Regional activity and effective connectivity within the frontoparietal network during precision walking with visual cueing: an fNIRS study.

Precision walking (PW) incorporates precise step adjustments into regular walking patterns to navigate challenging surroundings. However, the brain processes involved in PW control, which encompass cortical regions and interregional interactions, are not fully understood. This study aimed to investigate the changes in regional activity and effective connectivity within the frontoparietal network associated with PW. Functional near-infrared spectroscopy data were recorded from adult subjects during treadmill walking tasks, including normal walking (NOR) and PW with visual cues, wherein the intercue distance was either fixed (FIX) or randomly varied (VAR) across steps. The superior parietal lobule (SPL), dorsal premotor area (PMd), supplementary motor area (SMA), and dorsolateral prefrontal cortex (dlPFC) were specifically targeted. The results revealed higher activities in SMA and left PMd, as well as left-to-right SPL connectivity, in VAR than in FIX. Activities in SMA and right dlPFC, along with dlPFC-to-SPL connectivity, were higher in VAR than in NOR. Overall, these findings provide insights into the roles of different brain regions and connectivity patterns within the frontoparietal network in facilitating gait control during PW, providing a useful baseline for further investigations into brain networks involved in locomotion.

Effect of dual-task interaction combining postural and visual perturbations on cortical activity and postural control ability.

Previous studies have suggested cortical involvement in postural control in humans by measuring cortical activities and conducting dual-task paradigms. In dual-task paradigms, task performance deteriorates and can be facilitated in specific dual-task settings. Theoretical frameworks explaining these dual-task interactions have been proposed and debated for decades. Therefore, we investigated postural control performance under different visual conditions using a virtual reality system, simultaneously measuring cortical activities with a functional near-infrared spectroscopy system. Twenty-four healthy participants were included in this study. Postural stability and cortical activities after perturbations were measured under several conditions consisting of postural and visual perturbations. The results showed that concurrent visual and postural perturbations could facilitate cortical activities in the supplementary motor area and superior parietal lobe. Additionally, visual distractors deteriorated postural control ability and cortical activation of the supplementary motor area. These findings supported the theoretical framework of the "Cross talk model", in which concurrent tasks using similar neural domains can facilitate these task performances. Furthermore, it indicated that the cortical resource capacity and domains activated for information processing should be considered in experiments involving dual-task paradigms and training.

Coupled versus decoupled visuomotor feedback: Differential frontoparietal activity during curved reach planning on simultaneous functional near-infrared spectroscopy and electroencephalography.

INTRODUCTION: Interacting with the environment requires the planning and execution of reach-to-target movements along given reach trajectory paths. Human neural mechanisms for the motor planning of linear, or point-to-point, reaching movements are relatively well studied. However, the corresponding representations for curved and more complex reaching movements require further investigation. Additionally, the visual and proprioceptive feedback of hand positioning can be spatially and sequentially coupled in alignment (e.g., directly reaching for an object), termed coupled visuomotor feedback, or spatially decoupled (e.g., dragging the computer mouse forward to move the cursor upward), termed decoupled visuomotor feedback. During reach planning, visuomotor processing routes may differ across feedback types. METHODS: We investigated the involvement of the frontoparietal regions, including the superior parietal lobule (SPL), dorsal premotor cortex (PMd), and dorsolateral prefrontal cortex (dlPFC), in curved reach planning under different feedback conditions. Participants engaged in two delayed-response reaching tasks with identical starting and target position sets but different reach trajectory paths (linear or curved) under two feedback conditions (coupled or decoupled). Neural responses in frontoparietal regions were analyzed using a combination of functional near-infrared spectroscopy and electroencephalography. RESULTS: The results revealed that, regarding the cue period, curved reach planning had a higher hemodynamic response in the left SPL and bilateral PMd and a smaller high-beta power in the left parietal regions than linear reach planning. Regarding the delay period, higher hemodynamic responses during curved reach planning were observed in the right dlPFC for decoupled feedback than those for coupled feedback. CONCLUSION: These findings suggest the crucial involvement of both SPL and PMd activities in trajectory-path processing for curved reach planning. Moreover, the dlPFC may be especially involved in the planning of curved reaching movements under decoupled feedback conditions. Thus, this study provides insight into the neural mechanisms underlying reaching function via different feedback conditions.

