Exam 3 Behavioral Neuro

neuropsychology: definition, origins

definition: study of the relationships between brain function and behavior, with emphasis on humans

origins: Paul Broca discovered the link between specific damage located in the left frontal lob region and language difficulties

another example: Phineas Gage

Broc’as area

corresponds to Brodmann areas 44 and 45, located near motor cortex that controls face and mouth movements

Wernicke’s area

corresponds primarily to Brodmann area 22, adjacent to primary auditory cortex

damage to temporal lobe

memory disturbance

histological

brains sectioned postmortem and tissue stained with different dyes

contemporary techniques identify molecular, neurochemical, and morphological differences among neuronal types to relate these characteristics to behavior

brain lesions

used by Karl Lashley (1920s) to find location of memory in the brain

ablation: removal or destruction of tissue

Scoville removed hippocampus from HM to treat epilepsy, which produced amnesia (no longer able to form long-term memories

Stereotaxic apparatus

instrument that allows precise positioning of all brain regions relative to each other and landmarks on the skull

temporary reversible lesion techniques

regional cooling prevents synaptic transmission

local admin of a GAPA agonist increases local inhibition

brain stimultion

rats with electrodes in lateral hypothalamus eat whenever it is turned on; given the opportunity, rats will press a lever to obtain the current

deep brain stimulation: electrodes implanted in the brain stimulate a targeted area with a low-voltage electrical current to facilitate behavior (for Parkinson’s disease, depression, OCD)

deep brain stimulation for Parkinson’s

electrode implanted in subthalamic nucleus or globus pallidus in the brain - device sends continuous, adjustable electrical pulses to the brain - acting as a metronome to normalize signalling to reduce tremor and improve movement

surgery done in two parts, some of it while the patient is awake to verify effectiveness through motor test

transcranial magnetic stimulation (TMS)

procedure in which a magnetic coil is placed over the skull to stimulate the underlying brain

used either to induce behavior or to disrupt ongoing behavior

used in clinical therapy for depression, by influencing neural activity in a localized region

magnetic field easily passes through the skull and causes a population of neurons in the cerebral cortex to depolarize and fire

ways to measure brain’s electrical activity

single-cell recording

electroencephalography (EEG)

event-related potentials (ERP)

magnetoencepthalography (MEG)

single-cell recording

measuring single-neuron action potentials with fine electrodes

electrodes placed next to cells (extracellular recording) or inside them (intracellular recording)

can distinguish the activity of as many as 40 neurons at once with extracellular recording

EEG (electroencephalography)

measures summed graded potentials from many thousands of neurons

reveals features of the brain’s electrical activity

measures continuous, raw electrical brain activity

captures broad states like sleep

event-related potentials (ERPs)

largely the graded potentials on dendrites that a sensory stimulus triggers

complex electroencephalographic waveforms are related in time to a specific sensory event

to counter noise effects, the stimulus is presented repeatedly, and the recorded responses are averaged

so it’s EEG plus specific sensory stimulus

specialized, averaged subset of EEF data representing brain responses to specific stimuli

analyze fast, time-locked cognitive processing in milliseconds

magnetoencephalography (MEG)

neural activity, by generating an electrical field, also produces a magnetic field. Magnetic potentials are recorded from detectors placed outside the skull

permit a 3D localizations of the cell groups generating the measured field

noninvasive, safe imaging technique that maps brain activity by recording magnetic fields produced by electrical currents in neurons. With superior temporal and spatial resolution, it detects fast neural events (millisecond scale) to help surgeons pintpoint epilepsy foci, tumor locations, and functional areas (language/motor) before surgery

higher resolution than ERP, but more expensive

computed tomography (CT scane

x-ray beams passed through the brain at many different angles, creating many different images

images are combined with the use of computing and mathematical techniques to create a 3D image of the brain

gray matter density does not differ from white matter density enough for a CT scan to distinguish between the two

ventricles can be visualized because the fluid in them is far less dense

magnetic resonance imaging (MRI)

subject is placed in a long metal cylinder that has two sets of magnetic coils arranged at right angles. An additional radiofrequency coil (not shown) surrounds the head, perturbing the static magnetic fields to produce an MRI image of a horizontal section through the head, shown in dorsal view

electrical currents emitted by wobbling atoms are recorded by MRI to represent different types of tissues-cerebrospinal fluid, brain matter, and bone, for example-as lighter or darker, depending on the density of hydrogen atoms in the tissue

diffusion tensor imaging (DTI)

detects the directional movements of water molecules to image nerve fiber pathways in the brain

water molecules play a critical role in nerve fiber function and structure by facilitating electrical signaling and enabling neuroimaging

MRI can measure the diffusion of water molecules in white matter, allowing the visualization of nerve fiber tracts.

