You can habituate the Aplysia (reduced reaction to repeated stimuli)
You can sensitize Aplysia (strong reaction to normal stimuli as a result of exposure to intense
stimuli)
o The intense stimuli causes fascilitating interneurons of the Aplysia to excite serotonin
onto a postsynaptic terminals of many sensory neurons
o Serotonin blocks potassium channels in these membranes
o After later action potentials the membrane takes longer than usual to polarise, because
potassium is slow to flow out the cell
o Presynaptic neuron continues releasing its neurotransmitter for longer than usual
o Repeating this process causes the sensory neuron to synthesise new proteins that cause
long-term sensitization
This process shows how behavioural plasticity in terms of molecular events

Long-Term Potential in Vertibrates

 Experiments in mice show the phenomenon of long-term potentiation (LTP) could have
properties of learning and memory on cellular basis
o Long-term potentiation= One or more axons connected to a dendrite bombard it with a
rapid series of stimuli. The intense stimulation leaves some of the synapses potentiated
(more responsive to new input of the same type) for minutes, days, or weeks.
o Three properties are found
Specificity= If some of the synapses onto a cell have been highly active and
others have not, only the active ones become strengthened.
Cooperativity= Nearly simultaneous stimulation by two or more axons produces
LTP much more strongly than does repeated stimulation by just one axon.
Associativity= Pairing a weak input with a strong input enhances later response
to the weak input.
o In this regard, LTP matches what we would expect of Hebbian synapses.
o In some cases, a synapse that was almost completely inactive before
LTP becomes effective afterward
The opposite of LTP is long-term depression (LTD), a longterm decrease in response at a
synapse
o Like a compensatory process: For every strengthened synapse another synapse
weakens

AMPA synapses have AMPA receptors that are excited by the neurotransmitter glutamate, but
can also react to the drug AMPA
NMPA synapses have NMPA receptors that are excited by glutamate, but can also react to the
drug NMPA
o Both are ionotropic receptors (if stimulated they open channels to let ions enter the
postsynaptic cell)
AMPA opens sodium channels after glutamate excites it
NMPA opens only if besides glutamate a negative charge is inside the cell
Otherwise its channels are blocked by magnesium ions
o These magnesium ions are positively charged
 Only if the synapse is negatively charged, the magnesium ions are not
blocking the NMPA gates and let sodium and calcium enter
If enough AMPA receptors open its gate and enough sodium gets into the
synapse, magnesium ions are not blocking the gate and attached glutamate
opens NMPA channels to let sodium and calcium flow through the gate:
 With the NMDA receptors, calcium is able to enter the postsynapse
o It activates a protein called CaMKII (-calcium-calmodulin-dependent protein kinase
II)
o CAMKII releases a protein called CREB
o CREB regulates in the nucleus the expression of some genes
o This altered gene expression lasts for month or years and accounts for long-term
memory
This is an example of epigenetic change
The effects of CaMKII and CREB are magnified by BDNF (brain derived neurotrophin) =>
similar to NGF (nerve growth factor) from module 4.2

LTP depends on CaMKII, CREB, BDNF & others

o Those with the greatest production will undergo LTP
o It also depends on:
If the dendrites builds new AMPA receptors or moves old ones into better positions
The dendrite makes more branches and spines, thus forming additional synapses
with the same axon (recall from chapter 4, enriched experience leads to increased
branching)
Phosphate groups attach to certain AMPA receptors to make them more responsive
than before
In some cases, the neuron makes more NMDA receptors
Summary as in the book:
o Glutamate massively stimulates AMPA receptors
o The resulting depolarization enables glutamate to stimulate nearby NMDA receptors
o NMDA receptors let calcium enter the cell
o After a series of changes inside the cell the dendrites AMPA receptors are more
responsive to glutamate
o NMDA go back to normal
o Drugs blocking NMDA prevent establishment, but do not interfere with maintenance of
LTP
 Presynaptic changes:
o Extensive stimulation of the postsynaptic cells causes the release a retrograde
transmitter ( often nitric oxide (NO)) that travels back to the presynaptic cell to modify
it
o Thereby
the threshold of the presynaptic cell is reduced to produce action potentials
increases its release of neurotransmitter
expands its axon
and releases its neurotransmitter from additional sites along its axon
LTP reflects increased activity by the presynaptic neuron and increased responsiveness by the
postsynaptic neuron

