The validation of a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q).

OBJECTIVE: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability. METHODS: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson's disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman's correlation coefficients (rho) were used to determine construct validity, and Cronbach's alpha (α) was used to examine reliability. RESULTS: The interquartile range of the NFOG-Q scores was 10.0-25.3 (range 0-29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515-0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319-0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96). CONCLUSIONS: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD.

Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients.

The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes and evaluate how much dysregulation is associated with levodopa dose. Furthermore, to evaluate the effect of Opicapone, a catechol-o-methyl-transferase inhibitor, on vitamin B6 levels by monitoring the AST and ALT levels in patients treated with Levodopa-Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum vitamin B6 levels were measured (PD, n = 72 and controls, n = 31). The vitamin B6 level was compared with the total levodopa dose, clinical parameters, and blood homocysteine, albumin, and hemoglobin levels in PD patients. Correlations between vitamin B6 levels and AST and ALT levels, as well as the ratio ALT/AST, were analyzed. Changes in the AST and ALT levels and ALT/AST were analyzed in the patients treated with LCIG before and after the therapy (n = 24) and in the patients treated with LCIG + Opicapone before and after Opicapone treatment (n = 12). We found vitamin B6 levels were significantly lower in PD patients. Total levodopa dose and albumin levels were independently associated with vitamin B6 levels. Decreased vitamin B6 levels appeared as lower AST and ALT levels and ALT/AS. Treatment with LCIG decreased the AST and ALT levels and ALT/AST. Adjunctive therapy with Opicapone to LCIG ameliorated the decreased ALT and ALT/AST. We conclude that the ALT and ALT/AST can be useful parameters for monitoring vitamin B6 levels and Opicapone can ameliorate the dysregulated vitamin B6 in PD patients.

Adult-onset botulism in a Japanese woman with prolonged spore excretion.

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism.

[Antibody production capacity after COVID-19 vaccination in immune-mediated neuromuscular diseases under immunotherapy].

The post-vaccination antibody response in patients with immune-mediated neuromuscular diseases under immuno-suppressive therapy has not been sufficiently verified. The Japanese Society of Neurology has stated that coronavirus disease 2019 (COVID-19) vaccination should be given priority in patients with immunotherapy-associated neuromuscular diseases; however, data on antibody production to a novel mRNA vaccine are scarce in these patients. In this study, we aimed to measure residual antibody titers after the second dose and produced antibodies after the third dose of SARS-CoV-2 mRNA vaccine in 25 patients with neuromuscular diseases under immuno-suppressive therapy (disease group). We compared the disease group antibody titers with those of 829 healthy employees in our hospital (control group). The disease group included 17 patients with myasthenia gravis, 4 with multiple sclerosis, 3 with inflammatory muscle disease, and 1 with chronic inflammatory demyelinating polyneuropathies. Seven cases of the disease group showed negative antibody levels (<15.0 s/co) before the third vaccination, and antibody titers in the positive cases ranged from 16.9 to 4,589.0 s/co. Three of the seven antibody-negative cases turned positive after the third vaccination, and all but one of the antibody-positive cases showed a booster effect, with antibody titers after the third dose ranging from 245.1 to 85,374.0 s/co (1.0 to 885.0 times higher than those before vaccination). Although the immune response in the disease group was modest compared to the control group, in which antibody titers after the third vaccination ranged from 67.8 to 150,000 s/co (0.9 to 5,402.1 times higher than those before vaccination), the result indicated that a constant immune response was achieved under immuno-suppressive therapy. Even in the control group, three participants tested negative for residual antibody before the third inoculation, and four of the antibody-positive participants (27.7-24,054.0 s/co) lacked a booster effect after the third vaccination.

Neural correlates of impulsive compulsive behaviors in Parkinson's disease: A Japanese retrospective study.

