Evolutionary origin of alpha rhythms in vertebrates.

The purpose of this review extends beyond the traditional triune brain model, aiming to elucidate the evolutionary aspects of alpha rhythms in vertebrates. The forebrain, comprising the telencephalon (pallium) and diencephalon (thalamus, hypothalamus), is a common feature in the brains of all vertebrates. In mammals, evolution has prioritized the development of the forebrain, especially the neocortex, over the midbrain (mesencephalon) optic tectum, which serves as the prototype for the visual brain. This evolution enables mammals to process visual information in the retina-thalamus (lateral geniculate nucleus)-occipital cortex pathway. The origin of posterior-dominant alpha rhythms observed in mammals in quiet and dark environments is not solely attributed to cholinergic pontine nuclei cells functioning as a 10 Hz pacemaker in the brainstem. It also involves the ability of the neocortex's cortical layers to generate traveling waves of alpha rhythms with waxing and waning characteristics. The utilization of alpha rhythms might have facilitated the shift of attention from external visual inputs to internal cognitive processes as an adaptation to thrive in dark environments. The evolution of alpha rhythms might trace back to the dinosaur era, suggesting that enhanced cortical connectivity linked to alpha bands could have facilitated the development of nocturnal awakening in the ancestors of mammals. In fishes, reptiles, and birds, the pallium lacks a cortical layer. However, there is a lack of research clearly observing dominant alpha rhythms in the pallium or organized nuclear structures in fishes, reptiles, or birds. Through convergent evolution, the pallium of birds, which exhibits cortex-like fiber architecture, has not only acquired advanced cognitive and motor abilities but also the capability to generate low-frequency oscillations (4-25 Hz) resembling alpha rhythms. This suggests that the origins of alpha rhythms might lie in the pallium of a common ancestor of birds and mammals.

Neural Mechanisms of Neuro-Rehabilitation Using Transcranial Direct Current Stimulation (tDCS) over the Front-Polar Area.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation (NIBS) technique that applies a weak current to the scalp to modulate neuronal excitability by stimulating the cerebral cortex. The technique can produce either somatic depolarization (anodal stimulation) or somatic hyperpolarization (cathodal stimulation), based on the polarity of the current used by noninvasively stimulating the cerebral cortex with a weak current from the scalp, making it a NIBS technique that can modulate neuronal excitability. Thus, tDCS has emerged as a hopeful clinical neuro-rehabilitation treatment strategy. This method has a broad range of potential uses in rehabilitation medicine for neurodegenerative diseases, including Parkinson's disease (PD). The present paper reviews the efficacy of tDCS over the front-polar area (FPA) in healthy subjects, as well as patients with PD, where tDCS is mainly applied to the primary motor cortex (M1 area). Multiple evidence lines indicate that the FPA plays a part in motor learning. Furthermore, recent studies have reported that tDCS applied over the FPA can improve motor functions in both healthy adults and PD patients. We argue that the application of tDCS to the FPA promotes motor skill learning through its effects on the M1 area and midbrain dopamine neurons. Additionally, we will review other unique outcomes of tDCS over the FPA, such as effects on persistence and motivation, and discuss their underlying neural mechanisms. These findings support the claim that the FPA could emerge as a new key brain region for tDCS in neuro-rehabilitation.

Muscle synergy analysis yields an efficient and physiologically relevant method of assessing stroke.

