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Motor skill learning, the process of acquiring new motor skills, is critically important across the lifespan, from early development through adulthood and into older age, as well as in pathological conditions (i.e., rehabilitation). Extensive research has demonstrated that motor skill acquisition in young adults is accompanied by significant neuroplastic changes, including alterations in brain structure (gray and white matter), function (i.e., activity and connectivity), and neurochemistry (i.e., levels of neurotransmitters). In the aging population, motor performance typically declines, characterized by slower and less accurate movements. However, despite these age-related changes, older adults maintain the capacity for skill improvement through training. In this review, we explore the extent to which the aging brain retains the ability to adapt in response to motor learning, specifically whether skill acquisition is accompanied by neural changes. Furthermore, we discuss the associations between inter-individual variability in brain structure and function and the potential for future learning in older adults. Finally, we consider the use of non-invasive brain stimulation techniques aimed at optimizing motor learning in this population. Our review provides insights into the neurobiological underpinnings of motor learning in older adults and emphasizes strategies to enhance their motor skill acquisition., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Gooijers reports financial support was provided by Research Fund KU Leuven. S.P. Swinnen reports financial support was provided by Research Foundation Flanders. S.P. Swinnen reports financial support was provided by Excellence of Science. M. Hehl reports financial support was provided by Research Foundation Flanders. C. Seer reports financial support was provided by Research Foundation Flanders. M. Hehl reports financial support was provided by Research Fund KU Leuven. C. Seer reports financial support was provided by European Commission Marie Sklodowska-Curie Actions. S.P. Swinnen reports financial support was provided by Research Fund KU Leuven. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the 'GABA increase for better neural distinctiveness hypothesis'. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the 'GABA decrease to boost learning hypothesis', which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance., (© 2024. The Author(s).)

We aimed to investigate transfer of learning, whereby previously acquired skills impact new task learning. While it has been debated whether such transfer may yield positive, negative, or no effects on performance, very little is known about the underlying neural mechanisms, especially concerning the role of inhibitory (GABA) and excitatory (Glu) (measured as Glu + glutamine (Glx)) neurometabolites, as measured by magnetic resonance spectroscopy (MRS). Participants practiced a bimanual coordination task across four days. The Experimental group trained a task variant with the right hand moving faster than the left (Task A) for three days and then switched to the opposite variant (Task B) on Day4. The control group trained Task B across four days. MRS data were collected before, during, and after task performance on Day4 in the somatosensory (S1) and visual (MT/V5) cortex. Results showed that both groups improved performance consistently across three days. On Day4, the Experimental group experienced performance decline due to negative task transfer while the control group continuously improved. GABA and Glx concentrations obtained during task performance showed no significant group-level changes. However, individual Glx levels during task performance correlated with better (less negative) transfer performance. These findings provide a first window into the neurochemical mechanisms underlying task transfer., (© 2024. The Author(s).)

