Computational Psychiatry and Neurology

Knowledge of the cognitive functions of the major neurotransmitters significantly advances the field of computational psychiatry and neurology, which aim to bridge the gap between neuroscience, neurology and psychiatry by elucidating the cognitive computations underlying (mal)adaptive behaviors. Indeed, many of the major neuropsychiatric and neurological disorders are cognitive in nature. Definition of neuropsychiatric abnormality in terms of its cognitive mechanism is increasingly recognized to be important for diagnosis, prognosis and optimizing treatment development. We contribute to this, either within the group, or in collaborative efforts, by studying motivational and cognitive control in Parkinson’s disease, gambling addiction, eating disorder, ADHD, depression, anxiety, psychopathy, gambling addiction and schizophrenia.

Parkinson’s disease

In my early work, I put forward the ‘dopamine overdose hypothesis’ to account for the contrasting effects of dopaminergic medication on distinct cognitive functions in Parkinson’s disease. This hypothesis states that dopaminergic medication doses that are necessary to remediate the motor and cognitive deficits that are associated with severely depleted dopamine levels in the dorsal frontostriatal circuitry actually impair other cognitive functions by detrimentally ‘overdosing’ dopamine levels in relatively intact brain regions, such as the ventral striatum and prefrontal cortex (Cools et al., 2001; 2003; 2007; Cools, 2006). In recent work, we have demonstrated that such dopamine-induced cognitive and decision anomalies depend on the presence of a history of depression (Timmer et al., 2018).

In ongoing longitudinal cohort work (e.g. the Personalized Parkinson’s disease Project[RC1] , in collaboration with Rick Helmich [RC2] and Bas Bloem), we focus on identifying computational biomarkers for predicting disease progression and development of neuropsychiatric anomalies, including impulse control disorder and apathy.

Relevant papers

Parkinson’s disease

Timmer MHM, Sescousse G, Esselink RAJ, Piray P, Cools R (2018). Mechanisms underlying dopamine-induced risky choice in Parkinson’s disease with and without depression (history). Computational Psychiatry 2, 11-27

Timmer MHM, Esselink RAJ, Cools R (2018). Enhanced motivation of cognitive control in Parkinson’s disease. Eur J Neurosci 48(6):2374-2384

Timmer MHM, Sescousse G, Van der Schaaf ME, Esselink RAJ, Cools R (2017). Reward learning deficits in Parkinson’s disease depend on depression. Psychol Med 47:2302-2311

Fallon SJ, Smulders K, Esselink R, van de Warrenburg BP, Bloem BR, Cools R (2015). Differential optimal dopamine levels for set-shifting and working memory in Parkinson’s disease. Neuropsychologia 77:42-51.

Robbins TW, Cools R (2014). Cognitive Deficits in Parkinson’s Disease: A Cognitive Neuroscience Perspective. Movement Dis 29:597:607

Smittenaar P, Chase HW, Aarts E, Nusselein B, Bloem BR, Cools R (2012). Decomposing effects of dopaminergic medication in Parkinson’s disease on probabilistic action selection: learning or performance? Eur J Neurosci 35(7):1144-51

De Wit S, Barker RA, Dickinson A, Cools R (2011). Habitual versus goal-directed action control in Parkinson disease. J Cogn Neurosci. 23(5):1218-1229

Cools R, Rogers R, Barker RA, Robbins TW (2010). Top-down attentional control in Parkinson’s disease: salient considerations. J Cogn Neurosci 22(5):848-59

Cools R, Miyakawa A, Sheridan M, D'Esposito M (2010). Enhanced frontal function in Parkinson's disease. Brain 133:225-33

Cools R, Lewis SGJ, Clark L, Barker RA, Robbins TW (2007). L-DOPA disrupts activity in the nucleus accumbens during reversal learning in Parkinson’s disease. Neuropsychopharmacology 32 (1): 180-189

Cools R, Altamirano L, D’Esposito M (2006). Reversal learning in Parkinson’s disease depends on medication status and outcome valence. Neuropsychologia 44 (10):1663-1673

Cools R, Barker R A, Sahakian B J, Robbins T W (2003). L-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson’s disease. Neuropsychologia 41:1431-1441

Cools R, Barker RA, Sahakian BJ, Robbins TW (2001). Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands. Cereb Cortex 11:1136-1143

Gambling Addiction

van Holst R, Sescousse R, Janssen LK, Janssen M, Berry AS, Jagust WJ, Cools R (2018). Increased striatal dopamine synthesis capacity in gambling addiction. Biological Psychiatry 83: 1036-1043

Ojala K, Janssen L, Hashemi M, Timmer M, Geurts D, ter Huurne N, Cools R, and Sescousse G (2018). Dopaminergic drug effects on probability weighting during risky decision-making. eNeuro. Apr 6;5(2).

