Inferior parietal cortex represents relational structures for explicit transitive inference.

The human brain is distinguished by its ability to perform explicit logical reasoning like transitive inference. This study investigated the functional role of the inferior parietal cortex in transitive inference with functional MRI. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, the inferior parietal cortex, but not the hippocampus or lateral prefrontal cortex, was associated with transitive inference. The inferior parietal activity and functional connectivity were modulated by inference (new versus old pairs) and discrimination (true versus false pairs). Moreover, the new/old and true/false pairs were decodable from the inferior parietal representation. Second, the inferior parietal cortex represented an integrated relational structure (ordered and directed series). The inferior parietal activity was modulated by serial position (larger end versus center pairs). The inferior parietal representation was modulated by symbolic distance (adjacent versus distant pairs) and direction (preceding versus following pairs). It suggests that the inferior parietal cortex may flexibly integrate observed relations into a relational structure and use the relational structure to infer unobserved relations and discriminate between true and false relations.

Cross-frequency and inter-regional phase synchronization in explicit transitive inference.

Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, theta (4-7 Hz) and alpha oscillations (8-15 Hz) had distinct functional roles. Frontal theta oscillations distinguished between new and old pairs, reflecting the inference of new information. Parietal alpha oscillations changed with serial position and symbolic distance of the pairs, representing the underlying relational structure. Frontal alpha oscillations distinguished between true and false pairs, linking the new information with the underlying relational structure. Second, theta and alpha oscillations interacted through cross-frequency and inter-regional phase synchronization. Frontal theta-alpha 1:2 phase locking appeared to coordinate spectrally diverse neural activity, enhanced for new versus old pairs and true versus false pairs. Alpha-band frontal-parietal phase coherence appeared to coordinate anatomically distributed neural activity, enhanced for new versus old pairs and false versus true pairs. It suggests that cross-frequency and inter-regional phase synchronization among theta and alpha oscillations supports human transitive inference.

Tracking the habituation of the event-related EEG potential in automatic change detection using an auditory two-tone oddball paradigm.

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

White adipose tissue distribution and amount are associated with increased white matter connectivity.

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.

Basal Ganglia Atrophy as a Marker for Prodromal X-Linked Dystonia-Parkinsonism.

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.

Potential effects of a mobile stroke unit on time to treatment and outcome in patients treated with thrombectomy or thrombolysis: A Danish-German cross-border analysis.

BACKGROUND AND PURPOSE: A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation. METHODS: In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish (n = 122) and an adjacent German region (n = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability-adjusted life years (DALYs). RESULTS: For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (-15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP-$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP-$1.7M. CONCLUSION: The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany.

Associations Between Intertemporal Food Choice and BMI in Adult Women: An fMRI Study Using a Quasi-realistic Design.

BACKGROUND: Impulsivity resulting in unrestrained eating has been implicated as a contributing factor for obesity. Delay discounting (DD) tasks where individuals choose between a smaller immediate reward and a larger delayed reward provide useful data to describe impulsive decision-making and to determine the extent to which delayed rewards are discounted. OBJECTIVE: To study the association between body mass index(BMI) and delay discounting for food and money in adult women. METHODS: We used a DD task with real food rewards to investigate impulsive decision-making as related to BMI in participants who self-identified as women. Participants in group A had a mean BMI of 21.4 (n = 14), and participants in group B had a mean BMI of 32.2 (n = 14). Each group was tested in a hungry state during a single session. We performed fMRI during a DD task requiring participants to choose between a food item (one sandwich) constituting a smaller immediate reward and multiple food items (two, three, or four sandwiches) constituting a series of larger delayed rewards available at different intervals. The steepness of the discounting curve for food was determined from these decisions. Participants then completed a monetary discounting task to facilitate a comparison of the discounting of food and monetary rewards. RESULTS: Participants in group B discounted food rewards more steeply than monetary rewards. Decisions for delayed rewards led to increased activations of brain areas related to executive control on fMRI, such as the head of the caudate nucleus and the anterior cingulate cortex (ACC) in group A, but not group B participants. CONCLUSION: Our findings suggest that group B had difficulty deciding against the immediate food rewards due to insufficient recruitment of cortical control areas. Therefore, impulsivity is an important target for behavioral interventions in individuals with obesity.

Threatening an Illusory Limb: An Event-related Potential Study of the Rubber Hand Illusion.