BACKGROUND: Impulsive compulsive behaviors (ICBs) often disturb patients with Parkinson's Disease (PD), of which impulse control disorder (ICD) and dopamine dysregulation syndrome (DDS) are two major subsets. The nucleus accumbens (NAcc) is involved in ICB; however, it remains unclear how the NAcc affects cortical function and defines the different behavioral characteristics of ICD and DDS. OBJECTIVES: To identify the cortico-striatal network primarily involved in ICB and the differences in these networks between patients with ICD and DDS using structural and resting-state functional magnetic resonance imaging. METHODS: Patients with PD were recruited using data from a previous cohort study and divided into those with ICB (ICB group) and without ICB (non-ICB group) using the Japanese version of the Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease (J-QUIP). From these two groups, we extracted 37 pairs matched for age, sex, disease duration, and levodopa equivalent daily dose of dopamine agonists. Patients with ICB were further classified as having ICD or DDS based on the J-QUIP subscore. General linear models were used to compare gray matter volume and functional connectivity (FC) of the NAcc, caudate, and putamen between the ICB and non-ICB groups and between patients with ICD and those with DDS. RESULTS: We found no significant differences in gray matter volumebetween the ICB and non-ICB groups or between patients with ICD and those with DDS. Compared with the non-ICB group, the FC of the right NAcc in the ICB group was lower in the bilateral ventromedial prefrontal cortex and higher in the left middle occipital gyrus. Furthermore, patients with DDS showed higher FC between the right putamen and left superior temporal gyrus and higher FC between the left caudate and bilateral middle occipital gyrus than patients with ICD. In contrast, patients with ICD exhibited higher FC between the left NAcc and the right posterior cingulate cortex than patients with DDS. CONCLUSIONS: The functionally altered network between the right NAcc and ventromedial prefrontal cortex was associated with ICB in PD. In addition, the surrounding cortico-striatal networks may differentiate the behavioral characteristics of patients with ICD and those with DDS.

Decreased cerebrospinal fluid orexin levels not associated with clinical sleep disturbance in Parkinson's disease: A retrospective study.

Patients with Parkinson's disease (PD) often suffer from sleep disturbances, including excessive daytime sleepiness (EDS) and rapid eye movement sleep behavior disorder (RBD). These symptoms are also experienced by patients with narcolepsy, which is characterized by orexin neuronal loss. In PD, a decrease in orexin neurons is observed pathologically, but the association between sleep disturbance in PD and cerebrospinal fluid (CSF) orexin levels is still unclear. This study aimed to clarify the role of orexin as a biomarker in patients with PD. CSF samples were obtained from a previous cohort study conducted between 2015 and 2020. We cross-sectionally and longitudinally examined the association between CSF orexin levels, sleep, and clinical characteristics. We analyzed 78 CSF samples from 58 patients with PD and 21 samples from controls. CSF orexin levels in patients with PD (median = 272.0 [interquartile range = 221.7-334.5] pg/mL) were lower than those in controls (352.2 [296.2-399.5] pg/mL, p = 0.007). There were no significant differences in CSF orexin levels according to EDS, RBD, or the use of dopamine agonists. Moreover, no significant correlation was observed between CSF orexin levels and clinical characteristics by multiple linear regression analysis. Furthermore, the longitudinal changes in orexin levels were also not correlated with clinical characteristics. This study showed decreased CSF orexin levels in patients with PD, but these levels did not show any correlation with any clinical characteristics. Our results suggest the limited efficacy of CSF orexin levels as a biomarker for PD, and that sleep disturbances may also be affected by dysfunction of the nervous system other than orexin, or by dopaminergic treatments in PD. Understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.

Guillain-Barré Syndrome Associated with COVID-19 in a Japanese Male.