Sescousse G, Janssen L, Hashemi M, Timmer M, Geurts D, ter Huurne N, Clark L, Cools R (2016). Amplified striatal responses to near-miss outcomes in pathological gamblers. Neuropsychopharmacology 41(10):2614-23

Janssen L, Sescousse G; Hashemi M; Timmer M, ter Huurne N, Geurts D, Cools R (2015). Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers. Psychopharmacology 232(18):3345-53.

Depression

Timmer MHM, Sescousse G, Van der Schaaf ME, Esselink RAJ, Cools R (2017). Reward learning deficits in Parkinson’s disease depend on depression. Psychol Med 47:2302-2311

Huys QJM, Gölzer M, Friedel E, Heinz A, Cools R, Dayan P, Dolan RJ (2016). The specificity of Pavlovian regulation is associated with recovery from depression. Psychological Medicine 46(5):1027-35

Robinson OJ, Cools R, Carlisi CO, Sahakian BJ, Drevets WC (2012). Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder. Am J Psychiatry 169(2):152-9 [15.1]

ADHD

von Rhein D, Oldehinkel M, Beckmann CF, Oosterlaan J, Heslenfeld D, Hartman CA, Hoekstra PJ, Franke B, Cools R, Buitelaar JK, Mennes M (2016). Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry. 57(6):697-705.

Von Rhein D, Cools R, Zwiers MP, van der Schaaf M, Franke B, Luman M, Oosterlaan J, Heslenfeld DJ, Hoekstra PJ, Hartman CA, Faraone SV, van Rooij D, van Dongen EV, Lojowska M, Mennes M, Buitelaar J. (2015). Increased neural responses to reward in adolescents and young adults with Attention-deficit/Hyperactiviy Disorder and their unaffected siblings. J Am Acad Child Adolesc Psychiatry 54(5):394-402

Aarts E, van Holstein M, Hoogman M, Onnink M, Kan C, Franke B, Buitelaar J, Cools R (2015). Reward modulation of cognitive function in adult ADHD: a pilot study on the role of striatal dopamine. Behav Pharmacol 26(1-2):227-40

Anxiety

Ly V, Cools R, Roelofs K (2014). Aversive disinhibition of behavior and striatal signaling in social avoidance. Social Cogn Aff Neurosci 9(10):1530-6

Psychopathy

Geurts D, von Borries K, Volman I, Bulten B, Cools R*, Verkes R*. (2016). Neural connectivity during reward expectation dissociates psychopathic criminals from noncriminal individuals with high impulsive/antisocial psychopathic traits. Social Cognitive and Affective Neuroscience 11(8):1326-34

Ly V, Von Borries AKL, Brazil IA, Bulten BH, Cools R*, Roelofs K* (2016). Reduced transfer of affective value to instrumental behavior in violent offenders. Journal of Abnormal Psychology 125(5):657-63

Schizophenia

Culbreth AJ, Gold JM, Cools R & Barch DM (2016). Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia. Schizophrenia Bulletin 42(2):484-93

Ragland JD, Cohen NJ, Cools R, Frank MJ, Hannula DE, Ranganath C (2012). CNTRICS imaging biomarkers final task selection: Long-term memory and reinforcement learning. Schizophr Bull 38(1):62-72

Ragland JD, Cools R, Frank M, Pizzagalli DA, Preston A, Ranganath C, Wagner AD (2009). CNTRICS final task selection: long-term memory. Schizophr Bull 35(1):197-212

Cools R, Brouwer WH, de Jong R, Slooff C (2000). Flexibility, inhibition, and planning: frontal dysfunctioning in schizophrenia. Brain Cogn 43:108-12

Eating disorder

Janssen LK, Duif I, van Loon I, Wegman J, de Vries J, Cools R, Aarts E (2017). Loss of lateral prefrontal cortex control in food-directed attention and goal-directed food choice in obesity. Neuroimage 146:148-156

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Motivational & Cognitive Control

Computational Psychiatry and Neurology

Computational Psychiatry and Neurology