brain areas and neuroscience

Cerebellum and Anxiety Disorders

Benzodiazepine receptor in the cerebellum are linked to drug effects of ataxia.

Brain stem and strokes

Brain stem strokes affect both sides of the body, causing locked-in syndrome.

What does the destruction of grey matter cause?

The abolition of sexual behaviour.

What does central grey lesion cause in fear conditioning?

Impaired freezing behaviour.

What is grey matter’s role in fMRI?

Contrast between tissue types

CSF→grey matter→white matter

Grey matter in what area increases during practicing of a difficult juggling task?

MT / V5 - visual areas

How is CSF used in research of Alzheimer’s Disease?

Test CSF levels of B-amyloid or tau proteins using PET scans.

What is CSF’s role in T1 vs T2

Slowest T1 relaxation time - gives weaker signal, appears dark in T1-weighted images

Fastest T2 relaxation time - highest signal intensity, appears light in T2-weighted images

Ventricles and MR contrast

There is faster relaxation in brain tissue than in the ventricles

In what disorders are enlarged ventricles seen?

Schizophrenia

Alzheimer’s disease

What happens to the blood-brain barrier in a stroke?

Breaks down - influx of blood-borne immune cells into the brain

Reperfusion injury exacerbated by surgical intervention can lead to intracranial haemorrhage, damaging the BBB - this can be seen by the extravasation of a contrast agent

What happens to the cerebral cortex in Alzheimer’s disease?

Degeneration is involved in brain atrophy.

How is the vmPFC involved in decision making?

Tracks expected value in line with current goals

Lesions lead to inconsistent preferences and a deficient sense of guilt

How is the frontal pole involved in decision making?

Exploratory behaviour

How is the dlPFC involved in decision making?

Representation of information in here is associated with proactive control

What areas are associated with generating eye movements in decision making?

Parietal and dorsal PFC

How is vmPFC involved in anxiety disorders?

Signal increases as extinction of fear conditioning progresses

Individuals high in trait anxiety show impoverished pre-extinction vmPFC activity

What is seen in the PFC of people with OCD?

Overactivation in PFC to safety signals

Higher PFC activation predicted generalisation during reversal of fear conditioning

Stimulation of what brain area by TMS lead to thumb twitches, measured by EEG?

Left motor cortex

What pathway and where is involved in Schizophrenia?

Mesocortical dopaminergic pathway

From the VTA to the frontal cortex

Rats - Injuries in what area lead to the development of abnormal dopamine organisation in PFC?

Perinatal hippocampal injuries

Lower (what neurotransmitter) in (which area) was associated with symptom severity of SZ, and lower (what neuotransmitter) was associated with cognitive decline?

Glutamate

Medial frontal cortex

Glx - glutamate and glutamine

In which areas are reduced neurons and abnormal cellular structures found in SZ?

PFC

Hippocampus

Reduced proactive control in SZ is associated with lower representation of info in (what brain area)

Dorsolateral prefrontal cortex

Reduced BOLD activity is seen in what brain area in effort-based decision making in the brains of people with SZ?

Medial frontal cortex

In humans, which brain areas showed significantly lower response to blocked vs non-blocked reward-predicting stimuli?

Medial orbitofrontal cortex

Ventral putamen

Activation in what areas is correlated with the degree of behavioural blocking?

Orbitofrontal

What areas are associated with dopamine release in monkeys in response to surprising stimuli?

VTA

Substantia nigra

What kind of oscillations are lateralised during visual spatial attention?

Occipito-parietal alpha ocillations (10Hz)

Lesions in what areas lead to Balint’s syndrome?

Parieto-occipital lesions

What happens when occipital cortex is stimulated in TMS? (excitatory)

Phosphenes - perception of light in the absence of light input to the eye

What happens when occipital cortex is stimulated in TMS? (inhibitory)

Suppression of motor perception, decreased performance in letter identification task

What is a neural corelate of spatial attention?

Increased alpha oscillation supression in occipito-parietal regions

During cue-target interval in vixual attention task, alpha power decreases in hemisphrer contralateral to attended visual field

What causes ignoring the left side of images / objects and what does this suggest to us

Lesions at the temporo-parietal junction

This area contributes to spatial attention particularly in the left half of space

Higher what levels in the basal ganglia are linked to SZ symptom severity

Glutamate

Glutamine

What is the basal ganglia implicated in in decision making

The urgency signal is controlled by projections from the basal ganglia to cognitive and sensorimotor areas

How is the limbic system implicated in anxiety?

MacLean’s (1949) limbic system theory - hippocampus as the keyboard of emotions

How is the hippocampus involved in anxiety disorders?

Linked to the amygdala to provide memories and contexts

BZD receptors in the hippocampus are linked to anxiolytic and anti-convulsant effects

How is the hippocampus implicated in SZ?

Abnormal cell structure

Thinner parahippocampal gyri

May have a role in the impairment of relational memory, and reduced dlPFC activity

How is the hippocampus implicated in memory retrieval?