magnetic resonance spectroscopy (MRS)

MRI method that uses the hydrogen proton signal to determine the concentration of brain metabolites

useful in detecting persisting abnormalities in brain metabolism in disorders such as concussion

concussion caused “metabolic cascade” characterized by an immediate energy crisis, where the brain demands high energy to repair damage while simultaneously experiencing reduced glucose metabolism and impaired cerebral blood flow

functional brain imaging

when a brain region is active, the amount of blood, oxygen, and glucose flowing to the region increases

possible to infer changes in brain activity by measuring either blood flow or levels of the blood’s constituents, such as oxygen, glucose, and iron

brain activity increase - increase in oxygen produced by increased blood flow actually exceeds the tissue’s need for oxygen

changes in the oxygen content of the blood alter the magnetic properties of the water in the blood

fMRI

fMRI

fMRI allows for good spatial resolution of the brain activity’s source

because changes in blood flow take as long as 1/3 of a second, temporal resolution of fMRI is not as precise as that of EEG recordings and ERPs`

optical tomography

reflected infrared light is used to determine blood flow because oxygen-rich hemoglobin and oxygen-poor hemoglobin differ in their absorption spectra

light injectors (red) and detectors (blue) are distributed in an array across the head

light is injected through the scalp and skull penetrates the brain to a depth of about 2 centimeters. A small fraction of the light is reflected and captured by a detector on the scalp surface

positron emission tomography (PET)

radiotracer injection: a positron-emitting radionuclide is introduced into the body, concentrating in areas with high metabolic activity, such as cancer cells or the brain

the tracer decays and emits a positron (a positively charged antiparticle). When this positron interacts with a nearby electron, they destroy each other (annihilation)

this annihilation event creates two high-energy photons (gamma rays) that fly off in opposite directions

can detect relative amounts of a given neurotransmitter, the density of receptors, and metabolic activities associated with learning, brain poisoning, and degenerative processes

widely used to study cognitive function

marijuana: basic history

cannabis originated in central asia

first recorded in Pyramid texts - religious passages carved around 2350 BCE

several grains of cannabis found in the body of Rameses II, a great Egyptian Pharaoh

hair samples in mummies indicated high levels of cannabis use

China - evidence of hemp use dates back to 12k years ago

Chinese, Greeks, and Romans wrote about medical benefits

existed in Africa for ~2000 years, and during slave trades in 1500s made its way to Brazil and then later to North America

hemp extremely important during era of European imperialism - strong ropes needed for sailing, grew better in the American colonies

George Washington was a hemp grower!

1839 - William B. O’Shaughnessy discovered it was an anticonvulsant as well as a stimulant

• used in addictions to alcohol and opium, as well as for “hysterical insanity” and bipolar disorder

1890s and 1900s used for sedative, hypnotic, and anticonvulsant agents; lost appeal because of the wide variety of samples - standardization difficult

word ‘marijuana’ came from Mexico and California as a scare tactic to outlaw substance in 1913

1964 - Israeli chemists identified primary acting ingredient in cannabis - THC!

cannabinoids

cannabis plant contains phytocannabinoids that are similar to the body’s own endocannabinoids

bind to CB1 and CB2 receptors

CB1: retrograde messengers released from the postsynaptic cell body and are the most abundant metabolic subtypes in the entire brain

CB2: found mostly in the PNS

Cannabidol (CBD)

acts as a negative allosteric modulator of the CB1 receptors - changes the shape of the receptor, making it harder for THC to bind, thereby reducing the intoxicating effects of THC

does not directly fit into CB1 receptors, so this is why it is non-intoxicating

often works with CB2 receptors in the immune system and peripheral tissues to reduce inflammation and pain

Tetrahydrocannabinol (THC)

acts as a strong partial agonist of CB1 receptors, mimicking natural cannabinoids (like anandamide) to produce euphoria and psychoactive effects

directly fits into CB1 receptors in the brain

CB1 receptors target…

motor activity, thinking, motor co-ordination, appetite, short-term memory, pain perceptions, and immune cells.

Primarily in the CNS, including hippocampus and select parts of the cortex - mediate psychoactive effects

some in PNS to promote energy conservation

CB2 receptors target…

gut, kidneys, pancreas, adipose tissue, skeletal muscles, bone, eye, tumors, reproductive system, immune system, respiratory tract, skin, CNS, cardiovascular system, liver.

Found primarily in the PNS, and play a role in immune system function - inhibits pro-inflammatory proteins and enhances anti-inflammatory proteins

In CNS: found in glial cells

Why did people fight to legalize marijuana?