BACKGROUND: The rubber hand illusion (RHI) is a well-established method for studying body ownership: Given adequate concordance of visual, sensory, and proprioceptive stimuli, the individual experiences a rubber hand as his or her own. OBJECTIVE: To study the effects of a threat to the rubber hand. METHODS: We created a typical RHI paradigm but added threatening pain: Both the real hand of an individual and the rubber hand were stroked with a brush, either synchronously (RHI-inducing condition) or asynchronously (control condition), but only the rubber hand was then pricked with a needle to create a threatening pain condition. Event-related potentials (ERPs) were recorded in a group of 23 typically-developed individuals. ERP effects were source-localized using low-resolution electromagnetic tomography. RESULTS: The individuals consistently reported experience of the RHI during the experiment when the brush strokes were applied synchronously to both the real hand and the rubber hand. ERP analysis revealed that synchronous brush stroking gave rise to higher amplitude of frontal ERPs in the 100-200 ms range than asynchronous brush stroking, which was interpreted as reflecting the RHI. In the threatening pain condition, ERPs showed a greater positivity at frontocentral electrodes, source localized in the supplementary motor area (SMA). CONCLUSION: SMA activation could reflect a control mechanism over reflexive motor activity, facilitating a possible threat-related response. Further studies should address ERP effects and the extent of the RHI to standard and threat stimuli in a correlative fashion to further elucidate the functional significance of the neurophysiological findings.

Preserved Corticospinal Tract Revealed by Acute Perfusion Imaging Relates to Better Outcome After Thrombectomy in Stroke.

BACKGROUND: The indication for mechanical thrombectomy (MT) in stroke patients with large vessel occlusion has been constantly expanded over the past years. Despite remarkable treatment effects at the group level in clinical trials, many patients remain severely disabled even after successful recanalization. A better understanding of this outcome variability will help to improve clinical decision-making on MT in the acute stage. Here, we test whether current outcome models can be refined by integrating information on the preservation of the corticospinal tract as a functionally crucial white matter tract derived from acute perfusion imaging. METHODS: We retrospectively analyzed 162 patients with stroke and large vessel occlusion of the anterior circulation who were admitted to the University Medical Center Lübeck between 2014 and 2020 and underwent MT. The ischemic core was defined as fully automatized based on the acute computed tomography perfusion with cerebral blood volume data using outlier detection and clustering algorithms. Normative whole-brain structural connectivity data were used to infer whether the corticospinal tract was affected by the ischemic core or preserved. Ordinal logistic regression models were used to correlate this information with the modified Rankin Scale after 90 days. RESULTS: The preservation of the corticospinal tract was associated with a reduced risk of a worse functional outcome in large vessel occlusion-stroke patients undergoing MT, with an odds ratio of 0.28 (95% CI, 0.15-0.53). This association was still significant after adjusting for multiple confounding covariables, such as age, lesion load, initial symptom severity, sex, stroke side, and recanalization status. CONCLUSIONS: A preinterventional computed tomography perfusion-based surrogate of corticospinal tract preservation or disconnectivity is strongly associated with functional outcomes after MT. If validated in independent samples this concept could serve as a novel tool to improve current outcome models to better understand intersubject variability after MT in large vessel occlusion stroke.

Differences in Implicit Attitudes in West and East Germans as Measured by the Go/NoGo Association Task and Event-related EEG Potentials.

BACKGROUND AND OBJECTIVE: Implicit social cognition refers to attitudes and stereotypes that may reside outside conscious awareness and control but that still affect human behavior. In particular, the implicit favoritism of an ingroup, to which an individual belongs, as opposed to an outgroup, to which the individual does not belong, characterized as ingroup bias, is of interest and is investigated here. METHOD: We used a Go/NoGo association task (GNAT) and behavioral and electroencephalographic (event-related EEG potential [ERP] analysis) measures to investigate the implicit bias toward cities in East Germany, West Germany, and Europe, in 16 individuals each from West and East Germany (mixed gender, M age = 24). The GNAT assesses an individual's Go and NoGo responses for a given association between a target category and either pole (positive or negative) of an evaluative dimension. RESULTS: Behavioral measures revealed slightly faster reaction times to the combination of European city names and negative, as compared with positive, evaluative words in both groups. ERP analysis showed an increased negativity at 400-800 ms poststimulus in the incongruent conditions of East German city/positive word pairings (in West Germans) and West German city/positive word pairings (in East Germans). CONCLUSION: An implicitly moderately negative evaluation of Europe by both groups was exhibited based on the behavioral data, and an increased level of conflict arising from the "incongruent" pairings (ie, as manifestation of an implicitly negative attitude toward East Germany in West Germans, and toward West Germany in East Germans) was exhibited based on the electrophysiological data.

