Neuropsychological Neuropsychological Aspects of Frontal Lobe Aspects of Frontal Lobe

FunctionFunctionRussell M. Bauer, Ph.D.

February 27, 2006

Important ConceptsImportant Concepts

• Phylogenetically newest area of cortex• Exquisite connectivity based on feedback loops• Inhibitory/excitatory control• Farthest removed from external environment

(reflective, not reflexive)• Highly preprocessed, convergent projections

(emergent concepts)• Only neocortical representation of the limbic

system• Motivational/emotional interaction (goal-direction)

Symptoms of Frontal Lobe Symptoms of Frontal Lobe DamageDamage

• Elementary Neurological Defects• Skilled Movement Disorders• Language/Speech Disorders• Memory Disorders • Executive Deficits• Neuropsychiatric Disturbances

Frontal Lobe CortexFrontal Lobe Cortex

• Functional subdivisions:– Lateral (4, 6, 8-10, 43-

47)– Medial (6, 8-12, 24, 25,

32, 22)– Inferior (11-15, 25, 47)

• Another division:– Motor (4)– Premotor (6, 8, 43, 44,

45)– Prefrontal (9-15, 46, 47)

Neuropsychological Manifestations of Frontal Lobe Lesions III

Lateral Prefrontal Region (8,9,46)

Lesions in this region produce impairment in a variety of “executive” skills that cut across domains. Some degree of material-specificity is present, but relatively weak.

A) Fluency: impaired verbal fluency (left) or design fluency (right)

B) Memory impairments: defective recency judgment, metamemory defects, difficulties in memory monitoring

C) Impaired abstract concept formation and hypothesis testing

D) Defective planning, motor sequencing

E) Defective cognitive judgement and estimation

Tranel, 1992

Neuropsychological Manifestations of Frontal Lesions I

Frontal Operculum (44,45,47)

A) Left: Broca’s aphasia

B) Right: ‘expressive’ aprosodia

Superior Mesial (mesial 6, 24)

A) Left: akinetic mutism

B) Right: akinetic mutism

Bilateral lesions of mesial SMA (6) and anterior cingulate (24) produce more severe form of akinetic mutism

Tranel, 1992

Neuropsychological Manifestations of Frontal Lobe Lesions II

Inferior Mesial Region

A) Orbital Region (10, 11)

Lesions in this region produce disinhibition, altered social conduct, “acquired sociopathy”, and other disturbances due to impairment in fronto-limbic relationships

B) Basal Forebrain (posterior extension of inferior mesial region, including diagonal band of Broca, nucleus accumbens, septal nuclei, substantia innominata)

Lesions here produce prominent anterograde amnesia with confabulation (material specificity present, but relatively weak)

Tranel, 1992

General Organization of Frontal cortical-striatal-pallidal-thalamic-cortical loops

Dorsolateral LoopDorsolateral Loop

• Critical for executive function

• Damage produces– Inflexibility– Planning– Problem-solving– Goal-directed

behavior

Orbitofrontal LoopOrbitofrontal Loop

• Involved in social and emotional functioning

• Damage produces:– Disinhibition– Hyperactivity– Emotional lability– Aggressiveness– Reduce self-

awareness

Medial Frontal LoopMedial Frontal Loop

• Important in behavioral activation

• Damage results in– Akinetic mutism– Abulia– Impairments in

spontaneous initiation of behavior

Neuropsychological Neuropsychological DomainsDomains

• motor activity• attention• personality/emotion• perceptual organization• spatial/visual function• memory• cognitive skills• executive skills

Elementary Neurological Elementary Neurological Deficits in Frontal SyndromesDeficits in Frontal Syndromes• Contralesional hemiparesis • Re-emergence of primitive reflexes

• Gaze abnormalities (spontaneous eye-movements, conjugate gaze)

Frontal Lesions and Frontal Lesions and “Personality” (overall ‘emotional “Personality” (overall ‘emotional

tone’)tone’)• orbital syndrome

– emotional lability– disinhibition– exaggeration of pre-existing personality

traits

• medial/lateral syndrome– abulia/apathy– depression-like presentation– defects in self-initiation

Phineas Gage (Harlow, Phineas Gage (Harlow, 1868)1868)

