The Cerebellum

ImportanceRecovery after upper extremity peripheral nerve injury (PNI) surgery depends on changes in cortical neural patterns that support sensorimotor control. Task-based functional connectivity (FC) can characterize these changes, yet few studies have explored FC during ecologically fine motor valid tasks after PNI. ObjectiveTo investigate task-based FC with the left primary motor cortex (M1) during right hand drawing in individuals following right hand PNI surgery. ParticipantsForty-four right-handed adults, including 12 patients post PNI surgery (n = 8 with nerve repair, n = 4 with nerve transfer) and 32 healthy controls. MethodsAll participants underwent fMRI while performing a RH visuomotor precision drawing task. Seed-based connectivity analysis was performed to characterize the pattern of FC between left M1 and all voxels in the brain. We hypothesized that left M1 FC would differ between patients and controls, between Repair and Transfer groups, and covary with time since surgery. ResultsPatients (vs. controls) showed greater FC between left M1 and right visual and premotor cortices. Nerve transfer (vs. repair) showed greater FC between left M1 and right inferior parietal areas. Time since surgery was not linearly related to FC, though exploratory analyses suggested a negative association between log-time and FC between left M1 and right inferior parietal lobule. ConclusionAfter PNI surgery, visuomotor precision drawing involved distinct and behaviorally relevant neural patterns, which varied by task demand and potentially by surgical group despite clinical heterogeneity. Inferior parietal cortex may be especially engaged in early months after surgery (i.e. log-time). To improve recovery of upper limb function after PNI, clinical recommendations include incorporating early function-specific dexterous training, tailoring rehabilitation across surgical and recovery stages, and using multidimensional assessments of hand function.

Cerebellar ataxias are a rare group of disorders manifesting with motor incoordination and cognitive-affective deficits of variable severity. Although neurogenetic has revealed multiple mutations, the study of ataxias still relies on clinical evaluation, while the underlying neural network changes remain unclear. It has been argued that the less severe symptoms in congenital (like Joubert syndrome, JS) than in slowly progressive (SP) ataxias reflect a different interplay of alteration and compensation but direct evidence is still lacking. Moreover, it is unclear why, in front of a wide heterogeneity of molecular alterations, SPs show common clinical symptoms. To address these questions, we created brain digital twins for each participant by combining volumetry, graph theory analysis of structural and functional connectivity, and dynamical simulations using the virtual brain. We studied 8 JS (3 females, 21{+/-}6years), 8 SP (3 females, 20{+/-}5years) and 11 healthy controls (HC; 5 females, 21{+/-}2years).Volumetry quantified atrophy, graph metrics (centrality, segregation and integration) characterized topology, and neural dynamical simulations estimated excitation/inhibition balance, providing anatomo-physiological parameters within the somatomotor (SMN) and ventral attention (VAN) networks. Anatomo-physiological parameters were correlated with clinical/neuropsychological scores, and unsupervised clustering was applied to assess whether network features can discriminate between JS and SP beyond clinical classification. MRI morphometry confirmed selective vermis reduction in JS and a widespread cerebellar atrophy in SP compared to HC. In both ataxia groups, SMN and VAN showed reduced volume and structural connectivity but with different patterns of topological and dynamical alterations. In the SMN of SP, reduced centrality and excitation/inhibition balance depressed information transfer through the network. In the VAN of JS, reduced centrality, segregation, and integration, were detrimental but coexisted with a higher number of functional core nodes and an increased large-scale excitatory coupling, supporting compensatory reorganisation in extracerebellar nodes. Clustering confirmed that SMN better differentiates SP, whereas VAN better clusters JS. Importantly, anatomo-physiological parameters of network volume, topology, and dynamics correlated with patients motor and cognitive performance. In conclusion, primary cerebellar damage secondarily impacts large-scale brain networks, altered in both ataxia groups but compensated only in JS. Similar clinical symptoms in SP reflects the similarity of network changes, while differential involvement of SMN and VAN in JS and SP reflects the connectivity pattern of the lesioned areas inside these large-scale brain circuits. Importantly, anatomo-physiological parameters are sufficient to explain individual motor and cognitive performance, offering a basis for improved patient profiling and personalized therapies.

