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Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson's disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson's disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson's disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson's disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine., (© 2023. The Author(s).)

Background: In glioma patients, tumor growth and subsequent treatments are associated with various types of brain lesions. We hypothesized that cognitive functioning in these patients critically depends on the maintained structural connectivity of multiple brain networks., Methods: The study included 121 glioma patients (median age, 52 years; median Eastern Cooperative Oncology Group performance score 1; CNS-WHO Grade 3 or 4) after multimodal therapy. Cognitive performance was assessed by 10 tests in 5 cognitive domains at a median of 14 months after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-[ 18 F]fluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography were used to generate whole-brain fiber count-weighted connectivity matrices. The matrices were applied to a cross-validated machine-learning model to identify predictive fiber connections (edges), critical cortical regions (nodes), and the networks underlying cognitive performance., Results: Compared to healthy controls ( n  = 121), patients' cognitive scores were significantly lower in 9 cognitive tests. The models predicted the scores of 7/10 tests (median correlation coefficient, 0.47; range, 0.39-0.57) from 0.6% to 5.4% of the matrix entries; 84% of the predictive edges were between nodes of different networks. Critically involved cortical regions (≥10 adjacent edges) included predominantly left-sided nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥15 edges) included the default mode network's left temporal and bilateral posterior cingulate cortex., Conclusions: These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders., Competing Interests: N.G. has received honoraria from Telix Pharmaceuticals and Blue Earth Diagnostics. The other authors report no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Early auditory deprivation leads to a reorganization of large-scale brain networks involving and extending beyond the auditory system. It has been documented that visuomotor transformation is impaired after early deafness, associated with a hyper-crosstalk between the task-critical frontoparietal network and the default-mode network. However, it remains unknown whether and how the reorganized large-scale brain networks involving the auditory cortex contribute to impaired visuomotor transformation after early deafness. Here, we asked deaf and early hard of hearing participants and normal hearing controls to judge the spatial location of a visual target. Compared with normal hearing controls, the superior temporal gyrus showed significantly increased functional connectivity with the frontoparietal network and the default-mode network in deaf and early hard of hearing participants, specifically during egocentric judgments. However, increased superior temporal gyrus-frontoparietal network and superior temporal gyrus-default-mode network coupling showed antagonistic effects on egocentric judgments. In deaf and early hard of hearing participants, increased superior temporal gyrus-frontoparietal network connectivity was associated with improved egocentric judgments, whereas increased superior temporal gyrus-default-mode network connectivity was associated with deteriorated performance in the egocentric task. Therefore, the data suggest that the auditory cortex exhibits compensatory neuroplasticity (i.e. increased functional connectivity with the task-critical frontoparietal network) to mitigate impaired visuomotor transformation after early auditory deprivation., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: The gut microbiome is involved in autoimmunity. Data on its composition in chronic inflammatory demyelinating polyneuropathy (CIDP), the most common chronic autoimmune disorder of peripheral nerves, are currently lacking., Methods: In this monocentric exploratory pilot study, stool samples were prospectively collected from 16 CIDP patients (mean age 58 ± 10 years, 25% female) before and 1 week after administration of intravenous immunoglobulin (IVIg). Gut microbiota were analyzed via bacterial 16S rRNA gene sequencing and compared to 15 age-matched healthy subjects (mean age 59 ± 15 years, 66% female)., Results: The gut microbiota of CIDP patients showed an increased alpha-diversity (p = 0.005) and enrichment of Firmicutes, such as Blautia (p = 0.0004), Eubacterium hallii (p = 0.0004), or Ruminococcus torques (p = 0.03), and of Actinobacteriota (p = 0.03) compared to healthy subjects. IVIg administration did not alter the gut microbiome composition in CIDP in this short-term observation (p = 0.95)., Conclusions: The gut microbiome in IVIg-treated CIDP shows distinct features, with increased bacterial diversity and enrichment of short-chain fatty acid producing Firmicutes. IVIg had no short-term impact on the gut microbiome in CIDP patients. As the main limitation of this exploratory pilot study was small cohort size, future studies also including therapy-naïve patients are warranted to verify our findings and to explore the impact of long-term IVIg treatment on the gut microbiome in CIDP., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at emotional, motivational, cognitive, behavioural or somatic levels. Evidence indicates that depression is caused by disruption of bio-aminergic fibre tracts between prefrontal and limbic or striatal brain regions comprising different functional networks. Voxel-based lesion-symptom mapping studies reported discrepant findings regarding the association between infarct locations and depression. Inconsistencies may be due to the usage of sum scores, thereby mixing different symptoms of depression. In this cross-sectional study, we used multivariate support vector regression for lesion-symptom mapping to identify regions significantly involved in distinct depressive symptom domains and global depression. MRI lesion data were included from 200 patients with acute first-ever ischaemic stroke (mean 0.9 ± 1.5 days of post-stroke). The Montgomery-Åsberg Depression Rating interview assessed depression severity in five symptom domains encompassing motivational, emotional and cognitive symptoms deficits, anxiety and somatic symptoms and was examined 8.4 days of post-stroke (±4.3). We found that global depression severity, irrespective of individual symptom domains, was primarily linked to right hemispheric lesions in the dorsolateral prefrontal cortex and inferior frontal gyrus. In contrast, when considering distinct symptom domains individually, the analyses yielded much more sensitive results in regions where the correlations with the global depression score yielded no effects. Accordingly, motivational deficits were associated with lesions in orbitofrontal cortex, dorsolateral prefrontal cortex, pre- and post-central gyri and basal ganglia, including putamen and pallidum. Lesions affecting the dorsal thalamus, anterior insula and somatosensory cortex were significantly associated with emotional symptoms such as sadness. Damage to the dorsolateral prefrontal cortex was associated with concentration deficits, cognitive symptoms of guilt and self-reproach. Furthermore, somatic symptoms, including loss of appetite and sleep disturbances, were linked to the insula, parietal operculum and amygdala lesions. Likewise, anxiety was associated with lesions impacting the central operculum, insula and inferior frontal gyrus. Interestingly, symptoms of anxiety were exclusively left hemispheric, whereas the lesion-symptom associations of the other domains were lateralized to the right hemisphere. In conclusion, this large-scale study shows that in acute stroke patients, differential post-stroke depression symptom domains are associated with specific structural correlates. Our findings extend existing concepts on the neural underpinnings of depressive symptoms, indicating that differential lesion patterns lead to distinct depressive symptoms in the first weeks of post-stroke. These findings may facilitate the development of personalized treatments to improve post-stroke rehabilitation., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Clinical rating scales for tremors have significant limitations due to low resolution, high rater dependency, and lack of applicability in outpatient settings. Reliable, quantitative approaches for assessing tremor severity are warranted, especially evaluating treatment effects, e.g., of deep brain stimulation (DBS). We aimed to investigate how different accelerometry metrics can objectively classify tremor amplitude of Essential Tremor (ET) and tremor in Parkinson's Disease (PD). We assessed 860 resting and postural tremor trials in 16 patients with ET and 25 patients with PD under different DBS settings. Clinical ratings were compared to different metrics, based on either spectral components in the tremorband or pure acceleration, derived from simultaneous triaxial accelerometry captured at the index finger and wrist. Nonlinear regression was applied to a training dataset to determine the relationship between accelerometry and clinical ratings, which was then evaluated in a holdout dataset. All of the investigated accelerometry metrics could predict clinical tremor ratings with a high concordance (>70%) and substantial interrater reliability (Cohen's weighted Kappa > 0.7) in out-of-sample data. Finger-worn accelerometry performed slightly better than wrist-worn accelerometry. We conclude that triaxial accelerometry reliably quantifies resting and postural tremor amplitude in ET and PD patients. A full release of our dataset and software allows for implementation, development, training, and validation of novel methods.