The Fugl-Meyer Assessment is widely used to test motor function in stroke survivors. In the Fugl-Meyer Assessment, stroke survivors perform several movement tasks and clinicians subjectively rate the performance of each task item. The individual task items in the Fugl-Meyer Assessment are selected on the basis of clinical experience, and their physiological relevance has not yet been evaluated. In the present study, we aimed to objectively rate the performance of task items by measuring the muscle activity of 41 muscles from the upper body while stroke survivors and healthy participants performed 37 Fugl-Meyer Assessment upper extremity task items. We used muscle synergy analysis to compare muscle activity between subjects and found that 13 muscle synergies in the healthy participants (which we defined as standard synergies) were able to reconstruct all of the muscle activity in the Fugl-Meyer Assessment. Among the standard synergies, synergies involving the upper arms, forearms and fingers were activated to varying degrees during different task items. In contrast, synergies involving posterior trunk muscles were activated during all tasks, which suggests the importance of posterior trunk muscle synergies throughout all sequences. Furthermore, we noted the inactivation of posterior trunk muscle synergies in stroke survivors with severe but not mild impairments, suggesting that lower trunk stability and the underlying activity of posterior trunk muscle synergies may have a strong influence on stroke severity and recovery. By comparing the synergies of stroke survivors with standard synergies, we also revealed that some synergies in stroke survivors corresponded to merged standard synergies; the merging rate increased with the impairment of stroke survivors. Moreover, the degrees of severity-dependent changes in the merging rate (the merging rate-severity relationship) were different among different task items. This relationship was significant for 26 task items only and not for the other 11 task items. Because muscle synergy analysis evaluates coordinated muscle activities, this different dependency suggests that these 26 task items are appropriate for evaluating muscle coordination and the extent of its impairment in stroke survivors. Overall, we conclude that the Fugl-Meyer Assessment reflects physiological function and muscle coordination impairment and suggest that it could be performed using a subset of the 37 task items.

Altered Thalamic Connectivity Due to Focused Ultrasound Thalamotomy in Patients with Essential Tremor.

BACKGROUND: Although stereotactic ablation surgery is known to ameliorate involuntary movement dramatically, little is known regarding alterations in whole-brain networks due to disruption of the deep brain nucleus. To explore changes in the whole-brain network after thalamotomy, we analyzed structural and functional connectivity alterations using resting-state functional magnetic resonance imaging and diffusion tensor imaging in patients with essential tremor who had undergone focused ultrasound (FUS) thalamotomy. METHODS: Seven patients with intractable essential tremors and 7 age-matched healthy controls were enrolled in the study. The tremor score in essential tremor patients was assessed, and resting-state functional magnetic resonance imaging and diffusion tensor imaging were performed before and 3 months after left ventral intermediate nucleus thalamotomy using FUS. RESULTS: There was a significant improvement in the tremor of the right hand after FUS thalamotomy. Seed-based functional connectivity analysis revealed a significant increase in functional connectivity between the left thalamus and the caudal part of the dorsal premotor cortex after FUS thalamotomy. Structural connectivity analysis did not detect statistically significant changes between before and after FUS. There was no correlation between the changes in functional connectivity and tremor score. CONCLUSIONS: Although the number of cases is small, our results show that functional connectivity between the thalamus and the premotor cortex increases after the amelioration of tremors by FUS thalamotomy. The lack of correlation between increased functional connectivity and clinical tremor scores suggests that the observed increase in functional connectivity may be a compensatory change in the secondary sensorimotor changes that occur after thalamotomy.

Clarify Sit-to-Stand Muscle Synergy and Tension Changes in Subacute Stroke Rehabilitation by Musculoskeletal Modeling.

