PSYCH 417: EXAM 1

psychological views of the brain

monism
dualism
parsimony

monism (psychoneural identity hypothesis): mental states are identical to physical states of the brain, they exist as a single function

dualism: the mind and body are separate and function separately and independent entities

parsimony: the simplest explanation tends to be the most correct

allostatic load

cumulative physiological toll/prolonged adaptation on body’s major systems

accelerates bio aging through chronic stress

e.g., animals with higher metabolic rate —> shorter lifespan

3 dimensions of aging

1. biological: physiological functioning

2. psychological: cognitive & emotional functioning

3. social: milestones, “social clock”

aging terms

gerontology
geriatrics
lifespan
life expectancy

gerontology: study of aging across all 3 dimensions

geriatrics: diagnosis and treatment of age-related conditions; aging is not a disease

lifespan: max age attainable, under optimal conditions, “biological upper limit”

life expectancy: avg years expected to live, based on stats

4 factors that increase life expectancy

1. food prod & dist

2. sanitation & public health

3. medical advances

4. technology & living conditions

“The Twilight Zone": Long Live Walter Jameson”

Jameson: Civil War, over 2000 years old

Sam: dad

Susanna: daughter

difficulties of studying human aging

• time: long-term tracking

• variability: individual differences in aging

• confounds

• cohort effects

psychological aging studies

cross-sectional
longitudinal
pros vs cons?

• cross-sectional: compare different age groups at one point in time

  • pros: fast, inexpensive, easy

  • cons: correlational (not causational), infer differences (not changes)

• longitudinal: follow same individuals across multiple time points

  • pros: true within-person change, controls for cohort effect

  • cons: costly, time-intesive, attrition, cannot generalize easily

animal models in aging research

pros vs cons?

pros:

• shorter lifespan

• invasive procedures possible

• minimize genetic variability

• karger sample sizes

cons:

• ethical issues

functions & theories of aging

inbuilt program theory + con?
disposable soma theory + con?
terminal drop model

inbuilt program theory: prevents overpopulation by clearing older individuals to make way for younger generations

• con: most animals in the wild die before old age

disposable soma theory: body budgets limited energy resources

• prioritizes reproduction

• defers somatic cell maintenance/repair

• con: difficult to test directly in humans

terminal drop model: before death in old age (~5 years), there is a terminal drop in life satisfaction and physiological function

3 levels of biological aging damage

1. tissue: loss of collagen protein → reduced elasticity

2. cellular: decline in mitochondrial function → less energy

3. molecular: DNA mutations accumulate over time

Don’t Die: The Man Who Wants To Live Forever

Bryan Johnson

Son: Talmage

Project Blueprint: Level 1, 2, 3 protocol

jobs

• sandwich shop

• entrepreneur

• credit card salesman

• Braintree: paypal, venmo, etc.

challenges in assessing cognitive function in older adults

• increased individual variation

• test anxiety; lab coat syndrome

• test difficulty: designed for young adults, difficult for older adults

• decreased stamina: fatigue during long tests

• sensory & motor deficits: vision, hearing, etc., impairments

2 types of intelligence

crystallized
fluid

1. crystallized: accumulated knowledge and skills

   1. associated with older adults

2. fluid: novel problem-solving abilities, mental flexibility

   1. associated with younger adults

aging effects on life

attention
- simple
- complex
—sustained
—selective
—divided
—alternating
reaction time
creativity
language
executive functioning

attention:

• simple: immediate memory, relatively stable with slight decline

• complex: noticeable decline over time

  • sustained: focus on one task (e.g., driving a long time)

  • selective: focusing on relevant info (e.g., noisy room)

  • divided: multi-tasking

  • alternating: switching between tasks

reaction time: slows over time

creativity: declines with age

language: vocabulary intact, naming/recall and verbal fluency declines

executive functioning (EF): higher-order thoughts and control, declines with age

memory systems

declarative
- facts
- semantic
—hippocampus
—MTL
—diencephalon

1. medial temporal lobe (MTL) dependent

   1. declarative (explicit)

      1. facts (semantic)

      2. events (episodic)