JC polyomavirus (JCV) establishes an asymptomatic latent and/or persistent infection in most of the adult population. However, in immunocompromised individuals, JCV can cause a symptomatic infection of the brain, foremost progressive multifocal leukoencephalopathy (PML). In the past 2 decades, there has been increasing concern among patients and the medical community because PML was observed as an adverse event in individuals treated with modern (selective) immune suppressive treatments for various immune-mediated diseases, especially multiple sclerosis. It became evident that this devastating complication also needs to be considered beyond the patient populations historically at risk, including those with hematologic malignancies or HIV-infected individuals. We review the clinical presentation of PML, its variants, pathogenesis, and current diagnostic approaches. We further discuss the need to validate JCV-directed interventions and highlight current management strategies based on early diagnosis and restoring JCV-specific cellular immunity, which is crucial for viral clearance and survival. Finally, we discuss the importance of biomarkers for diagnosis and response to therapy, instrumental in defining sensitive study end points for successful clinical trials of curative or preventive therapeutics. Advances in understanding PML pathophysiology, host and viral genetics, and diagnostics in conjunction with novel immunotherapeutic approaches indicate that the time is right to design and perform definitive trials to develop preventive options and curative therapy for JCV-associated diseases., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objective: Although ample evidence highlights that the ipsilesional corticospinal tract (CST) plays a crucial role in motor recovery after stroke, studies on cortico-cortical motor connections remain scarce and provide inconclusive results. Given their unique potential to serve as structural reserve enabling motor network reorganization, the question arises whether cortico-cortical connections may facilitate motor control depending on CST damage., Methods: Diffusion spectrum imaging (DSI) and a novel compartment-wise analysis approach were used to quantify structural connectivity between bilateral cortical core motor regions in chronic stroke patients. Basal and complex motor control were differentially assessed., Results: Both basal and complex motor performance were correlated with structural connectivity between bilateral premotor areas and ipsilesional primary motor cortex (M1) as well as interhemispheric M1 to M1 connectivity. Whereas complex motor skills depended on CST integrity, a strong association between M1 to M1 connectivity and basal motor control was observed independent of CST integrity especially in patients who underwent substantial motor recovery. Harnessing the informational wealth of cortico-cortical connectivity facilitated the explanation of both basal and complex motor control., Interpretation: We demonstrate for the first time that distinct aspects of cortical structural reserve enable basal and complex motor control after stroke. In particular, recovery of basal motor control may be supported via an alternative route through contralesional M1 and non-crossing fibers of the contralesional CST. Our findings help to explain previous conflicting interpretations regarding the functional role of the contralesional M1 and highlight the potential of cortico-cortical structural connectivity as a future biomarker for motor recovery post-stroke. ANN NEUROL 2023;94:785-797., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy., Methods: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control., Results: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor., Conclusion: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis., 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 © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits., Methods: We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients., Results: Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, η p 2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, η p 2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients., Discussion: These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits., (© 2023 American Academy of Neurology.)

Introduction: Differences in dopaminergic motor response in Parkinson's disease (PD) patients can be related to PD subtypes, and previous fMRI studies associated dopaminergic motor response with corticostriatal functional connectivity. While traditional fMRI analyses have assessed the mean connectivity between regions of interest, an important aspect driving dopaminergic response might lie in the temporal dynamics in corticostriatal connections., Methods: This study aims to determine if altered resting-state dynamic functional network connectivity (DFC) is associated with dopaminergic motor response. To test this, static and DFC were assessed in 32 PD patients and 18 healthy controls (HC). Patients were grouped as low and high responders using a median split of their dopaminergic motor response., Results: Patients featuring a high dopaminergic motor response were observed to spend more time in a regionally integrated state compared to HC. Furthermore, DFC between the anterior midcingulate cortex/dorsal anterior cingulate cortex (aMCC/dACC) and putamen was lower in low responders during a more segregated state and correlated with dopaminergic motor response., Conclusion: The findings of this study revealed that temporal dynamics of fronto-striatal connectivity are associated with clinically relevant information, which may be considered when assessing functional connectivity between regions involved in motor initiation., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Due to the increasing prevalence of Alzheimer's disease (AD) and the limited efficacy of pharmacological treatment, the interest in non-pharmacological interventions, e.g., cognitive stimulation therapy (CST), to improve cognitive dysfunction and the quality of life of AD patients are on a steady rise., Objectives: Here, we examined the efficacy of a CST program specifically conceptualized for AD dementia patients and the neural mechanisms underlying cognitive or behavioral benefits of CST., Methods: Using neuropsychological tests and MRI-based measurements of functional connectivity, we examined the (neuro-) psychological status and network changes at two time points: pre vs. post-stimulation (8 to 12 weeks) in the intervention group ( n = 15 ) who received the CST versus a no-intervention control group ( n = 15 )., Results: After CST, we observed significant improvement in the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale, cognitive subsection (ADAS-cog), and the behavioral and psychological symptoms of dementia (BPSD) scores. These cognitive improvements were associated with an up-regulated functional connectivity between the left posterior hippocampus and the trunk of the left postcentral gyrus., Conclusion: Our data indicate that CST seems to induce short-term global cognition and behavior improvements in mild to moderate AD dementia and enhances resting-state functional connectivity in learning- and memory-associated brain regions. These convergent results prove that even in mild to moderate dementia AD, neuroplasticity can be harnessed to alleviate cognitive impairment with CST., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Behfar, Richter, Kural, Clemens, Behfar, Folkerts, Fassbender, Kalbe, Fink and Onur.)