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.

A novel method to measure sensory nerve conduction of the posterior antebrachial cutaneous nerve.

INTRODUCTION/AIMS: Posterior antebrachial cutaneous (PABC) nerve conduction studies could be useful for distinguishing PABC neuropathy from C7 radiculopathy. In the conventional method using an antidromic method, the sensory nerve action potential (SNAP) is sometimes followed by a large volume-conducted motor potential. In this report we describe a reliable nerve conduction study using an orthodromic method for recording SNAPs of the PABC nerve. METHODS: Thirty-six healthy volunteers participated in this study. PABC SNAPs were recorded by placing a surface-active electrode 2 cm anterior to the lateral epicondyle. The PABC nerve was stimulated 10 cm distal to the active recording electrode along a line from the recording point to the mid-dorsum of the wrist, midway between the radial and ulnar styloid processes. We also performed PABC nerve conduction studies using an antidromic method and compared the findings. RESULTS: PABC SNAPs were recorded bilaterally from all subjects. The mean peak-to-peak amplitude for SNAPs was 13.4 ± 4.8 µV. Mean maximum conduction velocity was 62.7 ± 3.9 m/s and mean negative peak conduction velocity was 51.2 ± 2.6 m/s. The mean side-to-side difference in amplitude was 22.1 ± 16.0%. The mean amplitude of SNAPs obtained by our method was 48.9% higher than that of SNAPs obtained by the conventional method (13.4 vs 9.0 µV; P < .001). In contrast to the conventional method, our method enabled SNAPs to be recorded without a volume-conducted motor potential. DISCUSSION: The higher mean amplitude of SNAPs with our method enables them to be obtained easily.

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.

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.

Association of the Yips and Musculoskeletal Problems in Highly Skilled Golfers: A Large Scale Epidemiological Study in Japan.

The yips are a set of conditions associated with intermittent motor disturbances that affect precision movement, especially in sports. Specifically, skilled golfers suffer from the yips, although its clinical characteristics and pathophysiology have not been well-studied. We surveyed skilled golfers to characterize their yips-related symptoms, to explore potential confounding factors associated with the yips. Golfers' demographic information, golfing-career-related history, musculoskeletal status and manifestations of the yips are surveyed. Among the 1576 questionnaires distributed, 1457 (92%) responses were received, of which 39% of golfers had experienced the yips. The median age and golfing careers were 48 and 28 years, respectively. Golfers who had experienced the yips were older and had longer golfing careers and more frequent musculoskeletal problems than those without experience of the yips. The multivariate logistic regression analysis revealed that a longer golfing career and musculoskeletal problems were independent factors associated with yips experience. More severe musculoskeletal problems were associated with higher odds of experiencing the yips. A positive association between the yips and musculoskeletal problems was also observed. The yips have similar characteristics to task-specific movement disorders, with a detrimental effect caused by excessive repetition of a routine task. These findings support the notion that the yips are a type of task-specific dystonia.

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/).

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.

Anatomical variations of the superficial branch of the radial nerve and the dorsal branch of the ulnar nerve: A detailed electrophysiological study.

