brown universitypaul malloy, ph.d.butler hospital the frontal lobes function and dysfunction

Brown UniversityBrown University Paul Malloy, Ph.D.Paul Malloy, Ph.D. Butler HospitalButler Hospital

The Frontal Lobes The Frontal Lobes Function and DysfunctionFunction and Dysfunction


Frontal lobes: HistoryFrontal lobes: HistoryThe frontal lobes as “silent areas”The frontal lobes as “silent areas”


Frontal lobes: HistoryFrontal lobes: HistoryPhineas Gage (Harlow, 1848)Phineas Gage (Harlow, 1848)


Frontal lobes: HistoryFrontal lobes: HistoryWartime Wartime TraumaTrauma

•Improvements in military medicine led to markedly improved survivability from head wounds in WWII and subsequent wars.•Low velocity shrapnel vs. high velocity projectiles.•Example: Luria and localization of function in Russian soldiers.


Frontal lobes: HistoryFrontal lobes: HistoryLeukotomy and lobotomyLeukotomy and lobotomy


Frontal lobes: HistoryFrontal lobes: HistoryAdvances in neuroimagingAdvances in neuroimaging


Frontal lobes: Comparative studiesFrontal lobes: Comparative studiesEvolutionEvolution

• Frontal lobes account for increasing proportion of cerebrum across phylogenetic spectrum (Fuster, 1980)

• Prefrontal areas are 33% of cerebral cortical surface in humans (Goldman-Rakic,1984)


Frontal lobes: Comparative studiesFrontal lobes: Comparative studiesWorking memory paradigmsWorking memory paradigms

• Spatial working memory tasks– Delayed response– Delayed alternation

• Feature working memory tasks– Delayed matching to sample– Delayed object alternation


Frontal lobes: Comparative studiesFrontal lobes: Comparative studiesWorking memory paradigmsWorking memory paradigms


Frontal lobes: DevelopmentFrontal lobes: DevelopmentAging and frontal functionsAging and frontal functions


Frontal lobes: Functional zonesFrontal lobes: Functional zones


Frontal zones: Primary motor functionsFrontal zones: Primary motor functions

• Brodmann area 4

• Input from ventral lateral thalamic nucleus, primary somatosensory area in parietal lobe

• Output to internal capsule

• Pyramidal motor functions


Frontal zones: Primary motor dysfunctionFrontal zones: Primary motor dysfunction

• Initially flacid hemiparesis or hemiplegia on contralateral side

• Later spastic hemiparesis or hemiplegia


Frontal zones: Premotor functionsFrontal zones: Premotor functions

• Brodmann area 6• Input from ventral anterior thalamic

nucleus and secondary somatosensory area• Output to motor area and connections via

corpus callosum to contralateral premotor area

• Integration of sensory and motor information

• Praxis


Frontal zones: Premotor dysfunctionFrontal zones: Premotor dysfunction

• Apraxia• Preserved postural praxis via

basal ganglia• Contralateral fine motor

deficits• Difficulty using sensory

feedback


Frontal zones: Frontal eye field functionsFrontal zones: Frontal eye field functions

• Brodmann area 8• Volitional eye movement

in contralateral visual field

• Active visual search


Frontal zones: Frontal eye field dysfunctionFrontal zones: Frontal eye field dysfunction

• Failure to move eyes volitionally to contralateral visual field

• Intact passive eye movement• Poor visual search


Frontal zones: Dorsolateral functionsFrontal zones: Dorsolateral functions

• Brodmann areas 46, 45,47,8, 9

• Executive functions– Integration of multimodal sensory

information

– Generation of multiple reponse alternatives

– Selection of appropriate response

– Maintenance of set, persistence

– Set shifting, flexibility

– Spatial working memory


Frontal zones: Dorsolateral dysfunctionFrontal zones: Dorsolateral dysfunction

• Difficulty integrating sensory information

• Generation of few, stereotyped response alternatives

• Poor judgement in response selection

• Impersistence

• Perseveration


Dorsolateral testsDorsolateral testsFigural fluencyFigural fluency


Dorsolateral testsDorsolateral testsLuria’s reciprocal hand movements & graphic designsLuria’s reciprocal hand movements & graphic designs


Dorsolateral testsDorsolateral testsPerseverations within and between Lurian tasksPerseverations within and between Lurian tasks


Dysexecutive effects on other testsDysexecutive effects on other tests


Frontal lobesFrontal lobesPoor organization of learning and recallPoor organization of learning and recall

Copy Free recall


Frontal zones: Orbital functionsFrontal zones: Orbital functions• Brodman areas 10,11,12,13,14• Input from limbic and olfactory systems (amygdala,

temporal pole, entorhinal cortex, olfactory nerve); inferotemporal lobe areas, ventral visual pathways

• Output to autonomic musculature and endocrine system (basal forebrain cholinergic system, caudate, and autonomic system)

• Modulation of affective and social behavior; “...preservation of behavioral regulation by external stimuli and its dissolution in the absence of external stimulation.”

