Week 11 Flashcards
Frontal Cortex
• Posterior - motor areas • Anterior – association area – prefrontal cortex (PFC) • Important subregions • Lateral PFC (lPFC) dorsal and ventral portions (dlPFC, vlPFC) • Frontal pole (FP) • Orbitofrontal cortex (OFC) – ventromedial • Medial frontal cortex (MFC)
Prefrontal Cortex
• Massively connected – links motor, perceptual, and limbic • Large input from thalamus – connects PFC with BG, CB, brainstem nuclei • Almost all cortical and subcortical areas influence PFC either directly or by only a synapse or 2 • Many projections to contralateral hemisphere • Many connections bidirectional
Prefrontal Cortex – Sensory Input
Dorsal/ventral sensory divisions extend into PFC Dorsal - motor and executive control functions for which spatial information is important Ventral – mediate emotional responses to things in the environment – emotional significance first requires recognition
Prefrontal Cortex – Motor Contro
• Emotional and cognitive processes exert control over behaviour • Serial/functional hierarchy • vmPFC/OFC (emotional processes) to dlPFC (cognitive control) to motor
Prefrontal Cortex – Emotional
• vmPFC/OFC • Closely connected with limbic structures, especially amygdala • Influence cognition and directly influence ANS • Drives, motivation, valence, and the assessment of the emotional significance of sensory stimuli • Part of a system encoding emotions and emotional responses
Prefrontal Cortex
• PFC half of FL in humans • Human PFC expansion – more about white matter than grey matter • Connections! • PFC matures late in development • May not be fully developed until mid 20’s • Grey matter peaks earlier • White matter later • Connections!!!
PFC Myelination
• Higher cognitive functions for which the prefrontal cortex (language, intelligence, and reasoning) heavily rely on intracortical and corticocortical connectivity • Do not reach full maturity until mid 20’s • Corticocortical axons that develop most between childhood and adulthood are those that run from PFC to posterior association cortex • Those axons are part of the top–down frontal efferent pathways critically involved in cognitive control
Dysfunction - Phineas Gage
• 1848, Phineas Gage working as a foreman when an accident shot a steel rod through the front of his skull • Survived and reportedly got to his feet and walked away • “I did not believe Mr. Gage's statement at that time ... Mr. Gage persisted in saying that the bar went through his head ... He got up and vomited; the effort of vomiting pressed out about half a teacupful of the brain [through the exit hole at the top of the skull], which fell upon the floor • Significant part of his left frontal lobe destroyed • Dramatic personality shift but memory and general intelligence seemed unimpaired after the accident • “most efficient and capable foreman ... a shrewd, smart business man, very energetic and persistent in executing all his plans of operation” • Social problems - now fitful, irreverent, and grossly profane, showing little deference for his fellows. • He was also impatient and obstinate, yet capricious and vacillating, unable to settle on any of the plans he devised for future action. • His friends said he was “no longer Gage." • Most serious mental changes were temporary • Became far more functional, and socially far better adapted • A social recovery hypothesis suggests that Gage's work as a stagecoach driver in Chile fostered this recovery by providing daily structure which allowed him to regain lost social and personal skills. • 1860, he began to have epileptic seizures and died a few months later
Dysfunction - Frontal Lobotomy
• Treatment of psychiatric disorders 1930’s to 1950’s (pre drugs) • Moniz pioneered based on reported effects of frontal lobectomy in chimps (won Nobel in 1949) • Isolate PFC rather than remove
Frontal Lobotomy
Transorbital sectioning • Electroshock anaesthesia • Icepick tapped through top of the orbit • Insert 5cm into brain and “wiggle” Leucotome • Insert 6 times with cutting wire retracted • Extrude cutting wire and rotate • Cut out a core of tissue • Anecdotal reports – patients were ‘stimulus-bound’: • Reacted to whatever was in front of them and did not respond to imaginary situations, rules, or plans for the future. • Some gained significant weight, and / or became sexually promiscuous • Could not form / sustain goals • Distracted by circumstances
Dysfunction - Frontal Astrocytoma
• Patient W.R - the man who had “lost his ego”
• Life changed after he earned his law degree - over 10
years from graduation:
• Had not taken the bar exam 4 years after graduation, or
even looked for a job
• No motivation
• Worked as instructor in a tennis club
• Family described him as ‘drifting’
• Poor state financially, borrowing from brother
• Eventually gave up tennis: became demotivated and
nonchalant during matches, not keeping score
• Lost interest in romantic pursuits
Frontal Astrocytoma
• Suffered a seizure in his last year of college
• No identifiable cause (on PET or CT) at the time
• CT re-done:
• extremely large astrocytoma
• Traversing along the callosal fibres, invading
extensively the lateral prefrontal cortex in the left
hemisphere, and considerably in the right
• Poor prognosis: death within ~1 year
• Response of W.R.: passive, detached, no rage,
minimal anguish, general absence of concern
Dysfunction - FTD
• Frontotemporal dementia or “Pick’s Disease”
• In 1892, Arnold Pick described a man who had
presented in life with progressive loss of speech
and dementia.