Substantia nigra integrity correlates with sequential working memory in Parkinson's disease.

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HC, 18 women). In neuromelanin-sensitive structural MRI, PD patients showed smaller SN than HC. In a digit ordering task with functional MRI, participants either recalled sequential digits in the original order ('pure recall') or rearranged the digits and recalled the new sequence ('reorder & recall'). PD patients performed less accurately than HC, accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the bilateral SN and all three basal ganglia regions. PD patients with larger SN tended to exhibit smaller ordering-related accuracy costs ('reorder & recall' versus 'pure recall'). This effect was fully mediated by the ordering-related caudate activation. Unlike HC, the ordering-related accuracy cost correlated with the ordering-related caudate activation but not subthalamic activation in PD. Moreover, the ordering-related caudate activation correlated with the SN area but not the daily dose of D2/3 receptor agonists. In PD, the daily dose of D2/3 receptor agonists correlated with the ordering-related subthalamic activation, which was not related to the accuracy cost. The findings suggest that damage to the SN may lead to sequential working memory deficits in PD, mediated by basal ganglia dysfunction.SIGNIFICANCELiu et al. demonstrate that damage to the substantia nigra (SN) correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson's disease (PD). In neuromelanin-sensitive MRI, PD showed smaller SN than healthy controls. In a digit ordering task with functional MRI, PD's lower task accuracy was accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the SN and basal ganglia. PD with larger SN exhibited greater ordering-related caudate activation and lower ordering-related accuracy cost when sequencing digits. PD with more daily exposure to D2/3 receptor agonists exhibited greater ordering-related subthalamic activation, which did not reduce accuracy cost. It suggests that the SN may affect sequencing performance by regulating the task-dependent caudate activation in PD.

Sweets for my sweet: modulation of the limbic system drives salience for sweet foods after deep brain stimulation in Parkinson's disease.

BACKGROUND: An increase in body weight is observed in the majority of patients with Parkinson's disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear. OBJECTIVES: To identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations. METHODS: We acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated. RESULTS: STN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images. CONCLUSIONS: Our findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

Prodromal X-Linked Dystonia-Parkinsonism is Characterized by a Subclinical Motor Phenotype.

BACKGROUND: Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease-modifying therapies at a time point where progressive neurodegeneration can still be modified. OBJECTIVES: The objective of this study was to determine whether motor or non-motor signs of the disease occur as indicators of a prodromal phase of X-linked dystonia-parkinsonism (XDP), a highly-penetrant monogenic movement disorder with striking basal ganglia pathology. METHODS: In addition to a comprehensive clinical assessment, sensor-based balance and gait analyses were performed in non-manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient-boosted trees (GBT) methodology was utilized to classify groups of interest. RESULTS: There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best-performing GBT-based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group. CONCLUSIONS: Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Gaze-contingent display technology can help to reduce the ipsilesional attention bias in hemispatial neglect following stroke.

BACKGROUND: Hemispatial neglect results from unilateral brain damage and represents a disabling unawareness for objects in the hemispace opposite the brain lesion (contralesional). The patients' attentional bias for ipsilesional hemispace represents a hallmark of neglect, which results from an imbalanced attentional priority map in the brain. The aim of this study was to investigate whether gaze-contingent display (GCD) technology, reducing the visual salience of objects in ipsilesional hemispace, is able to rebalance this map and increase awareness and exploration of objects in the neglected contralesional hemispace. METHODS: Using remote eye-tracking, we recorded gaze positions in 19 patients with left hemispatial neglect following right-hemisphere stroke and 22 healthy control subjects, while they were watching static naturalistic scenes. There were two task conditions, free viewing (FV) or goal-directed visual search (VS), and four modification conditions including the unmodified original picture, a purely static modification and two differently strong modifications with an additional gaze-contingent mask (GC-LOW, GC-HIGH), that continuously reduced color saturation and contrast of objects in the right hemispace. RESULTS: The patients' median gaze position (Center of Fixation) in the original pictures was markedly deviated to the right in both tasks (FV: 6.8° ± 0.8; VS: 5.5° ± 0.7), reflecting the neglect-typical ipsilesional attention bias. GC modification significantly reduced this bias in FV (GC-HIGH: d = - 3.2 ± 0.4°; p < 0.001). Furthermore, in FV and VS, GC modification increased the likelihood to start visual exploration in the (neglected) left hemifield by about 20%. This alleviation of the ipsilesional fixation bias was not associated with an improvement in detecting left-side targets, in contrast, the GC mask even decreased and slowed the detection of right-side targets. Subjectively, patients found the intervention pleasant and most of the patients did not notice any modification. CONCLUSIONS: GCD technology can be used to positively influence visual exploration patterns in patients with hemispatial neglect. Despite an alleviation of the neglect-related ipsilesional fixation bias, a concomitant functional benefit (improved detection of contralesional targets) was not achieved. Future studies may investigate individualized GCD-based modifications as augmented reality applications during the activities of daily living.

