Decreased short-latency afferent inhibition in individuals with mild cognitive impairment: A TMS-EEG study.

TMS combined with EEG (TMS-EEG) is a tool to characterize the neurophysiological dynamics of the cortex. Among the TMS paradigms, short-latency afferent inhibition (SAI) allows the investigation of inhibitory effects mediated by the cholinergic system. The aim of this study was to compare cholinergic function in the DLPFC between individuals with mild cognitive impairment (MCI) and healthy controls (HC) using TMS-EEG with the SAI paradigm. In this study, 30 MCI and 30 HC subjects were included. The SAI paradigm consisted of 80 single pulse TMS and 80 SAI stimulations applied to the left DLPFC. N100 components, global mean field power (GMFP) and total power were calculated. As a result, individuals with MCI showed reduced inhibitory effects on N100 components and GMFP at approximately 100 ms post-stimulation and on ß-band activity at 200 ms post-stimulation compared to HC. Individuals with MCI showed reduced SAI, suggesting impaired cholinergic function in the DLPFC compared to the HC group. We conclude that these findings underscore the clinical applicability of the TMS-EEG method as a powerful tool for assessing cholinergic function in individuals with MCI.

Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS-EEG study.

Major depressive disorder affects over 300 million people globally, with approximately 30% experiencing treatment-resistant depression (TRD). Given that impaired neuroplasticity underlies depression, the present study focused on neuroplasticity in the dorsolateral prefrontal cortex (DLPFC). Here, we aimed to investigate the differences in neuroplasticity between 60 individuals with TRD and 30 age- and sex-matched healthy controls (HCs). To induce neuroplasticity, participants underwent a paired associative stimulation (PAS) paradigm involving peripheral median nerve stimulation and transcranial magnetic stimulation (TMS) targeting the left DLPFC. Neuroplasticity was assessed by using measurements combining TMS with EEG before and after PAS. Both groups exhibited significant increases in the early component of TMS-evoked potentials (TEP) after PAS (P < 0.05, paired t-tests with the bootstrapping method). However, the HC group demonstrated a greater increase in TEPs than the TRD group (P = 0.045, paired t-tests). Additionally, event-related spectral perturbation analysis highlighted that the gamma power significantly increased after PAS in the HC group, whereas it was decreased in the TRD group (P < 0.05, paired t-tests with the bootstrapping method). This gamma power modulation revealed a significant group difference (P = 0.006, paired t-tests), indicating an inverse relationship for gamma power modulation. Our findings underscore the impaired neuroplasticity of the DLPFC in individuals with TRD.

Development of Artificial Intelligence for Determining Major Depressive Disorder Based on Resting-State EEG and Single-Pulse Transcranial Magnetic Stimulation-Evoked EEG Indices.

Depression is the disorder with the greatest socioeconomic burdens. Its diagnosis is still based on an operational diagnosis derived from symptoms, and no objective diagnostic indicators exist. Thus, the present study aimed to develop an artificial intelligence (AI) model to aid in the diagnosis of depression from electroencephalography (EEG) data by applying machine learning to resting-state EEG and transcranial magnetic stimulation (TMS)-evoked EEG acquired from patients with depression and healthy controls. Resting-state EEG and single-pulse TMS-EEG were acquired from 60 patients and 60 healthy controls. Power spectrum analysis, phase synchronization analysis, and phase-amplitude coupling analysis were conducted on EEG data to extract feature candidates to apply different types of machine learning algorithms. Furthermore, to address the limitation of the sample size, dimensionality reduction was performed in a manner to increase the quality of information by featuring robust neurophysiological metrics that showed significant differences between the two groups. Then, nine different machine learning models were applied to the data. For the EEG data, we created models combining four modalities, including (1) resting-state EEG, (2) pre-stimulus TMS-EEG, (3) post-stimulus TMS-EEG, and (4) differences between pre- and post-stimulus TMS-EEG, and evaluated their performance. We found that the best estimation performance (a mean area under the curve of 0.922) was obtained using receiver operating characteristic curve analysis when linear discriminant analysis (LDA) was applied to the combination of the four feature sets. This study showed that by using TMS-EEG neurophysiological indices as features, it is possible to develop a depression decision-support AI algorithm that exhibits high discrimination accuracy.

Modified Boyes' procedure for the multiple finger extensor tendon ruptures in patients with rheumatoid arthritis: A report of two cases.

Multiple subcutaneous extensor tendon ruptures in more than the ulnar three fingers sometimes occur in patients with rheumatoid arthritis accompanied by wrist deformity. In these situations, the flexor digitorum superficialis tendon of the middle finger (the FDS3 tendon) and that of the ring finger (the FDS4 tendon) are used for the transferred tendon (modified Boyes' procedure). Here, we treated two patients with rheumatoid arthritis, whose extensor tendons of more than three fingers were ruptured, using the modified Boyes' procedure. Case 1 had ruptures in four fingers (index through little), and Case 2 had ruptures in three fingers (middle through little). The FDS3 and FDS4 tendons were passed subcutaneously around the radial side of the wrist to the extensor sides and interlaced with the distal stump of the ruptured tendons. Switching of the finger movement was achieved smoothly in both cases. The post-operative evaluation showed an extension lag of -15° for the index finger 0° for the middle through the little fingers in Case 1, and 0° for the middle finger and -5° for the ring and little fingers in Case 2. The average post-operative extension lag was -3.5°. However, median nerve palsy occurred in both cases, and it gradually recovered. Stretching of the nerve by the correction of the wrist deformity and increased pressure in the carpal tunnel were supposed to be causes of this palsy. Modified Boyes' procedure is a useful method for more than three ulnar finger extensor tendon ruptures; however, post-operative median nerve palsy should be considered.

