ABSTRACT
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 electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends, and family in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.
Subject(s)
Brain , Social Behavior , Humans , PrivacyABSTRACT
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). The current study investigated whether ET impacts conflict control proficiency. Forty-one ET patients and 29 age-matched healthy controls (HCs) performed a conflict control task (Simon task). Participants were instructed to give a left or right response to a spatially lateralized arrow (direction of the arrow). When the action signaled by the spatial location and direction of the arrow were non-corresponding (induced conflict), the inappropriate action impulse required suppression. Overall, ET patients responded slower and less accurately compared to HCs. ET patients were especially less accurate on non-corresponding conflict (Nc) versus corresponding (Cs) trials. A focused analysis on fast impulsive response rates (based on the accuracy rate at the fastest reaction times on Nc trials) showed that ET patients made more fast errors compared to HCs. Results suggest impaired conflict control in ET compared to HCs. The increased impulsive errors seen in the ET population may be a symptom of deficiencies in the cerebello-thalamocortical networks, or, be caused by indirect effects on the cortico-striatal pathways. Future studies into the functional networks impacted by ET (cortico-striatal and cerebello-thalamocortical pathways) could advance our understanding of inhibitory control in general and the cognitive deficits in ET.
Subject(s)
Essential Tremor , Cerebellum , Humans , Impulsive Behavior/physiology , Reaction Time/physiologyABSTRACT
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 components of action control in FMD by using choice-reaction, stop-signal, and Simon tasks. METHODS: Thirty patients with an FMD were prospectively recruited from the University of Louisville Movement Disorders Clinic and compared with 53 healthy control subjects, recruited from the Vanderbilt University Medical Center Movement Disorders Clinic. FMD motor symptom severity was rated with the Simplified Functional Movement Disorder Rating Scale (S-FMDRS). By using a computer and handheld response grips, participants completed three action-control tasks (choice-reaction task, stop-signal task, and Simon task) that tested action initiation, action cancelation, and interference control over actions. Action-control measures were compared between groups with analyses of variance. RESULTS: Patients with FMD were less proficient in suppressing incorrect response impulses on the Simon task and were slower to stop on the stop-signal task compared with healthy control subjects. No significant correlation with neuropsychological measurements, S-FMDRS scores, and action-control measurements was observed. CONCLUSIONS: These results suggest that two forms of inhibitory control, selective impulse inhibition and global action cancelation, are impaired in patients with FMD, independent of slowing on go reaction times. Improved understanding of action control in FMD may help in the development of new diagnostic and therapeutic strategies.
Subject(s)
Conversion Disorder/physiopathology , Executive Function/physiology , Inhibition, Psychological , Motor Activity/physiology , Movement Disorders/physiopathology , Psychomotor Performance/physiology , Psychophysiologic Disorders/physiopathology , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3 receptor 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 proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n = 17) and without (n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [18F]fallypride, a high affinity D2-like receptor ligand that can measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BPND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D2/3 receptor BPND Group differences in regional D2/3 BPND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BPNDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.SIGNIFICANCE STATEMENT The biologic determinants of compulsive reward-based behaviors have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease patients with impulsive compulsive behaviors (ICBs). This is the first study to image a large cohort of ICB+ patients using positron emission tomography with [18F]fallypride, allowing quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in dopaminergic networks, including (1) D2-like receptor distinctions in the ventral striatum and putamen, and (2) a preservation of widespread dopaminergic projections emerging from the midbrain, which is associated with the severity of compulsive behaviors. This clearly illustrates the roles of D2/3 receptors and medication effects in maladaptive behaviors, and localizes them specifically to nigrostriatal and extrastriatal regions.