Improving Memory

Caffeine, amphetamine, or metamphetamine (Ritalin) drugs before or shortly after learning

improve storage of memory by increasing arousal
Emotionally stimulating experiences also help, by activating the amygdala
Cortisol just before the testing sometimes helps people access memory

Chapter 13: Cognitive Functions

Module 13.1 Lateralization of Function
The Left and Right Hemispheres
- each hemisphere connects so muscles and skin receptors contralateral body side
> exceptions: trunk and facial muscles (controlled by both), taste and smell are
> uncrossed
- lateralization: hemispheres have different functions
- they are connected through the corpus callosum (set of axons) through:
> anterior commissure and hippocampal commissure
Visual and Auditory Connections to the Hemispheres

> both human eyes connect to both

hemispheres

> information from the right visual field falls

into the left half of each retina which
connects to the left hemisphere

> at optic chiasm (cross) axons from the left

half of the right retina got o the right
hemisphere (and vice versa)

The Corpus Callosum and the Split-Brain Operation

- corpus callosum gets surgically damaged in severe epilepsy (episodes of excessive synchronized
neural activity, can result from mutations in genes that control GABA receptors, trauma, infection,
tumour, toxic)
> remove the focus point within corpus callosum where seizures begin
> or cut the whole thing
- split brain people remain fairly normal
> struggle on unfamiliar tasks when both hands are needed
> can use both hands independently in ways other people cannot
> hemispheres still do not act in complete isolation
- left hemisphere is responsible for speech production, whilst both hemispheres can comprehend
> split brain patients can understand with both hemispheres but only information
> shown to the left hemisphere can be vocalized
Split Hemispheres: Competition and Cooperation

- first weeks after split brain operation the hemispheres act like separate people sharing a body
- as time passes the brain learns to use smaller connections between hemispheres to make up for the
lost corpus callosum
- the interpreter: tendency of the left hemisphere to make up explanations for what the right
hemisphere did

The Right Hemisphere

- better than the left at comprehending spatial relationships

- focuses more on overall patterns whereas the left focuses on detail
- sees the 'bigger picture', relating whats been heard to the overall context
> without right hemisphere, left understanding would be very literal
- is more responsive to emotional processing
> more fine tuned to gestures, tone of voice, sarcasm, happiness or sadness of others

Development of Lateralization and Handedness

Anatomical Differences between Hemispheres

- plantum temporale (temporal cortex) is later in left hemisphere from when we are born >
resulting in right handedness

Maturation of the Corpus Callosum

- gradually grows and thickens as some axons are myelinated in childhood/adolescence

- matures through discarding many axons
> because there of overproduction in early development and two neurons connected
> to corpus callosum need to have corresponding functions
- connections that integrate info from both hemispheres develop between 3-5 y
> before some behaviors of children resemble adult split brain behaviors

Module 13.2 Evolution and Physiology of Language

- human language is distinct because of its productivity (ability to improvise new combinations to
represent new ideas)

Nonhuman Precursors of Language

Common Chimpanzees

- attempts to teach them language failed

> humans vocalize while breathing out, chimpanzees vocalize whilst breathing in
- when taught to communicate in symbols, it remained unclear whether they understood the
meaning
> their use was short in productivity
> used it to request and not to describe

Bonobos

- are similar to humans in many aspects (sex face to face, outside of fertile periods, build bonds,
male contributes to childcare)
- Kanzi could understand, follow instructions, describe, but not produce
> learned when he was young, learned by observation

Nonprimates

- african gray parrot could speak without food rewards

- has implications for how to teach people who do not learn language well
- our language has evolved from other species
- we cannot decide whether chimpanzees or parrots have language unless we define it more clearly

How Did Humans Evolve Language?

Possibilities:

- development of the phonological loop facilitated language

> stronger connections between auditory- and PF-cortex = better auditory memory
- language developed out of gestures
> especially mouth gestures in monkeys

Language: By-product of Intelligence or Specialized Adaption?

