In the image below, use arrows (5) to indicate which brain regions show increased activity and which show decreased activity in unipolar depression.
List 7 neurochemicals that are dysregulated in unipolar depression. Label (*) the 3 that are the most common targets of drug therapy. Label (-) the one impacted by ketamine treatment. Label (^) the one that is elevated both at baseline and in response to stressors.
serotonin *
dopamine *
norepinephrine *
cortisol ^
glutamate -
GABA
acetylcholine
List 4 examples of depression correlating with ovarian hormones.
menstrual cycle (↓ estradiol levels)
hormonal contraception
after childbirth (↓ estradiol levels)
after menopause (↓ estradiol levels)
List 3 common examples of sleep disruption in people with depression.
hard to fall asleep (onset insomnia)
decreased SWS (slow wave sleep, non-REM)
decreased latency to REM (quick to REM)
What is the relationship between sleep deprivation and the risk for developing depression?
sleep deprivation increases the risk of depression
What is opposite about cortisol in unipolar depression compared with PTSD?
Unipolar depression involves elevated cortisol while PTSD maintains low cortisol (at baseline and in response to stressor).
In depression, there is higher/lower concordance in MZ (monozygotic - identical) twins compared to DZ (dizygotic) twins.
higher
The heritability estimate (%) for major depressive disorder (MDD) is:
40-50%
The mood disorder with the greatest genetic risk is:
bipolar disease
True/False: The genetic risk for depressive disorders is disorder-specific. Explain why.
False. Genetic risk is related to the regulation of mood more than specific mood disorders, so it could manifest as different mood disorders in different people.
Genes that may play a role in the development of depression mainly involve which 2 neurotransmitter systems?
dopamine
serotonin
Describe the diathesis-stress model of psychiatric illness.
Psychiatric illness arises from a combination of diathesis (risk) including genetics & early developmental results or experiences, and stress (physical, mental, psychosocial). It's generally believed that with more "diathesis," less "stress" would be required for illness to manifest, while with less diathesis (or protective factors), more stress would be required.
How does the time course of antidepressant treatment match the neuroplasticity theory of depression better than the monoamine theory of depression?
Antidepressants increase monoamine transmission within hours, but take weeks to affect mood or behavior. This matches the neuroplasticity theory better because it provides time for downstream effects (neuroplastic changes) to occur and possibly lead to the behavior/mood effects of the drug.
What is a problem with the monoamine theory?
1. not everyone with depression responds to monoamine agonist drugs.
2. the time course of synaptic effects don't match that of behavioral effects.
What are the two neuroplastic processes thought to be disrupted in depression?
adult neurogenesis
neurotrophin production
Describe one piece of evidence that supports the neuroplasticity theory.
1. disruption of neuroplastic processes in animal models of depression.
2. increase in those neuroplastic processes with antidepressant treatment.
Which type of drug used in the treatment of mood disorders blocks the breakdown of dopamine, norepinephrine, & serotonin?
MAOI
Which two types of drugs used in the treatment of mood disorders block the reuptake of serotonin and norepinephrine?
SNRI
Tricyclics
Which type of drug used in the treatment of mood disorders is an NMDA-receptor antagonist used to treat otherwise drug-resistant depression?
ketamine
Which type of drug used in the treatment of mood disorders blocks the serotonin transporter?
SSRI
Describe electroconvulsive therapy (ECT) for depression.
seizure activity induced in anesthetized patient
Describe the Transcranial magnetic stimulation (TMS) treatment for depression.
stimulation of cortisol regions using a magnet applied to the scalp
Describe the Deep brain stimulation (DBS) treatment for depression.
implantation of stimulating electrodes in the brain, often in ACC (anterior cingulate cortex)
Describe Cognitive behavioral therapy (CBT) for depression.
approach that aims to identify and decrease negative thoughts, reduce stress, and improve interpersonal relationships.
Describe the functional connection between the prefrontal cortex and the amygdala.
The prefrontal cortex has a higher level evaluation of a situation and is capable of inhibiting the amygdala, applying negative feedback to the amygdala that creates a knee-jerk response to potential or perceived threats.
What 2 brain regions show increased activity in anxiety disorders?
amygdala
insula
What 2 brain regions show decreased activity in anxiety disorders?
prefrontal cortex (PFC)
ACC (anterior cingulate cortex)
What do changes in the activity of anxiety disorders mean for the functional connectivity between the prefrontal cortex and the amygdala?
harder for the prefrontal cortex to inhibit the amygdala
Describe the main findings regarding brain activity in social anxiety disorder.
seeing a fearful or angry face leads to increased activity in the amygdala (positively correlated with the severity of symptoms)
Describe the main findings regarding brain activity in GAD (generalized anxiety disorder).
