Neurological and Psychiatric Disorders

Question 1

Describe how networks of regions involved in social cognition are similar to networks
involved in self-awareness

Answer 1

Self-reflection is associated with activation in a network
of areas we’ve already seen to be important in social
cognition generally

TEMPOROPARIETAL JUNCTION, PRECUNEUS, TEMPORAL POLE, MEDIAL PREFRONTAL CORTEX,

Question 2

Describe how the mirror test works, what it demonstrates, and which species generally
pass it

Answer 2

• Only ~12 species can pass the mirror test, including
bonobos, chimpanzees, orangutans, elephants, bottlenose dolphins, orcas, and magpies — and humans by ~age 2

by the age of two, half of all children can recognize themselves via the mark test

Question 3

Describe hemispatial neglect

Answer 3

Hemispatial neglect: deficit in attention to/awareness of one side of space

right temporoparietal cortex

Question 4

Describe somatoparephrenia

Answer 4

Somatoparephrenia: failure to recognize limb as part of one’s own body

temporo-parietal junction damage

Question 5

Describe anosognosia

Answer 5

Anosognosia: lack of awareness/denial of condition

neuropsychological presentation which leads an affected person to be unaware and unable to acknowledge disease in himself. It often results in defects in reasoning, decision making, emotions, and feeling

William Douglas ~~ supreme court justice
stroke —> Anosognosia —> retired but still showed up —-> would become enraged

parietal lobe

Question 6

Describe dementia

Answer 6

Dementia: gradual deterioration of “higher” cognitive functions, e.g., memory, language, planning, judgment, social interaction, emotion regulation

deficits in memory = the main hallmark

Alzheimers is the most common cause of dementia

Question 7

Describe Alzheimer’s disease, the pathology associated with it, the symptoms, the
prevalence

Answer 7

plug analogy —> plug slowly starts falling out of socket —> lights eventually go dark

if you lose your episodic memory, your cognitive abilities..where is your sense of self

Core deficit: progressive impairment of episodic memory

Other impairments:
executive functions, e.g., planning, reasoning, problem solving, judgment, spatial navigation, language: anomia (difficulty finding words) or aphasia (more severe impairment in language production or comprehension)

———-

cerebral cortex covered in debris known as amyloid plaque and tangles

having extra copy of chromosome 21 will cause increased plaque build-up

————

after the age of 60, your likelihood of developing Alzheimers increases by half every five years, so by your 80s, you have a fifty/fifty chance of developing it
greater awareness and research funding are needed to find ways to prevent, treat, slow down, or even cure AD

characterized by abnormal protein deposits —beta amyloid plaques and neurofibrillary tangles —particularly in parietal lobe, medial temporal lobe, frontal lobes, and posterior cingulate cortex

PLAQUES AND TANGLES — normal part of neuron functioning, but seem to go awry in AD, abnormal amount — profound progression over time

characterized by abnormal protein deposits —beta amyloid plaques and neurofibrillary tangles —particularly in parietal lobe, medial temporal lobe, frontal lobes, and posterior cingulate cortex

plaques and tangles comprise proteins also found in healthy cells; but typical processes have gone awry in AD — they start to clump together and interfere with neuron communicate

Question 8

Describe how a brain of a person with Alzheimer’s disease differs from that of an agematched
control

Answer 8

When looking at coronal slices,

less cortical volume, lateral ventricle (bc of profound loss of tissue, ventricles becoming larger and larger bc cerebral spinal fluid takes up so much space), profound deterioration in medial temporal lobe

Question 9

Roughly describe where the plaques and tangles typically associated with Alzheimer’s disease tend to be located and how they spread as the disease advances

Answer 9

PLAQUES AND TANGLES — normal part of neuron functioning, but seem to go awry in AD, abnormal amount — profound progression over time

characterized by abnormal protein deposits —beta amyloid plaques and neurofibrillary tangles —particularly in parietal lobe, medial temporal lobe, frontal lobes, and posterior cingulate cortex

plaques and tangles comprise proteins also found in healthy cells; but typical processes have gone awry in AD — they start to clump together and interfere with neuron communicate

Question 10

Describe what we know about the causes of Alzheimer’s disease, the risk factors and protective factors associated with it, and how it is typically addressed by health professionals

Answer 10

cause unknown: likely a combination of genetic and environmental factors

risk factors: similar to those for heart disease, e.g., high cholesterol, high blood pressure, lack of exercise, smoking

Question 11

Define what reserve is and describe some factors associated with higher vs. lower reserve

Answer 11

“Reserve”: resilience in the face of damage to the
brain

Physical exercise, mental challenges (practicing new
hobbies, skills, etc.), education, social relationships,
and lower stress all associated with greater reserve

Question 12

Roughly locate and describe the basal ganglia and some of the many functions they are
involved in

Answer 12

Basal ganglia: gray matter structures deep within the brain; involved in motor control, higher-level cognition, motivation, judgement, etc.