Synaptic plasticity relies on the balance between excitation and inhibition in the brain. As the primary inhibitory and excitatory neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu), play critical roles in synaptic plasticity and learning. However, the role of these neurometabolites in motor learning is still unclear. Furthermore, it remains to be investigated which neurometabolite levels from the regions composing the sensorimotor network predict future learning outcome. Here, we studied the role of baseline neurometabolite levels in four task-related brain areas during different stages of motor skill learning under two different feedback (FB) conditions. Fifty-one healthy participants were trained on a bimanual motor task over 5 days while receiving either concurrent augmented visual FB (CA-VFB group, N = 25) or terminal intrinsic visual FB (TA-VFB group, N = 26) of their performance. Additionally, MRS-measured baseline GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) levels were measured in the primary motor cortex (M1), primary somatosensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and medial temporal cortex (MT/V5). Behaviorally, our results revealed that the CA-VFB group outperformed the TA-VFB group during task performance in the presence of augmented VFB, while the TA-VFB group outperformed the CA-VFB group in the absence of augmented FB. Moreover, baseline M1 GABA+ levels positively predicted and DLPFC GABA+ levels negatively predicted both initial and long-term motor learning progress in the TA-VFB group. In contrast, baseline S1 GABA+ levels positively predicted initial and long-term motor learning progress in the CA-VFB group. Glx levels did not predict learning progress. Together, these findings suggest that baseline GABA+ levels predict motor learning capability, yet depending on the FB training conditions afforded to the participants., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Neurological soft signs (NSS) are minor deviations in motor performance. During childhood and adolescence, NSS are examined for functional motor phenotyping to describe development, to screen for comorbidities, and to identify developmental vulnerabilities. Here, we investigate underlying brain structure alterations in association with NSS in physically trained adolescents. Male adolescent athletes (n = 136, 13-16 years) underwent a standardized neurological examination including 28 tests grouped into 6 functional clusters. Non-optimal performance in at least 1 cluster was rated as NSS (NSS+ group). Participants underwent T1- and diffusion-weighted magnetic resonance imaging. Cortical volume, thickness, and local gyrification were calculated using Freesurfer. Measures of white matter microstructure (Free-water (FW), FW-corrected fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt)) were calculated using tract-based spatial statistics. General linear models with age and handedness as covariates were applied to assess differences between NSS+ and NSS- group. We found higher gyrification in a large cluster spanning the left superior frontal and parietal areas, and widespread lower FAt and higher RDt compared with the NSS- group. This study shows that NSS in adolescents are associated with brain structure alterations. Underlying mechanisms may include alterations in synaptic pruning and axon myelination, which are hallmark processes of brain maturation., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Neurological soft signs (NSS) are minor deviations from the norm in motor performance that are commonly assessed using neurological examinations. NSS may be of clinical relevance for evaluating the developmental status of adolescents. Here we investigate whether quantitative force plate measures may add relevant information to observer-based neurological examinations., Methods: Male adolescent athletes (n = 141) aged 13-16 years from three European sites underwent a neurological examination including 28 tests grouped into six functional clusters. The performance of tests and functional clusters was rated as optimal/non-optimal resulting in NSS+/NSS- groups and a continuous total NSS score. Participants performed a postural control task on a Balance Tracking System measured as path length, root mean square and sway area. ANCOVAs were applied to test for group differences in postural control between the NSS+ and NSS- group, and between optimal/non-optimal performance on a cluster- and test-level. Moreover, we tested for correlations between the total NSS score and postural control variables., Results: There was no significant overall difference between the NSS+ and NSS- group in postural control. However, non-optimal performing participants in the diadochokinesis test swayed significantly more in the medial-lateral direction than optimal performing participants. Moreover, a lower total NSS score was associated with reduced postural control in the medial-lateral direction., Conclusion: Our findings demonstrate that