BackgroundAccumulating results suggest that reticulospinal tract (RST) excitability increases after stroke. While animal studies suggest this hyperexcitability may compensate for corticospinal tract (CST) damage, its role in motor function in people with stroke (PwS) remains debated. This study aimed to: (1) replicate findings of RST hyperexcitability in PwS using the StartReact paradigm, measuring acceleration of motor response to a startling auditory stimulus; (2) examine the relationship between RST hyperexcitability and motor impairments after stroke; and (3) explore whether RST hyperexcitability provides functional benefits in severely impaired PwS. MethodsForty-six PwS completed the StartReact paradigm and motor assessments (Fugl-Meyer, ARAT, grip strength, Modified Ashworth Scale). PwS were categorized into high StartReact effect and typical StartReact effect subgroups based on comparisons with a healthy control group (n=37). Severe impairment was defined as ARAT [≤]10. ResultsPwS exhibited significantly greater StartReact effects than controls. The high StartReact effect subgroup showed worse motor function, weaker grip strength, and higher spasticity. Among severely impaired PwS, high StartReact effect was not associated with improved grip strength. ConclusionsThese findings confirm the existence of RST hyperexcitability after stroke and suggest it is associated with poorer motor outcomes, likely due to reduced cortical input to the brainstem. The absence of functional benefit in severely impaired individuals supports the interpretation that RST hyperexcitability is a maladaptive rather than a compensatory reaction to brain damage. These findings provide insight into the neurophysiological mechanisms underlying motor impairments after stroke and do no imply direct clinical or therapeutic applications.

BackgroundAs therapeutic options emerge for hereditary spastic paraplegias (HSP), clinical trials require outcome measures that reflect disease aspects most important to patients. Patient priorities in HSP remain poorly defined. This study aimed to develop a regulatory-compliant framework of patient-prioritised health domains to evaluate treatment response in clinical trials. MethodsPatient-reported data on health impacts were collected via two multinational, multilingual online surveys conducted sequentially, including 616 and 504 patients across the clinical and genetic spectrum of HSP. Using a staged approach, we examined prevalence, relevance, and severity, focusing on health impacts that were (i) common (ii) sensitive to disease progression, (iii) highly relevant to patients, and (iv) showed strong severity-relevance correlation. Patient representatives contributed centrally to study design and prioritisation. FindingsOur patient-focused analysis yielded five highly prevalent and relevant core health domains: mobility, lower body function, autonomic dysregulation, pain, and psychosocial aspects. Ambulation and lower body function ranked highest across all disease stages. Among non-motor impacts, reduced ability to work, bladder incontinence, and fatigue were most relevant. In mild disease stages, reduced walking distance, reduced walking speed, and the urgency to empty the bladder were the most frequent and most relevant health impact. InterpretationThis work provides the most comprehensive patient-reported and disease stage specific profiling of HSP health impacts to date. It lays the necessary groundwork for developing patient-focused outcome tools capable of capturing treatment effects in future trials.

