Nelleke C van Wouwe

Nelleke C van Wouwe
University of Louisville | UL · Department of Neurological Surgery

PhD

About

68
Publications
9,965
Reads
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1,343
Citations
Introduction
The focus of my work is to understand the neural mechanism of inhibitory action control by means of neuromodulation (deep brain stimulation in STN, GPi, ViM), neurophysiology measurements and medication studies in patients with movement disorders (Parkinson’s Disease, Essential Tremor, Huntington's disease)
Additional affiliations
April 2012 - April 2016
Vanderbilt University
Position
  • PostDoc Position
July 2009 - December 2011
TNO
Position
  • Researcher
July 2004 - January 2009
Leiden University
Position
  • PhD Student

Publications

Publications (68)
Article
Full-text available
Essential tremor (ET) is a movement disorder characterized primarily by action tremor which affects the regulation of movements. Disruptions in cerebello-thalamocortical networks could interfere with cognitive control over actions in ET, for example, the ability to suppress a strong automatic impulse over a more appropriate action (conflict control...
Article
Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with...
Article
Background: Deep brain stimulation (DBS) for Parkinson’s Disease (PD) provides significant improvement of motor symptoms but can also produce neurocognitive side effects. A decline in Verbal Fluency (VF) is among the most frequently reported side effects. To date, identification of predictive factors routinely captured preoperatively that predict V...
Preprint
Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study immersive natural behavior for basic and clinical-translational research, and also requires addressing important logistical, technical, and ethical challenges. Hospital rooms provide the opportunity to rich...
Article
Full-text available
Parkinson's disease (PD) is a neurological disorder associated primarily with overt motor symptoms. Several studies show that PD is additionally accompanied by impairments in covert cognitive processes underlying goal-directed motor functioning (e.g., action planning, conflict adaptation, inhibition), and that dopaminergic medication may modulate t...
Article
Full-text available
Findings from previous research using the classic stop-signal task indicate that the subthalamic nucleus (STN) plays an important role in the ability to inhibit motor actions. Here we extend these findings using a stop-change task that requires voluntary action override to stop an ongoing motor response and change to an alternative response. Sixtee...
Article
Full-text available
Objective: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but it can also disrupt verbal fluency with significant costs to quality of life. The current study investigated how variability of bilateral active electrode coordinates along the superior/inferior, anterior/posterior, and lateral/medial axes in the subth...
Article
Full-text available
Patients with Parkinson’s disease (PD) often experience reductions in the proficiency to inhibit actions. The motor symptoms of PD can be effectively treated with deep brain stimulation (DBS) of the Subthalamic nucleus (STN), a key structure in the frontal-striatal network that may be directly involved in regulating inhibitory control. However, the...
Preprint
Parkinson’s disease (PD) is a neurological disorder associated primarily with overt motor symptoms. Several studies show that PD is additionally accompanied by impairments in covert cognitive processes controlling motor functioning (e.g., action planning, adaptation, inhibition), and that dopaminergic medication may modulate such action control. In...
Article
Full-text available
Football is played in a dynamic, often unpredictable, visual environment in which players are challenged to process and respond with speed and flexibility to critical incoming stimulus events. To meet this challenge, we hypothesize that football players possess, in conjunction with their extraordinary physical skills, exceptionally proficient execu...
Article
Objective: Despite being a major cause of neurological disability, the neural mechanisms of functional movement disorders (FMDs) remain poorly understood. Recent studies suggest that FMD is linked to dysfunctional motor and prefrontal regions that could lead to motor and cognitive impairments. The aim of this study was to investigate different com...
Article
Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off- and on-dopamin...
Article
Objectives: Essential tremor (ET) is a movement disorder characterized by action tremor which impacts motor execution. Given the disrupted cerebellar-thalamo-cortical networks in ET, we hypothesized that ET could interfere with the control mechanisms involved in regulating motor performance. The ability to inhibit or stop actions is critical for n...
Article
Full-text available
American football is played in a dynamic environment that places considerable demands on a player’s ability to make fast, precise reactions while controlling premature, impulsive reactions to spatial misinformation. We investigated the hypothesis that collegiate football players are more proficient than their non-athlete counterparts at controlling...
Article
Full-text available
Background Dopamine therapy in Parkinson disease (PD) can have differential effects on inhibitory action control, or the ability to inhibit reflexive or impulsive actions. Dopamine agonist (DAAg) medications, which preferentially target D2 and D3 receptors, can either improve or worsen control of impulsive actions in patients with PD. We have repor...
Article
The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3receptor expression are described in drug-seeking and addiction disorders. Parkinson’s disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a propor...
Data
The supplementary data section provides 1.) PET acquisition parameters; 2.) a full description of mean ROI volume and BPnd values; 3.) a measure of effect size for all ROI-based analyses; 4.) standard-space ROI visualization and standard-space ROI BPnd scatterplots; 5.) visualization of supplementary whole-brain voxel-wise analysis considering PD s...