April 2021 saw a widespread outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Osaka, Japan. We encountered the case of a 52-year-old man who had Guillain-Barré syndrome associated with coronavirus disease 2019 (COVID-19). After the relief of the respiratory symptoms owing to COVID-19, the patient experienced muscle weakness, which spread from his fingers to his extremities, and was unable to walk. Further examinations revealed mild protein elevation in the cerebrospinal fluid. In addition, nerve conduction studies showed demyelinating polyneuropathy, leading to the diagnosis of Guillain-Barré syndrome. After the administration of intravenous immunoglobulin and intravenous methylprednisolone, his symptoms drastically improved, and he was able to walk unaided 21 days after the onset of symptoms. On day 40, the patient was discharged with minimal muscle fatigue. Because Guillain-Barré syndrome associated with COVID-19 is expected to have a good prognosis, early diagnosis and treatment are important. Therefore, Guillain-Barré syndrome should be considered as a possible factor for muscle weakness during and after COVID-19 treatment.

Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study.

INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS: This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS: Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION: Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.

[Parkinson's Disease with Intolerable Painful Dystonia: Classification and Therapeutic Choices of Pain in Parkinson' Disease].

Disabling painful dystonia is one of the most burdensome symptoms that a patient with Parkinson's disease (PD) experiences. How do we treat disabling painful dystonia in PD? In this review, classification and mechanisms of pain and their management in PD especially for dystonia-related pain are described. Moreover, painful bilateral dystonic foot spasm is also an important development to be considered in the early stage of the disease. Recent classification of pain in PD does not involve this symptom, partly because this symptom is relatively unobserved due to early initiation of treatment in PD patients. Treatment options for dystonia-related pain are diverse and are necessarily contingent on the cause of dystonia in PD. Reducing L-dopa and other drugs is useful for patients with on-dystonia and dyskinesia-related pain in PD. Increasing L-dopa and other drugs are better for early morning dystonia and off-period dystonia-related pain in PD. Finally, as severe and troublesome painful dystonia is often challenging to treat, continuous dopaminergic stimulation such as treatment with levodopa-carbidopa intestinal gel is considered effective for these symptoms.

[The efficacy of eculizumab against post-thymectomy exacerbations in thymoma associated myasthenia gravis (MG)].

We report a 62-year-old woman with thymoma associated myasthenia gravis (MG). She had significant dysphagia and was treated with corticosteroids, intravenous immunoglobulin (IVIG), immunoadsorption plasmapheresis (IAPP), and immunosuppressive drugs, and the extended thymectomy. Her symptoms gradually improved, but 3 weeks after thymectomy, her bulbar symptoms recurred. Although she was treated with repeated IVIG and IAPP, her symptom remained. Finally, after starting eculizumab did her symptoms go into complete remission. This case suggests the efficacy of anti-complement therapy for postoperative exacerbation of MG.

Magnetoencephalography detects phase-amplitude coupling in Parkinson's disease.

To characterize Parkinson's disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson's disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson's disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8-12 Hz; beta, 13-25 Hz; gamma, 50-100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson's disease showed significant beta-gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P < 0.05). Finally, beta-gamma phase-amplitude coupling in the sensorimotor cortices correlated significantly with motor symptoms of Parkinson's disease (P < 0.05); beta- and gamma-band power did not. We thus demonstrated that beta-gamma phase-amplitude coupling in the resting state characterizes Parkinson's disease.

Cryptogenic new-onset refractory status epilepticus responded to anti-interleukin-6 treatment.

OBJECTIVE: The aim of this case report was to describe a potential anti-interleukin (IL)-6 treatment for cryptogenic new-onset refractory status epilepticus (C-NORSE). BACKGROUND: Although an underlying immune-mediated pathogenesis is considered present in some C-NORSE cases, many cases do not respond to classical immunotherapies. CASE REPORT: We describe the case of a 46-year-old woman with C-NORSE who achieved cessation of long-lasting status epilepticus following administration of tocilizumab, an IL-6 receptor-blocking antibody, although the final outcome was poor. CONCLUSIONS: Anti-IL-6 treatment may prove effective in stopping status epilepticus in some C-NORSE cases.

Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson's disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT.