NSS are related to postural control in adolescent athletes. Thus, force plate measures may add a quantitative, objective measurement of postural control to observer-based qualitative assessments, and thus, may complement clinical testing., Competing Interests: Declaration of Competing Interest YT receives funding from ERA-NET Neuron [01EW1707] and from the National Institutes of Health [NIH R01 HL141774-02] and [NIH R01 HD090191]. EK receives royalties for book chapters and received speaker honoraria and travel support from Medtronic, UCB, Livanova, and Eisai and has participated in clinical trials for Medtronic, UCB and Precisis, all unrelated to the submitted work. JSH receives funding for a Fellowship Award from Harvard Medical School Livingston and for a Young Investigator Grant sponsored by Mary and John Osterhaus and the Brain & Behavior Research Foundation. IKK receives grant funding from the National Institutes of Health (USA), the European Research Council, and the German Ministry of Education and Research. IKK receives funding for a collaborative project and serves as a paid scientific advisor for Abbott. She receives royalties for book chapters. Her spouse is an employee at Siemens AG., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Executive functions are higher-order mental processes that support goal-directed behavior. Among these processes, Inhibition, Updating, and Shifting have been considered core executive domains. In this meta-analysis, we comprehensively investigate the neural networks of these executive domains and we synthesize for the first time the neural convergences and divergences among the most frequently used executive paradigms within those domains. A systematic search yielded 1055 published neuroimaging studies (including 26,191 participants in total). Our study revealed that a fronto-parietal network was shared by the three main domains. Furthermore, we executed conjunction analyses among the paradigms of the same domain to extract the core distinctive components of the main executive domains. This approach showed that Inhibition and Shifting are characterized by a strongly lateralized neural activation in the right and left hemisphere, respectively. In addition, both networks overlapped with the Updating network but not with each other. Remarkably, our study detected heterogeneity among the paradigms from the same domain. More specifically, analysis of Inhibition tasks revealed differing activations for Response Inhibition compared to Interference Control paradigms, suggesting that Inhibition encompasses relatively heterogeneous sub-functions. Shifting analyses revealed a bilateral overlap of the Wisconsin Card Sorting Task with the Updating network, but this pattern was absent for Rule Switching and Dual Task paradigms. Moreover, our Updating meta-analyses revealed the neural signatures associated with the specific modules of the Working Memory model from Baddeley and Hitch. To our knowledge, this is the most comprehensive meta-analysis of executive functions to date. Its paradigm-driven analyses provide a unique contribution to a better understanding of the neural convergences and divergences among executive processes that are relevant for clinical applications, such as cognitive enhancement and neurorehabilitation interventions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Aging may be associated with motor decline that is attributed to deteriorating white matter microstructure of the corpus callosum (CC), among other brain-related factors. Similar to motor functioning, executive functioning (EF) typically declines during aging, with age-associated changes in EF likewise being linked to altered white matter connectivity in the CC. Given that both motor and executive functions rely on white matter connectivity via the CC, and that bimanual control is thought to rely on EF, the question arises whether EF can at least party account for the proposed link between CC-connectivity and motor control in older adults. To address this, diffusion magnetic resonance imaging data were obtained from 84 older adults. A fiber-specific approach was used to obtain fiber density (FD), fiber cross-section (FC), and a combination of both metrics in eight transcallosal white matter tracts. Motor control was assessed using a bimanual coordination task. EF was determined by a domain-general latent EF-factor extracted from multiple EF tasks, based on a comprehensive test battery. FD of transcallosal prefrontal fibers was associated with cognitive and motor performance. EF partly accounted for the relationship between FD of prefrontal transcallosal pathways and motor control. Our results underscore the multidimensional interrelations between callosal white matter connectivity (especially in prefrontal brain regions), EF across multiple domains, and motor control in the older population. They also highlight the importance of considering EF when investigating brain-motor behavior associations in older adults.

