Caroline Seer

Event-Related Potentials and Cognition in Parkinson's Disease: An Integrative Review.

Cognitive impairment is a common non-motor symptom of Parkinsons disease (PD), but the nature of cognitive changes varies considerably between individuals. According to the dual-syndrome hypothesis, one cluster of patients is characterized by deficits in executive function that may be related to fronto-striatal dysfunction. Other patients primarily show non-frontal cognitive impairments that progress rapidly to PD dementia (PDD). We provide a comprehensive review of event-related potential (ERP) studies to identify ERP measures substantiating the heterogeneity of cognitive impairment in PD. Our review revealed evidence for P3b and mismatch-negativity alterations in PDD, but not in non-demented PD, indicating that alterations of these ERPs constitute electrophysiological markers for PDD. In contrast, ERP correlates of executive functions, such as NoGo-P3, N2, and error(-related) negativity (Ne/ERN), appear to be attenuated in non-demented PD patients in a dopamine-dependent manner. Hence, ERP measures confirm and yield distinct electrophysiological markers for the heterogeneity of cognitive impairment in PD. We discuss limitations and open questions of the ERP approach and provide directions and predictions for future ERP research.

Cognitive caching promotes flexibility in task switching: evidence from event-related potentials.

Time-consuming processes of task-set reconfiguration have been shown to contribute to the costs of switching between cognitive tasks. We describe and probe a novel mechanism serving to reduce the costs of task-set reconfiguration. We propose that when individuals are uncertain about the currently valid task, one task set is activated for execution while other task sets are maintained at a pre-active state in cognitive cache. We tested this idea by assessing an event-related potential (ERP) index of task-set reconfiguration in a three-rule task-switching paradigm involving varying degrees of task uncertainty. In high-uncertainty conditions, two viable tasks were equally likely to be correct whereas in low-uncertainty conditions, one task was more likely than the other. ERP and performance measures indicated substantial costs of task-set reconfiguration when participants were required to switch away from a task that had been likely to be correct. In contrast, task-set-reconfiguration costs were markedly reduced when the previous task set was chosen under high task uncertainty. These results suggest that cognitive caching of alternative task sets adds to human cognitive flexibility under high task uncertainty.

Dual routes to cortical orienting responses: novelty detection and uncertainty reduction.

Sokolov distinguished between reactive and proactive variants of the orienting response (OR). The Novelty P3 is considered as an electrophysiological signature of the reactive OR. Recent work suggests that the proactive OR is reflected in frontally distributed P3 activity elicited by uncertainty-reducing stimuli in task-switching paradigms. Here, we directly compare the electrophysiological signatures of reactive and proactive ORs. Participants completed a novelty oddball task and a task-switching procedure while the electroencephalogram was measured. Novel and uncertainty-reducing stimuli evoked prominent fronto-centrally distributed Novelty P3 and Uncertainty P3 waves, respectively. We found a substantial negative correlation between Novelty P3 and Uncertainty P3 across participants, suggesting that reactive and proactive ORs converge on a common neural pathway, but also that distinguishable routes to orienting exist. Moreover, response accuracy was associated with reduced Novelty-P3 and enhanced Uncertainty-P3 amplitudes. The relation between Novelty P3 and Uncertainty P3 might serve as an index of individual differences in distractibility and cognitive control.

Meta-analytical and electrophysiological evidence for executive dysfunction in primary dystonia

Impaired motor control in primary dystonia has been linked to cortico-basal ganglia alterations that may also give rise to changes in executive functioning. However, no conclusive evidence for executive dysfunction in patients with primary dystonia has been reported yet. We conducted a meta-analysis of the relationship between primary dystonia and performance on the Wisconsin Card Sorting Test (WCST), an established test of executive functioning. Its results revealed a significant effect of medium size, indicating that primary dystonia is associated with moderate performance deficits on the WCST. Building on this finding, we conducted an event-related potential (ERP) study to elucidate the cognitive and neural mechanisms underlying executive dysfunction in primary dystonia. Eighteen patients with blepharospasm, a common form of primary focal dystonia, and 34 healthy matched controls completed a computerized version of the WCST. We specifically compared indicators of two distinct components of executive functioning: set shifting and rule inference. On a behavioral level, blepharospasm patients seemed to have particular difficulty integrating information to infer the correct task rule. In addition, P3a amplitude (as an electrophysiological marker of rule-inference processes) was selectively attenuated in blepharospasm patients. Executive dysfunction in blepharospasm can thus rather be attributed to a rule-inference deficit, whereas set-shifting abilities appear to be relatively unaffected by the disease. Moreover, P3a amplitude attenuation was related to disease duration, indicating that this ERP might serve as a neural indicator of disease progression and executive dysfunction in primary dystonia. These results demonstrate for the first time that pathophysiological alterations in primary dystonia might affect cortical activation for executive functioning.