- theory: humans have evolved bigger brains and language developed accidentally
> but whales have even bigger brains but no language
> not everyone with a full sized brain and normal intelligence has normal language
> williams syndrome: people can speak normally but have low intelligence
- theory: language as specialization
> Chomsky: language acquisition device (LAD) as a built in mechanism
> kids learn so quickly as if they were biologically prepared
> FOXP2 gene regulates proteins that promote synapse formation in cerebral cortex
> and has effects of jaw- and throat structures related to speaking
- language as specialization more compelling theory
- why did we evolve language?
> long period of dependency in childhood
> in this case: intelligence would be by-product of language
A Sensitive Period for Language Learning

- learning a second language before 12 can result in native-like proficiency

- bilinguals from infancy show bilateral activity during speech of both languages
> people who learn after age 6 show only left hemisphere activation for both
> languages
- bilinguals have better attention control
- a child who learns no language in critical period will not become proficient at any language later
in life

Brain Damage and Language

- as a way to study specializations for language
- aphasia = language impairment

Broca's Aphasia (Nonfluent Aphasia)

- is brain damage in left frontal cortex impairing production

- most cases of broca's aphasia relate to combined damage to more parts (not only broca's area is
responsible for speech production)
- people with broca's aphasia are awkward with a lot of communication forms: speaking, writing,
gesturing
- generally omit pronouns, prepositions, conjunctions (closed class words) "apple green" instead of
"the apple is green"
> have actual struggle saying closed class words out loud
> linked to difficulties understanding the meaning, not difficulties in pronunciation
- do have some residual knowledge of grammar
> can say when a sentence is grammatically incorrect but not how to improve it
> infer meaning themselves

Wernickes Aphasia (Fluent Aphasia)

- damage in left temporal cortex (near auditory cortex)

- can articulate themselves but make little sense
> omit nouns and verbs (open class words)
- have anomia: difficulties recalling object names
> make up names or describe it in other words
- have struggles with language comprehension of any form
> because sentences without nouns and verbs make little sense

Music and Language

- music as well as language relate to detecting small changes in sound
- high correlations between detection of changes in pitch of sounds and tone of voice
- whatever evolutionary process helped us develop language also helped us develop music
- we prefer music that resembles our language in tone and rhythms
> suggests that they are related

Dyslexia
- reading impairment in people who have adequate vision, motivation, cognitive skills and
educational opportunity
- more common in boys
- more common in English because it has a large number of irregular, nonphonetic spellings
- results out of difficulty converting symbols into sounds
- more likely to have bilateral symmetry (no enlarged planum temporale in left hemisphere)
- brain areas in parietal and temporal lope have lower than average gray matter
> can be cause as well as consequence of poor reading
- dysphonetic dyslexics: trouble sounding out words so they try to memorize words a whole, when
they don't recognize a word, they infer it from context (read 'laugh' as 'funny')
- dyseidetic dyslexics: can sound out words but fail to recognize words as a whole (read slow and
struggle with irregular spellings)
- dyslexia might result from poor auditory memory, difficulties detecting order of sounds and
attention focus problems
- can be treated with teaching them to focus on one word at the time (with a cut out sheet of paper)
> but changes their attention strategy in other activities too: are then not able to
> multitask anymore

Module 13.3 Conscious and Unconscious Processes and Attention

The Mind-Brain Relationship
- or mind body problem
- nearly everyone today rejects dualism
> law of conservation of matter and energy: nothing emerges from nothing or
> disappears into nothing
- alternative: monism
1. materialism = everything is matter, the mind doesn't exist
2. mentalism = the outside world doesn't exist unless a mind perceives it
3. identity position = mental processes ARE brain processes (consciousness = brain
3. activity)
- monism widely accepted
> brain activity and experience are inseparable
- Chalmers distinguishes easy and hard problems concerning consciousness
> easy: difference between sleep and wakefulness
> hard: why does consciousness exist at all? why does info-processing feel like
> something at all?
- today we are limited to easy problems before we can get to the hard one
Consciousness of a Stimulus
- conceptualized as: if a cooperative person reports awareness of one stimulus but not the other, he
or she was conscious of it
> research limited to people who can speak
- flash suppression: a dot on screen, followed by a flashing ring around it > makes people unable to
see the stationary dot
> strong response to flashing stimulus decreases response to steady stimulus