Background: MScanFit is a new motor unit number estimation (MUNE) technique applied in motor neuron diseases and polyneuropathies to assess clinical progression and underlying disease pathology. So far, its value in myopathies, especially myotonic dystrophies (MD), has not been investigated., Methods: Motor unit loss and characteristics of patients with genetically confirmed MD type 1 (n = 7) and type 2 (n = 5) were investigated using MScanFit of the abductor pollicis brevis muscle and compared to age-matched healthy controls. MUNE measures were correlated with muscle impairment determined by the MRC sum score and handgrip strength., Results: MScanFit detected motor unit loss in patients with MD (p = 0.017). There was no significant difference in motor unit loss between MD type 1 and type 2 (p = 0.64). CMAP-discontinuities which, when added up, exceed 50% of the CMAP amplitude were reduced in MD patients (p = 0.0284), but motor unit amplitudes were not significantly different (p = 0.0597). The motor unit loss strongly correlated with the MRC sum score (p = 0.014, Rho = 0.678)., Conclusions: Our study shows the feasibility of MScanFit in MD and its potential to serve as a surrogate marker for overall muscle impairment. Motor unit analysis indicates that neurogenic alterations in both MD subtypes might be present., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Beyond focal effects, stroke lesions impact the function of distributed networks. We here investigated (1) whether transcranial direct current stimulation (tDCS) alters the network changes induced by cerebral ischemia and (2) whether functional network parameters predict the therapeutic efficacy of tDCS in a mouse model of focal photothrombotic stroke., Methods: Starting 3 days after stroke, cathodal tDCS (charge density=39.6 kC/m²) was applied over 10 days in male C57Bl/6J mice under light anesthesia over the lesioned sensory-motor cortex. Functional connectivity (resting-state functional magnetic resonance imaging) was evaluated for up to 28-day poststroke, with global graph parameters of network integration computed., Results: Ischemia induced a subacute increase in connectivity accompanied by a significant reduction in characteristic path length, reversed by 10 days of tDCS. Early measures of functional network alterations and the network configuration at prestroke baseline predicted spontaneous and tDCS-augmented motor recovery., Discussion: Stroke induces characteristic network changes throughout the brain that can be detected by resting-state functional magnetic resonance imaging. These network changes were, at least in part, reversed by tDCS. Moreover, early markers of a network impairment and the network configuration before the insult improve the prediction of motor recovery., Competing Interests: Disclosures Dr Fink serves as spokesperson of a Collaborative Research Center (CRC 1451) funded by the deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

Background: Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been investigated in Alzheimer's disease (AD). Methods: 3T rs-fMRI data were obtained from healthy young controls (YC, n  = 26), healthy senior controls (SC, n  = 29), and AD patients ( n  = 35). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were analyzed, followed by the calculation of their concordance using Kendall's W for each brain voxel across time. Group differences in the concordance were compared globally, within seven intrinsic brain networks, and on a voxel-by-voxel basis with covariates of age, sex, head motion, and gray matter volume. Results: The global concordance was lowest in AD among the three groups, with similar differences for the single metrics. When comparing AD to SC, reductions of concordance were detected in each of the investigated networks apart from the limbic network. For SC in comparison to YC, lower global concordance without any network-level difference was observed. Voxel-wise analyses revealed lower concordance in the right middle temporal gyrus in AD compared to SC and lower concordance in the left middle frontal gyrus in SC compared to YC. Lower fALFF were observed in the right angular gyrus in AD in comparison to SC, but ReHo and DC showed no group differences. Conclusions: The concordance of resting-state measures differentiates AD from healthy aging and may represent a novel imaging marker in AD.

Recent developments in rodent brain imaging have enabled translational characterization of functional and structural connectivity at the whole brain level in vivo . Nevertheless, fundamental questions about the link between structural and functional networks remain unsolved. In this review, we systematically searched for experimental studies in rodents investigating both structural and functional network measures, including studies correlating functional connectivity using resting-state functional MRI with diffusion tensor imaging or viral tracing data. We aimed to answer whether functional networks reflect the architecture of the structural connectome, how this reciprocal relationship changes throughout a disease, how structural and functional changes relate to each other, and whether changes follow the same timeline. We present the knowledge derived exclusively from studies that included in vivo imaging of functional and structural networks. The limited number of available reports makes it difficult to draw general conclusions besides finding a spatial and temporal decoupling between structural and functional networks during brain disease. Data suggest that when overcoming the currently limited evidence through future studies with combined imaging in various disease models, it will be possible to explore the interaction between both network systems as a disease or recovery biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mahani, Kalantari, Fink, Hoehn and Aswendt.)

Background and Purpose: Status epilepticus (SE) is a neurological emergency due to prolonged seizure activity or multiple seizures without full recovery in between them. Prehospital SE management is crucial since its duration is correlated with higher morbidity and mortality rates. We examined the impact of different therapeutic strategies in the prehospital setting with a focus on levetiracetam., Methods: We initiated the Project for SE in Cologne, a scientific association of all neurological departments of Cologne, the fourth-largest city in Germany with around 1,000,000 inhabitants. All patients with an SE diagnosis were evaluated over 2 years (from March 2019 to February 2021) to determine whether prehospital levetiracetam use had a significant effect on SE parameters., Results: We identified 145 patients who received initial drug therapy in the prehospital setting by professional medical staff. Various benzodiazepine (BZD) derivatives were used as first-line treatments, which were mostly used in line with the recommended guidelines. Levetiracetam was regularly used ( n =42) and mostly in combination with BZDs, but no significant additional effect was observed for intravenous levetiracetam. However, it appeared that the administered doses tended to be low., Conclusions: Levetiracetam can be applied to adults with SE in prehospital settings with little effort. Nevertheless, the prehospital treatment regimen described here for the first time did not significantly improve the preclinical cessation rate of SE. Future therapy concepts should be based on this, and the effects of higher doses should in particular be reexamined., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Introduction: Dysarthria is highly prevalent in patients with Parkinson's disease (PD) and speech changes have already been detected in patients with prodromal PD on the acoustic level. However, the present study directly tracks underlying articulatory movements with electromagnetic articulography to investigate early speech alterations on the kinematic level in isolated REM sleep behavior disorder (iRBD) and compares them to PD and control speakers., Methods: Kinematic data of 23 control speakers, 22 speakers with iRBD, and 23 speakers with PD were collected. Amplitude, duration, and average speed of lower lip, tongue tip, and tongue body movements were analyzed. Naive listeners rated the intelligibility of all speakers., Results: Patients with iRBD produced tongue tip and tongue body movements that were larger in amplitude and longer in duration compared to control speakers, while remaining intelligible. Compared to patients with iRBD, patients with PD had smaller, longer and slower tongue tip and lower lip movements, accompanied by lower intelligibility. Thus, the data indicate that the lingual system is already affected in prodromal PD. Furthermore, lower lip and especially tongue tip movements slow down and speech intelligibility decreases if motor impairment is more pronounced., Conclusion: Patients with iRBD adjust articulatory patterns to counteract incipient motor detriment on speech to maintain their intelligibility level., Competing Interests: Declaration of competing interest The authors declare no financial or non-financial competing interests relevant to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Suppression of pathologically altered activity in the beta-band has previously been suggested as a biomarker for feedback-based neurostimulation in subthalamic deep brain stimulation (STN-DBS) for Parkinson's Disease (PD)., Objective: To assess the utility of beta-band suppression as a tool for contact selection in STN-DBS for PD., Methods: A sample of seven PD patients (13 hemispheres) with newly implanted directional DBS leads of the STN were recorded during a standardized monopolar contact review (MPR). Recordings were received from contact pairs adjacent to the stimulation contact. The degree of beta-band suppression for each investigated contact was then correlated to the respective clinical results. Additionally, we have implemented a cumulative ROC analysis, to test the predictive value of beta-band suppression on the clinical efficacy of the respective contacts., Results: Stimulation ramping led to frequency-specific changes in the beta-band, while lower frequencies remained unaffected. Most importantly, our results showed that the degree of low beta-band suppression from baseline activity (stimulation off) served as a predictor for clinical efficacy of the respective stimulation contact. In contrast suppression of high beta-band activity yielded no predictive power., Conclusion: The degree of low beta-band suppression can serve as a time-saving, objective tool for contact selection in STN-DBS., Competing Interests: Declaration of competing interest J.N.S. has received funding for an investigator-initiated trial (IIT; Reference number: ERP-2021-12740) and received speaker honoraria from Medtronic GmbH. T.A.D. received speaker honoraria from Medtronic GmbH. P.A. has received honoraria for lecturing fees and educational activities from Medtronic GmbH. V.V.V. received support für contributions to congresses from Boston Scientific and Medtronic GmbH. The authors declare that there are no additional disclosures to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Purpose: Cognitive decline is a frequent and debilitating non-motor symptom for patients with Parkinson's disease (PD). Metabolic alterations in the occipital cortex during visual processing may serve as a biomarker for cognitive decline in patients with PD., Methods: Sixteen patients with PD (Unified Parkinson's Disease Rating Scale Part 3, OFF, 38.69 ± 17.25) and 10 age- and sex-matched healthy controls (HC) underwent 7-T functional magnetic resonance spectroscopy (MRS) utilizing a visual checkerboard stimulation. Glutamate metabolite levels during rest versus stimulation were compared. Furthermore, correlates of the functional MRS response with performance in visuo-cognitive tests were investigated., Results: No differences in static MRS between patients with PD and HC were detected, but a dynamic glutamate response was observed in functional MRS in HC upon visual stimulation, which was blunted in patients with PD (F 1,22  = 7.13, p = 0.014; η p 2  = 0.245). A diminished glutamate response correlated with poorer performance in the Benton Judgment of Line Orientation test in PD (r = -0.57, p = 0.020)., Conclusions: Our results indicate that functional MRS captures even subtle differences in neural processing linked to the behavioral performance, which would have been missed by conventional, static MRS. Functional MRS thus represents a promising tool for studying molecular alterations at high sensitivity. Its prognostic potential should be evaluated in longitudinal studies, prospectively contributing to earlier diagnosis and individual treatment decisions., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequate first-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies. Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in a rodent model of acute autoimmune neuropathies, experimental autoimmune neuritis., Methods: Experimental autoimmune neuritis was induced in Lewis rats with the neurogenic P2-peptide. At the beginning of the recovery phase at day 18, the animals were treated with 1 mg/kg monastrol or sham and observed until day 30 post-immunisation. Electrophysiological and histological analysis for markers of inflammation and remyelination of the sciatic nerve were performed. Neuromuscular junctions of the tibialis anterior muscles were analysed for reinnervation. We further treated human induced pluripotent stem cells-derived secondary motor neurons with monastrol in different concentrations and performed a neurite outgrowth assay., Results: Treatment with monastrol enhanced functional and histological recovery in experimental autoimmune neuritis. Motor nerve conduction velocity at day 30 in the treated animals was comparable to pre-neuritis values. Monastrol-treated animals showed partially reinnervated or intact neuromuscular junctions. A significant and dose-dependent accelerated neurite outgrowth was observed after kinesin-5 inhibition as a possible mode of action., Conclusion: Pharmacological kinesin-5 inhibition improves the functional outcome in experimental autoimmune neuritis through accelerated motor neurite outgrowth and histological recovery. This approach could be of interest to improve the outcome of autoimmune neuropathy patients., (© 2023. The Author(s).)