INTRODUCTION: In this study we evaluated anatomic variations of the superficial branch of the radial nerve (SBRN) and the dorsal branch of the ulnar nerve (DBUN) electrophysiologically. METHODS: Antidromic nerve conduction studies (NCS) of the SBRN and DBUN were performed on healthy individuals. To identify individual responses from the distal branches of the SBRN and DBUN, sensory nerve action potentials of each finger (lateral side/medial side) were recorded. RESULTS: NCS were performed in 50 hands of 27 healthy control subjects. The thumb and the index finger were supplied by the SBRN in all cases. The lateral and medial sides of the third finger were supplied by the SBRN in 94.0% and 74.0% of the cases, but the lateral and medial sides of the fourth finger were supplied by the SBRN in only 10.0% and 2.0% of cases. The fifth finger and the medial side of the fourth finger were always supplied by the DBUN. The lateral side of the fourth finger was supplied by the DBUN in 98.0% of cases, but the lateral and medial sides of the third finger were supplied by the DBUN in 40.0% and 70.0% of cases. Dual innervation by the SBRN and DBUN was found in 34.0% and 46.0% of the lateral and medial sides of the third finger, but in only 8.0% and 2.0% of the lateral and medial sides of the fourth finger. DISCUSSION: There are considerable anatomic variations of the SBRN and DBUN in healthy individuals.

Optical brain imaging and its application to neurofeedback.

Besides passive recording of brain electric or magnetic activity, also non-ionizing electromagnetic or optical radiation can be used for real-time brain imaging. Here, changes in the radiation's absorption or scattering allow for continuous in vivo assessment of regional neurometabolic and neurovascular activity. Besides magnetic resonance imaging (MRI), over the last years, also functional near-infrared spectroscopy (fNIRS) was successfully established in real-time metabolic brain imaging. In contrast to MRI, fNIRS is portable and can be applied at bedside or in everyday life environments, e.g., to restore communication and movement. Here we provide a comprehensive overview of the history and state-of-the-art of real-time optical brain imaging with a special emphasis on its clinical use towards neurofeedback and brain-computer interface (BCI) applications. Besides pointing to the most critical challenges in clinical use, also novel approaches that combine real-time optical neuroimaging with other recording modalities (e.g. electro- or magnetoencephalography) are described, and their use in the context of neuroergonomics, neuroenhancement or neuroadaptive systems discussed.

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.

Relationship between the Diabetic Polyneuropathy Index and the Neurological Findings of Diabetic Polyneuropathy.

Objective To achieve an accurate quantification in diabetic polyneuropathy (DPN), we developed a new electrophysiological index that we called the DPN index. The relationship between the DPN index and the neurological findings in diabetic patients was assessed. Methods The DPN index was calculated by the mean value of percentages of four parameters (tibial compound muscle action potential amplitude / F wave minimum latency, sural sensory nerve action potential amplitude / sensory nerve conduction velocity) against the mean normal values. Twenty healthy subjects were recruited as a control group. Patients A total of 348 diabetic patients who were hospitalized in our hospital during the period from December 2016 to August 2019 were retrospectively studied. The correlations between the DPN index and five neurological findings (subjective sensory symptoms, diminished or absent Achilles tendon reflex, impaired tactile and vibration sense, low coefficient of variation of R-R interval) were evaluated. Results The DPN index in healthy subjects was 129.3±32.7%. The DPN index in diabetic patients with one or more neurological findings was significantly lower than that in diabetic patients without any neurological findings (p<0.01: 89.3±27.8% vs. 118.4±21.2%). For each of the five neurological findings, the DPN index in the group with an abnormality was significantly lower than that in the group without any abnormality (each p<0.01). Spearman's correlation coefficients indicated that a greater number of neurological findings resulted in a lower DPN index (r=-0.711, p<0.01). Conclusion Our study suggested that the DPN index is useful for evaluating the severity of DPN.

Motor Imagery Training With Neurofeedback From the Frontal Pole Facilitated Sensorimotor Cortical Activity and Improved Hand Dexterity.

