Understanding the Impact of Subthalamic Deep Brain Stimulation on Cognitive and Affective Processing

• Main Author: Irmen, Friederike
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2019
• Subjects: Neurosciences
• ISBN: 9781392368640; 1392368642

As neuromodulatory treatment, subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) undergoes a current paradigm shift, away from being seen as mainly a therapy to improve motor symptoms toward being a window to better understanding of nonmotor networks converging in the basal ganglia. Since the STN is a hub for the integration of cognitive and affective processes into the motor response, DBS impacts interaction of basal ganglia with motor, associative and affective brain regions. STN-DBS leads to cognitive and affective changes that either classify as improvements or disturbances of behaviour when compared to the baseline bias that PD has on nonmotor function per se. This thesis attempted to improve the understanding of mechanisms underlying DBS effects on cognitive and affective processing by assessing nonmotor DBS-effects in understudied domains like decision-making and emotional processing and to relate the findings to computational or anatomical reconstructions of basal ganglia-cortex interactions or STN functional anatomy. To this end, five studies are presented, the results of which are complementary in understanding local and global impact of DBS on the brain and associated nonmotor behavioural changes. Study 1 assessed impact of STN-DBS on emotional conflict processing in a perceptual decision-making task and found that DBS lead to the disability to slow down responses when cognitive control was required and at the same time to a blunting of a PD-inherent bias to process positive information more slowly than negative information. Coherently, Study 4 of this thesis compared response times in automatic movement versus movement that require cognitive control and found that DBS induced a disinhibition that was related to a disruption of cortex-STN coupling via the hyperdirect pathway. Study 2 also assessed changes in decision-making under DBS but in the domain of risk-reward trade-off decisions. Here, it was again found that a PD-specific bias, namely, to take too little risks, could be altered by STN-DBS. Specifically, when motor STN territory was stimulated, risk attitude normalized to a healthy level. This nonmotor benefit of effective STN-DBS is coherent with the results of Study 3 and 4, where impact on the STN motor territory was related to a normalization of depressive symptoms and a functional connectivity that was similar to that of healthy controls. Together, these studies imply that DBS of the STN motor territory induces improvements in value-based decision-making, depression and functional connectivity, while causing impairments in cognitive inhibition during the recruitment of cognitive control. Electrode misplacement however can lead to behavioural disturbances through impact on nonmotor networks like the left prefrontal cortex, the connectivity to which, if disrupted by DBS, explains worsening of depression. The results of this thesis are of high clinical value since they can aid refinement of DBS programming, inform tailored DBS therapy and help to better understand and in the future avoid DBS side effects.