Article
Full-text available
American football is played in a chaotic visual environment filled with relevant and distracting information. We investigated the hypothesis that collegiate football players show exceptional skill at shielding their response execution from the interfering effects of distraction (interference control). The performances of 280 football players from N...
Article
Full-text available
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors c...
Article
Basal ganglia dysfunction in Parkinson's disease (PD) is thought to generate deficits in action control, but the characterization of these deficits have been qualitative rather than quantitative. Patients with PD typically show prolonged response times on tasks that instantiate a conflict between goal-directed processing and automatic response tend...
Article
The present behavioral study delineates the impact of Parkinson's disease (PD) and of dopaminergic medication on action control over voluntary behavior. Previous studies reported either prolonged responding or stopping latencies in PD compared to healthy controls (HC). Few studies investigated the effects of dopaminergic medication on these process...
Article
A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward-driven behaviors, which can result in life-altering morbidity. The mesocorticolimbic dopamine network guides reward-motivated behavior; however, its role in this treatment-related behavioral phenotype is incompletely understood. Here, mesocor...
Article
Objectives: We investigated how broad motivational tendencies are related to the expression and suppression of action impulses in Parkinson's disease (PD). Methods: Sixty-nine participants with PD completed a Simon response conflict task and Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) scales based on Gray's (1987) r...
Article
We administered a stop-change paradigm, an extended version of the stop task that requires (a) stopping an ongoing motor response and (b) changing to an alternative (change) response. Performance of a group of patients diagnosed with Parkinson's disease (PD) and taking dopaminergic medication was compared with that of matched healthy control (HC) p...
Article
Background: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute...
Article
Objectives: In unpredictable situations, individuals often show tradeoffs between response initiation and inhibition speeds. We tested the hypothesis that Parkinson's disease (PD) motor subtypes differentially impact tradeoffs between these two action-oriented processes. We predicted that, compared to tremor dominant (TD) patients, predominant pos...
Article
Frontal-basal ganglia circuitry dysfunction caused by Parkinson's disease impairs important executive cognitive processes, such as the ability to inhibit impulsive action tendencies. Subthalamic Nucleus Deep Brain Stimulation in Parkinson's disease improves the reactive inhibition of impulsive actions that interfere with goal-directed behavior. An...
Article
Full-text available
Learning the contingencies between stimulus, action, and outcomes is disrupted in disorders associated with altered dopamine (DA) function in the BG, such as Parkinson's disease (PD). Although the role of DA in learning to act has been extensively investigated in PD, the role of DA in "learning to withhold" (or inhibit) action to influence outcomes...
Article
The current study aimed to shed more light on the role of dopamine in temporal attention. To this end, we pharmacologically manipulated dopamine levels in a large sample of Parkinson's disease patients (n=63) while they performed an attentional blink (AB) task in which they had to identify two targets (T1 and T2) presented in close temporal proximi...
Article
Evidence that Tourette's syndrome (TS) disrupts inhibitory motor control is highly mixed. The authors investigated inhibitory control of manual and vocal actions in young adults with relatively uncomplicated, persistent TS. Both TS and control groups showed similar response latencies when executing manual and vocal reactions, but individuals with T...
Article
Background: Parkinson's Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age, or disease duration impact the pattern of these distinctions is unclear. Objective: We examine if PD patients with predominant signs of postural instability an...
Article
Full-text available
Dopamine plays a key role in a range of action control processes. Here, we investigate how dopamine depletion caused by Parkinson's disease (PD) and how dopamine restoring medication modulate the expression and suppression of unintended action impulses. Fifty-five PD patients and 56 healthy controls (HCs) performed an action control task (Simon tas...
Article
Full-text available
Objectives: Huntington's disease (HD) is a neurodegenerative disorder that produces a bias toward risky, reward-driven decisions in situations where the outcomes of decisions are uncertain and must be discovered. However, it is unclear whether HD patients show similar biases in decision-making when learning demands are minimized and prospective ri...
Article
Full-text available
Freezing of gait is a disabling symptom of Parkinson's disease (PD) that involves failure to initiate and continue motor activity appropriately. PD disrupts fronto-basal ganglia circuitries that also implement the inhibition of responses, leading to the hypothesis that freezing of gait may involve fundamental changes in both initiation and inhibiti...
Article
Parkinson's disease (PD) is a neurodegenerative basal ganglia disease that disrupts cognitive control processes involved in response selection. The current study investigated the effects of PD on the ability to resolve conflicts during response selection when performance emphasized response speed versus response accuracy. Twenty-one (21) PD patient...
Article
Full-text available
Reliable applications of multimodal affective brain-computer interfaces (aBCI) require a detailed understanding of the processes involved in emotions. To explore the modality-specific nature of affective responses, we studied neurophysiological responses of 24 subjects during visual, auditory, and audiovisual affect stimulation and obtained their s...