Experiments using masking

- masking: brief visual stimulus is preceded and followed by by longer interfering stimulus (often a
pattern)
> backward masking: only brief stimulus followed by final stimulus
> when stimuli are masked, we have no consciousness of them
- when we are conscious: see and recognize things > gamma waves (precisely synchronized in
several areas) are evoked and spread widely
> being conscious of a stimulus means that it evokes more overall brain activity

Experiments using binocular rivalry

- two stimuli presented to each eye independently are competing for consciousness
- binocular rivalry: perception switches between the two stimuli
- some stimuli (e.g. facial expressions) hold attention longer than neutral ones (stripes)
- using a pulsating stimuli on one eye results in distinct brain activation for the pulsating and
stationary stimulus
- shifts are evident in fMRI scans - large scale activation in differing brain areas
> conscious stimuli virtually take over brain activity

The Fate of an Unattended Stimulus

- binocular rivalry experiments: when a word or even your name appears in the unattended field >
attention switches rapidly to that eye
- means that unattended stimuli are still somehow attended to
> brain detects it before you become conscious
- much of our brain activity is unconscious and even unconscious activity can influence behavior

Consciousness as a Threshold Phenomenon

- consciousness of a stimulus seems to be a yes-or-no thing

- when a stimulus activated enough neurons to some extend, activation magnifies and spreads over
much of the brain
- if a stimulus fails to reach that level it just fades away
- fMRI support: brains response is either weak or strong, not intermediate

The Timing of Consciousness

- phi phenomenon: dots appearing one by one later seem as if they were one dot that moves in a
circle (inferred that movement afterwards)
- word that sounds half way like dent or tent > depending on which sentence it appears in, you will
perceive it as either one or the other
- we are capable of becoming conscious of something after it is gone

Conscious and Unconscious People

- How the brains of conscious people differ from people who unconscious
- anaesthetic patients
> loosing consciousness marked by decreased overall activity
> especially between cerebral cortex and subcortical areas
> consciousness returns with increased activity between cerebral and subcortical
> further alertness returns with increased cortex activity
> with a loss of connectivity no stimulus can spread = reach consciousness
- people in a vegetative state can sometimes show wilful brain responses to verbal instructions
(indicating some consciousness)
- brief magnetic stimulation of one area results in spreading activation in conscious people and only
brief, local activation in sleeping, anesthetized or vegetative people

Attention
- attention is not a synonym of consciousness but closely related
> can be conscious without paying attention but not the reverse
- inattentional blindness (change blindness) = when something changes slowly or changes while
you blink you don't notice the change

Brain Areas Controlling Attention

- bottom-up: stimulus dependent attention

- top-down: intentional attention
> depends on PFC and parietal cortex
> evident in stroop task: hard to suppress reading (top down interfering with bottom up)
> makes you resist distraction

Spatial Neglect

- often in people with right hemisphere damage

> ignore left side of body and visual field
- mainly loss of attention rather than loss of sensation
> seeing the forest but only half of the trees
- can make these people aware of neglected side
> telling them to pay attention
 > or crossing over left (neglected) arm under right increases attention for neglected
> arm

Module 13.4 Social Neuroscience

- social neuroscience: study how genes, chemicals and brain areas contribute to social behavior

The Biology of Love

- pictures of the person you love result in brain activity
> of reward area, similar to that of drug addicts
> of hippocampus and other areas for memory and cognition
= what we call love combines motivation, emotions, memories and cognitions
- oxytocin (hormone) is released during and after child birth
> stimulates breast to produce milk
> promotes bonding in general
> both men and women release it during sex "love enhancing, magnifying hormone"
> in studies it increased attraction to partner not just everyone
> made men stand further away from attractive women
> results in greater attention to facial expressions
> increases conformity of opinions in in-group
> can increase attention to threats

Empathy and Altruism

- empathy: ability to identify with other people
> often towards people who are similar to us
> helpfulness depends on empathy
> stronger in humans than other species
- varying degrees of empathy and altruism are reflected in brain activity
- psychopaths show less empathetic brain activation
Chapter 14: Psychological Disorders
Module 14.1 Substance Abuse and Addiction
- addiction is a paradox: as it progresses pleasure become weaker whilst costs and risks increase

