Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson’s disease

Social Cognitive and Affective Neuroscience, 2017, 1594–1604 doi: 10.1093/scan/nsx090 Advance Access Publication Date: 11 July 2017 Original article Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson’s disease Friederike Irmen,1,2 Julius Huebl,2 Henning Schroll,2,3 Christof Brücke,2 Gerd-Helge Schneider,4 Fred H. Hamker,3 and Andrea A. Kühn1,2,5,6 1 € t zu Berlin, Berlin 10117 Germany, 2Department of Berlin School of Mind and Brain, Humboldt-Universita € tsmedizin Berlin, corporate member of Freie Universita € t Berlin, HumboldtNeurology, Charité – Universita 3 € t zu Berlin, and Berlin Institute of Health, Berlin 10117, Germany, Department of Neurosurgery, Universita € tsmedizin Berlin, corporate member of Freie Universita € t Berlin, Humboldt-Universita € t zu Charité – Universita Berlin, and Berlin Institute of Health, Berlin 10117, Germany, 4Department of Computer Science, Chemnitz University of Technology, 09111 Chemnitz, Germany, 5NeuroCure Cluster of Excellence, Charité – € tsmedizin Berlin, corporate member of Freie Universita € t Berlin, Humboldt-Universita € t zu Berlin, Universita and Berlin Institute of Health, Berlin 10117, Germany, and 6Deutsches Zentrum für Neurodegenerative Erkrankungen, 10117 Berlin, Germany € tsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Correspondence should be addressed to Andrea A. Kühn, Department of Neurology, Charité - Universita Germany. E-mail: Abstract The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson’s disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflictinduced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. Key words: subthalamic nucleus; deep brain stimulation; emotional conflict; stroop model; Parkinson’s disease Introduction The subthalamic nucleus (STN) is a key node in information processing during action selection receiving input via the hyperdirect and indirect pathway (Alexander and Crutcher, 1990; Nambu et al., 2002). Its functional role has been related to centre surround inhibition and supression of motor output of the basal ganglia during movement selection (Mink, 2003). More recently, evidence for a role of the STN in response slowing related to conflicting input has emerged (Brittain et al.,). It is presumed that the STN pauses basal ganglia motor output in response to conflict until the appropriate motor plan is set Received: 24 December 2016; Revised: 23 June 2017; Accepted: 30 June 2017 C The Author (2017). Published by Oxford University Press. V This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 1594 F. Irmen et al. (Frank et al., 2007). However, the STN’s conflict processing capacity goes beyond the motor domain. In fact, cumulative evidence points towards its role being a more general one, coordinating and weighing input from motor and non-motor brain regions to regulate behaviour (Aron and Poldrack, 2006; Frank and Claus, 2006; Baunez and Lardeux, 2011; Péron et al., 2013). Subthalamic deep brain stimulation (DBS) has become a guideline therapy for advanced Parkinson’s disease (PD) due to its high effectiveness in the control of motor symptoms and improvement in quality of life (Schüpbach et al., 2014). Despite its great therapeutic effect, clinical studies have revealed selective undesirable effects of STN DBS on cognition, behaviour and emotion (Mallet et al., 2007; Voon et al., 2008; Witt et al., 2008; Le Jeune et al., 2010; Maillet et al., 2016; Péron et al., 2013). In particular, STN DBS has been found to increase impulsive behav€ lbig et al., 2009; Florin et al., 2013; Brandt et al., 2015), iour (Ha with conflict-induced slowing turning into conflict-induced speeding with DBS (Frank et al., 2007). This process has been formalized using computational models such as the drift diffusion model of decision making predicting impulsive behaviour in the face of conflict if STN inhibitory activity is disrupted (Cavanagh et al., 2011; Green et al., 2013; Obeso et al., 2014). In line with this, patients with STN DBS make more erroneous choices when their stimulator is turned on, for instance, in the Stroop task, where they have to suppress reading a word while naming its colour (Jahanshahi et al., 2000; Witt et al., 2004). Lower accuracy in such action selection tasks involving conflict provides evidence for impaired response inhibition during STN DBS suggesting a role of the STN in inhibitory executive control (Jahanshahi et al., 2015; Zavala et al., 2015). Further support derives from neuroimaging studies presenting a close functional link of the STN and frontal areas of higher cognitive function via the hyperdirect pathway (Nambu et al., 2002). Yet, the STN has recently been found to also receive input from areas processing affective stimulus contents such as the basolateral amygdala (Lambert et al., 2012) or the orbitofrontal cortex (Le Jeune et al., 2008). In fact, new evidence extends the role of the STN to presenting a central hub for multi-level integration of motor, cognitive and affective information (Accolla et al., 2016). In the affective domain, the STN may play a crucial role in the temporal coordination of cortical and subcortical co-activation that is the foundation to affective sensation (Péron et al., 2013). Behavioural data supporting this notion includes studies showing DBS-induced impairments of emotion recognition and expression, especially in the domain of unpleasant emotions (Le Jeune et al., 2008; Péron et al., 2010). A crucial question yet unanswered is whether the STN modulates the integration of affective information in the motor output relative to a conflict signal. If the processing of conflicting affecti (...truncated)