Many individuals with limb apraxia after left-hemisphere stroke exhibit a lack of awareness of their tool-related action errors, i.e., unawareness of apraxia (UA; also called anosognosia of apraxia). Little is known about the prevalence of UA, the relationship between UA and apraxia severity, or its underlying mechanisms. Here, we assessed both the causes and consequences of UA. Based on a mechanistic model, we hypothesized that UA may arise because of deficits in representations signaling how tool-related movements should look and feel--a component of action knowledge--and that degradation of this knowledge impedes the detection of mismatches between planned and actual tool-related actions. We further predicted that a consequence of UA is a reduction in error-correction attempts. Fifty-six individuals with chronic LCVA gestured to show how to use tools. Immediately after the gesture production task, participants were asked if they made any errors. All participants also completed an action knowledge task to measure the integrity of tool-related movement goals. Individuals were denoted as exhibiting UA if they performed below a normative cutoff for apraxia yet reported making no errors. Our sample included 21 individuals with apraxia; of these, nearly half (48%) exhibited UA. These two groups made a comparable number of gesture errors and were of equivalent stroke severity, yet individuals with UA had significantly more impaired action knowledge. Additionally, individuals with UA were less likely to attempt to correct their errors compared to individuals who were aware of their apraxia. These data support the hypothesis that action knowledge (how tool actions look and feel) serves a key role in error detection and awareness of apraxia and may contribute to the difficulties with everyday tasks experienced by many people with apraxia.

BackgroundBalance instability is a major contributor to disability and falls in people with Parkinsons disease (PwP) and is often insufficiently explained by motor impairment alone. Altered awareness of motor control has been suggested to contribute to sensorimotor dysfunction in PwP, but its relationship with balance performance is poorly understood. ObjectiveTo determine whether awareness of balance control, assessed using a control detection task (CDT), differs between healthy controls (HC) and PwP, and whether CDT performance is associated with balance-related measures. MethodsHealthy older adults (n=20) and PwP (n=22) performed a standing version of the CDT based on center-of-pressure (COP) control, using a force plate. CDT accuracy was used as the primary outcome measure. Static balance during quiet standing was assessed using the COP trajectory length and rectangular area. Dynamic standing balance was assessed using the Index of Postural Stability (IPS). Group differences were examined by independent-samples t-tests. Correlations between CDT accuracy and balance measures were analyzed. ResultsThe PwP group showed significantly lower CDT accuracy. Higher CDT accuracy was associated with better static balance in the HC group and the combined sample, and with higher IPS primarily in the PwP group. ConclusionsMotor awareness during postural tasks is altered in PwP and is associated with balance control. These findings suggest that balance instability in Parkinsons disease may involve altered balance-related action-outcome monitoring in addition to motor dysfunction.

Practice-transfer paradigms are central to motor learning research, yet dynamic balance lacks standardized, internally valid practice-transfer task pairings. This study evaluated whether a mediolateral tilt board can serve as a valid transfer task for stabilometer-based balance assessment. Sixteen healthy young adults (20-35 years) completed a single session consisting of two 40-second trials on a mediolateral stabilometer and two 40-second trials on a mediolateral tilt board. Participants aimed to keep each platform horizontal during each trial. Performance outcomes were derived from platform deviation angle. Neuromuscular outcomes were derived from surface EMG of bilateral gluteus medius, vastus lateralis, and vastus medialis, including muscle synergy structure, bilateral co-activation index, RMS amplitude of muscle activation, and strategy ratios (hip-to-knee and asymmetry metrics). Between-task associations were assessed using Spearman correlations. Cross-task muscle synergy similarity was high (mean cosine similarity = 0.915 {+/-} 0.044) and close to within-task trial-to-trial similarity, indicating preserved modular coordination across devices. Performance metrics were moderately to strongly correlated between tasks (RMS deviation angle: {rho} = 0.621, p = 0.0089; time-in-balance: {rho} = 0.668, p = 0.0036). EMG-derived strategy metrics also correlated significantly across tasks, including bilateral co-activation ({rho} = 0.688, p = 0.0023), hip-to-knee ratio ({rho} = 0.765, p = 0.0003), hip asymmetry ratio ({rho} = 0.688, p=0.0023), and knee asymmetry ratio ({rho} = 0.679, p = 0.0028). In contrast, EMG RMS amplitude did not correlate across tasks ({rho} = -0.044, p = 0.873), suggesting task-specific gain of activation magnitude. Stabilometer and tilt board tasks shared a similar coordination structure and showed a high correlation in balance performance and neuromuscular strategy, supporting the tilt board as an internally valid transfer task for stabilometer-based dynamic balance paradigms. Similarity of tasks appears strongest at the level of modular control and strategy organization, with device-specific gain scaling of activation amplitude.