Subject(s)
Compulsive Behavior/diagnostic imaging , Limbic System/metabolism , Parkinson Disease/diagnostic imaging , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Substantia Nigra/metabolism , Aged , Benzamides , Compulsive Behavior/etiology , Compulsive Behavior/metabolism , Dopamine Agonists/pharmacology , Dopamine D2 Receptor Antagonists/pharmacology , Female , Humans , Limbic System/diagnostic imaging , Limbic System/drug effects , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/metabolism , Positron-Emission Tomography , Radiopharmaceuticals , Reward , Substantia Nigra/diagnostic imaging , Substantia Nigra/drug effectsABSTRACT
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 navigating many daily life situations such as driving or social interactions. The current study investigated the speed of action initiation and two forms of action control, response stopping and proactive slowing in ET. METHODS: Thirty-three ET patients and 25 healthy controls (HCs) completed a choice reaction task and a stop-signal task, and measures of going speed, proactive slowing and stop latencies were assessed. RESULTS: Going speed was significantly slower in ET patients (649 ms) compared to HCs (526 ms; F(1,56) = 42.37; p <.001; η 2 = .43), whereas proactive slowing did not differ between groups. ET patients exhibited slower stop signal reaction times (320 ms) compared to HCs (258 ms, F(1,56) = 15.3; p <.00; η 2 = .22) and more severe motor symptoms of ET were associated with longer stopping latencies in a subset of patients (Spearman rho = .48; p <.05). CONCLUSIONS: In line with previous studies, ET patients showed slower action initiation. Additionally, inhibitory control was impaired whereas proactive slowing remained intact relative to HCs. More severe motor symptoms of ET were associated with slower stopping speed, and may reflect more progressive changes to the cerebellar-thalamo-cortical network. Future imaging studies should specify which structural and functional changes in ET can explain changes in inhibitory action control. (JINS, 2019, 25, 156-164).
Subject(s)
Essential Tremor/physiopathology , Executive Function/physiology , Inhibition, Psychological , Psychomotor Performance/physiology , Reaction Time/physiology , Aged , Female , Humans , Male , Middle AgedABSTRACT
Learning the contingencies between stimulus, action, and outcomes is disrupted in disorders associated with altered dopamine (DA) function in the BG, such as Parkinson 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 is not as well understood. The current study investigated the role of DA in learning to act or to withhold action to receive rewarding, or avoid punishing outcomes, in patients with PD tested "off" and "on" dopaminergic medication (n = 19) versus healthy controls (n = 30). Participants performed a reward-based learning task that orthogonalized action and outcome valence (action-reward, inaction-reward, action-punishment, inaction-punishment). We tested whether DA would bias learning toward action, toward reward, or to particular action-outcome interactions. All participants demonstrated inherent learning biases preferring action with reward and inaction to avoid punishment, and this was unaffected by medication. Instead, DA produced a complex modulation of learning less natural action-outcome associations. "Off" DA medication, patients demonstrated impairments in learning to withhold action to gain reward, suggesting a difficulty to overcome a bias toward associating inaction with punishment avoidance. On DA medication, these patterns changed, and patients showed a reduced ability to learn to act to avoid punishment, indicating a bias toward action and reward. The current findings suggest that DA in PD has a complex influence on the formation of action-outcome associations, particularly those involving less natural linkages between action and outcome valence.
Subject(s)
Association , Dopamine Agents/pharmacology , Dopamine/physiology , Inhibition, Psychological , Motor Activity/physiology , Parkinson Disease/physiopathology , Punishment , Reward , Adult , Female , Humans , Male , Motor Activity/drug effects , Parkinson Disease/drug therapy , Young AdultABSTRACT
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 hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.