         1. hippocampus

         2. MTL

         3. diencephalon

Electroencephalogram (EEG)

EEG: first non-invasice measure of brain function

• detects pathologies (e.g., tumors)

• tracks arousal states

• high temporal resolution (high frequency of captures)

aging: ~10 Hz in younger adults, ~8 Hz in older adults

types of waves

• gamma:

• beta:

• alpha:

• theta:

• delta:

structural changes in the brain

decreased vs increased?
brain size, weight, volume
metabolic activity
neuron loss/shrinkage
ventricles
glial cells

decreased

• brain size: gyrus shrinks, sulci expands

  • loss of white/gray matter

• brian weight

• brain volume: neocortex, hippocampus, amygdala

• metabolic activity: PET scan

• neuron loss & shrinkage

increased

• ventricles

• glial cells: increased activity

memory impairment cause

neuronloss?
synaptic restructuring (hippocampus)?
—SSB, MSB, NSB

• not neuron loss (same # somas)

• synaptic restructuring in hippocampus

  • young → aged brain

  • SSB (single-syn boutan) → NSB (non-syn)

  • MSB (multi-syn) → SSB

  • MSB → MSB

• reduced dendritic spine density

LTP (long-term potentiation)

what is it?
5 characteristics
LTP induction vs decay

• does not only occur in hippocampus

• persistent, activity-dependent increase in synaptic strength, serving as a cellular model for learning and memory

5 key characteristics

1. rapid induction: triggered by brief HFS (high-freq stim)

2. long-lasting: can last for weeks

3. activity-dependent strengthening: increases with repeated activation (eventual saturation)

4. input specific: potentiation of restricted → activated synapses

5. broad anatomical presence: key learning-related regions

   • i.e., hippocampus, amygdala, neocortex, striatum and cerebellum

• LTP induction: rapid, activity-dependent strengthening of synaptic connections

  • comparable for young/aged hippocampus

• LTP decay: gradual, often use-dependent weakening (reversal) of this synaptic strength back to baseline

  • faster in aged hippocampus → weakens memory (synaptic basis)

spatial view vs place cells

spatial view: fire when a specific part of the environment in is view

• depends on what is seen

• i.e., humans

place: fire when the animal is in a specific location

• depends on where the animal is

• i.e., rodents

hippocampal memory loss

reversible or irreversible?
—neurogenesis
—synaptic plasticity
—cognition

lifestyle factors
—exercise
—periodic fasting
—heterochronic parabiosis

• not irreversible, can be partially restored

  • neurogenesis: exercise, caloric restriction, parabiosis

  • synaptic plasticity: exercise, caloric restriction, parabiosis

  • cognition: exercise, caloric restriction, plasma injection

• exercise: very good! for dendrites, neurons, etc.

• periodic fasting: reduces disease risk across species

• heterochronic parabiosis: joining a young and old mouse’s circulatory system together

  • young brain ages, old brain rejuvenates

  • similar to blood transfusion for humans

counterclockwise study (Ellen Langer, 1979)

• experimental group: immersed themselves in retreat, lived as if they were 20 years younger

  • outperformed control group (reminisced, not immersed) in all physical/cognitive measures

AD

AD: affects memory, cognition, from dementia

• differs from typical aging sx in 3 ways

  1. pattern

  2. frequency

  3. recovery

• no definitive diagnosis: must rule out everything else first

  • amyloid plaques: beta-amyloid clusters between neurons that block signaling

    • extracellular

    • result of misfolded, aggregated amyloid precursor protein (APP)

    • amyloid hypothesis: AD not caused by foreign invader, result of brain’s own protein being cut the wrong way

      • begins decades before dementia diagnosis/sx

  • neurofibrillary tangles: twisted taue protein inside neurons → collapse cell structure

    • intracellular

    • normally stabilizes microtubules → instead detaches and collapses

    • tau hypothesis: healthy tau → hyperphos → tau detaches → microtubule disintegrate → tau tangles → neuron dies

• disease progression stages

  • first: forgetfulness, memory loss

  • second: accelerated first stage sx, agitation, restless, repetition

  • final: complete d/o, loss of body function control, dependence

• mild cognitive impairment (MCI): normal aging sx, not AD

  • note: AD continuum

• disparity: disproportionately impacts black, hispanic, and female pops

• lifestyle: physical inactivity, obesity, smoking, HT, high cholesterol, poor diet

still alice

Alice Howland (?)