BackgroundTourette Syndrome (TS) is a neurodevelopmental movement disorder involving involuntary motor and vocal tics believed to be characterised by disordered neural inhibition. Cortical representations have previously been manipulated by disruptions in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). However, while facial tics are the most reported motor tic, it is unclear if facial sensorimotor representations differ in TS. MethodsSixteen individuals with Tourette Syndrome (TS) or chronic tic disorder and twenty typically developing (TD) control participants underwent 3-Tesla functional magnetic resonance imaging (fMRI). Blood-oxygenation level-dependent (BOLD) responses were measured during a block-design task comprising cued facial movements of common facial tics (blinking, grimacing and jaw clenching). Activations in bilateral pre- and post-central cortices and supplementary motor areas (SMA) were examined. Conjunction analyses identified voxels commonly and uniquely activated across movements within each group. ResultsBoth groups showed significant activations in the bilateral sensorimotor cortices and SMA in response to blink, grimace and jaw clench movements, with no significant between-group differences. Between-group similarities were lowest for unique blink maps. Common voxel maps also revealed low between-group similarity, with reduced sensorimotor activation and no shared SMA activation across movements in the TS group. ConclusionVoluntary facial sensorimotor representations do not differ between groups. However, low similarities between group unique blink maps may reflect greater prevalence of blinking tics in TS. Additionally, reduced overlap in sensorimotor activation and absent common SMA engagement across cued movements in the TS group may indicate altered motor integration or action initiation.

PurposeTranscranial direct current stimulation (tDCS) can noninvasively modulate activity in targeted brain regions. It is well established that the excitability of motor-related regions can increase when the target region is located beneath the anode (anodal tDCS), suggesting its potential to increase motor performance. Although such attempts have been widely examined, the results remain inconclusive. The purpose of this study was to assess the conditions under which anodal tDCS may improve motor performance in healthy adults. MethodsWe conducted a systematic review of studies on the use of anodal tDCS for improving motor performance in healthy adults. A computerized search was performed using the Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web to identify relevant studies published between January 1, 1990 and May 25, 2022. ResultsTwenty-five studies were included in the qualitative synthesis. For the meta-analysis, 25 trials (N=885) were extracted from 23 studies. There were significant effects of anodal tDCS on motor performance improvement, but with evidence of publication bias and substantial heterogeneity among the trials. Post-hoc analysis revealed that motor performance 24 hours after the application of anodal tDCS may benefit from stimulation. There was no marked effect related to stimulation intensity, duration, or whether stimulation was provided during motor performance. ConclusionsOur study clarified the current state of anodal tDCS use for motor performance enhancement and indicates that there is currently no reliable evidence to support its effectiveness. Further studies, particularly randomized controlled trials, are necessary to establish the reliability of these effects for future applications.

Tourette syndrome (TS) is a neurodevelopmental disorder of childhood onset characterised by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence. However, many individuals continue to have debilitating tics into adulthood. This indicates that there may be important differences between adults with TS for whom the clinical phenotype is more stable, and children and adolescents with the disorder who may be undergoing developmental neuroplastic changes linked to the reduction of their tics. Previous studies have used transcranial magnetic stimulation (TMS) to investigate changes in cortical motor excitability in individuals with TS, including measurement of resting motor threshold (RMT). However, the findings from these studies have been mixed, have varied between adult and child samples, and have often been based on small sample sizes. Here we report a multi-centre, mega-analytic, study in which RMT data collected from children and adults with TS at multiple research centres was pooled for analysis. Results confirmed that mean RMT was significantly increased in individuals with TS compared to neurotypical controls. However, this result can be explained by the more important findings that: (a) RMT for adults with TS did not differ from that of neurotypical adults; and (b) the rate that RMT decreases with age during childhood and adolescence is reduced in individuals with TS compared to controls. Thus, while neurotypical individuals reach an adult RMT level by ~12-13 years of age, individuals with TS are substantially delayed in doing so, and do not reach an adult RMT level until much later, at ~24 years of age. We conclude therefore that differences in measures of cortical excitability between children and adolescents with TS and chronologically age-matched neurotypical controls may likely reflect a developmental delay in the maturation of functional brain networks in individuals with TS, which may normalise with age.