In patients with meningioma, diagnosis and treatment planning are predominantly based on anatomical imaging using MRI or CT. Constraints of these imaging modalities include precise meningioma delineation-especially at the skull base, in the case of trans -osseus growth, and in tumors with complex geometry-and the differentiation of post-therapeutic reactive changes from meningioma relapse. Advanced metabolic imaging using PET may help to characterize specific metabolic and cellular features providing additional information beyond the information derived from anatomical imaging alone. Accordingly, the use of PET in meningioma patients is steadily increasing. This review summarizes recent advances in PET imaging helpful for improving the clinical management of patients with meningioma., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction/aims: Nonsystemic vasculitic neuropathy (NSVN) is characterized by a predominant lower limb involvement in many patients. Motor unit changes in upper extremity muscles have not been investigated in this subgroup but may be of interest for improving our understanding of the multifocal nature of the disease and counseling of patients about potential future symptoms. In this study we aimed to better understand subclinical motor involvement in the upper extremity muscles of patients with lower limb-predominant NSVN using the new motor unit number estimation (MUNE) method MScanFit., Methods: In this single-center, cross-sectional study, 14 patients with biopsy-proven NSVN, with no clinical signs of upper extremity motor involvement, were investigated and compared with 14 age-matched healthy controls. All participants were assessed clinically and by the MUNE method MScanFit to the abductor pollicis brevis muscle., Results: The number of motor units and peak CMAP amplitudes were significantly reduced in patients with NSVN (P = .003 and P = .004, respectively). Absolute median motor unit amplitudes and CMAP discontinuities were not significantly different (P = .246 and P = .1, respectively). CMAP discontinuities were not significantly correlated with motor unit loss (P = .15, rho = 0.4). The number of motor units did not correlate with clinical scores (P = .77, rho = 0.082)., Discussion: Both MUNE and CMAP amplitudes showed motor involvement in upper extremity muscles in lower limb-predominant NSVN. Overall, there was no evidence of significant reinnervation. Investigations of the abductor pollicis brevis muscle did not show a correlation with overall functional disability of the patients., (© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) cohorts have provided insights into the earliest neurodegenerative processes in α-synucleinopathies. Even though polysomnography (PSG) remains the gold standard for diagnosis, an accurate questionnaire-based algorithm to identify eligible subjects could facilitate efficient recruitment in research., Objective: This study aimed to optimize the identification of subjects with iRBD from the general population., Methods: Between June 2020 and July 2021, we placed newspaper advertisements, including the single-question screen for RBD (RBD1Q). Participants' evaluations included a structured telephone screening consisting of the RBD screening questionnaire (RBDSQ) and additional sleep-related questionnaires. We examined anamnestic information predicting PSG-proven iRBD using logistic regressions and receiver operating characteristic curves., Results: Five hundred forty-three participants answered the advertisements, and 185 subjects fulfilling inclusion and exclusion criteria were screened. Of these, 124 received PSG after expert selection, and 78 (62.9%) were diagnosed with iRBD. Selected items of the RBDSQ, the Pittsburgh Sleep Quality Index, the STOP-Bang questionnaire, and age predicted iRBD with high accuracy in a multiple logistic regression model (area under the curve >80%). When comparing the algorithm to the sleep expert decision, 77 instead of 124 polysomnographies (62.1%) would have been carried out, and 63 (80.8%) iRBD patients would have been identified; 32 of 46 (69.6%) unnecessary PSG examinations could have been avoided., Conclusions: Our proposed algorithm displayed high diagnostic accuracy for PSG-proven iRBD cost-effectively and may be a convenient tool for research and clinical settings. External validation sets are warranted to prove reliability. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

As nearly all brain functions, perception, motion, and higher-order cognitive functions require coordinated neural information processing within distributed cortical networks. Over the past decades, new theories and techniques emerged that advanced our understanding of how information is transferred between cortical areas. This review surveys critical aspects of interareal information exchange. We begin by examining the brain's structural connectivity, which provides the basic framework for interareal communication. We then illustrate information exchange between cortical areas using the visual system as an example. Next, well-studied and newly proposed theories that may underlie principles of neural communication are reviewed, highlighting recent work that offers new perspectives on interareal information exchange. We finally discuss open questions in the study of the neural mechanisms underlying interareal information exchange.