• linguistics professor

• studied neurons, children, language

• children, med school, law school, actress

1. began to forget her words at dinner and at a lecture, “lexicon”

2. forgot where her husband told her he would be

3. blurred vision while running

4. couldn’t remember bread pudding recipe

AD eyeblink conditioning

optogenetics

combining optical and genetic techniques to probe neural circuits as ms-timescale

• AD → reduces brain waves

• restoring brain waves → beneficial AD effects

non-genetic AD hypothesis

infectious agents:

environment toxins:

vascular:

neuroinflammation/oxidative stress:

cholinergic: degeneration of cholinergic neurons → project to hippocampus and neocortex

• loss of ChAT

gut microbiome: microbiota-gut-brain axis

• stress-AD connection: chronic stress →disrupts gut microbiome →neuroinflammation →accelerates AD

oral pathogen: periodontal bacteria → neuroinflammation

other emerging: BBB breakdown, viral triggers, mitochondrial dysfunction

PD

3 core/cardinal motor symptoms

1. resting tremor: present at rest only

2. muscular (cogwheel) rigidity: disruption of reciprocal inhibition

   1. increased muscle tone

3. bradykinesia: slowness of voluntary movement initiation

   1. note: finger tapping test

secondary signs

• gait disturbance

• hypomimia: vacant facial expression

• mood disorders

• sensory processing

• monotonous speech

brain areas

• substantia nigra: DA neuron loss, lewy body formation

• basal ganglia: regulates voluntary movements, DA regulates direct-indirect pathways

  • paradoxical movement: visual/stress pathways bypass BG → complex motor during stress

    1. DA loss weakens direct pathway → overactive indirect pathway

    2. overactive indirect pathway → overactive ACh (opposite DA)

    3. overactive ACh → bradykinesia & rigidity

PD treatments

PD: imbalance in ACh (increased) and DA (decreased)

• DA needs to cross BBB to increase, needs precursor

• tyr: cross BBB, converted into L-DOPA (which can convert into DA)

  • tyr → L-DOPA → DA (!) → NE → E

PD documentary

• MPPP → MPTP

neurotoxic models (PD)

• MPTP: converts to MPP+ → kills DA → EOPD

• 6-OHDA: selectively kills DA and NE neurons

• note: genes play a minor role when compared to neurotoxic models

PD treatments

dopaminergic

• L-DOPA: DA precursor, reduces tremors, negative side effects develop, drug becomes ineffective

• MAO inhibitors: blocks DA breakdown, slows sx progression

• COMT inhibitors: extends L-DOPA effect

• DA agonists: stimulate DA receptors

surgical

• deep brain stimulation (1990’s-present): stimulates STN, reduces overactive inhibition

  • controls sx, not a cure

• stem cell therapy (1990s-ongoing)

• fetal implantation (1980-90s)

• pallidotomy (1950s)

super agers

• cognitive ability comparable to 20 year olds

brain biology

• greater cortical thickness

• lower amyloid/tau accumulation

protective factors: positive, healthy lifestyle factors

• aerobic exercise

• cognitive engagement

3 trajectories of dying

1. cancer: short, predictable, terminal decline

2. chronic organ failure: long disability, unpredictable death

3. dementia: slow dissolution of self, no identifiable terminal phase

alpha & gamma waves

associated with high cognition

DECREASE in aging

becomes more evenly distributed in EEG scans

• ALL brain waves surge immediately after cardiac arrest, before leveling out

hCO vs t-hCO

hCO: human corticoid organoid (neuron)

t-hCO: transplanted human corticoid organoid (neuron)

• showed more “spikes” when injected with AP compared to hCO

• closely resembles hCO, with larger soma

chimeric brain (TS model)

chimeric brain model: transplanting human cells in rodent brains

TS: tourette’s syndrome

• shorter dendrites, higher spine density, reduced synaptic output

• very excitable