fallon higher cereb funct i ii iii 2007
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Fallon
Types of neocortex by general function
and locationPrimary sensory Sensory associationMultimodal associationPrimary motorPremotorPrefrontalCingulate
…..from Cortex II lecture slides
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The surface of the cortex is divided into four lobeswhich feature key localized functions, but functionsare usually elaborated in circuits that involve at least several cortical and subcortical areas
Frontal
Temporal
Parietal
Occipital
Frontal Lobe•personality•mood•planning•judgement•motor skills•social•ethics, morality
Parietal Lobe•somatosensory•spatial•comprehension•self•language
Temporal Lobe•language•auditory processing•visual perception• memory
Occipital Lobe•visual processing
…..from Cortex II lecture slides
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Symptoms of association cortex dysfunction
See Blumenfeld text Chapter 19 for excellent coverage of higher cerebral functions
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Loss of function from lesions of
association cortices• Agnosia-”without knowledge”-the inability to perceive or create meaning to sensory input (sensory association and multimodal cortices)-A normal perception stripped of meaning
• Aphasia-language disorder, inability to understand or express words as symbols (sensory association,multimodal, prefrontal)
• Amnesia-memory loss (association, prefrontal, limbic, hippocampal types)
• Apraxia
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Agnosias-examples for posteriorassociation cortex in parietal andtemporal lobes
Acalculia-impaired arithmetic calculationFinger agnosia-can’t name individual fingersRight-left disorientationParacusis-hear a sound, keep hearing it over and overEcholalia-repeating sounds heard over and overAllesthesia-report localization of stimuli on wrong side of the bodyHemi-neglect-sensory, motor, combined, conceptual typesAnosognosia-lack of awareness of the illnessAnosodiaphoria-aware of severe deficits but don’t care (Chicago Cubs fan syndrome)Hemiasomatognosia-Denial that the left half of body belongs to them
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Visual Agnosias,illusions-examples
Simultagnosia-cannot see visual scene as a whole, items jump around randomly.Dorsal type stops movement intermittentlyMicropsia, macropsia-visual objects wrong sizeMetamorphosia-distorted shape and size, Alice in Wonderland syndromePalinopsia-previously viewed object reappears sporadicallyPolyopia-see two or more images of the same objectErythropsia-unnatural coloring of the visual fieldProsopagnosia-can’t recognize people by face, but can by voice, touch
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Agnosias
Gerstmann’s syndrome-lower 7/39on left side-dysgraphia, dyscalcula,right left confusionfinger agnosia, dyslexia
Prosopagnosia-20/21(inferior temporal):Inability to recognizefaces
Dyslexia
Auditory agnosia
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Agnosias Sensory neglect-; superior parietalEspecially on non dom hem- get a right para-sylvian area syndrome-dressing apraxia, constructional apraxia, anosognosia (inability torecognize contra body, disease denial)
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Unilateral neglect
Non-dominant hem superior parietal strokes can causeneglect, even of visual memories. Patientswill describe only the right side of theirhome town square, mall. Asked to imaginethe same scene when turned 180o, they describethe other half, still neglecting their left visual field
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A broadly distributed networkof nearly half of cortex
Aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoatnt tihng is that the frist and lsat ltteer be in the rghit pclae. The rset can be a taotl mses and you can sitll raed it wouthit a porbelm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe.
FallonThompson 2001
Is the capacity for language predominantly genetically orenvironmentally determined? - twin study
Areas in red show high genetic impact- note dominant hemisphereWernicke and Broca areas
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Ideationalspeech area
Wernicke’sspeech area
Broca’s area
Semanticspeech area
Fallon Blumenfeld 2002
PrimaryLanguage Areas
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40
3922
43
47
4544 Visual
Somatosensory
Auditory
Ideational speech area of inferior parietal lobule influenced by sensory association areas-impact on reading/writing/speech
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Functional localization in
association cortices• Agnosia-”without knowledge”-the inability to perceive or create meaning to sensory input (sensory association and multimodal cortices) A normal percept stripped of meaning
• Aphasia-language disorder, inability to understand or express words as symbols (sensory association, multimodal, prefrontal)
• Amnesia-memory loss (association, prefrontal, limbic, hippocampal types)
• Apraxia
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Language related cortices-for dominant hemisphere
40 39
22
43
47
45 44
8
38
Ideationalspeech area-39, 40
Wernicke’sspeech area-22+39+40
Broca’s area-44+45
Semanticspeech area
-Speech apraxia orBroca’s aphasia-44/45
-Pure word deafness-22
-Pure word blindness-39/37 boundary
-Fluent aphasia or Wernicke’s aphasia-22/39/40-Conduction aphasia-43/underlying arcuate bundle-Agraphia-39/40-Anomia-nouns-38
37
FallonLeft side is dominant in 95% of righties, 60% of lefties
Basic distribution of cortical speech pathology
“Anterior aphasia”“Frontal”“Expressive”“Motor”“Non-fluent”(phrase length,content vsfunction words)
“Posterior”“Temporo-Parietal”“Receptive”“Sensory”“Fluent”
Broca’s Aphasia Wernicke’s Aphasia
Dominant side(usually left)
Non-dominant side(usually right)
SyntaxGrammar
ProsodyEmotional expression
FallonBlumenfeld
Blood supply of language cortices
Fallon Blumenfeld
Types of aphasia and their primary localization
Aphasia
Fluent?