Question 13

Describe Huntington’s disease – its cause, how it affects the brain, its symptoms, and what, if anything, is done to treat it. (Have a broad sense of how HD seems to affect the inhibitory pathway first and how this is associated with motor symptoms.)

Answer 13

PC

STRIATUM — MOTOR DISINHIBITION
• Huntington’s disease: rare neurodegenerative disorder

• Causes deterioration in caudate and putamen,
affecting inhibitory circuitry first.

• Symptoms:

motor disinhibition, esp. chorea: involuntary, restless,
dancelike movements

• Typically associated with early fatality because of severity of motor and cognitive decline
• Genetic basis identified but still
no cure

—>• In healthy people, the excitatory direct pathway and inhibitory indirect
pathway are balanced, facilitating control of voluntary movement; in HD
neurons of indirect, inhibitory pathway degenerate first

Question 14

Describe Parkinson’s disease – its potential causes, how it affects the brain, its symptoms, and its prevalence

Explain why it would be inaccurate to characterize Parkinson’s disease as just a “movement disorder.”

Answer 14

caused by destruction of dopamine-containing genes in the substantia nigra (50-80% of neurons in substantia nigra have died) —> with the loss dopamine, the inhibitory pathway becomes overactive, and the thalamus is unable to undergo excitation

Cause unknown: likely a combination of genetic and
environmental factors—• Certain gene variations seem to increase risk of PD —• Exposure to certain toxins/environmental factors also
increase risk of PD

PD classically thought of as a ”movement disorder,”
but considerable cognitive and affective symptoms

treatment: increasing dopamine activity, by using dopamine agonist medications or LEVODOPA, a biochemical precursor that the brain can convert into dopamine itself

Question 15

Describe treatments for Parkinson’s disease and how each works

Answer 15

• Medications increase dopamine activity
• Dopamine precursors, like levodopa (which can cross blood-brain barrier and be converted to dopamine (DA))
• Dopamine agonists, which can mimic the effects of DA in the brain

Question 16

Describe what happens to a small subset of people with PD taking dopamine agonists and why we think this might happen

Answer 16

—> Small subset of patients with PD taking dopamine agonists show impulse control disorders, such as pathological gambling, compulsive shopping, etc.

—> increased level of dopamine heightened the sense of reward

—> overwhelming desire/impulse

Question 17

Describe how deep brain stimulation works in general and how it is used in Parkinson’s disease

Answer 17

In DBS for PD, electrodes typically implanted in the subthalamic nucleus

“pacemaker in the brain”

sends electrical impulses to disrupt faulty brain circuits

—> has inhibitory effects on local neural activity

—> by inhibiting the inhibitory process —> exciting the ultimate target

Question 18

Broadly describe how depression is diagnosed based on the DSM-V

Answer 18

Diagnostic and Statistical Manual of Mental Disorders (DSM-5): Establishes symptom-based diagnostic criteria
for major psychiatric disorders

Question 19

Describe the different types of treatment for Major Depressive Disorder and how they work, including pharmacotherapy (MAOIs, tricyclics, SSRIs) and psychotherapy (esp. how CBT works)

Answer 19

psychotherapy ==counseling + behavioral training

pharmacotherapy ==antidepressant medications
———-> MAOIs (monoamine oxidase inhibitor):block the enzyme monoamine oxidase, which breaks down seratonin and other monoamines in the synaptic cleft —> life-threatening spikes in blood pressure bc foods like cheese and smoked meats are filled with them
————->tricyclic antidepressants ==blocks reuptake of monamines; first developed as an antiphsychotic; lethal in high doses
—————> SSRIs ==targeted to specific neurotransmitter systems ==boost serotonin levels by targeting neurotransmitter systems

somatic therapy==stimulation of brain
—————-> TMS (transcranial magnetic stimulation) mild;
—————-> ECT (electroconvulsive therapy) more invasive;

Cognitive behavioral therapy (CBT): structured, present-oriented psychotherapy aimed at solving current problems and coaching people to develop the skills to change their dysfunctional thinking and behavior.

Question 20

Describe the relative rates of effectiveness of SSRIs and CBT

Answer 20

• SSRIs and CBT have similar
rates of efficacy, though some
studies suggest that people
who complete a course of CBT
have lower rates of relapse
than those who stop taking
SSRIs

Question 21

Broadly describe similarities among hemispatial neglect, somatoparaphrenia, and anosognosia both in terms of symptoms and brain areas implicated

Answer 21

Hemispatial neglect: deficit in attention to/awareness of one side of space (right temporoparietal cortex)

Somatoparephrenia: failure to recognize limb as part of one’s own body (temporo-parietal junction damage)

Anosognosia: lack of awareness/denial of condition (parietal lobe )

Question 22

Explain different ways in which we make the distinction between neurological and psychiatric disorders and discuss ways in which this distinction may be useful and ways in which it might not be quite accurate

Answer 22

Schizophrenia = clearly psychiatric, Parkinson’s = clearly neurological … why?

