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Frontal Lobe Functions Pivotal Case: Phineas Gage What Did Change?

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Frontal Lobe Functions Pivotal Case: Phineas Gage What Did Change? Frontal Lobe Functions Fredric E. Rose, Ph.D. Winter 2006 Pivotal Case: Phineas Gage 9/13/1848 25 yo construction foreman for Rutland and Burlington RR in New England Used a tamping iron to fill holes in stones with sand over explosive powder in order to level the terrain Once forgot to put in sand… What did change? What did we learn from this? Pre-accident personality Responsible, intelligent, honest, well-liked by peers and elders, “the most efficient and capable man” according to employers Post-accident personality Disinhibited, irreverent, capricious, disrespectful of social conventions, unable to hold a job Equipotentiality v. Localization of Function Harlow (1868): some portion of the brain that was removed by the tamping rod was responsible for the restraint and well-mannered behavior that most people possess, and that Gage lost in the accident. 1 Gage Revisited (Science,1994) Damasio & Damasio Computer graphics to plot trajectory Ventromedial OFC region, sparing of Broca’s and other FL motor regions Region is responsible for decision-making regarding personal and social matters,as well as emotion processing Anatomy of the Frontal Lobes 3 prefrontal regions: Dorsolateral Orbitofrontal Mesial Frontal Lobe Circuitry Alexander, DeLong, & Strick (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381. Oculomotor Motor Dorsolateral Orbitofrontal Anterior Cingulate 2 Neurotransmitters Glutamate (corticostriatal, thalamocortical) GABA (basal ganglia) Dopamine (cortical, subcortical) Modulates all 3 circuits Acetylcholine (striatal) Open circuit influence) Serotonin (cortical, subcortical) Core Frontal Circuitry Frontal Cortex Glutamate (+) Glutamate (+) Thalamus Striatum GABA (-) GABA (-) Internal External Globus Pallidus GABA (-) Glutamate (+) Subthalamic Feifel (1999) Dorsolateral Circuit Functions Subserves executive function Behavioral responses to complex problems Activation of remote memories Environmental independence Shifting/maintaining cognitive sets Generating motor programs Verbal mediation of behavior 3 Executive Functions Planning Decision making Self-directed goal selection Monitoring, guiding, and directing behavior to achieve a goal Dorsolateral Circuit Dysfunction Poor organizational behavior Poor memory search strategies Environmental dependency Poor set shifting (perseveration) Verbal/manual dissociations Orbitofrontal Circuit Functions 2 parallel circuits: Lateral and Medial Personality Characteristics Empathy Civility Social appropriateness Environmental independence Emotional continence 4 Orbitofrontal Circuit Dysfunction Personality Changes Tactlessness Impulsivity Irritability Antisocial behavior Utilization/imitation behavior Mood disorders Obsessive-Compulsive disorder Orbitofrontal Syndrome Emotional lability (mood swings) Disinhibition Criminal behavior Unusual/impulsive sexual behavior Often lack awareness Anosmia Environmental Dependency Pseudopsychopathic Anterior Cingulate Functions Motivated Behavior Drive Spontaneity “Personhood” Creativity 5 Anterior Cingulate Dysfunction Akinetic mutism Indifference to pain Apathy Poverty of speech Psychic emptiness Excessive conformity Poor response inhibition Personality Changes Impairments in social skills inappropriate or bizarre social behavior “loosening" of normal social restraints Change in motivation apathy, withdrawal, lack of interest, and initiative Pseudodepression / pseudoretarded Summary of Personality/Behavioral Symptoms POSITIVE NEGATIVE Disinhibition Apathy Impulsivity Reduced initiative Vulgarity (Abulia) Irritability Reduced interest in daily activities/self- Emotional lability care Inappropriate laughter, crying Akinetic mutism Social withdrawal Bizarre behavior 6 Personality/Behavioral Assessment Observation Impulsive, disinhibited, environmentally dependent… Questionnaires Self-report Caregiver/family member Interviews Patient Family Secondary