Increased activity in the amygdala, and decreased activity in the prefrontal cortex while it can't inhibit the amygdala.
Describe the main findings regarding brain activity in anxiety in college students.
Emotion face task: increased activity in amygdala and insula (positive correlation between brain activity and anxiety measures).
Use arrows (3) to indicate which brain regions show increased activity & which show decreased activity in anxiety disorders. IncludeD the location of the insula.
Benzodiazepines (anxiety disorder treatment) are agonists for the ___________ receptor. Therefore, they inhibit/excite neural activity. As benzos work to control anxiety, activity decreases in these 2 brain regions:
GABA-A
inhibit
amygdala and insula
Risks of benzodiazepines (anxiety disorder treatment).
sedation
tolerance/withdrawal
abuse
What type of drug is used to treat depression, and is helpful in anxiety disorder especially when paired with cognitive-behavioral therapy?
SSRI (selective serotonin reuptake inhibitor)
What drug is an NMDA receptor agonist and works only in conjunction with CBT or extinction training?
DCS (D-cycloserine)
What is a common type of therapy used in the treatment of anxiety disorders?
CBT (cognitive behavioral therapy)
Indicate which stage of sleep is being described:
a. When you first fall asleep: ____________________
b. K-complexes and sleep spindles: _______________
c. Begin to see delta activity: ____________________
d. Slow-wave sleep: ___________________________
e. Synchronous activity of neurons: _______________
f. High brain activity; low muscle tone: ____________
g. Vivid story-like dreams are most likely: __________
h. Growth hormone is secreted: __________________
a. 1
b. 2
c. 3
d. 3
e. 3
f. REM
g. REM
h. REM
For each type of rhythm, indicate if it is circadian, ultradian, or circannual:
a. Sleep/wake cycle: _________________
b. Body temperature (in warm-blooded critters like humans): ___________
c. Migration: ______________
d. Hibernation: _______________
e. Melatonin secretion: _______________
f. Eating & drinking _________________
g. Testosterone secretion (males): ___________
a. circadian
b. circadian
c. circannual
d. circannual
e. circadian
f. circadian/ultradian (eat/drink more in a day - circadian; hunger/thirst many times per day - ultradian)
g. ultradian
Diagram and label the retinohypothalamic tract, including the types of cells it begins with in the retina, and the types of receptors it ends on in the SCN.
The SCN sends information to the ____________ gland, which secretes the hormone ______________.
pineal
melatonin
(the path from the SCN to the pineal is indirect with many stops/synapses)
Define the following terms:
a. Endogenous:
b. Free-running:
c. Zeitbeger:
d. Entrain:
e. Arrhythmic:
a. Endogenous: generated from within the body
b. Free-running: the rhythm without clues for the time of day
c. Zeitbeger: "time giver"; something (like light) that sets the biological clock.
d. Entrain: to set, as in, light entrains the clock.
e. Arrhythmic: lack of a regular circadian rhythm; occurs when the SCN is lesioned.
The sleep-wake cycle is generated from within and will continue even without knowledge of the time of day, and even without changes in lighting conditions. Therefore, the sleep-wake cycle is _______________________.
endogenous
A sleep-wake cycle that is occurring without cues for the time of day is _____________________.
free-running
Our sleep-wake cycle can be synchronized with lighting conditions, because light can set, or ____________________ the clock.
entrain
Comparing temperature, exercise, and light, which can all entrain the clock, light is the strongest ______________________.
zeitbeger
In the hamster study, when the SCN was lesioned, the hamster became ______________________.
arrhythmic
Clock, cycle, per, and cry are in a family called __________ genes. These genes are turned on, make their protein products, turn off, and the proteins degrade over a period of approximately _______ hours.
clock
24 hours
The proteins that turn on the per and cry genes are: ______________.
The proteins that turn off the per and cry genes are: ______________
clock and cycle
per and cry (negative feedback)
The retinohypothalamic pathway reaches cells of the SCN, allowing glutamate to act at ionotropic/metabotropic glutamate receptors. The 2nd messenger created by activity at this receptor enters the cell nucleus and activates/inhibits clock genes. This is the mechanism by which light entrains the clock.
metabotropic
activates
What stage of sleep is important for the consolidation of declarative memories? ___________
What stage of sleep is important for the consolidation of procedural memories? ___________
SWS (Stage 3)
REM
Diagram the movement through the stages of sleep during
the night.