Decomposing card-sorting performance: Effects of working memory load and age-related changes.

OBJECTIVE The Wisconsin Card Sorting Test (WCST) is often regarded as a prototypical neuropsychological test of set-shifting ability. However, it has been proposed that WCST performance involves cognitive processes other than set shifting, such as set maintenance and rule inference. Distinguishing between these processes is necessary for the meaningful interpretation of WCST performance deficits in neuropsychological populations. In the present studies, we aimed to concurrently measure processes of set shifting, set maintenance and rule inference in a computerized version of the WCST, and to dissociate these processes based on their dependence on working memory capacity. METHOD AND RESULTS In Study 1, we manipulated the number of card-sorting rules to vary the demands placed on working memory-dependent processes of rule inference. As predicted, integration errors as a novel measure of rule-inference efficiency were selectively affected by increasing the number of rules from 3 to 4. In Study 2, we examined age-related changes in set shifting, set maintenance, and rule inference. We found a specific association between age and integration errors, indicating that rule inference, but not set shifting or set maintenance, is affected in older individuals. CONCLUSIONS Rule inference on WCST-like card-sorting tasks appeared to be selectively impaired when the amount of information to be integrated in working memory increases or when working memory capacity is reduced (as in older individuals). Our findings indicate that measuring integration errors as an index of a distinct rule-inference process can improve the understanding and interpretability of WCST performance. (PsycINFO Database Record

Neural mechanisms underlying cognitive inflexibility in Parkinson's disease

Cognitive inflexibility is a hallmark of executive dysfunction in Parkinsons disease (PD). This deficit consistently manifests itself in a PD-related increase in the number of perseverative errors committed on the Wisconsin Card Sorting Test (WCST). However, the neural processes underlying perseverative WCST performance in PD are still largely unknown. The present study is the first to investigate the event-related potential (ERP) correlates of cognitive inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched control participants completed a computerized version of the WCST while the electroencephalogram (EEG) was recorded. Behavioral results revealed the expected increase in perseverative errors in patients with PD. ERP analysis focused on two established indicators of executive processes: the fronto-central P3a as an index of attentional orienting and the sustained parietal positivity (SPP) as an index of set-shifting processes. In comparison to controls, P3a amplitudes were significantly attenuated in PD patients. Regression analysis further revealed that P3a and SPP amplitudes interactively contributed to the prediction of perseverative errors in PD patients: The number of perseverative errors was only increased when both ERP amplitudes were attenuated. Notably, the two ERP markers of executive processes accounted for more than 40% of the variance in perseverative errors in PD patients. We conclude that cognitive inflexibility in PD occurs when the neural bases of multiple executive processes are affected by the pathophysiology of PD. The combined measurement of P3a and SPP might yield an electrophysiological marker of cognitive inflexibility in PD.

Executive Dysfunctions and Event-Related Brain Potentials in Patients with Amyotrophic Lateral Sclerosis.

A growing body of evidence implies psychological disturbances in amyotrophic lateral sclerosis (ALS). Specifically, executive dysfunctions occur in up to 50% of ALS patients. The recently shown presence of cytoplasmic aggregates (TDP-43) in ALS patients and in patients with behavioral variants of frontotemporal dementia suggests that these two disease entities form the extremes of a spectrum. The present study aimed at investigating behavioral and electrophysiological indices of conflict processing in patients with ALS. A non-verbal variant of the flanker task demanded two-choice responses to target stimuli that were surrounded by flanker stimuli which either primed the correct response or the alternative response (the latter case representing the conflict situation). Behavioral performance, event-related potentials (ERP), and lateralized readiness potentials (LRP) were analyzed in 21 ALS patients and 20 controls. In addition, relations between these measures and executive dysfunctions were examined. ALS patients performed the flanker task normally, indicating preserved conflict processing. In similar vein, ERP and LRP indices of conflict processing did not differ between groups. However, ALS patients showed enhanced posterior negative ERP waveform deflections, possibly indicating increased modulation of visual processing by frontoparietal networks in ALS. We also found that the presence of executive dysfunctions was associated with more error-prone behavior and enhanced LRP amplitudes in ALS patients, pointing to a prefrontal pathogenesis of executive dysfunctions and to a potential link between prefrontal and motor cortical functional dysregulation in ALS, respectively.