• When the patient died his brain was found to be
atrophied.
• This shrinkage had been caused by brain cells dying
in localized areas.
• This feature of localization is very different to
Alzheimer’s disease where the atrophy is more
generalized.
Frontotemporal Dementia (FTD)
Atrophy of frontal lobes and anterior temporal lobes ‘knife-edging’ – thinning of the gyri from neurodegeneration Atrophy with ventricular dilation Swollen neurons with abnormal tau protein inclusions
Frontotemporal Dementia (FTD)
Abnormal spontaneous behaviours during examination
• Inappropriate jocularity
• Echolalia (repeating the examiner’s words), echopraxia
(repeating the examiner’s gestures)
• Disinhibited approach or utilization behaviours
• Unkempt, depressed in early stages
During the first 2 years - “classic” frontal lobe syndromes:
• orbitofrontal dysfunction: aggressive and social
inappropriateness (may steal or demonstrate obsessive or
repetitive stereotyped behaviours), apathy and disinhibition
• dorsomedial or dorsolateral dysfunction: lack of concern,
apathy, or decreased spontaneity.
Speech and language
• Abnormalities often begin early and progress fast
• Memory impairment relatively less severe than
speech/language and behavioural changes
• Verbal output that is often nonfluent, with poor naming
of objects
Movement disorders
• Akinesia, plastic rigidity, or paratonia (involuntary
resistance) on motor examination
Perseveration
Frontal Lobe Dysfunction
• Patients with FL lesions often seem ok – no obvious
perceptual, motor, speech, intelligence, knowledge, LT
memory problems
• Unless damage bilateral and extensive
• Apathetic, distractible, impulsive
• Trouble making decisions, planning actions, understanding
consequences of actions, following rules
• Trouble organising and segregating timing of events in
memory and remembering sources of memories
• Loss of goal oriented behaviour – become stimulus driven –
reflexive behaviour that can’t inhibit
• Poor social control, inappropriateness, Irritability, aggression
• Deficits vary with location – different regions of PFC subserve
different processes
Prefrontal Cortex Functions
• Executive control - use perception, knowledge and goals to
bias selection of action and thoughts from many possible
• Supervisory functions so that we are
• Not just driven by emotion
• Not just driven by stimuli
• Planning and selection of goals
• Working memory, inhibition, control, interacting with the
environment
• Social and emotional decision-making
Working Memory
Baddeley and Hitch 1974
• Unitary short-term memory concept not enough to
explain how information is maintained and worked
on over short periods
• Limited capacity over the short term
• Performing mental operations (NOT rehearsal) on
contents of store
Working memory:
• Transient representation of task relevant info
• Interface between perception, LT memory, and action
• “Desktop of the mind”
• Enables goal oriented behaviour and decision making
• Keeps task relevant information active and
manipulates it to achieve goals
• Lateral PFC – interface between current perceptual
information and stored knowledge
Delayed Response Task
• Food in one of 2 wells (perception) • Cover wells and lower curtain • After delay raise curtain • Monkey chooses well for food • WM – must continue to represent location of food • Lesion latPFC – do poorly • Not general association problem though • Associate particular cue with food – lesioned monkeys ok with this Human version – Piaget’s Object Permanence test • Child observes experimenter hiding reward in one of two locations • Few seconds delay then encouraged to find the reward • Children <1 fail • Success parallels development of FL
Lateral PFC and WM
• Spatial vs working memory task (McCarthy et al 1994)
• fMRI
• Spatial WM task: respond when a stimulus appears at a
location that has been used previously
• Control colour task: respond when a red object appears
• Same display
• Enhanced lateral PFC activation during the WM task
Hypothesis – lateral PFC activation reflects a