OBJECTIVE: To assess the utility of examining the nigrostriatal system with MRI and dopamine transporter (DAT) imaging for evaluating the preclinical phase of Parkinson's disease (PD). METHODS: The subjects were 32 patients with early PD and a history of probable rapid eye movement sleep behavior disorder (RBD; PD group), 15 patients with idiopathic RBD (RBD group), and 24 age-matched healthy controls (HC group) who underwent neuromelanin and diffusion tensor MRI for analysis of the substantia nigra pars compacta (SNpc). The RBD and PD groups underwent DAT imaging. In the RBD group, totals of 39 MRI and 27 DAT imaging examinations were obtained longitudinally. For each value, intergroup differences and receiver operating characteristic analysis for diagnostic performance were examined statistically. RESULTS: The neuromelanin value was significantly lower and the diffusion tensor values except fractional anisotropy were significantly higher in the RBD and PD groups than in the HC group. The DAT specific binding ratio (SBR) was significantly lower in the PD group than in the RBD group. The areas under the receiver operating characteristic curves (AUCs) for neuromelanin/mean diffusivity value in the SNpc were 0.76/0.82 for diagnosing RBD and 0.83/0.80 for diagnosing PD. The area under the receiver operating characteristic curves for the SBR for discriminating PD from RBD was 0.87. CONCLUSION: MRI and DAT imaging may be useful for evaluating sequential nigrostriatal changes during the preclinical phase of PD. ADVANCES IN KNOWLEDGE: MRI detects nigrostriatal changes in both RBD and early PD, and DAT imaging detects nigrostriatal changes during the transition to PD in RBD.

Perception of yips among professional Japanese golfers: perspectives from a network modelled approach.

'Yips' in golf is a complex spectrum of anxiety and movement-disorder that affects competitive sporting performance. With unclear etiology and high prevalence documented in western literature, the perception and management of this psycho-neuromuscular problem among Japanese elite golfers is unknown. The objective of this study was to explore factors associated with yips, investigate the performance deficits and the strategies implemented to prevent yips. We surveyed approx. 1300 professional golfers on their golfing habits, anxiety and musculoskeletal problems, kinematic deficits, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis. 35% of the respondents had experienced yips in their career, their odds increasing proportionally to their golfing experience. Regardless of musculoskeletal symptoms, about 57% of all yips-golfers attributed their symptoms to psychological causes. Network analysis highlighted characteristic movement patterns, i.e. slowing, forceful or freezing of movement for putting, approach and teeing shots respectively. Golfers' self-administered strategies to relieve yips were mostly inconsequential. Within the limits of our self-reported survey, most golfers perceived yips as a psychological phenomenon despite evidence pointing to a movement-disorder. While self-administered interventions were satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early management of the problem.

Decreased frontotemporal connectivity in patients with parkinson's disease experiencing face pareidolia.

The precise neural underpinnings of face pareidolia in patients with Parkinson's disease (PD) remain unclear. We aimed to clarify face recognition network abnormalities associated with face pareidolia in such patients. Eighty-three patients with PD and 40 healthy controls were recruited in this study. Patients with PD were classified into pareidolia and nonpareidolia groups. Volumetric analyses revealed no significant differences between the pareidolia (n = 39) and nonpareidolia (n = 44) patient groups. We further observed decreased functional connectivity among regions of interest in the bilateral frontotemporal lobes in patients with pareidolia. Seed-based analysis using bilateral temporal fusiform cortices as seeds revealed significantly decreased connectivity with the bilateral inferior medial prefrontal cortices in the pareidolia group. Post hoc regression analysis further demonstrated that the severity of face pareidolia was negatively correlated with functional connectivity between the bilateral temporal fusiform and medial prefrontal cortices. Our findings suggest that top-down modulation of the face recognition network is impaired in patients with PD experiencing face pareidolia.

Neural networks associated with quality of life in patients with Parkinson's disease.

INTRODUCTION: The neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it. METHODS: Comprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks. RESULTS: The Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened. CONCLUSION: Fear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.

Prestimulus Low-Alpha Frontal Networks Are Associated with Pareidolias in Parkinson's Disease.