Cognitive Flexibility in Primary Dystonia.

Objectives Although primary dystonia is typically characterized as a movement disorder, it is also associated with cognitive alterations in the domain of executive functioning which may arise from changes in cortico-basal ganglia circuits. Specifically, in comparison to healthy controls, patients with dystonia show deficits in neuropsychological tests of cognitive flexibility. However, it is unclear whether cognitive inflexibility is caused by the pathomechanisms underlying primary dystonia or by confounding factors such as depression or symptom-related distraction.Methods The present study aimed to eliminate these confounds by examining cognitive flexibility in dystonia patients and in patients with similar motor symptoms but without a comparable central pathophysiology. Eighteen patients with primary blepharospasm, a common form of dystonia affecting the muscles around the eyes, and 19 patients with hemifacial spasm, a facial nerve disorder causing similar eyelid spasms, completed a computerized version of the Wisconsin Card Sorting Test (cWCST). The two groups were further compared on tests of global cognitive functioning, psychiatric symptoms, health status, and impulsiveness. Results Blepharospasm patients committed significantly more errors on the cWCST than patients with hemifacial spasm. Group differences were most pronounced with regard to integration errors, a measure of rule-inference processes on the cWCST. Integration errors were also associated with impulsiveness in patients with blepharospasm. Conclusions Primary blepharospasm is related to deficits in cognitive flexibility, even when blepharospasm patients are compared with patients who suffer from motor symptoms of non-dystonic origin. Our results support the possibility that cognitive inflexibility results from the specific pathophysiological processes underlying primary dystonia. (JINS, 2016, 22, 662-670).

Movement-related potentials in Parkinson’s disease

To date, many different approaches have been used to study the impairment of motor function in Parkinsons disease (PD). Event-related potentials (ERPs) are averaged amplitude fluctuations of the ongoing EEG activity that are time locked to specific sensory, motor or cognitive events, and as such can be used to study different brain processes with an excellent temporal resolution. Movement-related potentials (MRPs) are ERPs associated with processes of voluntary movement preparation and execution in different paradigms. In this review we concentrate on MRPs in PD. We review studies recording the Bereitschaftspotential, the Contingent Negative Variation, and the lateralized readiness potential in PD to highlight the contributions they have made to further understanding motor deficits in PD. Possible directions for future research are also discussed.

Neural correlates of cognitive set shifting in amyotrophic lateral sclerosis

OBJECTIVE Amyotrophic lateral sclerosis (ALS) has been associated with executive dysfunction, particularly in the domain of cognitive set shifting. In a recent event-related potential (ERP) study, shifting-related cortical activity on a complex set-shifting paradigm was found to be attenuated in patients with ALS. Here, we investigated whether this ERP change could also be observed in a simplified set-shifting task adapted for potential clinical use, and in ALS patients without overt cognitive impairment. METHODS Twenty-six patients and 28 matched healthy controls (HC) completed a set-shifting paradigm involving two task rules and explicit task cues. Cue-locked ERPs were analyzed. RESULTS ALS patients and HC did not differ in response latency or accuracy. In HC, cues that required shifting task rules elicited more positive parietal ERP waveforms than cues that signaled a rule repetition. This shifting-related amplitude modulation was absent in patients with ALS. The attenuation of ERP activity in ALS patients remained significant when participants with possible cognitive impairment were excluded. CONCLUSIONS Electrophysiological measures can detect ALS-related changes in the neural substrates of set shifting even when these changes do not become apparent in neuropsychological assessment. SIGNIFICANCE These findings illustrate the potential utility of ERPs as indicators of cognitive change in ALS.