Technical Note: Modulation of fMRI brainstem responses by transcutaneous vagus nerve stimulation.

Our increasing knowledge about gut-brain interaction is revolutionising the understanding of the links between digestion, mood, health, and even decision making in our everyday lives. In support of this interaction, the vagus nerve is a crucial pathway transmitting diverse gut-derived signals to the brain to monitor of metabolic status, digestive processes, or immune control to adapt behavioural and autonomic responses. Hence, neuromodulation methods targeting the vagus nerve are currently explored as a treatment option in a number of clinical disorders, including diabetes, chronic pain, and depression. The non-invasive variant of vagus nerve stimulation (VNS), transcutaneous auricular VNS (taVNS), has been implicated in both acute and long-lasting effects by modulating afferent vagus nerve target areas in the brain. The physiology of neither of those effects is, however, well understood, and evidence for neuronal response upon taVNS in vagal afferent projection regions in the brainstem and its downstream targets remain to be established. Therefore, to examine time-dependent effects of taVNS on brainstem neuronal responses in healthy human subjects, we applied taVNS during task-free fMRI in a single-blinded crossover design. During fMRI data acquisition, we either stimulated the left earlobe (sham), or the target zone of the auricular branch of the vagus nerve in the outer ear (cymba conchae, verum) for several minutes, both followed by a short 'stimulation OFF' period. Time-dependent effects were assessed by averaging the BOLD response for consecutive 1-minute periods in an ROI-based analysis of the brainstem. We found a significant response to acute taVNS stimulation, relative to the control condition, in downstream targets of vagal afferents, including the nucleus of the solitary tract, the substantia nigra, and the subthalamic nucleus. Most of these brainstem regions remarkably showed increased activity in response to taVNS, and these effect sustained during the post-stimulation period. These data demonstrate that taVNS activates key brainstem regions, and highlight the potential of this approach to modulate vagal afferent signalling. Furthermore, we show that carry-over effects need to be considered when interpreting fMRI data in the context of general vagal neurophysiology and its modulation by taVNS.

Effective connectivity underlying reward-based executive control.

Motivational influences on cognitive control play an important role in shaping human behavior. Cognitive facilitation through motivators such as prospective reward or punishment is thought to depend on regions from the dopaminergic mesocortical network, primarily the ventral tegmental area (VTA), inferior frontal junction (IFJ), and anterior cingulate cortex (ACC). However, how interactions between these regions relate to motivated control remains elusive. In the present functional magnetic resonance imaging study, we used dynamic causal modeling (DCM) to investigate effective connectivity between left IFJ, ACC, and VTA in a task-switching paradigm comprising three distinct motivational conditions (prospective monetary reward or punishment and a control condition). We found that while prospective punishment significantly facilitated switching between tasks on a behavioral level, interactions between IFJ, ACC, and VTA were characterized by modulations through prospective reward but not punishment. Our DCM results show that IFJ and VTA modulate ACC activity in parallel rather than by interaction to serve task demands in reward-based cognitive control. Our findings further demonstrate that prospective reward and punishment differentially affect neural control mechanisms to initiate decision-making.

The Role of the Subthalamic Nucleus in Sequential Working Memory in De Novo Parkinson's Disease.

BACKGROUND: Deficits in maintaining and manipulating sequential information online can occur even in patients with mild Parkinson's disease. The subthalamic nucleus may play a modulatory role in the neural system for sequential working memory, which also includes the lateral prefrontal cortex. OBJECTIVES: The objective of this study was to investigate neural markers of sequential working memory deficits in patients with de novo Parkinson's disease. METHODS: A total of 50 patients with de novo Parkinson's disease and 50 healthy controls completed a digit ordering task during functional magnetic resonance imaging scanning. The task separated the maintenance ("pure recall") and manipulation of sequences ("reorder & recall" vs "pure recall"). RESULTS: In healthy controls, individual participants' task accuracy was predicted by the regional activation and functional connectivity of the subthalamic nucleus. Healthy participants who showed lower subthalamic nucleus activation and stronger subthalamic nucleus connectivity with the putamen performed more accurately in maintaining sequences ("pure recall"). Healthy participants who showed greater ordering-related subthalamic nucleus activation change exhibited smaller accuracy costs in manipulating sequences ("reorder & recall" vs "pure recall"). Patients performed less accurately than healthy controls, especially in "reorder & recall" trials, accompanied by an overactivation in the subthalamic nucleus and a loss of synchrony between the subthalamic nucleus and putamen. Individual patients' task accuracy was predicted only by the subthalamic nucleus connectivity. The contribution of the subthalamic nucleus activation or activation change was absent. We observed no change in the lateral prefrontal cortex. CONCLUSIONS: The overactivation and weakened functional connectivity of the subthalamic nucleus are the neural markers of sequential working memory deficits in de novo Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Explicit Diagnostic Criteria for Transient Ischemic Attacks Used in the Emergency Department Are Highly Sensitive and Specific.