Article
Full-text available
Most studies on physiological effects of emotion-inducing images and sounds examine stimulus locked variables reflecting a state of at most a few seconds. We here aimed to induce longer lasting emotional states using blocks of repetitive visual, auditory, and bimodal stimuli corresponding to specific valence and arousal levels. The duration of thes...
Article
Full-text available
Moderne militaire operaties doen vanwege hun grote verscheidenheid aan stressoren een sterk beroep op de ‘mentale component’ van militair vermogen. Om optimaal te kunnen blijven presteren tijdens operaties, en om ook na uitzendingen gezond te blijven is het van belang dat militairen mentaal veerkrachtig zijn. De auteurs beschrijven een nieuw model...
Conference Paper
Full-text available
Both bio- and neurofeedback (training) protocols are hypothesized to be beneficial in the management of arousal states and psychological recuperation after aversive and potentially traumatic experiences. As military deployments in theatres like Iraq or Afghanistan imply an significant risk for potentially traumatic experiences and stress related ou...
Article
Full-text available
Reward-based decision-learning refers to the process of learning to select those actions that lead to rewards while avoiding actions that lead to punishments. This process, known to rely on dopaminergic activity in striatal brain regions, is compromised in Parkinson's disease (PD). We hypothesized that such decision-learning deficits are alleviated...
Article
Learning to select optimal behavior in new and uncertain situations is a crucial aspect of living and requires the ability to quickly associate stimuli with actions that lead to rewarding outcomes. Mathematical models of reinforcement-based learning to select rewarding actions distinguish between (1) the formation of stimulus-action-reward associat...
Article
Increasing evidence suggests that the control of retrieval of episodic feature bindings is modulated by the striatal dopaminergic pathway. The present study investigated whether this may reflect a contribution from the ventral or the dorsal part of the striatum. Along the lines of the overdose hypothesis in Parkinson's disease (PD), functions known...
Conference Paper
Full-text available
Reliable applications of affective brain-computer interfaces (aBCI) in realistic, multi-modal environments require a detailed understanding of the processes involved in emotions. To explore the modality-specific nature of affective responses, we studied neurophysiological responses (i.e., EEG) of 24 participants during visual, auditory, and audiovi...
Article
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During military operations soldiers often encounter extreme environmental circumstances like heat, cold, prolonged physical exercise, and disturbed sleep, which hamper their performance. Monitoring changes in physiological parameters may assist with adequate interventions to prevent the negative consequences and support recovery. The current study...
Article
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Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD). We determined computational measures of outcome eva...
Article
Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson's disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson's disease (n = 17) on performance in a Simon task...
Article
Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson’s disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson’s disease (n = 17) on performance in a Simon task...
Article
Full-text available
The ability to interact with a constantly changing environment requires a balance between maintaining the currently relevant working memory content and being sensitive to potentially relevant new information that should be given priority access to working memory. Mesocortical dopamine projections to frontal brain areas modulate working memory maint...
Article
Full-text available
The inhibitory control of actions has been claimed to rely on dopaminergic pathways. Given that this hypothesis is mainly based on patient and drug studies, some authors have questioned its validity and suggested that beneficial effects of dopaminergic stimulants on response inhibition may be limited to cases of suboptimal inhibitory functioning. W...
Article
Decision making often involves using prior contextual information to evaluate relevant events. A laboratory equivalent of context processing situations, the AX-Continuous Performance Task (AX-CPT), yields errors when a target probe appears in a nontarget context, or when a nontarget probe appears in a target context. According to goal-driven accoun...
Article
The primate cortex represents the external world in a distributed way, which requires for a mechanism that integrates the features of a processed event. Animal and patients studies suggest that feature binding in the visual cortex is under muscarinic-cholinergic control, whereas visuomotor integration is driven by the dopaminergic system. Consisten...
Article
The primate cortex represents the external world in a distributed fashion, which calls for a mechanism that integrates and binds the features of a perceived or processed event. Animal and patients studies provide evidence that feature binding in the visual cortex is driven by the muscarinic-cholinergic system, whereas visuo-motor integration may be...
Article
Full-text available
People integrate the features of perceived events and of action plans, as well as of episodic stimulus-response relations, into event files. We investigated whether the management of event files, and particularly the speed of updating the binding between the task-relevant stimulus feature and the response, correlates with fluid intelligence. Indeed...
Article
Top-down guidance of behavior in a complex and dynamically changing world is often based on information held in working memory. Such guidance serves to bias decision-making processes in directions consistent with externally set rules or internally maintained intentions. Orthogonal to this goal-driven guidance, decisions may be biased also by stimul...

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