Objective: Elevated cortisol levels have been frequently reported in Alzheimer's disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol levels, hippocampal volume, gray matter volume and memory performance in healthy aging and AD., Methods: In our cross-sectional study, we analyzed the relationships between morning serum cortisol levels, verbal memory performance, hippocampal volume, and whole-brain voxel-wise gray matter volume in an independent sample of 29 healthy seniors (HS) and 29 patients along the spectrum of biomarker-based AD., Results: Cortisol levels were significantly elevated in patients with AD as compared to HS, and higher cortisol levels were correlated with worse memory performance in AD. Furthermore, higher cortisol levels were significantly associated with smaller left hippocampal volumes in HS and indirectly negatively correlated to memory function through hippocampal volume. Higher cortisol levels were further related to lower gray matter volume in the hippocampus and temporal and parietal areas in the left hemisphere in both groups. The strength of this association was similar in HS and AD., Conclusion: In AD, cortisol levels are elevated and associated with worse memory performance. Furthermore, in healthy seniors, higher cortisol levels show a detrimental relationship with brain regions typically affected by AD. Thus, increased cortisol levels seem to be indirectly linked to worse memory function even in otherwise healthy individuals. Cortisol may therefore not only serve as a biomarker of increased risk for AD, but maybe even more importantly, as an early target for preventive and therapeutic interventions., Competing Interests: GF serves as an editorial board member of Cortex, Neurological Research and Practice, NeuroImage: Clinical, Zeitschrift für Neuropsychologie, and DGNeurologie. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dronse, Ohndorf, Richter, Bischof, Fassbender, Behfar, Gramespacher, Dillen, Jacobs, Kukolja, Fink and Onur.)

Background: We evaluated O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and MRI for early response assessment in recurrent glioma patients treated with lomustine-based chemotherapy., Methods: Thirty-six adult patients with WHO CNS grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1-3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (not later than two cycles). Tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR >1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. PET parameter thresholds were defined using ROC analyses to predict PFS of ≥6 months and OS of ≥12 months. MRI response assessment was based on RANO criteria. The predictive values of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates., Results: After treatment initiation, the median follow-up time was 11 months (range, 3-71 months). Relative changes of TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P ≤ .002) and OS (all P ≤ .045). At follow-up, the occurrence of new distant hotspots (n ≥ 1) predicted a worse outcome, with significantly shorter PFS (P = .005) and OS (P < .001). Time-to-peak changes did not predict a significantly longer survival. Multivariate survival analyses revealed that new distant hotspots at follow-up FET PET were most potent in predicting non-response (P < .001; HR, 8.578)., Conclusions: Data suggest that FET PET provides complementary information to RANO criteria for response evaluation of lomustine-based chemotherapy early after treatment initiation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

PET imaging using radiolabeled amino acids in addition to MRI has become a valuable diagnostic tool in the clinical management of patients with brain tumors. This review provides a comprehensive overview of PET studies in glioma patients with a mutation in the isocitrate dehydrogenase gene (IDH). A considerable fraction of these tumors typically show no contrast enhancement on MRI, especially when classified as grade 2 according to the World Health Organization classification of Central Nervous System tumors. Major diagnostic challenges in this situation are differential diagnosis, target definition for diagnostic biopsies, delineation of glioma extent for treatment planning, differentiation of treatment-related changes from tumor progression, and the evaluation of response to alkylating agents. The main focus of this review is the role of amino acid PET in this setting. Furthermore, in light of clinical trials using IDH inhibitors targeting the mutated IDH enzyme for treating patients with IDH-mutant gliomas, we also aim to give an outlook on PET probes specifically targeting the IDH mutation, which appear potentially helpful for response assessment., (© 2022. The Author(s).)

Abstract: Differentiating brain tumors from nonneoplastic lesions using conventional MRI may be challenging. Clinical symptoms often remain unspecific, and imaging findings from MRI may be inconclusive. We present the case of a 23-year-old woman in whom an MRI suggested a cerebral venous sinus thrombosis. On the other hand, additional atypical MRI findings raised doubts regarding the initial diagnosis. Given the need for a diagnostic procedure with higher sensitivity and specificity for neoplastic tissue, PET with the radiolabeled somatostatin receptor ligand DOTATATE ( 68 Ga-DOTA- d -Phe1-Tyr3-octreotate) was performed. DOTATATE PET facilitated the diagnosis of a falcine meningioma consistent with its value for the differential diagnosis of meningioma., Competing Interests: Conflicts of interest and sources of funding: The Cologne Clinician Scientist-Program of the Deutsche Forschungsgemeinschaft (FI773/15-1), Germany, supported this work. The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

For decades, several amino acid PET tracers have been used to optimize diagnostics in patients with brain tumors. In clinical routine, the most important clinical indications for amino acid PET in brain tumor patients are differentiation of neoplasm from nonneoplastic etiologies, delineation of tumor extent for further diagnostic and treatment planning (i.e., diagnostic biopsy, resection, or radiotherapy), differentiation of treatment-related changes such as pseudoprogression or radiation necrosis after radiation or chemoradiation from tumor progression at follow-up, and assessment of response to anticancer therapy, including prediction of patient outcome. This continuing education article addresses the diagnostic value of amino acid PET for patients with either glioblastoma or metastatic brain cancer., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD., Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests., Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores., Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To explore the reasons for and outcomes of non- or undertreatment with benzodiazepines (BZDs) in status epilepticus (SE)., Methods: We retrospectively analysed all SE patients from the urban area of Cologne over two years., Results: 328 SE patients were eligible, and only 72% were initially treated with BZDs. Of these, only 21.6% were treated sufficiently with BZDs according to current guidelines. SE patients not initially treated with BZDs were significantly older, had less often known epilepsy, had a prolonged arrival time to the emergency room, and presented more often with a non-generalised convulsive semiology. Regarding adequate dosages, patients with a generalised convulsive SE seemed to benefit from a sufficient BZD dosing with significantly shortened mean ventilation duration (37.1 to 208 h), decreased mean intensive care unit (1.7 to 5 days) and in-hospital stay (4.1 to 8.8 days). In contrary, aggressive BZD treatment in non-generalised convulsive SE resulted in a longer inpatient stay (9.2 to 5.8 days) and lower favourable outcome rates at discharge (16% to 63%)., Conclusions: The current SE treatment guidelines for first-line BZD therapy in SE were violated in most patients. Sufficient BZD dosing was beneficial in generalised convulsive SE, but not in other forms of SE. SE semiology might be crucial for treatment decisions with BZDs. Further treatment evidence especially in non-generalised convulsive SE is urgently needed., Competing Interests: Declaration of Competing Interest FK is supported by the Koeln Fortune Program / Faculty of Medicine, University of Cologne (472/2020). The funding is not related to this project. GRF received royalties from Spinger, Thieme and Hogrefe. He declared speaker honoraria from Bayer, Desitin, Ergo DKV, Forum für medizinische Fortbildung (FomF) GmbH, GSK, Medica Academy Messe Düsseldorf, Medicbrain Healthcare, Novartis, Pfizer, and Sportärztebund NRW. The remaining authors have no conflicts of interest., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: A fraction of patients with asymptomatic to mild/moderate acute COVID-19 disease report cognitive deficits as part of the post-COVID-19 syndrome. This study aimed to assess the neuropsychological profile of these patients., Methods: Assessment at baseline (three months or more following acute COVID-19) of a monocentric prospective cohort of patients with post-COVID-19 syndrome. Multidomain neuropsychological tests were performed, and questionnaires on depression, anxiety, fatigue, sleep, and general health status were administered., Results: Of the 58 patients screened, six were excluded due to possible alternative causes of cognitive impairment (major depression, neurodegenerative disease). Of the remaining 52 individuals, only one had a below-threshold screening result on Mini-Mental State Examination, and 13 scored below the cut-off on Montreal Cognitive Assessment. Extended neuropsychological testing revealed a neurocognitive disorder (NCD) in 31 (59.6%) participants with minor NCD in the majority of cases (n = 26). In patients with NCD, the cognitive domains learning/memory and executive functions were impaired in 60.7%, complex attention in 51.6%, language in 35.5%, and perceptual-motor function in 29.0%. Cognitive profiles were associated with daytime sleepiness but not with depression, anxiety, sleep quality, total general health status, or fatigue., Conclusion: Neurocognitive impairment can be confirmed in around 60% of individuals with self-reported deficits as part of post-COVID-19 syndrome following a mild acute COVID-19 disease course. Notably, screening tests cannot reliably detect this dysfunction. Standard psychiatric assessments showed no association with cognitive profiles. Longitudinal studies are needed to further evaluate the course of neurocognitive deficits and clarify pathophysiology., (© 2022. The Author(s).)