Comprehends?
Repeats?
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Broca’s aphasia-
Damage to Broca’s Area (BA 44,45) in dominant (left) hemisphere. Decreased premotor and motor aspects of speech.
Fluency is diminished, with phrase length less than 5 or 6 words, increased ratio of content words (nouns)to function words (articles, prepositions, syntax modifiers);agrammatism, telegraphic speech)
Poorer naming of items, and repetition of words is impaired.
Understanding/comprehension is intact, except for syntactically dependent structures (Dog bites man or man bites dog??)
Writing and reading is also slow, laborious (Broca’s Patient gets frustrated when being examined )
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Wernicke’s Aphasia
Damage to posterior superior temporal gyrus (BA 22) and adjacent inferior parietal (BA39) and temporo-occipital cortex (BA 37) in dominant hemisphere.Impaired comprehension of speechFluent aphasiaFull of nonsense words, empty speech, neologisms, paraphasia (jumbled, unintelligible speech)Impaired repetitonAnoganosia-unaware of their deficitAngry, paranoidCan have contralateral field loss, esp upper right quadrantWriting and reading also severely impaired (Examiner gets frustrated with Wernicke’s patients)*
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Fluent aphasia lesion-CT
R L
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Language/Speech Agnosias-examplesAlexia- loss of reading abilityAgraphia- loss of writing abilityAnomia-can’t name objects, various lesionsParaphasia- inappropriate word substitution. Semantic type substitute “water” for “jacuzzi”. Phonemic type substitutes “trap” for “flap” Global-impaired fluency, comprehension,repetition (full MCA infarct)Conduction-impaired repetition, normal fluency, comprehension. Lesion of arcuate fasciculus, overlying cx Transcortical- impaired fluency, comprehension,repetition is spared. Follows a watershed lesion or basal ganglia/thalamus lesionAprosodosia- Flat speech. Lesion of nondominant inf frontal
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AlexiawithoutAgraphialesion
(PCA infarct ofdominant occipital cortex andcorpus callosum)Blumenfeld 2002
Can write normallybut can’t read, eventheir own writing
Alexia with agraphiawith lesion ofdominant angulargyrus
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AlexiawithoutAgraphialesion
Blumenfeld 2002
Can write normallybut can’t read, eventheir own writing
Left visual field
Can have an emotional responseto what is seen, read (Right Wernicke connection OK)
Can’t understandwhat is read
(Motor cortexconnection OK)
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Alexia without agraphia lesion-MRI T2
R L
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But what’s worse, not remembering,or never being able to forget?
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Functional localization in
association cortices• Agnosia-”without knowledge”-the inability to perceive or create meaning to sensory input (sensory assoc, multimodal cortices)
A normal percept stripped of meaning• Aphasia-language disorder, inability to understand or express words as symbols (sensory association,multimodal, prefrontal)
• Amnesia-memory loss (association, prefrontal, limbic, hippocampal types)
• Apraxia-
FallonMemory
Acquisition ofnew, non-emotionalmemories-declarative
Hippocampal area
Precuneus-31episodic
Dorsal lateral prefrontal cortex-46Executive/short term memory
Amygdala-emotional memoryorganizer
Striatum-procedural
Cerebellum-Motor/procedural
Long term-everywhereGenetic-orbital/ant temp
Faces
FallonConvergence onto the final common pathway on the PFC pyramidal neuron..and its loops
Fallon et al 2003
Optional slide
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DARPP-rememberingPP-1-forgetting
Optional slide
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Functional localization in association cortices
• Agnosia-”without knowledge”-the inability to perceive or create meaning to sensory input (sensory assoc, multimodal cortices) A normal percept stripped of meaning
• Aphasia-language disorder, inability to understand or express words as symbols (sensory association,multimodal, prefrontal)
• Amnesia-memory loss (association, prefrontal, limbic, hippocampal types)
• Apraxia-Ideomotor type-inability to carry out actions in response to verbal commands, cannot formulate correct movement sequence. Also, there are dressing, gait, constructional, etc-poor localization in cortex, in dominant (skilled) hemisphere-esp premotor cortex BA 6