When do we have the most SWS? ________________
When do we have the most REM sleep? ___________
1st half of the night
2nd half
Describe 3 ways that sleep changes over the lifespan.
1. sleep less
2. spend less time in REM sleep
3. less SWS + more sleep disorders in older age
Describe evidence that sleep is important for brain development.
Humans and other animals that are born very underdeveloped sleep much more as babies compared to animals born more developed.
List 5 possible functions of sleep and an example or piece of evidence for each.
1. brain development (underdeveloped babies tend to sleep more)
2. energy conservation (metabolic rate decreases during sleep)
3. niche adaptation (sleep promotes us to sequester in a safe location when we would be inefficient and in danger in the environment)
5. memory formation (sleep is important before and after learning/studying - REM implicit, SWS explicit)
Adenosine is a breakdown product of ________, so the more active neurons there are, the more adenosine is created.
ATP
Consider a very active synapse. A retrograde neurotransmitter, adenosine is produced by the pre/post-synaptic cell and binds to receptors on the pre/post-synaptic cell. Because adenosine is excitatory/inhibitory, this increases/decreases further neurotransmitter release.
post-synaptic
pre-synaptic
inhibitory
decreases
_______________ is an adenosine receptor antagonist.
Caffeine
Describe "brainwashing."
CSF (cerebral spinal fluid) washes deeper into brain tissue during sleep compared to waking, cleaning out various chemicals, proteins, and waste products, including beta-amyloid which plays an important role in the pathogenesis of Alzheimer's disease.
2. Spinal cord: inhibition of motor neurons --> paralysis/low muscle tone
3. Midbrain: rapid eye movements
Of the following factors that are involved in sleep, indicate if each is circadian, homeostatic, or neural:
a. Melatonin: ___________________
b. Accumulation of adenosine: ________________________
c. Hypothalamic control: __________________________
d. Clock genes/proteins: __________________________
a. circadian
b. homeostatic
c. neural
d. circadian
Indicate the brain regions whose activity (or lack thereof)
are associated with the following dream content:
a. Emotional content: _____________________
b. Drives and motivations: _________________
c. Lack of logic, memory, and judgment: ________________________
d. Hallucinations (visual imagery, etc): _____________________
a. amygdala
b. hypothalamus
c. prefrontal cortex (PFC)
d. association cortex (not primary or secondary sensory cortex)
Sleep deprivation:
a. Define microsleep:
b. What is the effect of sleep deprivation on the immune system?
c. List 3 other effects of sleep deprivation:
a. very brief sleep
b. bad for the immune system; poor immune function
c. decreased reaction time, poor mood, poor concentration
What stages of sleep do we preferentially make up after a period of sleep deprivation?
SWS, REM
Compare and contrast benzodiazepine sleep aids with non-benzo sleep aids (consider the receptors they bind to and the kind of sleep they cause).
Both are GABA (R) agonists.
Benzos depress SWS and REM sleep; non-benzos don't so much.
List & describe three types of insomnia.
List 2 causes of insomnia.
onset (can't fall asleep), maintenance (can't stay asleep), termination (wake up too early)
pain
disease
(also stress and psychiatric illness)
Why are night terrors and sleepwalking most common in non-REM sleep?
because the paralysis of REM makes them impossible during REM
Define the following:
a. Sleep apnea
b. REM behavior disorder
c. Night terrors
a. Sleep apnea: stop breathing while asleep
b. REM behavior disorder: no paralysis, move around like acting out dreams
c. Night terrors: intense fear, sympathetic NS activation
Describe the following symptoms of narcolepsy:
a. Sleep attack
b. Cataplexy
c. Sleep paralysis
d. Hypnogogic hallucination
a. Sleep attack - fall asleep seemingly out of nowhere
b. Cataplexy - loss of muscle tone (temporary paralysis)
c. Sleep paralysis - awaken without regaining muscle tone
d. Hypnogogic hallucination - dream-like experience while awake
The neurotransmitter lost in narcolepsy is: ____________________
Narcolepsy is treated with: _________________________________
orexin (aka hypocretin)
stimulants
Provide an example of each:
Short-term memory
Working memory
Long-term memory (explicit)
Long-term memory (implicit)
Retrograde amnesia
Anterograde amnesia
Short-term memory: remembering a phone number long enough to dial it
Working memory: grocery shopping for a few items, mental math
Long-term memory (explicit): a vacation or party
Long-term memory (implicit): how to ride a bike
Retrograde amnesia: loss of memory of things before onset of amnesia
Anterograde amnesia: loss of ability to form new memories after onset of amnesia
Short-term memory (SMT) or long-term memory (LTM):
- Fades quickly if not rehearsed: _______________
- Infinite capacity: ___________________________
- Limited capacity (7+or-2): ___________________
- Remembered w/ proper cues: ________________
- Once forgotten, can’t be recalled: _____________
STM
LTM
STM
LTM
STM
Two factors that affect the effort or time needed for consolidation.
emotional salience/arousal
familiarity
Describe the testing effect.