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.

Activity changes in the ipsi- and contralesional parietal cortex and abnormal interhemispheric connectivity between these regions are commonly observed after stroke, however, their significance for motor recovery remains poorly understood. We here assessed the contribution of ipsilesional and contralesional anterior intraparietal cortex (aIPS) for hand motor function in 18 recovered chronic stroke patients and 18 healthy control subjects using a multimodal assessment consisting of resting-state functional MRI, motor task functional MRI, online-repetitive transcranial magnetic stimulation (rTMS) interference, and 3D movement kinematics. Effects were compared against two control stimulation sites, i.e. contralesional M1 and a sham stimulation condition. We found that patients with good motor outcome compared to patients with more substantial residual deficits featured increased resting-state connectivity between ipsilesional aIPS and contralesional aIPS as well as between ipsilesional aIPS and dorsal premotor cortex. Moreover, interhemispheric connectivity between ipsilesional M1 and contralesional M1 as well as ipsilesional aIPS and contralesional M1 correlated with better motor performance across tasks. TMS interference at individual aIPS and M1 coordinates led to differential effects depending on the motor task that was tested, i.e. index finger-tapping, rapid pointing movements, or a reach-grasp-lift task. Interfering with contralesional aIPS deteriorated the accuracy of grasping, especially in patients featuring higher connectivity between ipsi- and contralesional aIPS. In contrast, interference with the contralesional M1 led to impaired grasping speed in patients featuring higher connectivity between bilateral M1. These findings suggest differential roles of contralesional M1 and aIPS for distinct aspects of recovered hand motor function, depending on the reorganization of interhemispheric connectivity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis., Methods: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays., Results: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome., Conclusions: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels., Competing Interests: Declaration of Competing Interest Madlener, Doppler, Finke, Gerner, Lewerenz, Linsa, Mues, Paliantonis, Priller, Prüß, Rössling, Schirotzek, Senel, Sommer, Strippel, Süße, Tauber, Wandinger, Wickel: Nothing to report. Fink: Bayer, Desitin, GSK, Novartis, Pfizer: lectures. Kellingshaus: UCB Pharma, Eisai GmbH, LivaNova Europe: lectures, consultancies. Kraft: Böhringer-Ingelheim, Daichii-Sankyo, Pfitzer/BMS, Bayer: travel expenses, lectures. Kümpfel: Bayer Healthcare, Merck, Novartis Pharma, Roche Pharma: lectures, consultancies. Leypoldt: Alexion, Roche and Biogen AdvisoryBoard, Novartis, Bayer, Roche: lectures. Malter: UCB Pharma, EISAI GmbH: lectures, consultancies. Melzer: Biogen Idec, GlaxoSmith Kline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion Pharamceuticals, Fresenius Medical Care, Diamed, and BIAL: lectures, Euroimmun, Fresenius Medical Care, Diamed, Alexion Pharamceuticals, and Novartis Pharma: funding. Menge: Biogen, Novartis, Teva: lectures, Biogen: consultancies, travel expenses. Ringelstein: Novartis, Bayer, Roche, Alexion, Ipsen: lectures, Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Grifols, Roche and Merck: travel expenses. Urbanek: Böhringer-Ingelheim: lectures, Daichii-Sankyo: lectures, travel expenses, sPfitzer/BMS: travel expenses. Senel: Bayer, Biogen, Merck, Roche, and Sanofi Genzyme: lectures and/or consultancies; Celgene, TEVA: travel expenses. Sühs: Merck: lectures, travel expenses. Tauber: Teva, Biogen, Merck Serono und Roche: lectures, travel expenses. Thaler: Novartis: funding. Then Bergh: Actelion, Novartis: funding; Actelion, Bayer, Merck, Roche: lectures; Merck, Roche, Sanofi-Genzyme: Advisory Board; Actelion, Merck: travel expenses., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stroke patients show some degree of spontaneous functional recovery, but this is not sufficient to prevent long-term disability. One promising approach is to characterize the dynamics of stroke recovery genes in the lesion and distant areas. We induced sensorimotor cortex lesions in adult C57BL/6J mice using photothrombosis and performed qPCR on selected brain areas at 14, 28, and 56 days post-stroke (P14-56). Based on the grid walk and rotating beam test, the mice were classified into two groups. The expression of cAMP pathway genes Adora2a , Pde10a , and Drd2 , was higher in poor- compared to well-recovered mice in contralesional primary motor cortex (cl-MOp) at P14&56 and cl-thalamus (cl-TH), but lower in cl-striatum (cl-Str) at P14 and cl-primary somatosensory cortex (cl-SSp) at P28. Plasticity and axonal sprouting genes, Lingo1 and BDNF , were decreased in cl-MOp at P14 and cl-Str at P28 and increased in cl-SSp at P28 and cl-Str at P14, respectively. In the cl-TH, Lingo1 was increased, and BDNF decreased at P14. Atrx , also involved in axonal sprouting, was only increased in poor-recovered mice in cl-MOp at P28. The results underline the gene expression dynamics and spatial variability and challenge existing theories of restricted neural plasticity.

Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson's disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies., (© 2023. The Author(s).)