Subject(s)
Cerebral Cortex , Cerebrovascular Circulation/drug effects , Dopamine Agonists/adverse effects , Impulsive Behavior/drug effects , Parkinson Disease/drug therapy , Periaqueductal Gray , Ventral Striatum , Aged , Animals , Cerebral Cortex/blood supply , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/drug effects , Female , Humans , Impulsive Behavior/physiology , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Periaqueductal Gray/blood supply , Periaqueductal Gray/diagnostic imaging , Periaqueductal Gray/drug effects , Severity of Illness Index , Spin Labels , Ventral Striatum/blood supply , Ventral Striatum/chemistry , Ventral Striatum/diagnostic imaging , Ventral Striatum/drug effectsABSTRACT
Dopamine plays a key role in a range of action control processes. Here, we investigate how dopamine depletion caused by Parkinson 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 task). PD patients completed the task twice, once withdrawn from dopamine medications and once while taking their medications. PD patients experienced similar susceptibility to making fast errors in conflict trials as HCs, but PD patients were less proficient compared with HCs at suppressing incorrect responses. Administration of dopaminergic medications had no effect on impulsive error rates but significantly improved the proficiency of inhibitory control in PD patients. We found no evidence that dopamine precursors and agonists affected action control in PD differently. Additionally, there was no clear evidence that individual differences in baseline action control (off dopamine medications) differentially responded to dopamine medications (i.e., no evidence for an inverted U-shaped performance curve). Together, these results indicate that dopamine depletion and restoration therapies directly modulate the reactive inhibitory control processes engaged to suppress interference from the spontaneously activated response impulses but exert no effect on an individual's susceptibility to act on impulses.
Subject(s)
Dopamine Agonists/therapeutic use , Impulsive Behavior/physiology , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Reactive Inhibition , Visual Perception/physiology , Aged , Dopamine Agonists/pharmacology , Female , Humans , Impulsive Behavior/drug effects , Individuality , Male , Middle Aged , Neuropsychological Tests , Photic Stimulation , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Reaction Time/drug effects , Reaction Time/physiology , Visual Perception/drug effectsABSTRACT
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 risks and outcomes are known explicitly. We investigated how risk decision-making strategies and adjustments are altered in HD patients when reward contingencies are explicit. METHODS: HD (N=18) and healthy control (HC; N=17) participants completed a risk-taking task in which they made a series of independent choices between a low-risk/low reward and high-risk/high reward risk options. RESULTS: Computational modeling showed that compared to HC, who showed a clear preference for low-risk compared to high-risk decisions, the HD group valued high-risks more than low-risk decisions, especially when high-risks were rewarded. The strategy analysis indicated that when high-risk options were rewarded, HC adopted a conservative risk strategy on the next trial by preferring the low-risk option (i.e., they counted their blessings and then played the surer bet). In contrast, following a rewarded high-risk choice, HD patients showed a clear preference for repeating the high-risk choice. CONCLUSIONS: These results indicate a pattern of high-risk/high-reward decision bias in HD that persists when outcomes and risks are certain. The allure of high-risk/high-reward decisions in situations of risk certainty and uncertainty expands our insight into the dynamic decision-making deficits that create considerable clinical burden in HD.
Subject(s)
Cognition Disorders/etiology , Huntington Disease/complications , Huntington Disease/psychology , Reward , Risk-Taking , Adult , Decision Making/physiology , Female , Humans , Male , Middle Aged , Neuropsychological TestsABSTRACT
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 TS were slower at stopping their manual and vocal responses. While alterations in inhibitory motor control may not be a generalizable phenomenon in TS, these results add to an emerging literature suggesting that individuals with relatively uncomplicated TS, whose symptoms persist into adulthood, show disruption to inhibitory control mechanisms.
ABSTRACT
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 inhibition of motor actions. We asked whether PD patients who show freezing of gait show selective deficits in their ability to inhibit upper and lower extremity reactions. We compared older healthy controls, older PD controls without freezing of gait, and older PD participants with freezing of gait, in stop-signal tasks that measured the initiation (go trials) and inhibition (stop trials) of both hand and foot responses. When only go trials were presented, all three groups showed similar initiation speeds across lower and upper extremity responses. When stop-signal trials were introduced, both PD groups slowed their reactions nearly twice as much as healthy controls. While this adjustment helped PD controls stop their actions as quickly as healthy controls, PD patients with freezing showed significantly delayed inhibitory control of both upper and lower extremities. When anticipating the need to stop their actions urgently, PD patients show greater adjustments (i.e., slowing) to reaction speed than healthy controls. Despite these proactive adjustments, PD patients who freeze show marked impairments in inhibiting both upper and lower extremity responses, suggesting that freezing may involve a fundamental disruption to the brain's inhibitory control system.