Drug Mechanisms
- most of the commonly abused drugs derive from plants
- why have plants evolved chemicals that affect our brains?
> hormones and NTs are almost same across species
> if it attracts one, it attracts most
- agonist: drug that mimics or increases effect of a neurotransmitter
- antagonist: drug that blocks a neurotransmitter
- mixed agonist-antagonist: either one for some effects of neurotransmission or either at certain
doses
- affinity: drug has an affinity to a receptor if it binds to it
> vary from strong to weak
- efficacy: drugs tendency to activate a receptor
> a drug that binds to receptor but fails to stimulate it has high affinity but low
> efficacy
- drug effectiveness and side effects vary across individuals
> drugs work on several receptors and people vary in how many receptors they have

Similarities and Differences among Addictive Substances

- almost all drugs increase activity at dopamine or norepinephrine synapses

- nuleus accumbens: central to reinforcing experiences of all types
> addictive drugs activate it by releasing dopamine and norepinephrine here
-
- cocaine and amphetamines
> block reuptake of released dopamine or reverse the dopamine transporter gene
> (then releases dopamine instead of taking it back up)
> greater impulsiveness than opiate addictions
- opiates
> inhibit neurons that release GABA (inhibits firing of dopamine neurons)
> inhibiting an inhibitor = more net dopamine release
> addiction impairs learning more than stimulant addiction
- sexual excitement, music, sugar, gambling, gaming release dopamine in nucleus accumbens
- major depresson = little nucleus accumbens activity
- people often have more then one addiction

Cravings

- definition: insistent search for the activity

- even after long times, cravings can be triggered by cues
> cues increase activity in nucleus accumbens
- important difference between liking and wanting
> can have one without the other
> many addicts report more distress (wanting) than pleasure (liking)
- addictive substances alter receptors in nucleus accumbens
> become more responsive to addictive substance and cues related to it
 > less responsive for other types of reinforcement
> addiction hijacks reward systems because even sex becomes less rewarding
- repeatedly taking addictive drugs also disrupts activity in PFC
> less restraint of impulses
> no weighing of pros and cons (drink even when it is accompanied by foot shock)

Tolerance and Withdrawal

- tolerance: decrease in enjoyable drug effect as addiction proceeds

> leads to a constant increase of amounts
> is learned to a large extend (drug related cues in the environment activate
> mechanisms that counteract drugs)
> can be counteracted by extinction procedures
- withdrawal: body reacts strongly when it doesn't get drug when expected
> symptoms: anxiety, sweating, vomiting, diarrhea, hallucinations in severe cases
- addicts use drug to cope with stress
> stress of withdrawal symptoms relieved by drug
> then generalizes over to other situations

Predispositions
- genetic influences
> most genes found were also predictive of other disorders than addiction
> gene that controls dopamine type 4 receptor
> - comes in short or long form
> - long form is less sensitive, makes people have more cravings to compensate for
> - less than normal reinforcement
> gene that controls COMPT enzyme that breaks down dopamine
> - more active form of it breaks down more
> - people with this form are more impulsive and prefer immediate rewards
- environmental influences
> prenatal environment: drinking mothers make it more likely the child will drink
> (independent of whether she drinks when it is born)
> childhood environment determines whether children will develop impulse
 > problems when being predisposed with less sensitive GABA receptors
> adult environment important for late onset alcoholism
> - Type II (Type B) alcoholism: rapid onset before 25 (mostly men with family
> - history of alcoholism)
> - Type I (Type A) alcoholism: develop gradually after age 25 (depends more on
> - stressful life and less on genetics, less severe, more likely to be cured)

Behavioral Predictors of Abuse

- predispositions act by altering behavioral response to the substance

- alcoholism more likely among those that are impulsive, easily bored, sensation seeking and
outgoing in childhood
- sons of drinking fathers can themselves hold their drink well and are more likely to develop
addiction, alcohol also decreases stress in them more than in others

Treatments
- most turn to things like AA
- or go to a cognitive behavioral therapist who uses contingency management (rewards for
remaining drug free)

