A window into the mind-brain-body interplay: Development of diagnostic, prognostic biomarkers, and rehabilitation strategies in functional motor disorders.

BACKGROUND AND AIMS: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life. Despite their high prevalence, FMD often face delayed diagnosis and inadequate treatment, resulting in significant social and economic burdens. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the need for more evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. Consequently, symptoms are construed as perceptions of the body's state. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on an altered integration at the neural level of interoception, exteroception, and motor control. METHODS AND MATERIALS: Our proposal aims to elucidate the pathophysiological mechanisms of FMD through a three-stage research approach. Initially, a large cohort study will collect behavioral, neurophysiological, and MRI biomarkers from patients with FMD and healthy controls, employing eXplainable Artificial Intelligence (XAI) to develop a diagnostic algorithm. Subsequently, validation will occur using patients with organic motor disorders. Finally, the algorithm's prognostic value will be explored post-rehabilitation in one subgroup of patients with FMD. RESULTS: Data collection for the present study started in May 2023, and by May 2025, data collection will conclude. DISCUSSION: Our approach seeks to enhance early diagnosis and prognostication, improve FMD management, and reduce associated disability and socio-economic costs by identifying disease-specific biomarkers. TRIAL REGISTRATION: This trial was registered in clinicaltrials.gov (NCT06328790).

Linking abnormal neural activity patterns to motor deficits.

Abnormal activity in the cerebellar nuclei can be used to predict motor symptoms and induce them experimentally, pointing to potential therapeutic strategies.

Optimal Body Weights for Adults with Severe Motor and Intellectual Disabilities.

Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)2×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.

The contribution of EEG to assess and treat motor disorders in multiple sclerosis.

OBJECTIVE: Electroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS). METHODS: A comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses. RESULTS: In this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load). CONCLUSIONS: We highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks. SIGNIFICANCE: Some of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.

The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Virtual reality and motor imagery for early post-stroke rehabilitation.

BACKGROUND: Motor impairment is a common consequence of stroke causing difficulty in independent movement. The first month of post-stroke rehabilitation is the most effective period for recovery. Movement imagination, known as motor imagery, in combination with virtual reality may provide a way for stroke patients with severe motor disabilities to begin rehabilitation. METHODS: The aim of this study is to verify whether motor imagery and virtual reality help to activate stroke patients' motor cortex. 16 acute/subacute (< 6 months) stroke patients participated in this study. All participants performed motor imagery of basketball shooting which involved the following tasks: listening to audio instruction only, watching a basketball shooting animation in 3D with audio, and also performing motor imagery afterwards. Electroencephalogram (EEG) was recorded for analysis of motor-related features of the brain such as power spectral analysis in the [Formula: see text] and [Formula: see text] frequency bands and spectral entropy. 18 EEG channels over the motor cortex were used for all stroke patients. RESULTS: All results are normalised relative to all tasks for each participant. The power spectral densities peak near the [Formula: see text] band for all participants and also the [Formula: see text] band for some participants. Tasks with instructions during motor imagery generally show greater power spectral peaks. The p-values of the Wilcoxon signed-rank test for band power comparison from the 18 EEG channels between different pairs of tasks show a 0.01 significance of rejecting the band powers being the same for most tasks done by stroke subjects. The motor cortex of most stroke patients is more active when virtual reality is involved during motor imagery as indicated by their respective scalp maps of band power and spectral entropy. CONCLUSION: The resulting activation of stroke patient's motor cortices in this study reveals evidence that it is induced by imagination of movement and virtual reality supports motor imagery. The framework of the current study also provides an efficient way to investigate motor imagery and virtual reality during post-stroke rehabilitation.

Growth in infants, children and adolescents with unilateral and bilateral cerebral palsy.

To compare growth patterns during infancy, childhood and adolescence in children with unilateral and bilateral cerebral palsy (CP) phenotype and to assess the association with gross motor impairment, dysphagia and gestational age. We retrospectively studied 389 children with CP from a single center population in Munich, Germany. 1536 measurements of height and weight were tabulated and z-scored from 6 to 180 months of age. Generalized linear mixed model were used to examine the association between growth, GMFCS, dysphagia and gestational age by CP phenotype. Children with unilateral CP tend to grow similarly to their typically developed peers. In the main effect model, bilateral CP phenotype was significantly associated with decreased mean z-scores for height (ß [95% CI] - 0.953 [- 1.145, - 0.761], p < 0.001), weight (- 0.999 [- 1.176, - 0.807], p < 0.001) and BMI (ß [95% CI] - 0.437 [- 0.799, - 0.075]), compared with unilateral CP phenotype. This association remained significant in the interaction models. The height-for-age z-scores, weight-for-age decreased z-scores and BMI-for-age z-scores of children with bilateral CP and GMFCS III-V or dysphagia decreased more significantly than those of children with unilateral CP. Preterm birth was not significantly associated with decreased growth in height, weight and BMI. Reduced growth in children with bilateral CP was strongly associated with moderate to severe impairment in gross motor function (GMFCS III-V) and dysphagia.