1. novelty, sensation seeking - mesolimbic dopamine reward pathway

2. DARE and commercials were a disaster - close friend influence likely motivator for use

3. too many successful people smoke (like Snoop Dogg)

impact of THC on behavior

low to moderate doses impact behavior for about 2-3 hours

bloodshot eyes caused by dilation of blood vessels

dry mouth (cotton mouth) leads people to consume liquids more and appetite increases

impact of THC on sleeping stages

low doses - sedative effect, can cause a decrease in REM sleep and increase slow-wave (deep sleep)

higher doses - restlessness and reduced sleep - both REM and deep sleep levels are reduced

with tolerance, sleep latency decreases but REM sleep remains low

withdrawal of sleep has been known to cause previous users to report bizarre dreams

impact of THC on violence

Yes, 55% of adults and juveniles arrested for committing a crime tested positive… but

numerous longitudinal studies have failed to find a link between marijuana and violent acts, even with heavy users

consistence evidence that it leads to increased open-mindedness and tolerance for others

some studies found heavy use inhibits violent behavior

THC as a gateway drug?

Ongoing debate

• virtually all cocaine and heroine users tried marijuana first, but no evidence of causality

• people plan on trying various drugs - and THC often chosen before strong drugs

  • almost all people who drink alcohol started with soda

Common factor model:

a. individuals have a nonspecific, random propensity to want to try drugs and these people are evenly distributed across the population

b. the propensity is correlated with having an opportunity to use drugs

c. neither the use or opportunity to use marijuana is associated with hard drug initiation

Delta variations and behavior (synthetic marijuana)

Delta-9 THC: priamry psychoactive compound in cannabis, causing strong euphoric effects. Heavily regulated and legal only in specific jurisdictions

Delta-8 THC: a lighter version of Delta-9, causing milder intoxicating effects with potential for less anxiety or paranoia. Often derived from hemp.

Delta-10 THC: a less common, milder cannabinoid often described as stimulating or energizing. Usually produced synthetically from CBD.

unregulated and synthetically converted - carry risks of contamination, overdosing, and severe adverse reations

THC impact on short term memory vs long term memory

Short term memory: negative effect on verbal and episodic short-term memory - not unusual for users to start a sentence and stop halfway. In general it is difficult to maintain working memory because users are open to distraction

Long term memory: not rlly super effected??

high densities of CB1 receptors on prefrontal cortex and hippocampus

learning

a relatively permanent change in an organism’s behavior as a result of experiences

memory

the ability to recall or recognize previous experience

three basic processes of memory information

encoding - converting info into a form usable in memory

storage - retaining info in memory

retrieval - bringing to mind info stored to memory

classical conditioning

Pavlov’s dog example:

Before conditioning -

• unconditioned stimulus - food in mouth

• neutral stimulus - tone

• unconditioned response - salivation

During conditioning -

• neutral stimulus - tone + unconditioned stimulus - food in mouth → unconditioned response - salivation

After conditioning -

• conditioned stimulus - tone

• conditioned response - salivation

operant conditioning

an organism demonstrates that it has learned the association between its actions and the consequences

categories of memory

implicit memory, procedural memory, explicit memory

3-stage memory model

1. Sensory memory: briefest memory store, responsible for bringing into mind sensory impressions, such as sights and sounds, and retaining them in memory for a brief moment in time

2. Short-term memory (STM): allows us to hold info in mind for upwards of 30 seconds, 5-9 bits of information

3. Working memory: retaining STM despite a distractor

implicit memory

subconscious memory that can’t be explicitly retrieved

• procedural memory - memory of how to do things such as riding a bike, tying shoes, performing math equations, or playing an instrument - happens without conscious effort

• things like motor memories - basal ganglia and cerebellum

explicit memory

memory that can be consciously retrieved and said aloud

• Declarative memory: ability to account. Includes semantic memory (memory for facts), episodic memory (personal experiences), retrospective memory (memory of past experiences), prospective memory (memory of future actions)

• episodic and semantic: hippocampus, neocortex, amygdala

over time, information from certain memories that are temporarily stored in the hippocampus can be transferred to the neocortex as general knowledge

hippocampus

EXPLICIT MEMORIES

temporal lobe, where episodic memories are formed and indexed for later access

episodic - autobiographical

how did they figure out? HM had his hippocampus removed to treat epilepsy, and he was no longer able to form new episode memories

amygdala

EXPLICIT MEMORIES

almond shaped structure in the brain’s temporal lobe, attaches emotional significance to memories

important because strong emotional memories are difficult to forget

permanence of these memories suggests that interactions between the amygdala, hippocampus and neocortex are crucial in determining the stability of the memory - how effectively it is retained over time

IMPLICIT MEMORIES

plays a key role in forming new memories specifically related to fear - fearful memories able to be formed after only a few repetitions

basal ganglia

IMPLICIT MEMORY

structures lying deep within the brain and are involved in a wide range of processes such as emotion, reward processing, habit formation, movement, and learning

particularly involved in coordinating sequences of motor activity (like for an instrument or for playing basketball)

regions most affected by Parkinson’s disease

cerebellum

IMPLICIT MEMORY

most important in fine motor control - type that allows us to use chopsticks or press piano key a fraction more softly

