Cognitive flexibility versus stability: Role of dopamine (and noradrenaline)

The brain catecholamines dopamine (and noradrenaline) play important roles in complex cognitive functions such as working memory. This somewhat ill-defined term generally refers to the ‘on-line’ stabilization of task-relevant representations, but often also implies flexible updating of those representations in response to novel information. A dynamic task-dependent balance between these opponent functions is critically important for a wide range of cognitive abilities such as reasoning, language comprehension, planning, and spatial processing and has been associated most commonly with circuits connecting the prefrontal cortex with the striatum. One major goal of our group is to unravel the roles of the catecholamines in cognitive flexibility and in its tradeoff with cognitive stability.

Flexible updating and stabilization can be conceptualized as representing functionally opponent processes. If we update too readily, then we are likely to get distracted, rendering our behavior unstable. Conversely, if our representations are overly persistent or stable, then there is a danger of inflexibility and unresponsiveness to new information. In the lab, we use psychopharmacology, cognitive science,  functional magnetic resonance imaging and dopamine PET imaging to study the catecholaminergic modulation of working memory. We test the hypothesis that the balance between cognitive flexibility and stability is adjusted depending on task demands, and sensitive to challenges of the catecholamine system, for example, with methylphenidate, or tyrosine supplementation. Evidence so far indicates that the same dopaminergic drug (or disorder) can have opposite effects on task performance depending on demands for cognitive stability and flexibility (Fallon et al., 2016; Cools et al., 2010). Moreover, effects of dopaminergic drugs on cognitive stability and flexibility are accompanied by modulation of distinct prefrontal and striatal brain regions respectively (Cools et al., 2011; 2007). We are currently working on further psychopharmacological studies, for example with patients with Parkinson’s disease, to study the role of noradrenaline in the tradeoff between cognitive flexibility and stability in working memory.

Relevant papers

Fallon SJ, Van der Schaaf ME, ter Huurne N, Cools R (2017). The neurocognitive cost of enhancing cognition with methylphenidate: improved distractor resistance but impaired updating. J Cogn Neurosci 29(4):652-663

Boot N, Baas M, van Gaal S, Cools R, De Dreu CKW (2017). Creative Cognition and Dopaminergic Modulation of Fronto-striatal Networks: Integrative Review and Research Agenda. Neuroscience & Biobehavioral Reviews 78:13-23

Goldfarb EV, Frobose MI, Cools R, Phelps RA (2017). Stress and cognitive flexibility: Cortisol increases are associated with enhanced updating but impaired switching. J Cogn Neurosci 29(1):14-24

Van Schouwenburg MR, den Ouden H, Cools R (2015). Selective attentional enhancement and inhibition of fronto-posterior connectivity by the basal ganglia during attention switching. Cerebral Cortex 25(6):1527-34

Bloemendaal M; van Schouwenburg M; Miyakawa A; Aarts E; D'Esposito M; Cools R (2015). Dopaminergic modulation of distracter-resistance and prefrontal delay period signal. Psychopharm 232(6):1061-70

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.

Van Schouwenburg MR, Onnink AMH; ter Huurne N; Kan CC, Zwiers MP, Hoogman M, Franke B, Buitelaar JK, Cools R (2014). Cognitive flexibility depends on white matter microstructure of the basal ganglia. Neuropsychologia 53:171-7

Beeler JA, Cools R, Luciana M, Ostlund S, Petzinger G (2014). A kinder, gentler dopamine…Highlighting dopamine’s role in behavioural flexibility. Front Neurosci 8:4

Stelzel C, Fiebach CJ, Cools R, Tafazoli S, D’Esposito M (2013). Dissociable fronto-striatal effects of dopamine D2 receptor stimulation on cognitive vs. motor flexibility. Cortex 49(10):2799-811

Van Schouwenburg MR, Zwiers MP, van der Schaaf ME, Geurts DE, Schellekens AF, Buitelaar JK, Verkes RJ, Cools R (2013) Anatomical connection strength predicts dopaminergic drug effects on fronto-striatal function. Psychopharm 227(3):521-31

Van Schouwenburg M, O'Shea J, Mars R, Rushworth R, and Cools R (2012). Controlling human striatal cognitive function via the frontal cortex. J Neurosci 32(16):5631-7

Cools R (2011). Dopaminergic control of the striatum for high-level cognition. Curr Opin Neurobiol 21:402-407

Cools R and D’Esposito M (2011). Inverted-U-Shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 69(12):e113-25.

Van Schouwenburg M, Den Ouden H, Cools R (2010). The human basal ganglia modulate fronto-posterior connectivity during attention shifting. J Neurosci 30:9910-9918.

Van Holstein M, Aarts E, van der Schaaf ME, Geurts DE, Verkes RJ, Franke B, van Schouwenburg MR, Cools R (2011). Human cognitive flexibility depends on dopamine D2 receptor signaling. Psychopharm 218(3):567-78.

Van Schouwenburg M, Aarts E, Cools R (2010). Dopaminergic Modulation of Cognitive Control: Distinct Roles for the Prefrontal Cortex and the Basal Ganglia. Curr Pharm Des 16(18):2026-32 [3.6]

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

Van Schouwenburg M, Den Ouden H, Cools R (2010). The human basal ganglia modulate fronto-posterior connectivity during attention shifting. J Neurosci 30:9910- 9918

Cools R, Gibbs SE, Miyakawa A, Jagust W, D'Esposito M (2008). Working memory capacity predicts dopamine synthesis capacity in the human striatum. J Neurosci 28(5):1208-12

Cools R, Sheridan M, Jacobs EJ, D’Esposito MD (2007). Impulsive personality predicts dopamine-dependent changes in fronto-striatal activity during component processes of working memory. J Neurosci 27(20): 5506-5514

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

Lewis SJ, Cools R, Robbins TW, Dove A, Barker RA, Owen AM (2003). Using executive heterogeneity to explore the nature of working memory deficits in Parkinson's disease. Neuropsychologia 41(6):645-54

Cools R, Stefanova E, Barker RA, Robbins TW, Owen AM (2002) Dopaminergic modulation of high-level cognition in Parkinson’s disease: The role of prefrontal cortex revealed by PET. Brain 125: 584-594

Cools R, Barker RA, Sahakian BJ, and Robbins TW (2001). Mechanisms of cognitive set flexibility in Parkinson’s disease. Brain 124:2503-2512

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