• Working memory for feature information• Integration of memory and emotional valence• Smell discrimination


Frontal zones: Orbital dysfunctionFrontal zones: Orbital dysfunction

• Disinhibition, socially inappropriate behavior

• Failure on feature working memory tasks

• Anosmia• Confabulation


Orbital testsOrbital tests

• Go-NoGo tasks

• UPSIT

• Frontal Systems Behavior Scale (FrSBe)

• SIGO interview for behavior change


Orbital testsOrbital testsChanges in smell with agingChanges in smell with aging


Disinhibition and intrusion in drawingDisinhibition and intrusion in drawing


Frontal zones: Cingulate/SMA functionsFrontal zones: Cingulate/SMA functions

• Brodman areas 24, 32

• Connections with older cortical and deep limbic structures

• Drive and motivation

• Environmental exploration

• Complex attention


Frontal zones: Cingulate/SMA dysfunctionFrontal zones: Cingulate/SMA dysfunction

• Apathy, akinetic mutism

• Alien hand syndrome

• Complex attentional deficits, delayed habituation


Frontal lobes: Alien hand syndromeFrontal lobes: Alien hand syndrome


Frontal lobes: Subcortical connectionsFrontal lobes: Subcortical connections

• Parallel but separate connections to caudate and thalamus

• Topographic mapping of caudate and thalamus

• Subcortical white matter connections– Long tracts– Cortical U-fibers

• Small subcortical lesions can mimic large cortical lesions


Frontal lobes: Subcortical connectionsFrontal lobes: Subcortical connectionsThalamusThalamus

dorsomedial

Dorsolateral prefrontal

Dorsolateralcaudate

Lateral dorsomedial

Globus Pallidus

VA & MDThalamus

Ventromedialcaudate

MedialGlobus pallidus

Anterior Cingulate

Nucleusaccumbens

RostrolateralGlobus Pallidus

MDThalamus

Orbital prefrontal

VA & MDThalamus


Frontal lobes: Subcortical connectionsFrontal lobes: Subcortical connectionsThalamusThalamus


Frontal lobes: Subcortical connectionsFrontal lobes: Subcortical connectionsWhite matterWhite matter

uncinate fasciculuslong tracts to posterior association areas

cortical u-fibers


Frontal lobes: Cortical connectionsFrontal lobes: Cortical connections


Frontal lobes: Other signs and syndromesFrontal lobes: Other signs and syndromes

• “Frontal release” signs– Disappear with normal development, reappear

in aging or frontal systems dysfunction– Snout, suck, glabellar, grasp

• Gegenhalten vs. cogwheeling

• Frontal or magnetic gait


Clinical examplesClinical examples


Frontal lobes: DementiaFrontal lobes: DementiaKorsakoff’s syndromeKorsakoff’s syndrome

This 42 year old man was admitted from a rest home, where he had been displaying a number of problematic behaviors, including compulsive eating of all the vegetables in the garden, and perseverative stuffing of toilets with paper. PMH = Severe alcohol abuse. He had impulsively gone to Florida with a barmaid, and spent all his money. He was “rescued” by his wife, but was unable to return to work as a bartender. He was eventually place in a rest home. NP testing = severe anterograde/retrograde amnesia, moderately severe deficits in executive abilities, marked inertia, abulia, and apathy.


Korsakoff’s syndrome: Korsakoff’s syndrome: Intrusions and disinhibitionIntrusions and disinhibition


Frontal lobes: TraumaFrontal lobes: TraumaLocalization of TBILocalization of TBI

from Courville, 1941


Frontal lobes: TraumaFrontal lobes: TraumaContusion with hemorrhageContusion with hemorrhage

Case history: This 57 year old man was found unconscious by his family, and was thought to have struck his head in a fall. LOC x few hours, but remained confused for the next few days. Sent to a nursing facility, but had repeated arguments with staff, made sexually inappropriate and racist remarks, and was hospitalized. NP testing = severe dysexecutive and disinhibitory deficits, which affected his performance on other tasks.


Frontal lobes: TraumaFrontal lobes: TraumaContusion with hemorrhageContusion with hemorrhage


Dementia of the frontal type vs. Alzheimer’s diseaseDementia of the frontal type vs. Alzheimer’s disease

• Early changes in behavior/personality

• Neuropsychological deficits in executive and inhibitory functions, no frank amnesia

• Relative sparing of posterior functions (must be dissociated from dysexecutive problems)

• Anterior atrophy

• Preservation of personality & social behavior

• Neuropsychological deficits in naming and construction, with frank amnesia after delay

• Relative sparing of anterior functions

• Generalized and hippocampal atrophy


Frontal lobes:DementiaFrontal lobes:DementiaFrontal typeFrontal type

This 56 year old man presented with a one year history of progressive decline in memory and judgment, and several demotions at work. He had displayed a number of socially inappropriate behaviors, such as visiting a neighbor's swimming pool without invitation, neglect of his personal hygiene, and uncharacteristic episodes of anger dyscontrol. NP testing revealed prominent deficits on tests of executive and self-regulatory functions, failures on memory testing typical of frontal impairment (e.g. perseverative and intrusion errors).


Frontal lobes:DementiaFrontal lobes:DementiaFrontal typeFrontal type


Frontal lobes: DementiaFrontal lobes: Dementia Frontotemporal dementiaFrontotemporal dementia

Normal elderlyFrontal dementia


5/29/2002


MMSE: 16

6/2002


MMSE: 25

3/2003


6/2002 MMSE: 16

3/2003 MMSE: 25

brown universitypaul malloy, ph.d.butler hospital the frontal lobes function and dysfunction

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