Medications to combat alcohol use

Ethyl alcohol Acetaldehyde Acetic acid

metabolized to toxic acetaldehyde dehydrogenase enzyme converts it to

- people who have a gene that produces less acetaldehydrogenase matabolize acetalhyde more
slowly
> when they drink they accumulate acetalhyde and have unpleasant side effects
> China, Japan
- Antabuse drug makes you sick when drinking
> blocks the enzyme that converts acetaldehyde to acetic acid
> moderately effective, has a lot to do with persons own determination
> people often rather stop the pill then alcohol
- Revia drug blocks opiate receptors and therefore decreases pleasure in drinking

Medications to combat Opiate abuse

- heroin is an artificial substance invented as a 'safer alternative' to morphine

- idea still persists that people who can't quit opiates should switch to a less harmful drug
- methadone, activates the same receptors and exerts same effects as heroin or morphine
> can be taken orally = avoid needle infections
> develops and leaves slower = less of a rush, less withdrawal symptoms
- people who take alternative drugs live longer and healthier
- don't end addiction, just satisfy cravings in a less dangerous way

Module 14.2 Mood Disorders

Major Depressive Disorder
- changes in the synapses to the nucleus acumens make them less sensitive to reward
- absence of happiness more reliable symptom then increased sadness
- less common in kids, after 14 years more common in females
- often comes in episodes broken up by normal moods
> first episode is usually longer and triggered by esp. stressful event
> the more episode you had the easier it gets to have another one

Genetics

- no gene strong link to depression

- relatives of early onset (before 30) depression have high risk of depression and many other
psychological disorders
- relatives of late onset depression have high probability of circulatory problems
- serotonin transporter gene (does the reuptake) - its effects vary with environment
> two short forms of the gene increases risk of depression in response to major
> stressors

-
> two long forms: reverse
> one short, one long: intermediate

Abnormalities in Hemispheric dominance

- people with depression have decreased activity in left PFC (associated with happiness) and
increased activity in right PFC
> represents a predisposition
- most people gaze to right during verbal tasks, depressed people gaze to left

Antidepressant Drugs
- drugs earlier were usually found by trial and error
- today tested in tubes first (less use of laboratory animals)

Types of Antidepressants

- tryclics
> block transporter proteins that reabsorb serotonin, dopamine, and norepinephrine,
> back into presynapse
 > also block histamine = produces drowsiness
> block acetylcholine = dry mouth, trouble peeing
> block some sodium channels = heart irregularities
- SSRIs
> similar to tryclics but specific to serotonin
> same effectiveness but less side effects

-
- SNRIs
> block reuptake of serotonin and norepinephrine
- monoamide oxidase inhibitors MAOIs
> block MAO enzyme (metabolizes serotonin in inactive forms)
> presynapse has more serotonin available for release
> only used when nothing else works
> patients on this drug must avoid tyramine (in cheese and raisins) because a combination of
tyramine and MAOIs increases blood pressure

-
- atypical antidepressants (everything not discussed abvove)
> ketamine: antagonizes NMDA type glutamate receptors, increases formation of new synapses
and produces rapid antidepressant effects on people that didn't respond to anything else
> st. John's wort (herb) available without prescription, seems to have same effects as
antidepressants but dangerous side effect: increases effectiveness of enzyme that breaks down
toxins (including all other medication you may need)

Why are Antidepressants effective?

- theory: they increase mood by increasing NTs in synaptic cleft

> conflicts with the fact that they only work after a while
- most depressed people have lower than average of the neurotrophin brain-derived neurotropic
factor (BDNF) important for synaptic plasticity, learning, proliferation of new neurons in the
hippocampus
> low BDNF = smaller than average hippocampus
> some studies indicate antidepressants increase BDNF levels
> proliferation or neurons in hippocampus appears important for antidepressant
> effects = capacity to make new neurons makes it easier to learn new ways of coping
> importance of new learning explains why antidepressants don't elevate moods of
> undepressed people: they aren't burdened with discouraging thoughts that have to
> be unlearned

Are Antidepressants effective?