Assessing heading exposure in football is important when exploring the association between heading and brain alterations. To this end, questionnaires have been developed for use in adult populations. However, the validity of self-report in adolescents remains to be elucidated. Male youth soccer players (n = 34) completed a questionnaire on heading exposure after a two-week period, which included matches and training sessions. Self-reported numbers were compared to observation (considered reference). In total, we observed 157 training sessions and 64 matches. Self-reported heading exposure correlated with observed heading exposure (Spearman's rho 0.68; p < 0.001). Players systematically overestimated their heading exposure by a factor of 3 with the random error of 46%. Area under the curve was 0.87 (95% CI 0.67-1) utilizing self-report for identifying players from high- and low-exposure groups. Thus, in this study, self-reported data could be used to group youth players into high and low heading exposure groups, but not to quantify individual heading exposure.

Aging is associated with profound alterations in motor control that may be exacerbated by age-related executive functioning decline. Executive functions span multiple facets including inhibition (suppressing unwanted response tendencies), shifting (switching between cognitive operations), and updating (managing working memory content). However, comprehensive studies regarding the contributions of single facets of executive functioning to movement control in older adults are still lacking. A battery of nine neuropsychological tasks was administered to n = 92 older adults in order to derive latent factors for inhibition, shifting, and updating by structural equation modeling. A bimanual task was used to assess complex motor control. A sample of n = 26 young adults served as a control group to verify age-related performance differences. In older adults, structural equation models revealed that performance on the most challenging condition of the complex motor task was best predicted by the updating factor and by general executive functioning performance. These data suggest a central role for working memory updating in complex motor performance and contribute to our understanding of how individual differences in executive functioning relate to movement control in older adults.

Objective: Parkinson's Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Cognitive impairments have been reported using the event-related potential (ERP) technique. Patients show reduced novelty P3 (nP3) amplitudes in oddball experiments, a response to infrequent, surprising stimuli, linked to the orienting response of the brain. The nP3 is thought to depend on dopaminergic neuronal pathways though the effect of dopaminergic medication in PD has not yet been investigated., Methods: Twenty-two patients with PD were examined "on" and "off" their regular dopaminergic medication in a novelty 3-stimulus-oddball task. Thirty-four healthy controls were also examined over two sessions, but received no medication. P3 amplitudes were compared throughout experimental conditions., Results: All participants showed sizeable novelty difference ERP effects, i.e. n d P3 amplitudes, during both testing sessions. An interaction of diagnosis, medication and testing order was also found, indicating that dopaminergic medication modulated n d P3 in patients with PD across the two testing sessions: We observed enhanced n d P3 amplitudes from PD patients who were off medication on the second testing session., Conclusion: Patients with PD 'off' medication showed ERP evidence for repetition-related enhancement of novelty responses. Dopamine depletion in neuronal pathways that are affected by mid-stage PD possibly accounts for this modulation of novelty processing., Significance: The data in this study potentially suggest that repetition effects on novelty processing in patients with PD are enhanced by dopaminergic depletion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Executive dysfunction is a well-documented, yet nonspecific corollary of various neurological diseases and psychiatric disorders. Here, we applied computational modeling of latent cognition for executive control in amyotrophic lateral sclerosis (ALS) patients. We utilized a parallel reinforcement learning model of trial-by-trial Wisconsin Card Sorting Test (WCST) behavior. Eighteen ALS patients and 21 matched healthy control participants were assessed on a computerized variant of the WCST (cWCST). ALS patients showed latent cognitive symptoms, which can be characterized as bradyphrenia and haphazard responding. A comparison with results from a recent computational Parkinson's disease (PD) study (Steinke et al., 2020, J Clin Med) suggests that bradyphrenia represents a disease-nonspecific latent cognitive symptom of ALS and PD patients alike. Haphazard responding seems to be a disease-specific latent cognitive symptom of ALS, whereas impaired stimulus-response learning seems to be a disease-specific latent cognitive symptom of PD. These data were obtained from the careful modeling of trial-by-trial behavior on the cWCST, and they suggest that computational cognitive neuropsychology provides nosologically specific indicators of latent facets of executive dysfunction in ALS (and PD) patients, which remain undiscoverable for traditional behavioral cognitive neuropsychology. We discuss implications for neuropsychological assessment, and we discuss opportunities for confirmatory computational brain imaging studies.

Little is known about how stimulus- and response-based interference might interact to contribute to the costs of switching between cognitive tasks. We analyzed switch costs in a novel cued task-switching/card-matching paradigm in a large study (N = 95). We reasoned that interference from previously active task sets may be contingent upon the retrieval of these task sets via stimulus processing, or alternatively, via response processing. We examined the efficacy of these two factors through eligibility manipulations. That is, stimulus/response features that were capable of retrieving task sets from the previous trial remained eligible (or not) on the current trial. We report three main findings: first, no switch costs were found when neither stimulus features, nor response features, were adequate for the retrieval of the previously executed task sets. Second, we found substantial switch costs when, on switch trials, stimulus features kept the previously executed task eligible, and we found roughly equivalent switch costs when the previously executed response remained eligible. Third, evidence for stimulus-induced switch costs was exclusively observed when previously executed responses remained ineligible. These data indicate that stimulus-based interference, and of importance, response-based interference, contribute comparably to switch costs. Possible interpretations of non-additive switch costs are discussed.