Neuro—observable brain abnormality
psych—if there isnt

Neurological if it affects movement, sensory input and
perception, attention, memory, spatial navigation,
reasoning, etc.

Psychiatric if it affects emotion, emotional regulation,
motivation, personality, social behavior, etc.?

problematic — there are often behavioral effects (that fall into the psychiatric category) that have neural correlates (and vice versa)

problematic — in psych, there may be brain abnormalities that we cannot detect

Question 23

Explain how the regions typically affected first and most by Alzheimer’s disease are associated with primary symptoms of the disease

Answer 23

pa

how Alzheimers affects frontal lobe
loos of motivation—->bizarre inappropriate behavior

Question 24

Explain how the areas that are most in-demand in our lives are the ones most affected by Alzheimer’s disease

Answer 24

hubs of functional activity correlated with amyloid plaque developments

Question 25

Explain what the researchers at MIT did in the “Bringing Gamma Back” episode of Radiolab – describe the methods, results, and significance of this work. Explain how, although this work is interesting, we may want to be cautious in our enthusiasm about this technology helping people with Alzheimer’s disease

Answer 25

gamma frequency == beat that rises above all others when you are completing a task that requires focused attention

betaamaloid buildup

exposure to lights flickering at the beat of gamma: enlarged microglia that then ate up the betaamaloid

Enlarged microglia consumed more beta amyloid —> The mice performed better on a maze task
—> The mice performed better on a maze task

Question 26

Explain the graph depicting Alzheimer’s disease and reserve. Be able to describe what it displays and some key characteristics of it

Answer 26

In AD patients cognitive reserve theory predicts that the clinical manifestation of advancing AD pathology would be delayed in patients with higher exposure to cognitive, social and physical activities.

Question 27

Describe the case of the “frozen addicts” and explain why this was an important event in our understanding of Parkinson’s disease

Answer 27

symptoms, caused by a bad batch of synthetic heroin, were indistinguishable from those associated with Parkinson’s disease, a degenerative nerve disorder

doctor administered L-dopa – the only known effective treatment – and “unfroze” his patient

found that the synthetic heroin inadvertently laced with a toxin that had destroyed substantia nigra
neurotoxic contaminant = MPTP.

—> animal model
—> discovery of this molecule proved of immense scientific importance :

Question 28

Explain how most neurological and psychiatric disorders are typically thought to be a
result of gene-by-environment interaction and provide evidence supporting this idea

Answer 28

Most neurological and psychiatric disorders not caused by a single gene.

• Different genes may interact with each other, and these genes also interact with environmental factors.

• Genes and environmental factors may be protective or harmful, in different
combinations.

Question 29

Explain how serendipity is an important factor in drug discovery

Answer 29

“Serendipity” in drug discovery implies the finding of one thing while looking for something else.

drug discovery: MAOIs monamine oxidase inhibitors
—> block the action of monoamine oxidase, the enzyme that breaks down monoamines in the synaptic cleft
—> discovered in the 1950s, after observations that some tuberculosis patients undergoing treatment were experienced relief of depressed mood

Early versions of antidepressants were originally
developed as drugs to treat tuberculosis
• The first anti-psychotic was originally developed as
a sedative
• Psilocybin, used to alter states of consciousness in
healthy adults, was found to produce lasting
improvements in mood
• Ketamine, used to model psychosis in healthy
adults, was similarly found to produce lasting
improvements in mood

Question 30

Describe the monoamine hypothesis and how it came about and why the aspirin-headache
example might be relevant in this case

Answer 30

Monoamine hypothesis: Suggests that MDD caused
by a deficiency in monoamine neurotransmitters
(e.g., dopamine, norepinephrine, serotonin)

Scientists once thought that simply increasing the amount of monoamines in the brain would treat the symptoms of depression —> meaning that depression itself must be caused by low levels of monoamines, particularly serotonin —> . It appears that even though antidepressants increase serotonin, a lack of serotonin doesn’t cause depression (kind of like aspirin treats a headache, but headaches are not caused by a lack of aspirin).

Question 31

Explain the methods and key results – the ones we discussed in class – of the McGrath et al study and how this represents potentially a turning point in our understanding of how to treat depression and potentially other disorders

biomarker for CBT vs SSRI

Answer 31

anterior insula:

greater activity with SSRI —> decreased depression
lower activity with CBT —> decreased depression

• Lower activity in anterior insula (AI): Improve with CBT, not with SSRI
• Higher activity in anterior insula: Improve with SSRI (escitalopram;
Lexapro), not with CBT

Lower activity in AI correlated with greater reduction in depression scale score with CBT

• Higher activity in AI correlated with greater reduction in depression scale score with SSRI