Subject(s)
Inhibition, Psychological , Motor Activity/physiology , Parkinson Disease/physiopathology , Aged , Female , Foot/physiopathology , Gait Disorders, Neurologic/physiopathology , Hand/physiopathology , Humans , Male , Middle Aged , Parkinson Disease/psychology , Reaction TimeABSTRACT
Deep brain stimulation of the subthalamic nucleus is an effective treatment for the clinical motor symptoms of Parkinson's disease, but may alter the ability to learn contingencies between stimuli, actions and outcomes. We investigated how stimulation of the functional subregions in the subthalamic nucleus (motor and cognitive regions) modulates stimulus-action-outcome learning in Parkinson's disease patients. Twelve Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus completed a probabilistic stimulus-action-outcome task while undergoing ventral and dorsal subthalamic nucleus stimulation (within subjects, order counterbalanced). The task orthogonalized action choice and outcome valence, which created four action-outcome learning conditions: action-reward, inhibit-reward, action-punishment avoidance and inhibit-punishment avoidance. We compared the effects of deep brain stimulation on learning rates across these conditions as well as on computed Pavlovian learning biases. Dorsal stimulation was associated with higher overall learning proficiency relative to ventral subthalamic nucleus stimulation. Compared to ventral stimulation, stimulating the dorsal subthalamic nucleus led to a particular advantage in learning to inhibit action to produce desired outcomes (gain reward or avoid punishment) as well as better learning proficiency across all conditions providing reward opportunities. The Pavlovian reward bias was reduced with dorsal relative to ventral subthalamic nucleus stimulation, which was reflected by improved inhibit-reward learning. Our results show that focused stimulation in the dorsal compared to the ventral subthalamic nucleus is relatively more favourable for learning action-outcome contingencies and reduces the Pavlovian bias that could lead to reward-driven behaviour. Considering the effects of deep brain stimulation of the subthalamic nucleus on learning and behaviour could be important when optimizing stimulation parameters to avoid side effects like impulsive reward-driven behaviour.
ABSTRACT
BACKGROUND: Deep brain stimulation (DBS) for Parkinson disease 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. Preoperative factors that could predict VF decline have yet to be identified. OBJECTIVE: To develop predictive models of DBS postoperative VF decline using a machine learning approach. METHODS: We used a prospective database of patients who underwent neuropsychological and VF assessment before both subthalamic nucleus (n = 47, bilateral = 44) and globus pallidus interna (n = 43, bilateral = 39) DBS. We used a neurobehavioral rating profile as features for modeling postoperative VF. We constructed separate models for action, semantic, and letter VF. We used a leave-one-out scheme to test the accuracy of the predictive models using median absolute error and correlation with actual postoperative scores. RESULTS: The predictive models were able to predict the 3 types of VF with high accuracy ranging from a median absolute error of 0.92 to 1.36. Across all three models, higher preoperative fluency, digit span, education, and Mini-Mental State Examination were predictive of higher postoperative fluency scores. By contrast, higher frontal system deficits, age, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease scored by the patient, disease duration, and Behavioral Inhibition/Behavioral Activation Scale scores were predictive of lower postoperative fluency scores. CONCLUSION: Postoperative VF can be accurately predicted using preoperative neurobehavioral rating scores above and beyond preoperative VF score and relies on performance over different aspects of executive function.