The neural mechanisms of cognitive dysfunctions in neurological diseases remain poorly understood. Here, we conjecture that this unsatisfying state-of-the-art is in part due to the non-specificity of the typical behavioral indicators for cognitive dysfunctions. Our study addresses the topic by advancing the assessment of cognitive dysfunctions through computational modeling. We investigate bradyphrenia in Parkinson's disease (PD) as an exemplary case of cognitive dysfunctions in neurological diseases. Our computational model conceptualizes trial-by-trial behavioral data as resulting from parallel cognitive and sensorimotor reinforcement learning. We assessed PD patients 'on' and 'off' their dopaminergic medication and matched healthy control (HC) participants on a computerized version of the Wisconsin Card Sorting Test. PD patients showed increased retention of learned cognitive information and decreased retention of learned sensorimotor information from previous trials in comparison to HC participants. Systemic dopamine replacement therapy did not remedy these cognitive dysfunctions in PD patients but incurred non-desirable side effects such as decreasing cognitive learning from positive feedback. Our results reveal novel insights into facets of bradyphrenia that are indiscernible by observable behavioral indicators of cognitive dysfunctions. We discuss how computational modeling may contribute to the advancement of future research on brain-behavior relationships and neuropsychological assessment., Competing Interests: The authors declare no conflict of interest.

Objectives: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric condition characterized by motor and vocal tics. There is undoubtedly basal ganglia involvement, which are also important for cognitive processes including performance monitoring and interference resolution. We investigated these functions in adult patients with GTS compared to healthy controls (HCs)., Methods: We compared a group of N = 23 adult patients with GTS to N = 27 HC on a flanker task during an EEG recording. Reaction times and error rates were recorded, as well as N2 and N e /ERN amplitudes. The N2 is an index of interference resolution. The N e /ERN is a negative fronto-central component, occurring when participants make mistakes., Results: Patients' reaction times were enhanced on incongruent trials compared to HC. Electrophysiological data revealed more frontal components, as well as significantly increased N e /ERN amplitudes in patients with GTS compared to HC (p = 0.026)., Conclusions: Altered electrophysiological correlates of error processing in adult patients with GTS compared to HC cannot be attributed to differential error probabilities. Potentially, patients recruit compensatory resources from frontal networks to maintain behavioural performance., Significance: This study gives further insight into cognitive deficits of patients with GTS, and the underlying neural processes of these functions., Competing Interests: Declaration of Competing Interests The authors have no competing interests to declare., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Isolated dystonia manifests with involuntary muscle hyperactivity, but the extent of cognitive impairment remains controversial. We examined the executive functions in blepharospasm while accounting for motor symptom-related distractions as a factor often limiting the interpretability of neuropsychological studies in dystonia. Our control group comprised of patients with hemifacial spasm, which is a condition producing similar motor symptoms without any central nervous system pathology. Nineteen patients with blepharospasm and 22 patients with hemifacial spasm completed a flanker task. Stimulus congruency on the current trial, on the preceding trial, and a response sequence served as independent variables. We analyzed the response time and accuracy. Gross overall group differences were not discernible. While congruency, congruency sequence, and response sequence exerted the expected effects, no group differences emerged with regard to these variables. A difference between patients with blepharospasm and those with hemifacial spasm consisted in longer reaction times when responses had to be repeated following stimulus incongruency on the preceding trial. We conclude that patients with blepharospasm seem to have difficulties in repeating their responses when incongruency on preceding trials interferes with habit formation or other forms of fast routes to action. Our specific finding may provide an opportunity to study altered basal ganglia plasticity in focal dystonia.