BackgroundAlthough neurogenic orthostatic hypotension (nOH) is a common and debilitating feature of multiple system atrophy (MSA), little is known about the burden of symptoms in the real world. ObjectivesTo design and conduct a cross-sectional community-based research survey targeting patients with MSA, with and without nOH. MethodsWe recruited patients with MSA to complete an anonymous online survey covering three core themes: 1) timely diagnosis, 2) nOH pharmacotherapy and refractory symptoms, and 3) confidence in physician knowledge. Responses were grouped by pre-specified diagnostic certainty levels. Relationships between symptoms, function, and pharmacotherapy were assessed using univariate and multivariate methods. ResultsWe analyzed 259 respondents with a self-reported diagnosis of MSA (age: M=64.38, SD=8.09 years; 44% female). In total, 42% also had a diagnosis nOH; 40% had symptoms highly suspicious of nOH, but no diagnosis; and 21% reported having never had their blood pressure measured in the standing position at a clinical visit. Treatment with a pressor agent was independently associated with the presence of other symptoms of autonomic failure. Each additional nOH symptom reported increased the odds of requiring pharmacotherapy by 18%. Yet, despite anti-hypotensive medication use, 97% of patients reported limitations in their ability to bathe, cook, or arise from a chair/bed with 76% needing caregiver support for refractory nOH symptoms. ConclusionsThis cross-sectional representative sample shows nOH is underrecognized and undertreated in MSA patients, leading to substantial functional limitations. It is our hope that these findings are leveraged for planning future trials and advocating for better treatments.

Neural mechanisms underlying handedness remain poorly understood. We used functional magnetic resonance imaging (fMRI) to study performance of a visually guided drawing task with each hand. We hypothesized that the left superior parietal lobule supports drawing with either hand, and individuals with chroninc peripheral nerve injury (PNI) to the dominant hand use the same mechanism as healthy adults. Methods33 right-handed adults (23 healthy, 10 patients) underwent fMRI while performing a precision drawing task, alternating between the right hand (RH) and left hand (LH). 20 regions of interest (12 a priori and 8 post-hoc) were examined for LH>RH effects on BOLD magnitude and on functional connectivity (FC) modulation via generalized psychophysiological interaction. ResultsDuring LH drawing, contralateral primary motor cortex (M1) had lower magnitude, and greater FC with two networks of equal-or-greater magnitude: left M1-dorsal premotor, and intrahemispheric parieto-temporal network. Contralateral M1 also had reduced interhemispheric FC with inferior parietal lobule, which exhibited lower magnitude. Patient group did not interact with these effects. ConclusionsThree neural mechanisms differentiate LH from RH drawing. First, a left hemisphere bimanual control network engages intrahemispherically (directly) during RH drawing and interhemispherically (indirectly) during LH drawing. Second, LH drawing increases engagement of a contralateral network that may reflect increased task demands. Third, RH drawing increases engagement of an interhemispheric tool use network. The first and third networks may explain the dominant hands performance advantages. PNI patients use the same mechanisms, highlighting their potential as a neuromodulatory target to enhance LH performance after RH impairment.