Background: Pareidolias are visual phenomena wherein ambiguous, abstract forms or shapes appear meaningful due to incorrect perception. In Parkinson's disease (PD), patients susceptible to visual hallucinations experience visuo-perceptual deficits in the form of pareidolias. Although pareidolias necessitate top-down modulation of visual processing, the cortical dynamics of internally generated perceptual priors on these visual misperceptions is unknown. Objectives: To study prestimulus-related electroencephalography (EEG) spectral and network abnormalities in PD patients experiencing pareidolias. Methods: Twenty-one PD in-patients and 10 age-matched controls were evaluated. Neuropsychological assessments included tests for cognition, attention, and executive functions. Pareidolias were quantified by using the "noise pareidolia test" with simultaneous EEG recording. The PD patients were subdivided into two groups-those with high pareidolia counts (n = 10) and those without (n = 11). The EEG was analyzed 1000 msec before stimulus presentation in the spectral domain (theta, low-alpha, and high-alpha frequencies) with corresponding graph networks to evaluate network properties. Statistical analysis included analysis of variance and multiple regression to evaluate the differences. Results: The PD patients with high pareidolia counts were older with lower scores on neuropsychological tests. Their prestimulus EEG low-alpha band showed a tendency toward higher frontal activity (p = 0.07). Graph networks showed increased normalized clustering coefficient (p = 0.05) and lower frontal degree centrality (p = 0.005). These network indices correlated positively to patients' pareidolia scores. Discussion: We suggest that pareidolias in PD are a consequence of an abnormal top-down modulation of visual processing; they are defined by their frontal low-alpha spectral and network alterations in the prestimulus phase due to a dissonance between patients' internally generated mental processing with external stimuli. Impact statement Pareidolias in Parkinson's disease (PD) are considered to be promising early markers of visual hallucinations and an indicator of PD prognosis. In certain susceptible PD patients, pareidolias can be evoked and studied. Here, via electroencephalography, we aimed at understanding this visual phenomenon by studying how neural information is processed before stimulus presentation in such patients. Using spectral and graph network measures, we revealed how top-down modulated internally generated processes affect visual perception in patients with pareidolias. Our findings highlight how prestimulus network alterations in the frontal cortex shape poststimulus pareidolic manifestations in PD.

Effect of Neurofeedback Facilitation on Poststroke Gait and Balance Recovery: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that supplementary motor area (SMA) facilitation with functional near-infrared spectroscopy-mediated neurofeedback (fNIRS-NFB) augments poststroke gait and balance recovery, we conducted a 2-center, double-blind, randomized controlled trial involving 54 Japanese patients using the 3-meter Timed Up and Go (TUG) test. METHODS: Patients with subcortical stroke-induced mild to moderate gait disturbance more than 12 weeks from onset underwent 6 sessions of SMA neurofeedback facilitation during gait- and balance-related motor imagery using fNIRS-NFB. Participants were randomly allocated to intervention (28 patients) or placebo (sham: 26 patients). In the intervention group, the fNIRS signal contained participants' cortical activation information. The primary outcome was TUG improvement 4 weeks postintervention. RESULTS: The intervention group showed greater improvement in the TUG test (12.84 ± 15.07 seconds, 95% confidence interval 7.00-18.68) than the sham group (5.51 ± 7.64 seconds, 95% confidence interval 2.43-8.60; group difference 7.33 seconds, 95% CI 0.83-13.83; p = 0.028), even after adjusting for covariates (group × time interaction; F 1.23,61.69 = 4.50, p = 0.030, partial η2 = 0.083). Only the intervention group showed significantly increased imagery-related SMA activation and enhancement of resting-state connectivity between SMA and ventrolateral premotor area. Adverse effects associated with fNIRS-mediated neurofeedback intervention were absent. CONCLUSION: SMA facilitation during motor imagery using fNIRS neurofeedback may augment poststroke gait and balance recovery by modulating the SMA and its related network. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with gait disturbance from subcortical stroke, SMA neurofeedback facilitation improves TUG time (UMIN000010723 at UMIN-CTR; umin.ac.jp/english/).

