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 , 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  Environmental independence  Shifting/maintaining cognitive sets  Generating motor programs  Verbal mediation of behavior

3

 Planning

 Decision making

 Self-directed goal selection

 Monitoring, guiding, and directing behavior to achieve a goal

Dorsolateral Circuit Dysfunction

 Poor organizational behavior

 Poor 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 , 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 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