Reward can enhance motor performance. However, its potential to counteract motor fatigability, a reduction in motor performance during sustained movements, remains underinvestigated. This could be particularly relevant in neurological conditions such as multiple sclerosis, where increased motor fatigability is a prominent symptom. One form of motor fatigability is motor slowing, a decline in movement speed over time evoked by fast, repetitive movements. In this study, we investigated whether the possibility to earn reward attenuates motor slowing, and examined associated changes in muscle activity and pupil size, a putative marker of physical effort. Participants performed a wrist tapping task at maximal voluntary speed with or without the possibility of earning a reward. We found that wrist tapping induced motor slowing and that slowing was significantly reduced by reward. Over time, tapping became more costly as indicated by higher muscle activity and coactivation per tap. This was accompanied by a sustained pupil dilation, which could not solely be explained by tapping speed. These findings suggest that, rather than restoring efficient motor control, reward attenuates motor slowing by allowing participants to access a performance reserve and invest more resources into the task, reflected by increased muscle activation per tap and sustained pupil dilation.

Background and objectivesSTXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. MethodsIn this cross-sectional study, we included ambulatory patients aged 6 years or older with genetically confirmed STXBP1-RD. Instrumented 3D Gait Analysis (i3DGA) was performed to objectively quantify gait. Functional mobility was assessed with the Functional mobility scale (FMS) and Mobility Questionnaire 28 (MobQues28). Caregiver health-related quality of life was evaluated using the PedsQL-Family Impact Module (PedsQL-FIM). We explored associations between gait, functional mobility, STXBP1-variant type and clinical features (ID, age at seizure onset, seizure frequency, age at onset of independent walking). Correspondence between i3DGA and the Edinburgh Visual Gait Score (EVGS), an observational gait assessment, was investigated. ResultsEighteen participants were included. Compared to typically developing peers, individuals with STXBP1-RD had significantly reduced walking speed, step and stride length. Gait patterns were highly variable, with the most frequent pattern being an externally rotated foot progression angle (FPA), present in 11/18 participants. At home, 93.75% of the participants (16/18) walked independently, yet community mobility was more variable: 11/16 (68.75%) walked independently, 2/16 (12.50%) with aid and 3/16 (18.75%) used a wheelchair, indicating increasing limitations with distance and environmental complexity. Earlier acquisition of independent walking strongly predicted later unassisted ambulation at community level (p<0.001). Median MobQues28 score was 57.14% and median PedsQL-FIM score was 60.42%, indicating a moderate level of mobility limitations and reduced health-related quality of life of caregivers. EVGS was highly positive correlated with i3DGA (p= 0.001). DiscussionQuantitative gait analysis in individuals with STXBP1-RD demonstrates heterogenous kinematic deviations, with an externally rotated FPA emerging as the most common pattern. Age at independent walking was a clinically relevant predictor of later functional mobility. EVGS showed strong correspondence with i3DGA and may offer a more practical, semi-quantitative assessment for broader use. These findings inform clinical decision-making and guide the selection of scalable outcome measures for natural history studies and interventional trials.