Post-stroke patients exhibit distinct muscle activation electromyography (EMG) features in sit-to-stand (STS) due to motor deficiency. Muscle activation amplitude, related to muscle tension and muscle synergy activation levels, is one of the defining EMG features that reflects post-stroke motor functioning and motor impairment. Although some qualitative findings are available, it is not clear if and how muscle activation amplitude-related biomechanical attributes may quantitatively reflect during subacute stroke rehabilitation. To better enable a longitudinal investigation into a patient's muscle activation changes during rehabilitation or an inter-subject comparison, EMG normalization is usually applied. However, current normalization methods using maximum voluntary contraction (MVC) or within-task peak/mean EMG may not be feasible when MVC cannot be obtained from stroke survivors due to motor paralysis and the subject of comparison is EMG amplitude. Here, focusing on the paretic side, we first propose a novel, joint torque-based normalization method that incorporates musculoskeletal modeling, forward dynamics simulation, and mathematical optimization. Next, upon method validation, we apply it to quantify changes in muscle tension and muscle synergy activation levels in STS motor control units for patients in subacute stroke rehabilitation. The novel method was validated against MVC-normalized EMG data from eight healthy participants, and it retained muscle activation amplitude differences for inter- and intra-subject comparisons. The proposed joint torque-based method was also compared with the common static optimization based on squared muscle activation and showed higher simulation accuracy overall. Serial STS measurements were conducted with four post-stroke patients during their subacute rehabilitation stay (137 ± 22 days) in the hospital. Quantitative results of patients suggest that maximum muscle tension and activation level of muscle synergy temporal patterns may reflect the effectiveness of subacute stroke rehabilitation. A quality comparison between muscle synergies computed with the conventional within-task peak/mean EMG normalization and our proposed method showed that the conventional was prone to activation amplitude overestimation and underestimation. The contributed method and findings help recapitulate and understand the post-stroke motor recovery process, which may facilitate developing more effective rehabilitation strategies for future stroke survivors.

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.

Classification of Motor Impairments of Post-Stroke Patients Based on Force Applied to a Handrail.

Many patients suffer from declined motor abilities after a brain injury. To provide appropriate rehabilitation programs and encourage motor-impaired patients to participate further in rehabilitation, sufficient and easy evaluation methodologies are necessary. This study is focused on the sit-to-stand motion of post-stroke patients because it is an important daily activity. Our previous study utilized muscle synergies (synchronized muscle activation) to classify the degree of motor impairment in patients and proposed appropriate rehabilitation methodologies. However, in our previous study, the patient was required to attach electromyography sensors to his/her body; thus, it was difficult to evaluate motor ability in daily circumstances. Here, we developed a handrail-type sensor that can measure the force applied to it. Using temporal features of the force data, the relationship between the degree of motor impairment and temporal features was clarified, and a classification model was developed using a random forest model to determine the degree of motor impairment in hemiplegic patients. The results show that hemiplegic patients with severe motor impairments tend to apply greater force to the handrail and use the handrail for a longer period. It was also determined that patients with severe motor impairments did not move forward while standing up, but relied more on the handrail to pull their upper body upward as compared to patients with moderate impairments. Furthermore, based on the developed classification model, patients were successfully classified as having severe or moderate impairments. The developed classification model can also detect long-term patient recovery. The handrail-type sensor does not require additional sensors on the patient's body and provides an easy evaluation methodology.

Intensity dependency of peripheral nerve stimulation in spinal LTP induced by paired associative corticospinal-motoneuronal stimulation (PCMS).

Paired associative corticospinal-motoneuronal stimulation (PCMS) induces plasticity at synapses between corticospinal tracts (CSTs) and spinal motoneurons (SMs). We investigated the effects of peripheral nerve electrical stimulation (PNS) intensity on PCMS-induced plasticity. PCMS consisted of 180 paired stimuli of transcranial magnetic stimulation (TMS) over the left primary motor cortex with PNS on the right ulnar nerve at the wrist. We compared effects induced by different PNS intensities: supramaximal, twice and three times sensory threshold intensities. For evaluating efficacy of the synapse between CSTs and SMs, single-pulse TMS was delivered at cervicomedullary junction level, and cervicomedullary motor-evoked potentials (CMEPs) were recorded from the right first-dorsal interosseous muscle before and after PCMS. PCMS with the supramaximal PNS intensity increased CMEP amplitude. The facilitatory effect of PCMS with the supramaximal PNS was larger than those of PCMS with weaker PNS intensities. Sham TMS with the supramaximal PNS showed no CMEP changes after the intervention. PNS intensity of PCMS influences the magnitude of synaptic plasticity induction between the CSTs and SMs at the spinal level, and the supramaximal intensity is the best for induction of long-term potentiation-like effects. The PNS intensity may influence the number of activated SMs by axonal backpropagating pulses with PNS which must overlap with descending volleys induced by TMS.