representation of the task goal and interfaces with task
relevant LT representations elsewhere
• fMRI study – encode faces / delay / retrieve
• Intact and scrambled faces – remember only faces –
vary number
• Probe after delay – does it match one of the learned
• Bilateral lPFC rises with
encoding and sensitive to
demands
• Sustained response during
delay - greater for 3 or 4 than 1
or 2
• Compare lPFC with FFA – FFA
drops during delay (but not to
baseline; lPFC sustains;
encoding – FFA leads lPFC but
retrieval lPFC leads FFA
WM and Concept Formation
Wisconsin Card Sorting Test (WCST) • Concept formation • Concept shifting • Concept perseveration • Combine info from present and recent past, manipulate it and come up with a new response
WCST
Rule – colour, shape, or number
• Concept formation – guess a rule
• Concept shifting – change rule if incorrect
• Concept perseveration – keep the rule if it works
Then – experimenter changes the rule without saying
anything
• Normal performance – find the category and shift when
conditions change
• Impaired – inability to find the category and/or inability to shift or
switch
• Perseveration with same category even after changed conditions (e.g.
FTD)
• Information must be integrated with information that was
relevant in previous trials (what the category was, what the E
said)
• S must retain knowledge about the relevance of features, and
manipulate this information on-line
WCST – Task Switching
Computerised WCST (Konishi et al. 1998)
• Function of prefrontal cortex - Inhibit dimension that is not
relevant
• Isolating shift-related signals using the temporal resolution
of fMRI
• Transient activation of the posterior part of the bilateral
inferior frontal sulci
• Activation larger as the number of dimensions (relevant
stimulus attributes that had to be recognized) were
increased
• Suggest the inferior frontal areas play an essential role in the
flexible shifting of cognitive sets
Decision Making
• Brain is a decision making device using perceptual, memory,
and motor capabilities to support decisions that determine
actions
• Decisions simple (get up or not) to complex (who to vote for)
• Why do people make apparently irrational decisions?
• Considering evolution – should decide to not eat sweet, fatty
pastry, and do some exercise but evolution (survive)–
maximise calorie intake and conserve energy
• What is irrational in our present context may not be irrational
given the environment our brains evolved in
• Reach decisions in different ways – action outcome or
stimulus-response
• Action-outcome – evaluation of expected outcomes – repeat
and consistently get same outcome, decision may become
habitual – stimulus-response
Decision Making - Value
• Economic models of decision making – first compute
value of options and compare
• Primary reinforcers – food, water, sex – direct survival
benefit – value hardwired but with some flexibility
• Secondary reinforcers – money, status – no intrinsic
value but association with other forms of reinforcement
• Factors in representation of value
• Payoff – kind and amount
• Probability
• Cost (including temporal discounting)
• Context – internal or external state, novelty
• Preference
• Subjective value can be different person to person and
hour to hour
Representation of Value
Monkeys – electrodes in ACC, lPFC, OFC
• Manipulate cost, prob, payoff
• Choose between 2 pictures – each
associated with specific value (juice)
• Vary value along one dimension while
holding the other 2 fixed
• ACC – many cells that responded to all
3 – suggest overall measure of value
• If only 1 dimensions – usually payoff
or prob
• If respond to cost, then usually
something else also
Human fMRI - look at regions preferentially activated by
different value dimensions
• OFC – activation tied to variation in payoff
• Striatum – related to effort (cost)
• lPFC – probability
• mPFC (and lateral parietal) activity correlated with
delay b/w action and payoffWhat happens with high short term value but adverse long term value?