BackgroundPeri-synaptic astrocyte processes (PAPs) play a fundamental role in synapse formation and function. Central afferent synapse loss and astrocyte dysfunction greatly impede sensory-motor circuitry in spinal muscular atrophy (SMA) disease progression, however mechanisms underpinning tripartite synapse dysfunction remains to be fully elucidated. The aims of this study were to further define PAP and motor neuron synaptic defects in human SMA disease pathology and implement a therapeutic intervention strategy to improve motor neuron function. MethodsWe derived astrocyte monocultures and motor neuron astrocyte co-cultures from healthy and SMA patient induced pluripotent stem cell (iPSC) lines to assess intrinsic astrocyte filopodia defects and phenotypes occurring at the synapse-PAP interface, respectively, using cell surface capture mass spectrometry proteomics, confocal and super resolution microscopy, synaptogliosome isolation, and electrophysiology. ResultsSMA astrocytes demonstrated intrinsic filopodia actin defects featuring low abundance of actin-associated cell surface N-glycoproteins, and decreased filopodia density and CDC42-GTP levels after actin remodeling stimulation. This phenotype is likely driven by the significant reduction of CD44 and phosphorylated ezrin, radixin and moesin ERM proteins (pERM) within SMA astrocyte filopodia. The dual combination of SMN1 gene therapy and forskolin treatment, an adenylyl cyclase activator leading to increased cyclic adenosine monophosphate (cAMP) levels and actin signaling pathway stimulation, led to extensive branching and increased filopodia density of SMA astrocytes during actin remodeling. SMA patient-derived motor neuron and astrocyte co-cultures, particularly samples derived from male patient iPSC lines, demonstrated a significant decrease in synapse number, actin-associated pre-synaptic neurotransmitter release protein, synapsin I (SYN1), and PAP-associated expression of pERM and glutamate transporter, EAAT1. Our astrocyte-targeted SMN1 augmentation and forskolin treatment paradigm restored SYN1 protein levels within the SMA synaptogliosome, resulting in significant increases in motor neuron synapse formation and function, but did not fully restore PAP-associated proteins levels at the synapse. ConclusionsSMA astrocytes demonstrate intrinsic actin-associated defects within filopodia, which correlates with decreased pERM levels at tripartite motor neuron synapses. We also define a SMN- and cAMP-targeted treatment paradigm that significantly increases pre-synaptic neurotransmitter release protein levels to improved SMA motor neuron synapse formation and function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/714618v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1257ab8org.highwire.dtl.DTLVardef@19c0010org.highwire.dtl.DTLVardef@c84552org.highwire.dtl.DTLVardef@3f1e62_HPS_FORMAT_FIGEXP M_FIG C_FIG

Dorsal (PMd) and ventral (PMv) premotor cortices can modulate contralateral primary motor cortex (M1) excitability, but their distinct interhemispheric influence via transcranial magnetic stimulation (TMS) remains unclear. Single-pulse TMS over PMd, PMv and M1 assessed transcallosal inhibition via the ipsilateral silent period (iSP). Dual-site TMS examined short-(10 ms inter-stimulus interval [ISI]), long-(50 ms ISI) and non-callosal-(0 ms ISI) interhemispheric inhibition (IHI). An iSP was elicited from PMd, PMv, and M1, with distinctly evoked iSP parameters. The iSP magnitude was greatest from M1, followed by PMd and then PMv, while iSP duration was greatest for M1 and showed no differences between PMd and PMv. Dual-site TMS revealed that PMd and M1 inhibited contralateral M1 excitability across all ISIs, while PMv showed inhibition at 0-and 50-ms ISIs. PMd and M1 demonstrated greater short-IHI compared to PMv, all demonstrating similar long-IHI, and PMd demonstrating greater non-callosal-IHI than M1. PMv displayed distinct IHI across ISIs, PMd showed differences across most ISIs and M1 demonstrated the fewest differences across ISIs. Longer iSP duration related to greater long-IHI magnitude elicited from PMd and PMv. Our findings demonstrate differential IHI from PMd and PMv on contralateral M1, which may inform neuromodulation strategies in rehabilitation contexts.

Dystonia treatment evaluation in cerebral palsy (CP) is limited by the lack of clinician-assessed scales linking dystonia severity to functional impact. We asked 7 pediatric movement disorder specialists to review videos of 27 children with CP while performing an upper extremity task and while walking. Experts rated arm and leg dystonia severity using the Global Dystonia Severity Rating Scale (GDRS) and task-specific functional impact on a five-point scale adapted from the Dyskinetic Cerebral Palsy Functional Impact Scale. Arm GDRS scores correlated with functional impact on the upper extremity task (linear regression R2=0.48, p=0.0005). Leg GDRS scores correlated with gait impact (R2=0.43, p=0.001). A four-point increase in total GDRS corresponded to a one-point worsening in combined functional impact. By demonstrating how expert-rated limb dystonia severity correlates with task-specific functional impact in children with CP, these results could help clinically identify functionally-meaningful differences in dystonia severity.