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone., Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments., Methods: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months., Results: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III., Conclusion: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL., Methods: In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores., Results: Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits., Conclusion: In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients., (© 2023. The Author(s).)

Objectives: Whether treatment response in patients with Parkinson disease depends on brain atrophy is insufficiently understood. The goal of this study is to identify specific atrophy patterns associated with response to dopaminergic therapy and deep brain stimulation., Materials and Methods: In this study, we analyzed the association of gray matter brain atrophy patterns, as identified by voxel-based morphometry, with acute response to levodopa (N = 118) and subthalamic nucleus deep brain stimulation (N = 39). Motor status was measured as a change in points on the Unified Parkinson's Disease Rating Scale III score. Baseline values were obtained before surgery, after cessation of dopaminergic medication for at least 12 hours; response to medication was assessed after administration of a standardized dose of levodopa. Response to deep brain stimulation was measured three months after surgery in the clinical condition after withdrawal of dopaminergic medication., Results: Although frontoparietal brain gray matter loss was associated with subpar response to deep brain stimulation, there was no significant link between brain atrophy and response to levodopa., Conclusion: We conclude that response to deep brain stimulation relies on gray matter integrity; hence, gray matter loss may present a risk factor for poor response to deep brain stimulation and may be considered when making decision regarding clinical practice., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction: In addition to physical and cognitive symptoms, patients with multiple sclerosis (MS) have an increased risk of experiencing mental health problems., Methods: This narrative review provides an overview of the appearance and epidemiology of affective symptoms in MS such as depression, anxiety, bipolar disorder, euphoria, and pseudobulbar affect. Furthermore, the association between affective symptoms and quality of life and the currently used diagnostic instruments for assessing these symptoms are considered whereby relevant studies published between 2009 and 2021 were included in the review., Results: Patients with mild and moderate disability more frequently reported severe problems with depression and anxiety than severe mobility problems. Apart from the occurrence of depression, little is known about the association of other affective symptoms such as anxiety, bipolar disorder, euphoria, and pseudobulbar affect and subsyndromal symptoms, which fail to meet the diagnostic criteria but are nevertheless a significant source of distress. Although there are a few recommendations in the research to perform routine screenings for diagnosable affective disorders, a standardized diagnostic procedure to assess subsyndromal symptoms is still lacking. As the applied measurements are diverse and show low accuracy to detect these symptoms, patients who experience affective symptoms are less likely to be identified., Discussion: In addition to the consideration of definite psychiatric diagnoses, there is an unmet need for a common definition and assessment of disease-related affective symptoms in MS. Future studies should focus on the improvement and standardization of a common diagnostic procedure for subsyndromal affective symptoms in MS to enable integrated and optimal care for patients., (© 2022. The Author(s).)

Background: Previous studies on left hemisphere (LH) stroke patients reported effector-specific (hand, fingers, bucco-facial) differences in imitation performance. Furthermore, imitation performance differed between meaningless (ML) and meaningful (MF) gestures. Recent work suggests that a gesture's meaning impacts the body-part specificity of gesture imitation., Methods: We tested the hypothesis that the gesture's meaning (ML vs MF) affects the lesion correlates of effector-specific imitation deficits (here: bucco-facial vs arm/hand gestures) using behavioural data and support vector regression-based lesion-symptom mapping (SVR-LSM) in a large sample of 194 sub-acute LH stroke patients., Results: Behavioural data revealed a significant interaction between the effector used for imitation and the meaning of the imitated gesture. SVR-LSM analyses revealed shared lesion correlates for impaired imitation independent of effector or gesture meaning in the left supramarginal (SMG) and superior temporal gyri (STG). Besides, within the territory of the left middle cerebral artery, impaired imitation of bucco-facial gestures was associated with more anterior lesions, while arm/hand imitation deficits were associated with more posterior lesions. MF gestures were specifically associated with lesions in the left inferior frontal gyrus and the left insular region. Notably, an interaction of effector-specificity and gesture meaning was also present at the lesion level: A more pronounced difference in imitation performance between the effectors for ML (versus MF) gestures was associated with left-hemispheric lesions in the STG, SMG, putamen, precentral gyrus and white matter tracts., Conclusion: The current behavioural data show that ML gestures are particularly sensitive in assessing effector-specific imitation deficits in LH stroke patients. Moreover, a gesture's meaning modulated the effector-specific lesion correlates of bucco-facial and arm/hand gesture imitation. Hence, it is crucial to consider gesture meaning in apraxia assessments., 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 © 2023. Published by Elsevier Inc.)

Background and Purpose: Sex differences in the clinical findings and the polysomnographic presentation of patients with obstructive sleep apnea (OSA) are compelling current research issues. For example, patients suffering from obstructive sleep apnea are predominantly male. While women are older than men and tend to have a higher body mass index, men typically present with a more severe form of obstructive sleep apnea. Using polysomnography, we investigated a German cohort, subdivided per severity levels of obstructive sleep apnea (apnea-hypopnea index: ≥5 to < 15/h (mild), ≥15 to < 30/h (moderate), and ≥30/h (severe)) to provide a detailed analysis of breathing and sleep parameters, accounting for body position effects and severity of illness. A deeper understanding of sex differences may allow targeted diagnosis and treatment adjustment., Patients and Methods: This retrospective study included a cohort of 1242 German patients (940 male, 302 female) who underwent overnight polysomnography at the private sleep laboratory "Intersom Köln", Center for Sleep Medicine and Sleep Research. In 1125 subjects (878 male, 247 female), obstructive sleep apnea was diagnosed. All patients were examined between January 01, 2018 and December 31, 2020, comparing anthropometric, sleep morphological, and respiratory polysomnographic findings., Results: Female patients with obstructive sleep apnea were significantly older than male patients (60.9 ± 12.3 vs. 56.9 ± 12.5 years, P < .001), also among OSA subgroups per OSA severity. The body mass index was similar in male and female patients (29.6 ± 5.1 vs. 29.2 ± 7.3 kg/m 2 , P > .05), including the three subgroups. Men were more likely to have severe obstructive sleep apnea (46.9%) than women (35.2%). Women exhibited a higher proportion of slow-wave sleep than men (129.4 ± 52.8 vs. 104.2 ± 53.2 min; P < .001). The apnea-hypopnea index of total sleep time was significantly greater in male than female patients (32.9 ± 21.2 vs. 27.2 ± 20.2 per hour; P < .001). Female patients had a higher apnea-hypopnea index during rapid-eye-movement (REM) sleep (34.0 ± 23.8 vs. 31.8 ± 22.3 per hour; P = .171). A statistically significant difference in the apnea-hypopnea index during REM sleep between sexes was found when the obstructive sleep apnea severity was considered. Women had a lower apnea-hypopnea index in non-rapid eye-movement (NREM) sleep than men (25.7 ± 21.1 vs. 32.7 ± 22.3 per hour; P < .001). The oxygen desaturation index (29.9 ± 20.3 vs. 22.4 ± 19.4%; P < .001) and an oxygen desaturation below 90% (9.4 ± 14.0 vs. 6.8 ± 11.7%; P = .003) was greater in men than in women. In severe obstructive sleep apnea, the oxygen desaturation index was similar between the sexes (45.0 ± 17.8 vs. 41.1 ± 20.9%; P = .077). Male patients showed a higher supine apnea-hypopnea-index than female patients. (45.7 ± 26.7 vs 36.1 ± 22.7 per hour; P < .001)., Conclusion: The present noninvasive, retrospective registry study is the first to examine sex differences in OSA in such a large German population in terms of respiratory and sleep parameters, taking into account the effects of body position and severity of the disease. We could confirm and extend observations from previous studies. Female patients were significantly older than the male patients. The apnea-hypopnea index was higher in male than in female patients. Women showed a higher apnea-hypopnea index in REM sleep and a lower one in NREM sleep. Men were desaturated more often and were more affected by supine-dependent obstructive sleep apnea than women. Contrary to the literature, there were no significant differences in body mass index (BMI) between the sexes. With increasing age and BMI, the gender differences become less significant., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Stigma is significant in Parkinson's disease (PD). However, no specific tool is available to assess stigma in PD comprehensively., Objective: This pilot study aimed to develop and test a stigma questionnaire specific to PD patients (PDStigmaQuest)., Methods: Based on a literature review, clinical experience, expert consensus, and patients' feedback, we developed the preliminary, patient-completed PDStigmaQuest in German language. It included 28 items covering five stigma domains: uncomfortableness, anticipated stigma, hiding, experienced stigma, and internalized stigma. In this pilot study, 81 participants (PD patients, healthy controls, caregivers, and health professionals) were included to investigate the acceptability, feasibility, comprehensibility, and psychometric properties of the PDStigmaQuest., Results: The PDStigmaQuest showed 0.3% missing data points for PD patients and 0.4% for controls, suggesting high data quality. Moderate floor effects, but no ceiling effects were found. In the item analysis, most items met the standard criteria of item difficulty, item variance, and item-total correlation. Cronbach's alpha was > 0.7 for four of five domains. PD patients' domain scores were significantly higher than healthy controls' for uncomfortableness, anticipated stigma, and internalized stigma. Feedback to the questionnaire was predominantly positive., Conclusion: Our results indicate that the PDStigmaQuest is a feasible, comprehensive, and relevant tool to assess stigma in PD and helps to understand the construct of stigma in PD further. Based on our results, the preliminary version of the PDStigmaQuest was modified and is currently validated in a larger population of PD patients for use in clinical and research settings.