Subject(s)
Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Deep Brain Stimulation/adverse effects , Globus Pallidus , Humans , Neuropsychological Tests , Parkinson Disease/surgery , Subthalamic Nucleus/physiologyABSTRACT
OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment to improve motor symptoms in Parkinson's disease (PD). The Globus Pallidus (GPi) and the Subthalamic Nucleus (STN) are the most targeted brain regions for stimulation and produce similar improvements in PD motor symptoms. However, our understanding of stimulation effects across targets on inhibitory action control processes is limited. We compared the effects of STN (n = 20) and GPi (n = 13) DBS on inhibitory control in PD patients. METHODS: We recruited PD patients undergoing DBS at the Vanderbilt Movement Disorders Clinic and measured their performance on an inhibitory action control task (Simon task) before surgery (optimally treated medication state) and after surgery in their optimally treated state (medication plus their DBS device turned on). RESULTS: DBS to both STN and GPi targets induced an increase in fast impulsive errors while simultaneously producing more proficient reactive suppression of interference from action impulses. CONCLUSIONS: Stimulation in GPi produced similar effects as STN DBS, indicating that stimulation to either target increases the initial susceptibility to act on strong action impulses while concomitantly improving the ability to suppress ongoing interference from activated impulses. SIGNIFICANCE: Action impulse control processes are similarly impacted by stimulating dissociable nodes in frontal-basal ganglia circuitry.
Subject(s)
Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Subthalamic Nucleus/physiology , Globus Pallidus/physiology , Parkinson Disease/therapy , Treatment OutcomeABSTRACT
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 maintenance and flexibility. Recent neurocognitive and neurocomputational work suggests that dopamine release is transiently enhanced by induced positive affect. This ERP study investigated the role of positive affect in different aspects of information processing: in proactive control (context maintenance and updating), reactive control (flexible adaptation to incoming task-relevant information), and evaluative control in an AX-CPT task. Subjects responded to a target probe if it was preceded by a specific cue. Induced positive affect influenced the reactive and evaluative components of control (indexed by the N2 elicited by the target and by the error-related negativity elicited after incorrect responses, respectively), whereas cue-induced proactive preparation and maintenance processes remained largely unaffected (as reflected in the P3b and the contingent negative variation components of the ERP).
Subject(s)
Affect/physiology , Brain/physiology , Evoked Potentials/physiology , Adult , Analysis of Variance , Contingent Negative Variation/physiology , Electroencephalography , Female , Humans , Male , Memory, Short-Term/physiology , Photic Stimulation , Reaction Time/physiologyABSTRACT
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. In this reaction time task, conflict between premature response impulses and goal-directed action selection is manipulated. We applied distributional analytic methods to separate the strength of the initial response impulse from the proficiency of inhibitory control engaged subsequently to suppress the impulse. Patients with Parkinson's disease were tested when stimulation was either turned on or off. Mean conflict interference effects did not differ between controls and patients, or within patients when stimulation was on versus off. In contrast, distributional analyses revealed two dissociable effects of subthalamic nucleus stimulation. Fast response errors indicated that stimulation increased impulsive, premature responding in high conflict situations. Later in the reaction process, however, stimulation improved the proficiency with which inhibitory control was engaged to suppress these impulses selectively, thereby facilitating selection of the correct action. This temporal dissociation supports a conceptual framework for resolving past paradoxical findings and further highlights that dynamic aspects of impulse and inhibitory control underlying goal-directed behaviour rely in part on neural circuitry inclusive of the subthalamic nucleus.
Subject(s)
Deep Brain Stimulation/adverse effects , Impulsive Behavior/psychology , Parkinson Disease/psychology , Subthalamic Nucleus/physiology , Aged , Cognition/physiology , Female , Humans , Impulsive Behavior/etiology , Inhibition, Psychological , Male , Middle Aged , Parkinson Disease/therapy , Prefrontal Cortex/physiology , Psychomotor Performance/physiology , Reaction Time/physiologyABSTRACT
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 was employed to reduce the number of measurement instruments to monitor physiological variables, especially with respect to adequate sleep prediction. We compared three instruments with respect to their effectiveness in predicting sleep; the Equivital, Sensewear, and Actiwatch. Additionally, we investigated the added value of cardio-respiratory to accelerometer signals to estimate sleep duration. The Equivital model (based on acceleration data) and Sensewear predict sleep and wake as accurate as the commonly used Actiwatch model, and the cardio-respiratory Equivital data further improve accuracy and specificity. In sum, the current study provides an indication that the Equivital system (or any other chestband that measures 3-dimensional acceleration plus other physiological variables) might be interchanged with an Actiwatch for sleep prediction.