BackgroundPhysical activity has been associated with better reading comprehension and reduces cognitive load (CL), but the role of brain volume in modulating this relationship remains unclear. Therefore, this study aims to determine whether the gray matter volume in key regions modulates the effects of different physical activity modalities on reading comprehension and associated CL. MethodsThirteen male adolescents (12-13 years). Adolescents with MRI data participated in a randomized cross-over trial comparing three conditions: 1) sedentary behavior (SC, emulating a school class), 2) moderate-intensity continuous training (MICT), and 3) cooperative high-intensity interval training (C-HIIT), with physical activity conditions duration adjusted to match SC energy expenditure. Gray matter volumes were measured in the bilateral hippocampus, left pars opercularis, and the brainstem. CL was assessed via pupil dilation during reading using eye-tracking. Reading comprehension was measured through seven-question multiple-choice tests with expert-validated items. ResultsC-HIIT demonstrated superior effects on both CL and reading comprehension compared to MICT and SC, with significant brain volume modulation effects across all examined regions. Brain volume interactions with physical activity modalities systematically modified the pattern of cognitive responses, with C-HIIT consistently benefiting from these modulations, whereas the effects of MICT were generally attenuated. ConclusionThis study suggests that selecting the appropriate physical activity modality may be relevant for cognitive outcomes during reading in adolescents. C-HIIT yielded lower CL and better reading comprehension, and these effects were not explained by brain volume alone but by its interaction with exercise modality.

Background: High school students may be able to communicate health topics to peers and adults. Yet, few studies have evaluated the role of high school students in community health initiatives, making them an underutilized group for disseminating health information. We pilot tested stroke education across five high schools using varied delivery approaches as a preliminary step toward evaluating youth stroke education to improve community health. Methods: In April-May 2025, five high schools in Connecticut and New York participated in stroke education. The format was designed to fit the needs of each school and included an 8-session classroom curriculum (Derby, CT), after-school club meetings (New Haven, CT; Long Island, NY), and one large assembly (Bridgeport, CT). Developed by teachers and neurology providers, the curriculum covered stroke risk factors, symptoms, and emergency response. Students completed a 15-point assessment adapted from the validated Stroke Action Test before, immediately after, and 4-6 weeks post-intervention; data were collected between April and July 2025. Results: Of 112 students completing the pre-test, 99 (88%) completed the immediate post-test and 51 (46%) the delayed follow-up. Average scores rose from 47% pre-intervention to 75% post and 70% at 4-6 weeks. All schools scored <50% on pre-tests suggesting poor baseline stroke knowledge. Conclusion: This pilot suggests that stroke education can be delivered to high school students across varied settings and may support knowledge gains up to 6 weeks. Limitations included small sample sizes and missing follow-up data. If validated in larger studies, this adaptable, teacher-supported approach could offer a scalable public health strategy for improving community stroke preparedness.

Response inhibition, the ability to suppress contextually inappropriate actions, is a cornerstone of cognitive control and is commonly assessed using paradigms such as the go/no-go task. However, traditional go/no-go paradigms rely on binary outcomes such as commission errors, which offer limited insight into the dynamic, graded behavioral adjustments underlying successful stopping. The present study developed a novel mouse-tracking go/no-go paradigm with a dynamic start to capture inhibitory processes during ongoing execution. Twenty-three healthy young adults completed the task in two sessions separated by approximately one week to evaluate the test-retest reliability of standard behavioral measures (error rates and reaction times), and three kinematic features: path length, mean velocity, and mean acceleration. Results revealed robust differences between go and no-go trials across all measures. Successful inhibition was characterized by significantly shorter path lengths and reduced mean velocity and acceleration compared to go trials. Critically, all measures demonstrated moderate-to-good test-retest reliability across sessions, with intraclass correlation coefficients ranging from .75 to .85 for go trials and from .59 to .83 for no-go trials. These findings establish construct validity and psychometric reliability of the current mouse-tracking go/no-go paradigm. The demonstrated stability of these measures provides the methodological foundation for their use in cross-sectional, longitudinal, and intervention research targeting inhibitory control.