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.

A Parkinson's disease patient displaying increased neuromelanin-sensitive areas in the substantia nigra after rehabilitation with tDCS: a case report.

Previous studies have reported that transcranial direct current stimulation (tDCS) of the frontal polar area (FPA) ameliorated motor disability in patients with Parkinson's disease (PD). Here we report changes in neuromelanin (NM) imaging of dopaminergic neurons before and after rehabilitation combined with anodal tDCS over the FPA for 2 weeks in a PD patient. After the intervention, the patient showed clinically meaningful improvements while the NM-sensitive area in the SN increased by 18.8%. This case study is the first report of NM imaging of the SN in a PD patient who received tDCS.Abbreviations FPA: front polar area; PD: Parkinson's disease; NM: neuromelanin; DCI: DOPA decarboxylase inhibitor; STEF: simple test for evaluating hand function; TUG: timed up and go test; TMT: trail-making test; SN: substantia nigra; NM-MRI: neuromelanin magnetic resonance imaging; MCID: the minimal clinically important difference; SNpc: substantia nigra pars compacta; VTA: ventral tegmental area; LC: locus coeruleus; PFC: prefrontal cortex; M1: primary motor cortex; MDS: Movement Disorder Society; MIBG: 123I-metaiodobenzylguanidine; SBR: specific binding ratio; SPECT: single-photon emission computed tomography; DAT: dopamine transporter; NIBS: noninvasive brain stimulation; tDCS: transcranial direct current stimulation; MAOB: monoamine oxidase B; DCI: decarboxylase inhibitor; repetitive transcranial magnetic stimulation: rTMS; diffusion tensor imaging: DTI; arterial spin labeling: ASL.

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.

Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index.

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. This study included 31 patients with subacute aphasia and 24 healthy controls. We assessed the expressive function of patients and calculated the PSIs of three motor language-related regions: frontofrontal, left frontotemporal, and right frontotemporal. Then, we evaluated post-stroke network alterations by comparing PSIs of the patients and controls and by analyzing the correlations between PSIs and aphasia scores. The frontofrontal PSI (beta band) was lower in patients than in controls and positively correlated with aphasia scores, whereas the right frontotemporal PSI (delta band) was higher in patients than in controls and negatively correlated with aphasia scores. Evaluation of artifacts suggests that this association is attributed to true synchrony rather than spurious synchrony. These findings suggest that post-stroke aphasia is associated with alternations of two different networks and point to the usefulness of EEG PSI in understanding the pathophysiology of aphasia.

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.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

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.

Lower limb muscle strengthening exercises in patients with early-stage amyotrophic lateral sclerosis: a case series study.

[Purpose] We investigated whether patients with early-stage amyotrophic lateral sclerosis can improve their voluntary strength with a physical therapy program. [Participants and Methods] This retrospective case series study at a single university hospital included 13 patients with amyotrophic lateral sclerosis (amyotrophic lateral sclerosis functional rating scale-revised ≥35, modified functional ambulation categories score ≥4). Physical therapy was performed for 3 weeks. We investigated knee extension muscle strength and modified functional ambulation categories scores at the start and end of the therapy and calculated the improvement rate of knee extension muscle strength. We performed a regression analysis of the relationship between knee extension muscle strength at the start of the study and the improvement rate. [Results] The knee extension muscle strength improved significantly; however, the effect size was small (0.13). The modified functional ambulation categories scores did not improve significantly. The knee extension muscle strength at the start of the therapy was negatively correlated with the improvement rate (logarithmic transformed linear regression: adjusted R2=0.27). [Conclusion] A short-duration exercise program improved lower limb muscle strength in patients with early-stage amyotrophic lateral sclerosis. Additionally, we found that patients with weaker lower limb muscle strength at the start of the therapy demonstrated greater improvement at the end of the therapy.

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

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.