A feasibility randomized controlled trial of a NICU rehabilitation program for very low birth weight infants.

Motor disability is common in children born preterm. Interventions focusing on environmental enrichment and emotional connection can positively impact outcomes. The NICU-based rehabilitation (NeoRehab) program consists of evidence-based interventions provided by a parent in addition to usual care. The program combines positive sensory experiences (vocal soothing, scent exchange, comforting touch, skin-to-skin care) as well as motor training (massage and physical therapy) in a gestational age (GA) appropriate fashion. To investigate the acceptability, feasibility and fidelity of the NeoRehab program in very low birthweight (VLBW) infants. All interventions were provided by parents in addition to usual care. Infants (≤ 32 weeks' GA and/or ≤ 1500 g birthweight) were enrolled in a randomized controlled trial comparing NeoRehab to usual care (03/2019-10/2020). The a priori dosing goal was for interventions to be performed 5 days/week. The primary outcomes were the acceptability, feasibility and fidelity of the NeoRehab program. 36 participants were randomized to the intervention group and 34 allocated to usual care. The recruitment rate was 71% and retention rate 98%. None of the interventions met the 5 days per week pre-established goal. 97% of participants documented performing a combination of interventions at least 3 times per week. The NeoRehab program was well received and acceptable to parents of VLBW infants. Programs that place a high demand on parents (5 days per week) are not feasible and goals of intervention at least 3 times per week appear to be feasible in the context of the United States. Parent-provided motor interventions were most challenging to parents and alternative strategies should be considered in future studies. Further studies are needed to evaluate the relationship between intervention dosing on long term motor outcomes.

Development of coordination and muscular fitness in children and adolescents with parent-reported ADHD in the German longitudinal MoMo Study.

This study examined the development of muscular fitness and coordination in children and adolescents with and without attention deficit hyperactivity disorder (ADHD) over a period of 11 years. Data was collected in three measurement waves as part of the longitudinal, representative Motorik-Modul (MoMo) study in Germany (2003-2006, 2009-2012, 2014-2017). The overall sample comprised 2988 participants (253 with ADHD, 65% males; 2735 non-ADHD, 47% males; mean age 9 years). Structural equation modeling was conducted, and the estimated models had a good fit. No differences in muscular fitness were observed between participants with and without ADHD. Participants with ADHD had a lower coordinative performance at first measurement than those without ADHD. The difference in coordinative performance persisted throughout the study period.

MRI of Transcallosal White Matter Helps to Predict Motor Impairment in Multiple Sclerosis.

Background Altered callosal integrity has been associated with motor deficits in patients with multiple sclerosis (MS), but its contribution to disability has, to the knowledge of the authors, not been investigated by using multiparametric MRI approaches. Purpose To investigate structural and functional interhemispheric MRI substrates of global disability at different milestones and upper limb motor impairment in MS. Materials and Methods In this cross-sectional study, healthy control patients and patients with MS (between January 1, 2008, and December 31, 2016) were retrospectively selected from our hospital database. Clinical assessment included Expanded Disability Status Scale (EDSS), nine-hole peg test, and digital finger tapping test. By using structural and resting-state functional MRI sequences, probabilistic tractography of hand corticospinal tract fibers, and transcallosal fibers between hand-motor cortices (hereafter, referred to as hand-M1), supplementary motor areas (SMAs), premotor cortices (PMCs), and voxel-mirror homotopic connectivity (VMHC) were analyzed. Random forest analyses identified the MRI predictors of clinical disability at different milestones (EDSS scores of 3.0, 4.0, 6.0) and upper limb motor impairment (nine-hole peg test and finger tapping test z scores < healthy control patients 5th percentile). Results One-hundred thirty healthy control patients (median age, 39 years; interquartile range, 31-50 years; 70 women) and 340 patients with MS (median age, 43 years; interquartile range, 33-51 years; 213 women) were studied. EDSS 3.0 predictors (n = 159) were global measures of atrophy and lesions together with damage measures of corticospinal tracts and transcallosal fibers between PMCs and SMAs (accuracy, 86%; P = .001-.01). For EDSS 4.0 (n = 131), similar predictors were found in addition to damage in transcallosal fibers between hand-M1 (accuracy, 89%; P = .001-.049). No MRI predictors were found for EDSS 6.0 (n = 70). Nine-hole peg test (right, n = 161; left, n = 166) and finger tapping test (right, n = 117; left, n = 111) impairments were predicted by damage in transcallosal fibers between SMAs and PMCs (accuracy range, 69%-77%; P = .001-.049). VMHC abnormalities did not explain clinical outcomes. Conclusion Structural, not functional, abnormalities at MRI in transcallosal premotor and motor white matter fibers predicted severity of global disability and upper limb motor impairment in patients with multiple sclerosis. The informative role of such predictors appeared less evident at higher disability levels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Barkhof and Pontillo in this issue.