Testing yourself helps you learn information because each time you force active recall, the memory is reconsolidated and becomes stronger.
Recreate the diagram on the neural substrates of memory, including WM and all types of LTM with the brain regions important for each.
What does it mean that “cells that fire together wire together”?
When a presynaptic neuron successfully activates a postsynaptic neuron and both are now firing APs, the synapses between them strengthen, so in the future, it's easier for the pre- to activate the post-.
What is a Hebbian Synapse?
a synapse that has strengthened because of simultaneous firing of the pre- and post-synaptic cells
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
More neurotransmitter is released
stronger signal to activate the postsynaptic cell
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
Enlargement of the postsynaptic membrane
Paired with more glutamate receptors or another spine leads to stronger communication (on its own won't make a difference).
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
Stimulation of the terminal by interneuron
Through presynaptic facilitation, this would further depolarize the axon terminal leading to more NT release.
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
Development of new dendritic spine and axon terminal
There's a new point of contact between the 2 neurons, so more signal (NT) and more response (spine/receptors).
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
More AMPA receptors inserted into postsynaptic membrane
Causes a greater response in the postsynaptic cell (more/larger EPSPs) and quicker activation of NMDA receptors.
Diagram the following synaptic changes that accompany synapse strengthening & describe why that change strengthens the synapse:
Increase in AMPA receptor conductance of sodium and potassium
Large EPSPs and quicker activation of NMDA receptors.
AMPA receptor, NMDA receptor, or both:
a. Activated by glutamate
b. Ionotropic receptor
c. Channel fluxes sodium and potassium
d. Channel fluxes sodium and calcium
e. Channel blocked by magnesium
f. Requires both glutamate and depolarization to flux ion(s)
a. both
b. both
c. AMPA
d. NMDA
e. NMDA
f. NMDA
What ion is required for LTP (long-term potentiation)? _________________
What gas neurotransmitter is required for LTP? ________
calcium
NO
List 5 pieces of evidence for LTP (long-term potentiation) as a model of learning and memory.
1. LTP is elicited by high-frequency activity experimentally, and that mimics normal neural activity observed during learning.
2. Learning itself can produce LTP in the brain.
3. LTP is greatest in parts of the brain involved in learning and memory.
4. Learning and LTP follow the same time course.
5. Drugs that block LTP interfere with learning and drugs that enhance LTP enhance learning.
List and define the 4 A’s of dementia.
Amnesia - memory loss
Agnosia - loss of ability to recognize and name things
Apraxia - loss of knowledge of how to do things
Aphasia - loss of language
What are 3 risk factors for Alzheimer’s disease?
age
previous head injury
genetics (extra copies or mutations in gene for APP; gene for presenilin; ApoE4 allele)
Plaques are found within/between neurons.
Plaques are formed by a 42-amino acid protein called:
That protein is cut from a larger transmembrane protein called:
The enzyme complexes that cut the larger protein are called:
between
beta-amyloid (or A-beta-42)
amyloid precursor protein (APP)
secretases
Describe 2 examples of the genetic risk for AD which involve APP.
1. mutations in the gene - account for 10% of early-onset AD.
2. 3 copies of the gene - on chromosome 21, people with Downs syndrome (trisomy 21) have 3 copies - the risk of early-onset AD is very high.
Describe the following:
a. Brain atrophy
b. Microbleeds
a. Brain atrophy: loss of brain tissue - seen in the AD brain by enlarged fissures/sulci and enlarged ventricles.
b. Microbleeds: multiple tiny blood vessel ruptures (mini-strokes).
Tangles are found within/between neurons.
Tangles are formed by a protein called:
The normal function of that protein in its healthy form is:
Another disease that we see the abnormal protein in (as well as plaques) is:
within
tau
Function: to stabilize the structure of microtubules which allow transport of things up and down the axon.
chronic traumatic encephalopathy (CTE)
Draw a lateral view of the brain and identify where the majority of
plaques and tangles are found.