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Prefrontal cortex functions:(If comic Steven Wright was a neurologist)
•A clear conscience is usually the sign of a bad memory
•A fool and his money are soon partying
•Hard work pays off in the future. Laziness pays off now
•A conscience is what hurts when all your other parts feel good
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Blumenfeld 2002Neuroanatomy throughClinical Cases
Sectors of theFrontal Lobe
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Blumenfeld 2002Neuroanatomy throughClinical Cases
Sectors of theFrontal Lobe
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Frontal Lobe FunctionFrontal Lobe FunctionFUNCTIONFUNCTION DYSFUNCTIONDYSFUNCTION
Emotional ExpressionEmotional Expression Inaccurate ExpressionInaccurate Expression
EmpathyEmpathy Lack of ConcernLack of Concern
Ambition/DriveAmbition/Drive Apathy/IndifferenceApathy/Indifference
Social AwarenessSocial Awareness Pride and AppearancePride and Appearance
Planning and SequencingPlanning and SequencingLoss of FutureLoss of Future
Flexible AttentionFlexible Attention Don’t Learn from MistakesDon’t Learn from Mistakes
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Functions of the Prefrontal Cortex: “Memory of the Future”Or “How would I look back on what I’m about to do”
“maybe I shouldn’tdo that”
Risk/Reward DecisionsBehavioral InhibitionEthics and MoralityExtraversion/Introversion
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Functions of the Prefrontal Cortex: “Memory of the Future”Or “How would I look back on what I’m about to do”
D.T.L.H.
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Progression of Myelination: Axons
For all the cortical layers, myelination starts in primary cortices, then spreads to their association cortices, proximally to distally. The last area to myelinate is the frontal pole.
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Progression of dopamine innervationof the prefrontal cortex:The last system in the brain to mature
The lamination of DAinput to the prefrontal cortexis not complete until about18 years of age. This is typicallywhen the “dopamine” disorderslike schizophrenia reallybecome obvious
Fallon Thompson 2004
Optional slide
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Onset of adaptive behaviors in infants and children-Pt 2
Onset of 1st phase: 10-12 moNarcissism, grandiosity, self, hyperactivity,exploratory, learning to deal with mother
Hedonic dopamine phase in right orbital cortex, Onset of 2nd phase: 16-18 moDevelopment of “shame” as parents give child disapproving looks, hyper, elated behavior, becomes inhibited, urine and feces provoke disgust response, learning to deal with father
Inhibition of dopamine loops, norepinephrine increases, cortisol up, endorphins down as right orbital cortex matures-
Optional slide
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Gene-environment-lesion interactions:
A quadrillion unique humans are possible
And
Examples from psychopathology
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Genetic impact on brain and behavior:
A quadrillion unique humans are possible basedon genetics alone
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MonoaminesCatecholamines Serotonin
COMT (frontal cortex)
MAO-A
MAO-A, MAO-B
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‘vv’ - high COMT activity
LOW synaptic dopamine
Arnsten and Arnsten and Goldman-Rakic, 1986Goldman-Rakic, 1986Arnsten et al., 1994Arnsten et al., 1994Murphy et al., 1994, Murphy et al., 1994, 1996 a,b, 19971996 a,b, 1997Williams andWilliams and Goldman-Rakic, 1995Goldman-Rakic, 1995Verma and Verma and Moghaddam, 1996Moghaddam, 1996
‘vm’ – intermediate
‘mm’ – low activity
HIGH synaptic dopamine
Predicted relative effects of COMT Predicted relative effects of COMT genotype on prefrontal cortical functiongenotype on prefrontal cortical function
______Optimal________
Optional slide
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D1 Receptors:Inverted U-Shaped Curve
Low DA High DA
Greatest dopamine effectsin Frontal Lobe
Normal behavior
Schiz,ManiaOCD
SchizADHD
Depression
Low, Noisy output High Output of PFC
But uncoupled from ext.
(Cf Yerkes-Dodson law) Fallon
Optional slide
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= SNP(Single Nucleotide Polymorphism)
... A C T T T G A ...