To develop a real-time neurofeedback system from the anterior prefrontal cortex (aPFC) using functional near-infrared spectroscopy (fNIRS) for motor rehabilitation, we investigated the effects of motor imagery training with neurofeedback from the aPFC on hand dexterity and cerebral hemodynamic activity during a motor rehabilitation task. Thirty-one right-handed healthy subjects participated in this study. They received motor imagery training six times for 2 weeks under fNIRS neurofeedback from the aPFC, in which they were instructed to increase aPFC activity. The real group subjects (n = 16) were shown real fNIRS neurofeedback signals from the aPFC, whereas the sham group subjects (n = 15) were shown irrelevant randomized signals during neurofeedback training. Before and after the training, hand dexterity was assessed by a motor rehabilitation task, during which cerebral hemodynamic activity was also measured. The results indicated that aPFC activity was increased during the training, and performance improvement rates in the rehabilitation task after the training was increased in the real group when compared with the sham group. Improvement rates of mean aPFC activity across the training were positively correlated with performance improvement rates in the motor rehabilitation task. During the motor rehabilitation task after the training, the hemodynamic activity in the left somatosensory motor-related areas [premotor area (PM), primary motor area (M1), and primary somatosensory area (S1)] was increased in the real group, whereas the hemodynamic activity was increased in the supplementary motor area in the sham group. This hemodynamic activity increases in the somatosensory motor-related areas after the training correlated with aPFC activity during the last 2 days of motor imagery training. Furthermore, improvement rates of M1 hemodynamic activity after the training was positively correlated with performance improvement rates in the motor rehabilitation task. The results suggest that the aPFC might shape activity in the somatosensory motor-related areas to improve hand dexterity. These findings further suggest that the motor imagery training using neurofeedback signals from the aPFC might be useful to patients with motor disability.

Involvement of cortical dysfunction in frequent falls in patients with Parkinson's disease.

INTRODUCTION: Gait and balance disorders are common clinical features of Parkinson's disease (PD). Although falls significantly affect the activities of daily living (ADL) and quality of life (QOL) of patients with PD, the underlying neural mechanisms associated with frequent falls in PD patients are still unclear. METHODS: Hypothesizing that the cerebral cortex would contribute to frequent falls in PD, we obtained 3D T1-weighted images from 91 non-dementia patients with PD and performed voxel-based morphometric analysis (VBM). Gray matter volume was compared between patients with and without frequent falls to investigate the structural basis for frequent falls in PD. As an ancillary analysis, we also performed resting-state functional magnetic resonance analysis using data from 58 patients. RESULTS: Among the 91 patients, 36 had experienced frequent falls. Gray matter volume in the right superior temporal gyrus (STG) and the right inferior parietal lobule (IPL) of these patients was significantly lower than that of the non-frequent fallers. There was also a significant correlation between fall frequency and gray matter volume in these two regions. Additionally, resting-state functional analysis revealed lower connectivity in the right posterior perisylvian region, including in the IPL and STG, in frequent fallers than in non-frequent fallers. CONCLUSION: Frequent falls in PD are associated with structural and functional abnormality of the cerebral cortex including the right IPL and STG.

Influence of placement sites of the active recording electrode on CMAP configuration in the trapezius muscle.

OBJECTIVE: We investigated how the active electrode placement site influences compound muscle action potential (CMAP) configuration of the upper trapezius muscle (TM). METHODS: A nerve conduction study of the accessory nerve was performed, and the CMAPs obtained with two different placement sites, i.e., placement of the active recording electrode on the belly of the upper TM (CMAP-A) and placement of the electrode 2 cm behind the belly (CMAP-B), were compared. CMAPs were also obtained with the active recording electrode placed in the supraspinous fossa (CMAP-C). RESULTS: All CMAPs were recorded from 21 healthy volunteers. The mean peak-to-peak amplitude of CMAP-B was 3.4 mV higher than that of CMAP-A (11.0 ±â€¯4.0 mV vs. 14.4 ±â€¯4.9 mV; P < 0.01). The mean peak-to-peak amplitude of CMAP-C was 10.3 ±â€¯5.0 mV. CONCLUSIONS: CMAP of the upper TM was always higher when the active recording electrode was placed 2 cm behind the belly of the muscle. SIGNIFICANCE: When stimulating the accessory nerve, a current spread occurs to the C5 spinal nerve root and another CMAP originating from the supraspinatus muscle occurs in the supraspinous fossa. The volume conduction from the supraspinatus muscle affects the active recording electrode on the TM, resulting in an increase in CMAP amplitude.