Memory is state-dependent

Illustrated by intracerebral inactivation of Nucleus reuniens (RE) - a midline thalamic nucleus which interconnects mPFC with hippocampus using muscimol

How is the hippocampus implicated in sex differences in behaviour?

Male prairie voles have larger hippocampus for spatial learning

Human, rat males display sex differences

Human fMRI - men may use their hippocampus more than women in order to navigate a virtual maze

How is the hippocampus involved in decision making?

Retrieval of LTM associated with hippocampus

New experiences require neurona activity in the hippocampus in order to be stored in LTM

How is the hippocampus implicated in Alzheimer’s disease?

Severe degeneration iof the hippocampus is involved in brain atrophy

How is the amygdala implicated in anxiety disorders?

• Amygdala implicated in fear reaction to threat, and prediction - it is overactive in an anxiety state

• Amygdala shows heightened response to frightened eyes

• Signal in amygdala reduces over fear extinction

• Individuals high in trait anxiety show increased amygdala responsivity to phasic fear cues

• Amygdala is activated during avoidance choices

• Arachnophobes show greater amygdala responses to phobic pictures as well as fear and disgust pictures

• Amygdala hyperactivation in GAD

• BZD receptor in amygdala linked to anxiolytic, anti-convulsive effects

• Amygdala responses to fearful faces linked to serotonin system - healthy individuals with short allele of serotonin transporter show increased amygdala response to fearful faces

• In patients with depression, amygdala response to fearful faces  by 8 week SSRI treatment

How is the amygdala implicated in schizophrenia?

Grey matter is reduced in the amygdala bilaterally

How is the amygdala involved in sexual behaviour

• Medial amygdala destruction in men disrupts sexual behaviour

• Mating causes production of Fos protein

• Neurons in women contain estrogen and progesterone receptors

• Sexually dimorphic nucleus of the preoptic area (SDN-POA) and posterodorsal medial amygdala (MePD)

  • SDN-POA masculinised by testosterone during critical prenatal period

  • MePD volume and cell size depends on testosterone action in adulthood

How is the amygdala implicated in Pavlovian Instrumental Transfer?

Specific PIT depends on the integrity of the basolateral amygdala vs General PIT on the central nucleus

How is the amygdala involved in emotion?

• Functional-anatomical model of conditioned fear - central role for amygdala

• Unity of auditory thalamus -> auditory cortex (tone) and somatosensory thalamus ->somatosensory cortex (shock) in the lateral amygdala -> central amygdala -> freezing, blood pressure, hormones

What happens when you lesion different areas of the amygdala

• Much more freezing in sham and basal lesions than central and lateral lesions

• Central and lateral amygdala required for conditioned fear

What do neurons in the lateral amygdala encode?

CS-US pairing

Fire in response to the tone when the tone is paired with a foot shock

What happens when the amygdala is damaged in humans?

Impairs conditioned fear, measured using skin-conductance response

What happens to the amygdala in a conditioned fear paradigm?

When an unconditioned shock to the wrist is paired with a conditioned stimulus, there isn’t much difference in fMRI brain activity

This doesn’t support the role of the amygdala, but doesn’t rule it out

What happens to the thlamus in SZ

Grey matter is reduced in the left thalamus and caudate

What is the effect of BZD receptors in the ventromedial hypothalamus?

Appetite stimulant

What role does the hypothalamus play in sex differences?

Puberty is triggered by hypothalamic secretion of GnRH

What sex differences are seen in the human preoptic area (POA) of the hypothalamus?

• Fliers and Swaab (1985)

  • One nucleus in POA of hypothalamus larger in volume, cell number in males than females

  • Authors named the nucleus SDN (sexually dimorphic nucleus)

• Allen et al (1989)

  • Studied four nuclei in POA which they named interstitial nuclei of the anterior hypothalamus (INAH) 1-4

  • INAH1 corresponded to SDN of Fliers and Swaab (1985) but did not differ between sexes - INAH4 also didn't differ

  • INAH2 and 3 larger in men than females

• LeVay (1991)

  • No significant sex differences in INAH1,2,4

  • Replicated INAH3 larger in heterosexual men than women

  • INAH3 did not differ between homosexual men and heterosexual women

  • Substantial overlap - not too reliable

What roles does the hypothalamus play in emotion - lesion studies and conditioned fear?

• Lateral hypothalamus lesion - impairment in blood pressure response

What role doe the hypothalamus have in learning about time?

• Suprachiasmatic nucleus in the hypothalamus

• Metabolic rate in SCN appears to vary as function of day-night cycle

• Lesions of SCN abolish circadian regularity of foraging and sleeping in rats

• SCN receives direct and indirect inputs from visual system which could keep circadian rhythms entrained with real day/nigh cycle

What is the effect of BZD receptors in the reticular formation?

Muscle relaxant, sedative, perhaps a hypnotic

How is the VTA involved in blocking and unblocking

Bliocking / unblocking is associated with dopamine release in the VTA / substantia nigra in monkeys