- not for all people, more for people with bad depression
- depression comes in phases, so by the time the patient has tried several different drugs and found a
one that seems to work, this might just be a high in the process of depression

Alternatives to Antidepressant Drugs

- psychotherapy seems equally effective as drugs
- placebo effect occurs in both
- both increase metabolism in same areas
- psychotherapy advantage: less relapse
- people receiving both treatments recover better than either alone
-

Exercise

- regular exercise cheapest treatment

- exercise in rats increases serotonin, BDNF and sensitivity to reward

Electroconvulsive Therapy (ECT)

- electrically induced seizure

- only for very severe depression when not responding to anything else
- applied every other day for about two weeks
- memory impairments do not occur when applied to right hemisphere
- increases proliferation of neurons in hippocampus
- alters gene expression
- high relapse

Altered Sleep Patterns

- almost all depressed people have sleep problems

- sleeping patterns resemble healthy people travelling time zones west
> enter REM sleep early
> awake early
- staying up all night makes depressed people less depressed until the next nights sleep
> sleep deprivation may cause astrocytes to release adenosine (antidepressant
> effects)
> combining sleep deprivation and antidepressants sometimes works
- altering sleeping schedules to normal helps for a while but then circadian rhythm shifts back

Deep Brain Stimulation

- last call
- battery powered device implanted in brain delivering periodic stimulation to certain brain areas
- still in experimental stage
- might be refined by use of optogenetic stimulation

Bipolar Disorder
- mania: restless activity, excessive self confidence, loss of inhibition
- bipolar I: full on manic episodes
- bipolar II: mild (hypomanic) episodes
- onset in the 20s, equal in men and women
> men more often bipolar I

Treatments

- lithium: mood stabilizer

> dosage difficult: too low ineffective, too high toxic
- valproate and carbamazepine
> sometimes given with antidepressants
- antidepressants are risky because they can cause switch between episodes
- lithium, valproate and carbamazepine
> decrease number of AMPA glutamate receptors in hippocampus
> block synthesis of brain chemical arachidonic acid (produced during brain
 > inflammation, common in bipolar)
> consistent adequate sleep decreases risk for manic episode

Seasonal Affective Disorder (SAD)

- possible to treat it with bright light for an hour each day
- faster effects than antidepressants

Module 14.3 Schizophrenia

Diagnosis
- split mind doesn't mean multiple personalities but split between emotional and intellectual
experiences
> giggle/cry for no reason or react blunt to bad news
- to be diagnosed one must have delusions, hallucinations or disorganized speech plus another
symptom
- positive symptoms: add something that should be absent
> delusions, hallucinations, disorganized speech
- negative symptoms: subtract behaviors that should be present
> more stable and more difficult to treat
- cognitive symptoms: thought and reasoning limitations
> interpret things literally because they don't understand concepts
> trouble focusing
- is probably a family of related disorders, not single entity
- impairments of attention and working memory are central

Differential Diagnosis of Schizophrenia

- differential diagnosis: rules out other conditions with similar symptoms

> "not attributable to other medical condition"
> substance abuse more likely than Schizo to produce visual hallucinations
> brain damage to temporal or PFC produce Schizo like symptoms
> undetected hearing deficits
> Huntingtons disease
 > Nutritional abnormalities (people react to some allergies or deficiencies with
> delusions or hallucinations)

Demographic Data

- more prevalent in cities than rural areas

> toxic substances, less social support
- more common, more severe, earlier onset in men

Genetics
- has genetic basis but doesn't depend on single gene
- the closer you are related to a Schizophrenic, the higher the probability you get it too
> monozygotic twins more concordance
> dizygotic more concordance than normal siblings (same genetic resemblance but twins always
more similar environments)
- higher probability for people relates to bipolar person

Adopted Children Who Develop Schizophrenia

- if so, disorder more prevalent among biological relatives

- pregnant women with Schizophrenia provide bad prenatal environment because they often drink,
shitty diet etc.
> often birth complications
- dysfunctional adoption family heightens risk to develop disorder

Efforts to Locate a Gene

- not due to a single gene = would have been weeded out by natural selection
- DISC1 (disrupted in schizophrenia 1) gene
> controls differentiation and migration of neurons in development, production of
> dendric spines, and the generation of new neurons in the hippocampus
> rare variants of it are more common in Schizophrenia
- may depend on mutations of several genes or microdeletion (of chromosome parts) disrupting
brain development
> consistent with the fact that schizophrenia is somewhat more common among old
> fathers

The Neurodevelopmental Hypothesis

- states that prenatal or neonatal influences produce minor brain abnormalities that make the
developing brain more vulnerable to other disturbances
> minor brain abnormalities and major disorders of behavior