Subject(s)
Polysomnography/instrumentation , Signal Processing, Computer-Assisted/instrumentation , Sleep/physiology , Wakefulness/physiology , Adult , HumansABSTRACT
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. Sixteen patients diagnosed with Parkinson's disease (PD) and 16 healthy control participants (HC) performed the stop-change task. PD patients completed the task when deep-brain stimulation (DBS) of the STN was turned on and when it was turned off. Behavioral results indicated that going, stopping, and changing latencies were shortened significantly among PD patients during STN DBS, the former two reductions replicating findings from previous DBS studies using the classic stop-signal task. The shortened go latencies observed among PD patients fell within the control range. In contrast, stopping latencies among PD patients, although reduced significantly, continued to be significantly longer than those of the HC. Like go latencies, stop-change latencies were reduced sufficiently among PD patients for them to fall within the control range, a novel finding. In conclusion, STN DBS produced a general, but differential, improvement in the ability of PD patients to override motor actions. Going, stopping, and stop-change latencies were all shortened, but only going and stop-change latencies were normalized.
Subject(s)
Deep Brain Stimulation , Executive Function/physiology , Inhibition, Psychological , Motor Activity/physiology , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Psychomotor Performance/physiology , Subthalamic Nucleus/physiopathology , Aged , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
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 subthalamic nucleus (STN) or the globus pallidus interna (GPi) contribute to changes in verbal fluency. We predicted that electrode location in the left hemisphere would be linked to changes in fluency, especially in the STN. METHODS: Forty PD participants treated with bilateral DBS targeting STN (n = 23) or GPi (n = 17) completed verbal fluency testing in their optimally treated state before and after DBS therapy. Normalized atlas coordinates from left and right active electrode positions along superior/inferior, anterior/posterior, and lateral/medial axes were used to predict changes in fluency postoperatively, separately for patients with STN and GPi targets. RESULTS: Consistent with prior studies, fluency significantly declined pre- to postsurgery (in both DBS targets). In STN-DBS patients, electrode position along the inferior to superior axis in the left STN was a significant predictor of fluency changes; relatively more superior left active electrode was associated with the largest fluency declines in STN. Electrode coordinates in right STN or GPi (left or right) did not predict fluency changes. INTERPRETATION: We discuss these findings in light of putative mechanisms and potential clinical impact.
Subject(s)
Cognitive Dysfunction/etiology , Deep Brain Stimulation , Globus Pallidus , Implantable Neurostimulators , Parkinson Disease/drug therapy , Postoperative Complications , Subthalamic Nucleus , Aged , Deep Brain Stimulation/adverse effects , Female , Functional Laterality , Humans , Implantable Neurostimulators/adverse effects , Male , Middle Aged , Neuropsychological TestsABSTRACT
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 precise role of the STN in stopping control is unclear. The STN consists of functional subterritories linked to dissociable cortical networks, although the boundaries of the subregions are still under debate. We investigated whether stimulating the dorsal and ventral subregions of the STN would show dissociable effects on ability to stop. We studied 12 PD patients with STN DBS. Patients with two adjacent contacts positioned within the bounds of the dorsal and ventral STN completed two testing sessions (OFF medication) with low amplitude stimulation (0.4 mA) at either the dorsal or ventral contacts bilaterally, while performing the stop task. Ventral, but not dorsal, DBS improved stopping latencies. Go reactions were similar between dorsal and ventral DBS STN. Stimulation in the ventral, but not dorsal, subregion of the STN improved stopping speed, confirming the involvement of the STN in stopping control and supporting the STN functional subregions.