“Prior to his accident, he was a religious, family-loving, honest and hard-working man who was described after his frontal injury as ‘fitful, irreverent, indulging at times in the grossest profanity…impatient of restraint or advice when it conflicts with his desires…obstinate, devising many plans of operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible’” (Benson, 1994)

Frontal Lobe Symptoms Relevant to Frontal Lobe Symptoms Relevant to Emotion and PersonalityEmotion and Personality

• NOT independent of cognitive impairments• Poor self-monitoring and self-reflection• Defective arousal and orienting responses• Affective changes

– Witzelsucht and Moria (Oppenheim)– Depression with lack of concern

• “Acquired sociopathy” (Damasio) – unconcern for punishment

Somatic Marker HypothesisSomatic Marker Hypothesis

• Biasing signals from body are integrated in the decision-making and emotional parts of the brain (VMPFC) and used to regulate decision-making under uncertainty

• Markers signal value and bolster attention and working memory

• Case EVR (tumor of VMPFC) – became unable to make decisions despite good NP performance; unsuitable choices for business partners, friends, etc.

• EVR impaired in psychophysiological responses to positive and threatening information

• Much of the data for SM hypothesis is based on the Iowa Gambling Task

Activation during anticipation (risky decisions – safe decisions) superimposed on T1 image for all subjects. Overall score on IGT was correlated with the amount of activity in medial frontal lobe during risky decisions.

Fukui, et al. (2005). Neuroimage, 24, 253-259.

Motor Deficits in Frontal Motor Deficits in Frontal SyndromesSyndromes

• Two dominant behavioral syndromes:

– hyperactivity

– apathy/abulia

• Contralesional hemiparesis; in less severe form, contralateral reduction in speed or dexterity

• Ideomotor apraxia – impaired skilled movement in nonhemiparetic hand/extremity

• Motor impersistence- failure to maintain motor activity; test with eye closure, tongue protrusion

• Impaired verbal control over conscious motor acts - inability to invoke verbal rules(e.g., Go-No Go); inability to use verbal intentions to guide behavior (e.g., don’t drink the water)

Motor Deficits (cont’d)Motor Deficits (cont’d)

• Defects in motor programming and sequencing - recursive writing sequences

• Impaired guidance and error correction

• Poverty of movement without weakness, hemiparesis, or abnormality in tone (intentional disorder)

Cortex

Striatum

SNcThalamus(VA, VL)

SNr

MGP

Simplified Direct Loop - Voluntary Movement Dysfunctional System

SNc = substantia nigra pars compacta, MGP = medial globus pallidus , SNr = substantia nigra pars reticulata.

In the dysfuntional system, the striatum receives excitatory projections from the cortex, but input from the SNc is impaired due to a reduction ofdopamine. This reduced input from the SNc results in the striatum not receiving enough excitatory input to exert its inhibitory influence over the MGPand SNr. The MGP and SNr, free of inhibition from the striatum, provide inhibitory influence over the thalamus thus preventing the thalamus fromproviding excitatory output to the cortex. This inhibition of the thalamus and lack of cortical activation results in an impairment or poverty of movement.

Excitatory ( glutamatergic )

Inhibitory (GABA- ergic)

Excitatory ( dopaminergic-D1)

Faded red and green links representinhibition or lack of excitation of theprevious structure

Tests of Frontal Motor FunctionTests of Frontal Motor Function

• hand-grip strength• finger tapping speed• static steadiness• manual dexterity • maze coordination• complex tests of praxis

Frontal Lobes and AttentionFrontal Lobes and Attention

• Inhibition/gating of sensory transmission through thalamic interaction

Cortex

Thalamus

Nucleus Reticularis

Selective Engagement and Disengagement of Cortex

Excitatory cortical projections to the thalamus (A) course through the nucleus reticularis (NR) synapsing on inhibitory thalamicinterneurons (B), reticulo-thalamic neurons (C), and providing arborizing collaterals (D). The direct cortical projection to the thalamicinterneuron (B) results in the inhibition of thalamo-cortical projection (E). This inhibition of thalamo-cortical projections results in thedisengagement (inhibition) of select cortical areas. The reticulo-thalamic neuron (C) synapses on, and inhibits, a thalamic interneuron(F), resulting in excitation of the thalamo-cortical neuron (G). This excitation of the thalamo-cortical projection results in the engagementof select cortical areas. The collateral (D) synapses on, and inhibits, a reticulo-thalamic neuron (H) which synapses on a thalamicinterneuron (I). The thalamic interneuron (I) inhibits the thalamo-cortical neuron (J) resulting in the disengagement of select corticalareas.