Cognitive flexibility has been studied in two separate research traditions. Neuropsychologists typically rely on rather complex assessment tools such as the Wisconsin Card Sorting Test (WCST). In contrast, task-switching paradigms are used in experimental psychology to obtain more specific measures of cognitive flexibility. We aim to contribute to the integration of these research traditions by examining the role of the key factor that differs between the WCST and experimental task-switching paradigms: rule uncertainty. In two experimental studies, we manipulated the degree of rule uncertainty after rule switches in a computerized version of the WCST. Across a variety of task parameters, reducing rule uncertainty consistently impaired the speed and accuracy of responses when the rule designated to be more likely turned out to be incorrect. Other performance measures such as the number of perseverative errors were not significantly affected by rule uncertainty. We conclude that a fine-grained analysis of WCST performance can dissociate behavioural indicators that are affected vs. unaffected by rule uncertainty. By this means, it is possible to integrate WCST results and findings obtained from task-switching paradigms that do not involve rule uncertainty., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Executive dysfunctions are a frequently described non-motor symptom in patients with Parkinsonös disease (PD). However, the nature, extent, variability, and determinants of executive dysfunctions in PD are still poorly understood. To improve the characterization of executive dysfunctions in PD, we conducted a meta-analysis of the studies administering the Wisconsin Card Sorting Test (WCST) to patients with PD and healthy controls. We included k = 161 studies, which allowed us to precisely estimate the size of PD-related WCST deficits and to run powerful tests for potential moderators of these deficits. We found robust WCST deficits in PD, which were medium-to-large in size. These deficits were most pronounced in patients tested after withdrawal from dopaminergic medication and in samples characterized by severe motor impairment and long disease duration. Substantial WCST impairment was also detected in non-demented, non-depressed, and never-medicated patients with PD as well as after conservatively correcting for publication bias. Based on these findings, impaired WCST performance can be considered as a major hallmark of executive dysfunction in PD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Performance deficits on the Wisconsin Card Sorting Test (WCST) in patients with prefrontal cortex (PFC) lesions are traditionally interpreted as evidence for a role of the PFC in cognitive flexibility. However, WCST deficits do not occur exclusively after PFC lesions, but also in various neurological and psychiatric disorders. We propose a multi-component approach that can accommodate this pattern of omnipresent WCST deficits: the WCST is not a pure test of cognitive flexibility, but relies on the effective functioning of multiple dissociable cognitive components. Our review of recent efforts to decompose WCST performance deficits supports this view by revealing that WCST deficits in different neurological disorders can be attributed to alterations in different components. Frontoparietal changes underlying impaired set shifting seem to give rise to WCST deficits in patients with amyotrophic lateral sclerosis, whereas the WCST deficits associated with primary dystonia and Parkinson's disease are rather related to frontostriatal changes underlying deficient rule inference. Clinical implications of these findings and of a multi-component view of WCST performance are discussed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Motor symptoms in Gilles de la Tourette syndrome (GTS) have been related to changes in frontostriatal brain networks. These changes may also give rise to alterations in cognitive flexibility. However, conclusive evidence for altered cognitive flexibility in patients with GTS is still lacking. Here, we meta-analyzed data from 20 neuropsychological studies that investigated cognitive flexibility in GTS using the Wisconsin Card Sorting Test (WCST). Results revealed medium-sized GTS-related performance deficits, which were significantly modulated by age: Whilst being substantial in children and adolescents with GTS, WCST deficits seem to dissolve in adult patients with GTS. This age-related normalization of WCST performance might result from the compensatory recruitment of cognitive control in adult patients with GTS. We addressed this possibility by examining neural correlates of proactive and reactive cognitive control in an event-related potential (ERP) study. We analyzed cue- and target-locked ERPs from 23 adult patients with GTS and 26 matched controls who completed a computerized version of the WCST. Compared to controls, patients with GTS showed a marked increase in parietal cue-locked P3 activity, indicating enhanced proactive cognitive control. We conclude that the additional recruitment of proactive cognitive control might ensure flexible cognitive functioning in adult patients with GTS., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Executive dysfunctions affect up to 50% of the patients with amyotrophic lateral sclerosis (ALS). Executive dysfunctions have been identified as negative prognostic factor and can affect quality of life in patients and their caregivers. Assessment of executive dysfunction may be impeded by the patients' motor impairments. Event-related potentials (ERP) have been proposed as a tool to overcome these assessment difficulties. The error(-related) negativity (N e /ERN) is an ERP which can be recorded with minimal motor requirements for the patient., Methods: We compared response-synchronized ERP amplitudes of 18 ALS patients and 19 healthy controls (HC) obtained on error trials on a flanker task. We also evaluated the relation between N e /ERN amplitudes and executive functions as assessed by standardized neuropsychological measures., Results: While response-synchronized ERP amplitudes were generally unaffected by ALS, we found an ALS-associated relation between N e /ERN amplitudes and executive functions. ALS patients with poorer executive functioning showed attenuated N e /ERN amplitudes., Conclusions: Our data suggest that N e /ERN amplitudes reflect ALS-associated impairment of executive functions, potentially due to disturbances in neural networks that involve the anterior cingulate cortex., Significance: Assessment of N e /ERN amplitudes might provide a cost-efficient and non-invasive marker for executive dysfunction in ALS., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Monitoring one's actions is essential for goal-directed performance. In the event-related potential (ERP), errors are followed by fronto-centrally distributed negativities. These error(-related) negativity (N e /ERN) amplitudes are often found to be attenuated in patients with Parkinson's disease (PD) compared to healthy controls (HC). Although N e /ERN has been proposed to be related to dopaminergic neuronal activity, previous research did not find evidence for effects of dopaminergic medication on N e /ERN amplitudes in PD. We examined 13 PD patients "on" and "off" dopaminergic medication. Their response-locked ERP amplitudes (obtained on correct [N c /CRN] and error [N e /ERN] trials of a flanker task) were compared to those of 13 HC who were tested twice as well, without receiving dopaminergic medication. While PD patients committed more errors than HC, error rates were not significantly modulated by dopaminergic medication. PD patients showed reduced N e /ERN amplitudes relative to HC; however, this attenuation of response-locked ERP amplitudes was not specific to errors in this study. PD-related attenuation of response-locked ERP amplitudes was most pronounced when PD patients were on medication. These results suggest overdosing of dopaminergic pathways that are relatively spared in PD, but that are related to the generation of the N e /ERN, notably pathways targeted on the medial prefrontal cortex.

Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Cognitive impairment is a common non-motor symptom of Parkinson's 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 (N e /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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The capability of the human brain for Bayesian inference was assessed by manipulating probabilistic contingencies in an urn-ball task. Event-related potentials (ERPs) were recorded in response to stimuli that differed in their relative frequency of occurrence (.18 to .82). A veraged ERPs with sufficient signal-to-noise ratio (relative frequency of occurrence > .5) were used for further analysis. Research hypotheses about relationships between probabilistic contingencies and ERP amplitude variations were formalized as (in-)equality constrained hypotheses. Conducting Bayesian model comparisons, we found that manipulations of prior probabilities and likelihoods were associated with separately modifiable and distinct ERP responses. P3a amplitudes were sensitive to the degree of prior certainty such that higher prior probabilities were related to larger frontally distributed P3a waves. P3b amplitudes were sensitive to the degree of likelihood certainty such that lower likelihoods were associated with larger parietally distributed P3b waves. These ERP data suggest that these antecedents of Bayesian inference (prior probabilities and likelihoods) are coded by the human brain.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The human brain predicts events in its environment based on expectations, and unexpected events are surprising. When probabilistic contingencies in the environment are precisely instructed, the individual can form expectations based on quantitative probabilistic information ('inference-based learning'). In contrast, when probabilistic contingencies are imprecisely instructed, expectations are formed based on the individual's cumulative experience ('experience-based learning'). Here, we used the urn-ball paradigm to investigate how variations in prior probabilities and in the precision of information about these priors modulate choice behavior and event-related potential (ERP) correlates of surprise. In the urn-ball paradigm, participants are repeatedly forced to infer hidden states responsible for generating observable events, given small samples of factual observations. We manipulated prior probabilities of the states, and we rendered the priors calculable or incalculable, respectively. The analysis of choice behavior revealed that the tendency to consider prior probabilities when making decisions about hidden states was stronger when prior probabilities were calculable, at least in some of our participants. Surprise-related P3b amplitudes were observed in both the calculable and the incalculable prior probability condition. In contrast, calculability of prior probabilities modulated anteriorly distributed ERP amplitudes: when prior probabilities were calculable, surprising events elicited enhanced P3a amplitudes. However, when prior probabilities were incalculable, surprise was associated with enhanced N2 amplitudes. Furthermore, interindividual variability in reliance on prior probabilities was associated with attenuated P3b surprise responses under calculable in comparison to incalculable prior probabilities. Our results suggest two distinct neural systems for probabilistic learning that are recruited depending on contextual cues such as the precision of probabilistic information. Individuals with stronger tendencies to rely on calculable prior probabilities seem to have better adapted expectations at their disposal, as indicated by an attenuation of their P3b surprise responses when prior probabilities are calculable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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, ((c) 2016 APA, all rights reserved).)