• vmPFC (incl OFC) activity correlated with taste preference
independent of health
• dlPFC associated with degree of control – more activity if preferred but
unhealthy item rejected than if same item selected
• Hypothesis – vmPFC forecasts short term value, dlPFC evolved later to
modulate primary value signals to incorporate longer term
considerations
• OFC key in value while more lateral modulate control on value
representations or actions associated with them
Decision Making - Reward
• Subcortical areas represent reward info – dorsal and
ventral striatum, HT, amygdala, lat habenula
• A lot of work on dopamine – but interplay of many NTs
• Dopaminergic cells in midbrain – SN and ventral
tegmentum (VTA)
• SN project to dorsal striatum (BG and motor circuits)
• VTA project 2 pathways
• mesolimbic (emotional) – nucleus accumbens (vent
striatum), amygdala, hippocampus, ACC
• mesocortical – medial FL
Dopamine (DA) and reward – Olds and Milner (1954)
• Rats with implanted electrodes – can push a lever at
will to activate
• Some pressed rarely, some constantly
• High activity – electrodes activating dopaminergic
pathways (recall – PD and l-DOPA and side effects)
• More recent – DA activation not related to size of
reward but to expectancy of reward – especially active
when reward unexpected – role in reinforcement and
decision making
Dopamine and Prediction Error
• Shultz et al. – classical conditioning with monkeys and recording from dopaminergic neurons in VTA • Light (CS) followed by juice (US) • Early training – burst of activity after juice (unexpected reward) • With training – burst after juice decreased and cells started to fire after light (CS) • DA not representing the reward - prediction error • Initially juice not expected so burst when get it • Light not expected but know that it means juice - DA • Learn light/juice relationship – light means juice coming, so getting juice is expected - no DA • DA not representing the reward - prediction error • Initially juice not expected so burst when get it • Light not expected but know that it means juice - DA • Learn light/juice relationship – light means juice coming, so getting juice is expected - no DA
Social and Emotional Judgement
• Choosing how to act: integrate incoming info with
pre-existing info about goals, values and current
social situation
• Patient “Elliot” (Damasio 1994) - tumour invading
OFC bilaterally
• Lack of concern for social rules, decreased social
awareness and empathy
Anticipation of rewards and punishments (Bechara et al.
1996)
• Skin conductance and
card selection
• Selection followed by
reward or punishment
• Only controls developed
anticipatory SCRs
• Patients emotionally
insensitive to future
outcomes
OFC and Psychopathy
• Sociopath/psychopath – antisocial personality disorder
• Pervasive pattern of disregard for the safety and rights of others -
lack of empathy; a tendency to be contemptuous of the rights,
interests, or feelings of others; and an excessively high selfappraisal
• 3 or more of the following traits:
• Regularly breaks or flouts the law
• Constantly lies and deceives others
• Is impulsive and doesn’t plan ahead
• Can be prone to fighting and aggressiveness
• Has little regard for the safety of others
• Irresponsible, can’t meet financial obligations
• Doesn’t feel remorse or guilt
A case of Acquired Sociopathy
• JS, 56yo male, engineer (Blair and Cipolotti, 2000)
• Premorbid: quiet and rather withdrawn, no
psychiatric history
• Right frontal trauma, incl OFC
• High levels of aggression and callous disregard of
others
• Lack of remorse
• Contrast with
• CLA: dysexecutive syndrome, no sociopathy
• Five prison inmates: developmental psychopathy
A case of Acquired Sociopathy
In contrast to CLA and inmates, JS showed
• Poor recognition of visually presented emotions
• Reduce autonomic response to visually presented
emotions
• Poor identification of social behaviour violations:
lower skin conductance response and disgust than
control Ss
• Suggested that impairment is due to a reduced
