Impulsivity and Deep Brain Stimulation “Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism” Michael J. Frank, Johan Samanta, Ahmed A. Moustafa, Scott Sherman Reviewed by XXXXX Hypotheses 1. 2. 3. Patients will show lack of reinforcement learning. Medication will impair negative feedback learning. DBS will impair high conflict slowing response. Definitions Reinforcement Learning – Learning with positive or negative feedback Negative Feedback Learning – Learning after making error High Conflict Slowing Response – Pause before making win/win or lose/lose decisions “Should you vacation in Montreal or Rome?” “Should you eat chocolate fondue or tiramisu?” Neither option crosses “critical decision threshold” (STN) Participants Demographics Sex ratio Years NAART Hoehn & Yahr Years Group n n filt (m:f) Age Education (# correct) stage diag Seniors 27 22 7:15 66.0 (1.7) 16.2 (1.2) 44.0 (1.9) N/A N/A ON Med 15 12 7:5 67.8 (2.1) 17.8 (1.2) 42.9 (2.3) 2.4 (0.2) 8.8 (0.8) OFF Med 14 9 6:3 67.6 (2.5) 19.2 (1.4) 43.5 (3.1) 2.3 (1.9) 9.5 (1.4) 2.3 (0.2) 14.4 (1.5) 2.8 (0.3) 15.2 (1.8) PD patients ON DBS OFF DBS 17 14 15 12 13:2 11:1 64.5 (2.8) 62.3 (3.3) 14.2 (1.5) 14.4 (1.2) 39.9 (2.4) 39.0 (2.9) Exclusion Criteria Significant medical history Concurrent illness (Schizophrenia, Manic Depression) History of drug abuse/alcoholism Advanced symptoms (stage V) MMSE<24 (to screen for dementia) Additional medications thought to confound findings Methods Four Groups of Participants On/Off medication On/Off DBS (stimulating in the STN) Probabilistic Selection Task Training AB (A=80%), CD (C=70%), EF (E=60%) Training (AB=65%, CD=60%, EF=50%) Test Novel test pairs Measured number of correct responses and response times *non-specific keys for response Example of Training Training A 80% B 20% Correct! Incorrect No response detected Measurements Positive Feedback Learning – Choosing “A” in novel test pairs Negative Feedback Learning – Avoiding “B” in novel test pairs Compared to positive feedback learning Conflict Effects – Reaction times of novel test pairs with similar reinforcement values as compared to those with dissimilar values Testing for Negative Feedback Learning Impairment Testing for High-Conflict Slowing Response Impairment Results 1. 2. Feedback learning unaffected in on/off DBS groups On DBS group differed from off DBS group in conflict effects 3. 4. On DBS seemed to even speed up with high conflict pairs No change in high-conflict slowing response in on/off medication groups On medication group was impaired at negative feedback learning. Results (cont.) In on DBS group, the more severe the impairment of high-conflict slowing response, the more errors On DBS responded faster to high-conflict win/win pairs as opposed to lose/lose pairs Impairment of Negative Reinforcement for On Medication Group Impairment of High-Conflict Slowing Response for On DBS Group Confirmation of Results “Retrograde DBS procedure” Off DBS retested with stimulators turned on Same results found as with on DBS group Control group also retested with same time delay No change in conflict-induced slowing response Off Medication group retested with different time delay No change in conflict-induced slowing response Applications Two roles of Basal Ganglia in decision making 1. One area of striatum is composed of “Go” neurons (D1 receptors) 2. Another area of the striatum is composed of “No Go” neurons (D2 receptors) Seek reinforcement Dopamine increases with reinforcement Avoid non-reinforcing stimuli Dopamine decreases without reinforcement Medications prevent decrease in dopamine necessary for negative feedback learning Applications (cont.) STN provides “Hold Your Horses” response when decision-conflict is high Two theories of how DBS works 1. 2. DBS acts as lesion DBS over-activates STN Neurons in the STN are firing all the time instead of selectively during high-conflict decision making With impairment in negative feedback learning and lack of high-conflict slowing response it is easy to understand how one could begin to gamble Critique of Study Pros Controlled for age and education Controlled for motor deficiencies Control group Control group retested Cons Attrition DBS groups had more years diagnosed No random assignment Additional Research Contarino et al. found that hypersexuality and hypomania may be caused by DBS Desbonnet et al. found premature responding in rats with STN stimulation Uslaner and Robinson found that STN lesions in rats increased impulsive action Smeding et al. conducted case study of patient who began DBS and acquired gambling addiction Thanks!