= Glutamatergic (excitatory) = GABA-ergic (inhibitory)

Dashed lines represent inhibited neuron (neuron unable to exert it’s influence on downstream neuron).

A

J

C

B

G F

E

HI

D

Proposed Endogenously-Evoked Inhibition LoopDysfunctional System

Frontal Lobe

Striatum

SNc

Intralaminar(CMPf)

SNr

MGP

Excitatory (glutamatergic)

Inhibitory (GABA-ergic)

Excitatory (dopaminergic-D1)

Faded red and green links representinhibition or lack of excitation of theprevious structure

Proposed Endogenously-Evoked Inhibition LoopDysfunctional System

Frontal Lobe

Striatum

SNc

Intralaminar(CMPf)

SNr

MGP

Excitatory (glutamatergic)

Inhibitory (GABA-ergic)

Excitatory (dopaminergic-D1)

Faded red and green links representinhibition or lack of excitation of theprevious structure

Attentional Defects in Frontal Attentional Defects in Frontal DiseaseDisease

• attention-focusing• attention-maintenance• attention-selectivity

– interference susceptibility– Poor goal-dependent filtering of

irrelevant stimuli

• attention-shifting

Tests of Attentional FunctionTests of Attentional Function

• span tests (DS, Sentence Rep)• cancellation tasks (simple and

conditional)• sustained attention

– PASAT– Trail Making Test– Digit Symbol

• qualitative features from other tests

Frontal Lobes and MemoryFrontal Lobes and Memory

• Classic studies of delayed response (DR) and delayed alternation (DA)

• Dorsolateral and frontal polar lesions produce greatest deficits• DR = dorsal? DA = ventral?

Human Frontal Memory Human Frontal Memory DefectsDefects

• Short-term memory– deficits in working memory

• Learning– susceptibility to proactive interference– shallow semantic encoding– impairment in “voluntary memorizing”– impaired “directed forgetting”

• Long-term memory– recall deficits relative to recognition– impaired memory for temporal order– impaired recency judgments– Contamination of “true memory” with “inert stereotypes”

TableGrill

OunceCrayonFablePencil

Grill Fable

Human Frontal Memory Deficits Human Frontal Memory Deficits (cont’d)(cont’d)

• Impairments in “metamemory”– failure of emergent awareness– poor self-monitoring and self-correction– poor knowledge of content of memory

system (e.g., poor connection between search and FOK)

– deficits in source memory– poor strategy use– impaired memory for self-generated

responses

Frontal “Executive” Frontal “Executive” SkillsSkills

• a working definition of “executive” skill

• relevant skill domains– planning– goal establishment– anticipation– cognitive estimation– hypothesis testing (TOTE)

An MBA’s Model of the BrainAn MBA’s Model of the Brain

Cognitive Deficits in Frontal Cognitive Deficits in Frontal SyndromesSyndromes

• impaired abstract thinking– tendency to interpret abstract concepts

concretely (e.g., proverbs, similarities)– tendency to be “pulled” to more

immediately available sensory information• impaired verbal reasoning• impairments in memory

– organizational role– informational - specific memory capacities

of frontal lobe (e.g., working memory; retrieval)

Design Fluency

Examiner

Patient

Utilization Behavior

Tests Tapping ‘Frontal’ Tests Tapping ‘Frontal’ Cognitive DefectsCognitive Defects

• Wisconsin Card Sorting Test• Halstead Category Test• Shipley-Hartford Analogic Reasoning• Trail-Making A and B• Porteus Mazes (planning)• Constructional Tasks (ROCF, BD)• practically any other test calling for

response production and organization!

Theories of Frontal Lobe Function

• Pribram (1960): Feedback• Teuber (1964): Corollary discharge• Nauta (1971): interoceptive (limbic) and

exteroceptive (sensory, association) connectivity

• Fuster (1980): temporal organization• Shallice (1978): information processing• Luria (1973): hierarchical model