ability to generate expectations of others’ negative
emotional reactions, in particular anger
• In healthy individuals, these representations act to
suppress behaviour that is inappropriate in specific
social contexts
• Propose that the OFC may be implicated specifically
either in the generation of these expectations or the
use of these expectations to suppress inappropriate
behaviour
Goal Oriented Behaviour
• Long term
goals
• Short
term goals
• Hierarchy
of goals
• Subgoals
• Conflicting
goals
• Habits to
supress
• Executive function
• Use perception, knowledge and goals to bias selection
of action and thoughts from many possible
• Override automatic thoughts and behaviours
• Cognitive flexibility – act and think in novel ways
• Cognitive control essential for purposeful goaloriented
behaviour
• Basic function of the PFC is the representation and
execution of organized goal-directed action
• Executive functions of the PFC serve that
superordinate function in one way or another
• Goals of an organism (especially human) vary
immensely, so do the timescale and means to
achieve them
• Also variable are the motives for action and the
emotions that accompany it, as well as their
influence at any step in the pursuit of a goal
Goal Oriented Behaviour
• Need plan of action that draws on experience
• Tailored to current environment
• Flexible and adaptive to deal with unforeseen
• Monitor actions and stay on target
• Constrain desire and follow rules
• Inhibit habits and override urges
• Consider 2 PF control systems
• Lateral PFC (and FP)
• Supports GOB
• Works with cortex to form working memory
• Planning; simulating consequences; initiating, inhibiting,
shifting behaviour
• Medial FC
• Guiding and monitoring behaviour
• Works with lPFC
• Monitor ongoing activity to modulate cog control to achieve
goals
Anterior Cingulate Cortex
• Input from limbic structures, including amygdala, the thalamus and the striatum, as well as the brainstem • Output to prefrontal cortical areas
ACC – Monitoring Function
• Was thought to be part of the limbic system (modulation of autonomic responses) • Now shown to have attentional / monitoring functions • Considering and evaluating appropriate goals and subgoals on the basis of affective feedback
ACC – Monitoring Function
1. Dense projections from the ACC to the motor cortex and spinal cord =motor control, esp willed action: overcoming inertia when initiating actions and fighting competing well-established or innate tendencies 2. Reciprocal connections with the lateral prefrontal cortex (PFC) – cognition, esp conflict monitoring (not errors as such, rather the presence of conflict) 3. Extensive afferents from the midline thalamus and the brainstem nuclei point to the importance of arousal/drive state for ACC engagement – increased activation with increased need for arousal
ACC – Emotion
• ACC as a way-station / hub / amplifier of emotional
signals
• Emotional signals can be interoceptive (eg heart rate,
breathing) or exteroceptive (meaning in environment
eg horrible scenes)
• ACC participates in the experiential processing and
response to emotion cues – conscious experience of
emotion
Key Learnings
• PFC – executive control; supervisory; more than
stimulus bound or emotionally driven
• PFC – goal oriented behaviour
• Anterior FL association area – prefrontal cortex (PFC) –
especially lateral PFC (dlPFC and vlPFC, OFC)
• PFC massively connected (bidirectionally) with whole
brain
• Lateral PFC – motor control; OFC – emotional
involvement
• PFC matures late in development (mid 20’s for
myelination)
• Phineas Gage – personality shift (social and
motivational)
• Lobotomy – stimulus bound (goal oriented behaviour)
• Frontal astrocytoma - motivation
• FTD – social, motivational, concern
• Lateral PFC and WM – delayed response task, WCST
(concept formation and switching)
• Decision making – value and reward
• Dopamine as an indication of prediction error
• OFC and acquired sociopathy
• GOB – lateral PFC supports; medial (ACC) guides and
monitors