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).

To date, many different approaches have been used to study the impairment of motor function in Parkinson's 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., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modeling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities) by two (likelihoods) design. Five computational models of cognitive processes were compared with the observed behavior. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted) S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model's success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modeling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modeling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

Objective: Executive dysfunctions in patients suffering from amyotrophic lateral sclerosis (ALS) are often described but poorly understood. Specifically, research on patients' ability to flexibly shift between cognitive sets is still scarce and unsystematic. The present study set out to compensate for this lack by providing an in-depth analysis of ALS-related set-shifting impairments., Method: We first present a quantitative overview of the literature revealing that the Wisconsin Card Sorting Test (WCST) is sensitive to set-shifting impairments in ALS. Moreover, we evaluated patients' performance on a computerized task-switching paradigm modeled after the WCST to elucidate the neurocognitive processes underlying their set-shifting impairments. Twenty-one ALS patients and 21 age- and education-matched controls were required to respond to changing task demands while their EEG was being measured., Results: Behavioral results revealed significant set-shifting deficits in patients suffering from ALS. Executive deficits were accompanied by substantial alterations of event-related brain activity. While switch cues elicited a more positive posterior event-related potential (ERP) waveform than repeat cues in healthy controls, ERP amplitudes did not vary as a function of switching demand in ALS patients. Individual differences in posterior switch positivity were reliably associated with patients' performance on neuropsychological tests of executive functioning., Conclusions: The absence of switch-related ERP modulations appears to be a sensitive indicator of executive deficits in ALS patients. Our results suggest that ALS compromises the frontoparietal brain networks involved in anticipatory set-shifting, rendering patients unable to flexibly adapt to changes in environmental contingencies., ((c) 2015 APA, all rights reserved).)

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.

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.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study was conducted by the Technical University of Munich-Weihenstephan on behalf of the Department of Education of the city of Munich. A total of 82 children as well as their parents and 23 kindergarten teachers in five Munich kindergartens were questioned about their food preferences, and their sociocultural data were gathered. The results showed that the nationality and the religion of the mother were fundamental to the origin and consolidation of the eating habits of the children. Other important und influencing factors were: the peer group and the teachers in the kindergarten, the father's job, the sex and the age of the children. When comparing the food preferences of the children and their role models, it was found that the preferences and aversions were more similar to those of their own mothers/teachers/members of the peer group than to those of children of other peer groups, other parents or other teachers.