... A T T T T G A ...
general population
genomic sequences
An extremely large number of An extremely large number of SNPs--millions-- have been SNPs--millions-- have been detected within the general detected within the general population and can change population and can change quickly in human evolutionquickly in human evolution
The presence of millions of SNPs leads to multiple trillionsof individual human beings based on genetic variability alone
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Person A Person B Person C
High riskAllele/SNP
Low riskAllele/SNP
High riskAllele/SNP
Low riskAllele/SNP
High riskAllele/SNP
Low riskAllele/SNP
GENE LOADS
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Person A Person B Person C
High riskallele
Low riskallele
High riskallele
Low riskallele
High riskallele
Low riskallele
SerotoninTransporterLong
SerotoninTransporterShort
SerotoninTransporterLong
SerotoninTransporterShort
SerotoninTransporterLong
SerotoninTransporterShort
MAO-AHigh active
MAO-ALow active
MAO-AHigh active
MAO-ALow active
MAO-AHigh active
MAO-ALow active
COMTHigh active
COMTLow active
COMTHigh active
COMTLow active
COMTHigh active
COMTLow active
Low Hostility Average Hostility High Hostility
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Person A Person B Person C
High riskallele
Low riskallele
High riskallele
Low riskallele
High riskallele
Low riskallele
SerotoninTransporterLong
SerotoninTransporterShort
SerotoninTransporterLong
SerotoninTransporterShort
SerotoninTransporterLong
SerotoninTransporterShort
MAO-AHigh active
MAO-ALow active
MAO-AHigh active
MAO-ALow active
MAO-AHigh active
MAO-ALow active
COMTHigh active
COMTLow active
COMTHigh active
COMTLow active
COMTHigh active
COMTLow active
Low Hostility Average Hostility High Hostility
These are variants of genesin the normal population.These are not mutants.So what makes one a“reasonable person”?
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Gene-environment-lesion interactions:
A quadrillion unique humans are possible
And
Examples from psychopathology
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David Berkowitz
Aileen Wuornos Ted Bundy
Albert FishJohn Gacy
Charles MansonBeltway Snipers
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Palpatine: Darth Sidiousaka His Imperial Majesty Emperor Palpatine of the Galactic Empire
Movie characters inspiring real killers
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Issei Sagawa
Hannibal Lecter
Albert Fish
HAL 9000
Ed Gein*
*Ed Gein inspired Psycho, The Texas Chainsaw Massacre, The Silence of the Lambs
Real killers inspiring movie characters
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Tommy(Joe Pesci)
In “Goodfellas”
Excellent portrayal of a psychopathic killer
Frank Booth(Dennis Hopper)
in‘Blue Velvet’
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The sociopath-born or made?
Low cortisol in boys-correlations with cruelty to animals,violence, forcing sexual acts, weapon use
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FallonAnderson/ Damasio 1999
Damage at 16 months age
Adult lack of moralreasoning
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Psychopathic murderer
Amen 2004
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Normal40 yo
Normal 80 yo
Adultmurderer
Teenagedmurderer
AT
AT
ORBATAT
ORB ORBAT
ORB
Orbital cortex (ORB) and anterior temporal cortex (AT)
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Brain areas most likely to be damaged or altered in psychopaths
Orbital cortex
Anterior cingulate
Frontalpole
Ventromedial
Anterior medial temporal
and amygdala
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There is one major group of single nucleotide polymorphisms (SNPs) in the MAO-A gene; A combination in onegroup results is low MAO-A activityand very high serotonin levels,and is associated with High Riskfor violence and aggression
In humans, a Dutch kindred with a missense mutation in the MAO-A gene was described : hemizygous males, representing functional gene knockouts, exhibited a pattern of impulsively violent criminal behaviour for generations (Brunner 1993).
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MonoaminesCatecholamines Serotonin
COMT (frontal cortex)
MAO-A
MAO-A, MAO-B
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Structural data: MAOA Low vs High MAO-A expression
Meyer-Lindenberg et al 2006 PNAS
Low MAO-Aactivity, highserotonin levels,hyper-reactive amygdala High Risk,
Femalesshow noeffect ofgenotype
Male at high risk haveIncreased orbital volumes
Optional slide
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Meyer-Lindenberg et al 2006 PNAS
Emotional memory scores- response in left amygdala in Males is higher in high risk (MAO-AL) individuals
Hyper-responsiveleft amygdalain High Riskmales
Optional slide
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Caspi and colleagues (2002) also found that the highrisk genotype (ie low levels of MAO-A; high levels ofserotonin) affects responses to harsh environmentalstressors. The genetically high risk adolescents and adultswho were also maltreated as children were much morelikely to develop conduct disorder, antisocial personalitydisorder, and to be convicted for violent crimes.
Gene-Environment Interactions
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DorsalPFC
OrbitalCortex
Amygdala
NucleusAccumbens
DA
DA
_
_Competition among
prefrontal and limbic cortices for control
of DA influencein nucleus accumbens
DorsalAnteriorCingulate
VentralAnteriorCingulate
CRH VTADopamine
Net Motor Output, i.e., Behavior:Do it or Don’t Do it?
GO DON’T GO
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Fallon
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