Introduction: In clinical practice, differentiating between age-related gray matter (GM) atrophy and neurodegeneration-related atrophy at early disease stages, such as mild cognitive impairment (MCI), remains challenging. We hypothesized that fined-grained adjustment for age effects and using amyloid-negative reference subjects could increase classification accuracy., Methods: T1-weighted magnetic resonance imaging (MRI) data of 131 cognitively normal (CN) individuals and 91 patients with MCI from the Alzheimer's disease neuroimaging initiative (ADNI) characterized concerning amyloid status, as well as 19 CN individuals and 19 MCI patients from an independent validation sample were segmented, spatially normalized and analyzed in the framework of voxel-based morphometry (VBM). For each participant, statistical maps of GM atrophy were computed as the deviation from the GM of CN reference groups at the voxel level. CN reference groups composed with different degrees of age-matching, and mixed and strictly amyloid-negative CN reference groups were examined regarding their effect on the accuracy in distinguishing between CN and MCI. Furthermore, the effects of spatial smoothing and atrophy threshold were assessed., Results: Approaches with a specific reference group for each age significantly outperformed all other age-adjustment strategies with a maximum area under the curve of 1.0 in the ADNI sample and 0.985 in the validation sample. Accounting for age in a regression-based approach improved classification accuracy over that of a single CN reference group in the age range of the patient sample. Using strictly amyloid-negative reference groups improved classification accuracy only when age was not considered., Conclusion: Our results demonstrate that VBM can differentiate between age-related and MCI-associated atrophy with high accuracy. Crucially, age-specific reference groups significantly increased accuracy, more so than regression-based approaches and using amyloid-negative reference groups., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Magnetic resonance imaging (MRI) is currently explored as supplemental tool to monitor disease progression and treatment response in various neuromuscular disorders. We here assessed the utility of a multi-parametric magnetic resonance imaging (MRI) protocol including quantitative water T 2 mapping, Dixon-based proton density fat fraction (PDFF) estimation and diffusion tensor imaging (DTI) to detect loss of spinal motor neurons and subsequent muscle damage in adult SMA patients., Methods: Sixteen SMA patients and 13 age-matched controls were enrolled in this prospective, longitudinal study. All participants underwent MRI imaging including measurements of Dixon-based PDFF and DTI of the sciatic nerve. SMA patients furthermore underwent measurements of muscle water T 2 (T 2w ) of the biceps femoris muscle (BFM) and quadriceps femoris muscle (QFM). Ten participants returned for a second scan six months later. MRI parameter were correlated with clinical data. All patients were on nusinersen treatment., Results: There were significantly higher intramuscular fat fractions in the BFM and QFM of SMA patients compared to healthy controls at baseline and after 6 months. Furthermore, T2 values significantly correlated positively with intramuscular fat fractions. The Hammersmith functional motor scale significantly correlated with the QFM's intramuscular fat fractions. DTI scans of the sciatic nerve were not significantly different between the two groups., Conclusion: This study demonstrates that, water T 2 mapping and Dixon-based PDFF estimation may distinguish between adult SMA patients and controls, due to massive intramuscular fat accumulation in SMA. More extensive long-term studies are warranted to further evaluate these two modalities as surrogate markers in SMA patients during treatment., (© 2022. The Author(s).)

Background: Although post-stroke depression (PSD) is known to disrupt motor rehabilitation after stroke, PSD is often undertreated and its relationship with motor impairment remains poorly understood., Methods: In a longitudinal study design we investigated, which factors at the early post-acute stage may increase the risk for PSD symptoms. We were especially interested in whether interindividual differences in the motivational drive to engage in physically demanding tasks indicate PSD development in patients suffering from motor impairments. Accordingly, we used a monetary incentive grip force task where participants were asked to hold their grip force for high and low rewards at stake to maximize their monetary outcome. Individual grip force was normalized according to the maximal force prior to the experiment. Experimental data, depression, and motor impairment were assessed from 20 stroke patients (12 male; 7.7 ± 6.78 days post-stroke) with mild-to-moderate hand motor impairment and 24 age-matched healthy participants (12 male)., Results: Both groups showed incentive motivation as indicated by stronger grip force for high versus low reward trials and the overall monetary outcome in the task. In stroke patients, severely impaired patients showed stronger incentive motivation, whereas early PSD symptoms were associated with reduced incentive motivation in the task. Larger lesions in corticostriatal tracts correlated with reduced incentive motivation. Importantly, chronic motivational deficits were preceded by initially reduced incentive motivation and larger corticostriatal lesions in the early stage post-stroke., Conclusions: More severe motor impairment motivates reward-dependent motor engagement, whereas PSD and corticostriatal lesions potentially disturb incentive motivational behavior, thereby increasing the risk of chronic motivational PSD symptoms. Acute interventions should address motivational aspects of behavior to improve motor rehabilitation post-stroke., 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 © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)