Symptom Locus and Symptom Origin Incongruity in Runner's Dystonia - Case Study of an Elite Female Runner.

Objectives: Runner's dystonia is a task-specific dystonia that occurs in the lower limbs and trunk, with diverse symptomatology. We aimed to identify the origin of a dystonic movement abnormality using combined three-dimensional kinematic analysis and electromyographic (EMG) assessment during treadmill running. Participant: A 20-year-old female runner who complained of right-foot collision with the left-leg during right-leg swing-phase, which mimicked right-ankle focal dystonia. Results: Kinematic and EMG assessment of her running motion was performed, which showed a significant drop of the left pelvis during right-leg stance-phase, and a simultaneous increase of right hip adductor muscle activity. This resulted in a pronounced adduction of the entire right lower limb with respect to the pelvis segment. Trajectories of right foot were seen to encroach upon left-leg area. Discussion: These findings suggested that the symptom of this runner was most likely a form of segmental dystonia originating from an impaired control of hip and pelvis, rather than a distal focal ankle dystonia. Conclusion: We conclude that, for individualized symptom assessment, deconstructing the symptom origin from its secondary compensatory movement is crucial for characterizing dystonia. Kinematic and EMG evaluation will therefore be a prerequisite to distinguish symptom origin from secondary compensatory movement.

Ocular fixations and presaccadic potentials to explain pareidolias in Parkinson's disease.

In Parkinson's disease, a precursor phenomenon to visual hallucinations presents as 'pareidolias' which make ambiguous forms appear meaningful. To evoke and detect pareidolias in patients, a noise pareidolia test was recently developed, although its task-dependent mechanisms are yet to be revealed. When subjected to this test, we hypothesized that patients exhibiting pareidolias would show altered top-down influence of visual processing allowing us to demonstrate the influence of pareidolic illusionary behaviour in Parkinson's disease patients. To that end, we evaluated eye-movement strategies and fixation-related presaccadic activity on scalp EEG when participants performed the test. Twelve healthy controls and 21 Parkinson's disease patients, evaluated for cognitive, visuo-spatial and executive functions, took a modified computer-based version of the noise pareidolia test in a free-viewing EEG eye-tracking experiment. Eye-tracking metrics (fixation-related durations and counts) documented the eye movement behaviour employed in correct responses (face/noise) and misperceptions (pareidolia/missed) during early and late visual search conditions. Simultaneously, EEG recorded the presaccadic activity in frontal and parietal areas of the brain. Based on the noise pareidolia test scores, we found certain Parkinson's disease patients exhibited pareidolias whereas others did not. ANOVA on eye-tracking data showed that patients dwelled significantly longer to detect faces and pareidolias which affected both global and local search dynamics depending on their visuo-perceptual status. Presaccadic activity in parietal electrodes for the groups was positive for faces and pareidolias, and negative for noise, though these results depended mainly on saccade size. However, patients sensitive to pareidolias showed a significantly higher presaccadic potential on frontal electrodes independent of saccade sizes, suggesting a stronger frontal activation for pareidolic stimuli. We concluded with the following interpretations (i) the noise pareidolia test specifically characterizes visuo-perceptual inadequacies in patients despite their wide range of cognitive scores, (ii) Parkinson's disease patients dwell longer to converge attention to pareidolic stimuli due to abnormal saccade generation proportional to their visuo-perceptual deficit during early search, and during late search, due to time-independent alteration of visual attentional network and (iii) patients with pareidolias show increased frontal activation reflecting the allocation of attention to irrelevant targets that express the pareidolic phenomenon. While the disease per se alters the visuo-perceptual and oculomotor dynamics, pareidolias occur in Parkinson's disease due to an abnormal top-down modulation of visual processing that affects visual attention and guidance to ambiguous stimuli.