Motor Cortex Supplementary Motor Area Sequencing, timing, and proper initiation of voluntary movements. PET studies Specific vs random motor sequence magining this movement. Injury – disorder of motor planning, organization, and initiation Secondary Motor Cortex (cont.) Premotor Area Sequencing, timing, and proper initiation of voluntary movements. BUT… more in external cue readiness, such as the interval between CUE and GO. Cingulate Motor Area Emotional or motivational impetus for movement (when reward is involved) Injury – lack of spontaneous motor activity, reduced speech output 7 Measures of SMC Functioning Written Alternating Sequences Perseveration: the inability to stop behaviors once they have started •Motor Impersistence: a form of distractibility in which patients only briefly sustain a motor action in response to a command such as "Raise your arms" or "Look to the right." Measures of SMC Functioning (cont.) Luria 3-Step Fist, Edge, Palm Go-No Go (also Orbital-PFC – disinhibition) Multiple Loops 8 Apraxia Inability to execute purposeful, complex motor acts, despite physical ability, comprehension, and willingness. Ideomotor Apraxia: Gestures to command Motor representations in Parietal Lobe, but Premotor Cortex (including SMA) translates into movements Frontal Release Signs FL lesions (nonlocalized; dementia) can produce a return of primitive reflexes: Grasp Sucking/”Snout” Groping Utilization behavior 9 Summary of Motor Symptoms of FL Disorder Poor motor sequencing Poor initiation of movements Dysarthria Apraxia Frontal release signs Assessing Executive Functions Anatomy of the Frontal Lobes 3 prefrontal regions: Dorsolateral Orbitofrontal Mesial 10 Divide these 6 stimuli into 2 groups based on a shared characteristic. Now do it again based on another shared characteristic. Stroop Color-Word Test Red Blue Green Red Blue Red Blue Green Green Green Red Blue Blue Red Blue Red Green Blue Green Blue Red Green Blue Green Green Red Red Red Stroop Color-Word Test XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX 11 Stroop Color-Word Test Red Blue Green Red Blue Red Blue Green Green Green Red Blue Blue Red Blue Red Green Blue Green Blue Red Green Blue Green Green Red Red Red Wisconsin Card Sorting Test Deck of cards with different stimuli on each Patient sorts the deck into 4 piles according to “key” cards Told only if right or wrong on each sort Letter Fluency Sec C F L 0 Cat F*ck! Lips Car Lever 15 Fudge Catch Fever List 30 Catching Fudge Lemon Caterpillar Fudge 45 Fever Crayon Fiddle SPEED FACTORS 60 Cabbage Flower -poor initiation -poor maintenance 12 F C Trail Making Test A G E B D H A D A Trail Making Test B 4 1 2 B C 3 Rey-Osterrieth Complex Figure copy 13 So, what are “Executive Functions”? Generate a list and identify the theme. Planning Organizing Selective attention What’s the common thread? Problem-solving Executive functions are complex functions that allow one to Initiating engage in effective and efficient Inhibiting goal-directed behavior. Self-monitoring Abstract thinking Mental flexibility FL Memory Functions Working Memory Retrieval Source Memory Working Memory Serial 7’s Put this in order with letters first, then numbers: “L-4-C-2-M-8”. Spell “WORLD” backwards. What does these have in common? Define ‘working memory.’ What are the 2 main components? an active system for temporarily storing and manipulating information needed in the execution of complex cognitive tasks 14 Working Memory (pp. 169-170) Baddeley (1986): WM has 3 components Central executive Articulatory phonological loop Visual-spatial sketch pad Goldman-Rakic (1988) Dorsolateral prefrontal cortex holds information “on line” while it is processed (monkey research). Confirmed by PET and fMRI Paced Auditory Serial Addition Task (PASAT) EXAMINER PATIENT 4 “7” 3 “11” Phonological Loop E 8 “10” M or I 2 T “5” Visual-spatial Sketchpad 3 “10” 7 “15” 8 N-back C me n Ti A N q 2-Back Q target X c 1-Back target 0-Back target Phonological Loop or Visual-spatial Sketchpad 15 Spatial Span Task Phonological Loop or Visual-spatial Sketchpad 16.
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