Prenatal and Neonatal Environment

- intermediate risk factors: old father, city life, childhood parasite infection (toxoplasma gondii
impairs brain development)
- low risk factors: poor prenatal nutrition, premature birth, lbw, birth complications, maternal
stress, head injuries in early childhood, if mother is rh-negative and child is rh-positive
(immunologically rejecting child), season of birth effect (children born in winter, mothers injected
by viruses in fall)

Mild Brain Abnormalities

- less gay and white matter

- larger ventricles
- hippocampus smaller
- slow development of dorsolateral PFC
> weaker connections to other brain areas
> less activity during tasks of attention and memory
> Schizophrenics struggle with switching cards in Wisconsin Card Sorting Test
- Schizophrenics have larger right plantum temporale (normal people have larger in left hemisphere)
- lower overall left hemisphere activity

Long Term Course

- outcome varies
> some recover after one episode, some go back and forth and some deteriorate
- whatever causes schizophrenia happens before or during first episode
> after brain only changes slightly

Early Development and Later Psychopathology

- if neurodevelopmental hypothesis holds, why does it only start in 20s?

> many who later develop Schizophrenia show other abnormalities since infancy
> dorsolateral PFC matures slowly
> minor initial brain damage develops worse with age when it is supposed to take
> over functions

Treatments
Antipsychotic Drugs and Dopamine

- chlorpromazine: relieves positive symptoms (not in use anymore)

- neuroleptics: antipsychotics including phenotiazines and butyrophenones
> behavioral effects develop gradually
> block dopamine receptors
- dopamine hypothesis of Schizophrenia: Schizophrenia results from excess activity at dopamine
synapses in certain brain areas (basal ganglia)
> drugs working on dopamine receptors (amphetamines etc.) can induce substance-
> induced psychotic disorder
> people with Schizophrenia have twice as many dopamine D2 receptors
-
Role of Glutamate

- glutamate hypothesis of Schizophrenia: states that problem is partly due to deficient activity at
glutamate synapses in PFC
> in many areas dopamine inhibits glutamate release or vice versa
= increased dopamine has same effect as decreased glutamate
> Schizophrenics have decreased glutamate release in PFC
> amphetamines, cocaine, LSD can induce only positive symptoms
> "angel dust" phencyclidine (PCP) drug inhibits some glutamate receptors and
> produces positive and negative symptoms
> PCP and ketamine produce no effects until after puberty (like Schizophrenia)
> PCP produces relapses in recovered Schizophrenics
- glycine binds to a glutamate receptor and increases its efficiency
> could be used as treatment because increasing overall glutamate would kill
> neurons by overstimulation

Other Medications

- brain has several dopamine pathways

- mesolimbocortical system (from midbrain to PFC and limbic system)
> drugs block dopamine transmission here but also in mesostriatal system (projects
> to basal ganglia - resulting in tardive dyskinesia)
- atypical antipsychotics do not induce this
> work less on dopamine receptors but counteract serotonin receptors and increase
> glutamate release
> other side effects like weight gain and impaired immune system though

Module 14.4 Autism Spectrum Disorder

- more common today
> because it is not called retardation anymore or because its more prevalent?

Symptoms and Characteristics

- Aspergers Syndrome: mild autism
- is a range of disorders from mild to severe impairments
- more common in boys
- primary characteristics:
> deficits in social and emotional exchange
> deficits in nonverbal communication
> stereotyped behaviors (repetitive)
> resistance to change in routines
> unusually weak or strong responses to stimuli
- many have cerebellum damage (clumsiness and impaired eye movements)
- also connected to talents
> better than average at detecting motion by visual stimuli

Genetics and Other Causes

- most cases result from new mutations or microdeletions
> most stem from father, esp. old ones
- topiosomerase: enzyme regulating the repair and replication of DNA
> autists often have mutation on the gene controlling topiosomerase
> impair expression of genes important for brain development
- prenatal environment can play a role
> mothers that develop antibodies attacking certain brain proteins of baby
- women taking folic acids (vitamin B9) during pregnancy (important for development of NS) have
less chance of getting an autistic child
Treatments
- risperidone (antipsychotic) sometimes used to control repetitive behaviors
- therapies focus on reinforcing non-repetitive behavior