BACKGROUND: Making a correct diagnosis of a transient ischemic attack (TIA) is prone to errors because numerous TIA mimics exist and there is a shortage of evidence-based diagnostic criteria for TIAs. In this study, we applied for the first time the recently proposed explicit diagnostic criteria for transient ischemic attacks (EDCT) to a group of patients presenting to the emergency department of a large German tertiary care hospital with a suspected TIA. The aim was to determine the sensitivity and specificity of the EDCT in its clinical application. METHODS: A total of 128 patients consecutively presenting to the emergency department of the University Hospital of Lübeck, Germany, under the suspicion of a TIA were prospectively interviewed about their clinical symptoms at the time of presentation. The diagnosis resulting from applying the EDCT was compared to the diagnosis made independently by the senior physicians performing the usual diagnostic work-up ("gold standard"), allowing calculation of sensitivity and specificity of the EDCT. RESULTS: EDCT achieved a sensitivity of 96% and a specificity of 88%. When adding the additional criterion F ("the symptoms may not be better explained by another medical or mental disorder"), specificity significantly increased to 98%. CONCLUSIONS: The data show that the EDCT in its modified version as proposed by us are a highly useful tool for clinicians. They display a high sensitivity and specificity to accurately diagnose TIAs in patients referred to the emergency department with a suspected TIA.

Enriched Music-supported Therapy for chronic stroke patients: a study protocol of a randomised controlled trial.

BACKGROUND: Residual motor deficits of the upper limb in patients with chronic stroke are common and have a negative impact on autonomy, participation and quality of life. Music-Supported Therapy (MST) is an effective intervention to enhance motor and cognitive function, emotional well-being and quality of life in chronic stroke patients. We have adapted the original MST training protocol to a home-based intervention, which incorporates increased training intensity and variability, group sessions, and optimisation of learning to promote autonomy and motivation. METHODS: A randomised controlled trial will be conducted to test the effectiveness of this enriched MST (eMST) protocol in improving motor functions, cognition, emotional well-being and quality of life of chronic stroke patients when compared to a program of home-based exercises utilizing the Graded Repetitive Arm Supplementary Program (GRASP). Sixty stroke patients will be recruited and randomly allocated to an eMST group (n = 30) or a control GRASP intervention group (n = 30). Patients will be evaluated before and after a 10-week intervention, as well as at 3-month follow-up. The primary outcome of the study is the functionality of the paretic upper limb measured with the Action Research Arm Test. Secondary outcomes include other motor and cognitive functions, emotional well-being and quality of life measures as well as self-regulation and self-efficacy outcomes. DISCUSSION: We hypothesize that patients treated with eMST will show larger improvements in their motor and cognitive functions, emotional well-being and quality of life than patients treated with a home-based GRASP intervention. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov and identified as NCT04507542 on 8 August 2020.

Neural Plasticity in a French Horn Player with Bilateral Amelia.

Precise control of movement and timing play a key role in musical performance. This motor skill requires coordination across multiple joints, muscles, and limbs, which is acquired through extensive musical training from childhood on. Thus, making music can be a strong driver for neuroplasticity. We here present the rare case of a professional french horn player with a congenital bilateral amelia of the upper limbs. We were able to show a unique cerebral and cerebellar somatotopic representation of his toe and feet, that do not follow the characteristic patterns of contralateral cortical and ipsilateral cerebellar layout. Although being a professional horn player who trained his embouchure muscles, including tongue, pharyngeal, and facial muscle usage excessively, there were no obvious signs for an expanded somatosensory representation in this part of the classic homunculus. Compared to the literature and in contrast to control subjects, the musicians' foot movement-related activations occurred in cerebellar areas that are typically more related to hand than to foot activation.