Default Mode Network (DMN)

large scale brain network - primarily involving the medial prefrontal cortex, posterior cingulate cortex, and inferior parietal regions - that activates during wakeful rest, self-referential thought, daydreaming, and remembering the past

it is suppressed during goal-directed tasks (acting on default mode when mind is not focused on external world)

when active - most active during downtime or introspection and deactivates when attention is shifted to external tasks

overactive DMN linked to overthinking, anxiety, and depression - acting as a rumination machine that replays failures

disorders: abnormalities in DMN associated with Alzheimer’s disease, Parkinson’s, autism, and schizophrenia

• amyloid plaques are dense, insoluble clusters of misfolded amyloid-beta protein fragments that accumulate between nerve cells in the brain - hallmark of Alzheimer’s disease - blocking communication between neurons - inflammation and cell death

DMN and alcohol

alcohol acutely disrupts the DMN by decreasing connectivity, particularly in the right hippocampus and middle temporal gyrus

this reduction in DMN activity contributes to decreased self-awareness, lowered inhibition, and a temporary calming of mental “chatter” or rumination

acute consumption - alcohol acts as a “dimmer switch” for DMN - reducing activity

heavy drinkers - decreased DMN connectivity in these areas correlated w stronger cravings for alcohol

chronic use - long-term alterations within the DMN - reduced connectivity between nodes (neuron cell bodies) meaning white matter (connections between nodes) damage

DMN and meditation

meditation reduces activity in the DMN, by focusing on present-moment awareness; reducing mental chatter, decreasing anxiety, improving focus

reduced activity - in medial prefrontal cortex and posterior cingulate cortex - which are core nodes of DMN

reduced mind wandering: by reducing DMN activity, meditation decreases the “monkey mind” or constant self-referential thoughts

DMN and mind wandering

mind-wandering is a cognitive process in which people spontaneously have thoughts that are unrelated to their current activities - those with negative affect may have thoughts associated w mood disorders like negative thoughts about the past

transcranial direct current stimulation (tDCS) - non invasive low risk neuromodulation technique using weak electrical currents to modulate neuronal activity - to treat depression, chronic pain, and stroke rehabilitation

research:

• tDCS did not change mind-wandering frequency after hearing criticism, but it did change what people mind-wandered about. Specifically, inhibitory stimulation decreased the frequency of negative mind-wandering thoughts about the past

salience network (SN)

large scale brain system, anchored in the anterior insula and anterior cingulate cortex

detects, integrates, and filters relevant internal and external stimuli

acts as a network moderator, switching between the brain’s internap processing (DMN) and external processing (CEN)

generates control signals and causally mediates the switching between the DMN and the CEN

allows individuals to stay vigilant when meeting unexpected environmental events

resting state signals of DMN anticorrelated with that of the SN

sensory memory

processed through specialized sensory cortex areas within the brain, acting as a temporary “holding cell” for info for only a few seconds

key regions include the occipital lobe, temporal lobe, parietal lobe (touch), and the olfactory bulb

amyloid plaques vs tau tangles

Amyloid plaques: develop between neurons from misfolded proteins

Tau tangles: develop within neurons, abnormal insoluble clumps of protein that accumulate inside neurons, serving as a primary biomarker for Alzheimer’s disease - normally bind to and stabilize microtubules, which act as tracks for moving nutrients and molecules within neurons

Alzheimer’s disease - memory

explicit memories are impaired

implicit memories stay intact in the early to mid stages - including habits and skills

working memory decline

Parkinson’s disease (PD).- memory

loss of dopamine producing neurons

cognitive impairment, depression, apathy

episodic memory decline noticeable in earlier stages than semantic

working memory decline usually present at time of diagnosis

UNLIKE ALZHEIMER’S - early deficits in procedural/implicit memory, while long term memory often spare till later stages

memory retrieval issues

Huntington’s disease (HD) - memory

episodic memory decline noticeable in earlier stages than semantic

working memory decline usually present at time of diagnosis

explicit memory impacted early on

implicit memory also affected, particularly in new motor skill learning and sequence learning

schizophrenia

impairs episodic memory, while leaving semantic memory less impacted

explicit memory impaired whereas implicit memory is not

working memory impairment - stable cognitive deficit in schizophrenia

dementia

significant memory losses

damage to neurons, connections, specific brain parts have atrophy, and overall reduced independence is the ultimate behavioral cause

DMN, SN, CEN majorly damaged

hippocampus first noticeable atrophy

sever decline in explicit memory, preserving implicit memory