Safety and efficacy of levodopa-carbidopa intestinal gel: results from an open-label extension study in Japanese, Korean and Taiwanese patients with advanced Parkinson's disease.

OBJECTIVES: Levodopa-carbidopa intestinal gel (LCIG) was developed to reduce motor complications in Parkinson's disease (PD) caused by pulsatile levodopa plasma concentrations following oral levodopa administration. Dyskinesia and 'wearing off' symptoms can vary between Asian and Caucasian patients with PD, thus highlighting the importance of assessing the effectiveness of LCIG in an Asian population. Efficacy and safety of LCIG were previously assessed in a 12-week open-label study; we report the efficacy and safety of at least 52 weeks of LCIG treatment in Japanese, Taiwanese, and Korean patients with advanced PD in the ongoing extension study. METHODS: In this interim analysis of a phase III, open-label, multicenter extension study in Japan, South Korea, and Taiwan [ClinicalTrials.gov identifier: NCT02082249/JapiCTI-142482], the mean change from baseline to final visit in 'off' time, as reported in the PD symptom diary, was normalized to a 16-h waking day. Changes in Parkinson's Disease Questionnaire-39 (PDQ-39) summary index and domains scores were also analyzed. Adverse events (AEs) were recorded. RESULTS: Of the 28 patients enrolled (21 Japanese, 3 Taiwanese, 4 Korean), 27 completed at least 52 total weeks of treatment, and 25 patients were continuing in the study at data cutoff. The mean [standard deviation (SD)] 'off' time was significantly reduced by 4.6 (3.1) h/day (p < 0.001, n = 28). Patients experienced significant improvements in quality of life, as recorded by the mean change from baseline in PDQ-39 summary index (p < 0.001). All patients had at least one AE; three patients (11%) discontinued due to an AE. There were two deaths (sepsis and drowning), both of which the investigator considered unrelated to LCIG treatment. CONCLUSIONS: These data suggest that LCIG treatment is efficacious, safe, and well tolerated in Japanese, Taiwanese, and Korean patients with advanced PD, thus confirming the consistency of LCIG treatment in patients with advanced PD.

Quantifying changes in nigrosomes using quantitative susceptibility mapping and neuromelanin imaging for the diagnosis of early-stage Parkinson's disease.

OBJECTIVE: To quantify nigral changes with a focus on their spatial variation within the substantia nigra pars compacta (SNpc) for diagnosing early-stage Parkinson's disease (PD). METHODS: The study participants were 18 patients with early-stage PD (PD group) and 18 healthy controls (HC group) who underwent quantitative susceptibility mapping (QSM) and neuromelanin imaging. The QSM and neuromelanin values in each whole SNpc containing the entire nigrosome and dorsolateral SNpc containing nigrosome 1 were calculated. The neuromelanin area was defined as the volume with a signal-to-noise ratio higher than that of the background region. The significance of intergroup differences in the QSM value and neuromelanin area in each SNpc region was tested. Logit (p) was used to estimate the probability of PD in relation to the QSM value and the neuromelanin area, and receiver operating characteristic analyses were performed for each value. RESULTS: In both SNpc, QSM values were significantly higher and neuromelanin areas were significantly lower in the PD group compared with the HC group (p < 0.05). The respective areas under the receiver operating characteristic curve for the two groups were 0.70/0.73 for the QSM value, 0.81/0.78 for the neuromelanin area in the whole/dorsolateral SNpc, and 0.86 for logit (p) in relation to the QSM value of the dorsolateral SNpc and the neuromelanin area of the whole SNpc. CONCLUSION: Comprehensive MRI assessment of the abnormality involving the nigrosomes can yield a high diagnostic performance for early-stage PD. Advances in knowledge: Focusing on spatial differences in nigral changes within the SNpc can increase the sensitivity of the detection of PD-related neurodegenerative changes.