Investigation of Spatiotemporal Profiles of Single-Pulse TMS-Evoked Potentials with Active Stimulation Compared with a Novel Sham Condition.

Identifying genuine cortical stimulation-elicited electroencephalography (EEG) is crucial for improving the validity and reliability of neurophysiology using transcranial magnetic stimulation (TMS) combined with EEG. In this study, we evaluated the spatiotemporal profiles of single-pulse TMS-elicited EEG response administered to the left dorsal prefrontal cortex (DLPFC) in 28 healthy participants, employing active and sham stimulation conditions. We hypothesized that the early component of TEP would be activated in active stimulation compared with sham stimulation. We specifically analyzed the (1) stimulus response, (2) frequency modulation, and (3) phase synchronization of TMS-EEG data at the sensor level and the source level. Compared with the sham condition, the active condition induced a significant increase in TMS-elicited EEG power in the 30-60 ms time interval in the stimulation area at the sensor level. Furthermore, in the source-based analysis, the active condition induced significant increases in TMS-elicited response in the 30-60 ms compared with the sham condition. Collectively, we found that the active condition could specifically activate the early component of TEP compared with the sham condition. Thus, the TMS-EEG method that was applied to the DLPFC could detect the genuine neurophysiological cortical responses by properly handling potential confounding factors such as indirect response noises.

Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. METHODS: We examined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. RESULTS: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). LIMITATIONS: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. CONCLUSION: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.

Characteristics of health-related quality of life and related factors in patients with brain tumors treated with rehabilitation therapy.

BACKGROUND: Rehabilitation therapy during hospitalization is effective in improving activities of daily living (ADL) and physical function in patients with brain tumors. However, there are few studies on the effect of rehabilitation therapy on health-related quality of life (HRQOL) in patients with brain tumors. Additionally, the EuroQol-5Dimension-5Level (EQ-5D-5L) index score has not been reported as an outcome. This study aimed to investigate the HRQOL of patients with brain tumors who underwent rehabilitation therapy and investigated the factors affecting the EQ-5D-5L index score from various perspectives, including various brain tumor type and recurrence. In addition, we examined the relationship between the EQ-5D-5L index score, disease-specific HRQOL scale, and ADL. METHODS: Patients with brain tumors who underwent treatment and rehabilitation at Single tertiary care academic medical center were included in this cross-sectional study. We used the EQ-5D-5L, European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30, and EORTC quality of life questionnaire brain cancer module to evaluate HRQOL. ADL were assessed using the functional independence measure (FIM). The relationship between each HRQOL assessment score and the FIM was analyzed, and the influence of related factors was assessed by multiple regression analysis. RESULTS: This study included 76 patients. The EQ-5D-5L index score was 0.689 for all patients with brain tumors and 0.574 for those with glioblastomas, which was the lowest value. There was a moderate correlation between the EQ-5D-5L index score and FIM (r = 0.627, p < 0.001). In addition, the EQ-5D-5L index score was significantly correlated with most of the items of the disease-specific HRQOL scale. Multiple regression analysis revealed that glioblastoma histology (coefficient: - 0.373, p = 0.005) and recurrence (coefficient: - 0.273, p = 0.020) were independent factors affecting the EQ-5D-5L index score. CONCLUSIONS: Patients with glioblastoma undergoing rehabilitation have reduced HRQOL, which was influenced by glioblastoma histology and recurrence.

Changes in depressive symptoms among family caregivers of patients with cancer after bereavement and their association with resilience: A prospective cohort study.

OBJECTIVES: To elucidate changes in depressive symptoms after bereavement and the impact of pre-loss resilience on such changes and on the extent of complicated grief and posttraumatic growth. METHODS: Prospective cohort surveys were provided to family caregivers of patients with cancer in four palliative care units (PCUs) before and after bereavement. Pre-loss Connor-Davidson Resilience Scale scores, pre- and post-loss Patient Health Questionnaire-9 scores, post-loss Brief Grief Questionnaire scores, and the expanded Posttraumatic Growth Inventory scores were determined. RESULTS: Out of 186 bereaved family caregivers, 71 (38.2%) responses were analyzed, among which 47% pre-loss and 15% post-loss responses suggested to be a high risk for major depressive disorder (MDD). Approximately 90% of family caregivers at a high risk for post-loss MDD were already at a high risk for pre-loss MDD. Even after adjustment of the background variables as covariates, the interaction effect between family caregivers' pre-loss depressive symptoms and resilience on post-loss depressive symptoms was observed (F = 7.29; p < 0.01). Moreover, pre-loss resilience was not associated with other bereavement outcome measures. CONCLUSIONS: Among family caregivers of patients with cancer in PCUs, 47% and 15% had high risk for MDD before and after bereavement, respectively. Moreover, pre-loss resilience mitigated post-loss depressive symptoms among family caregivers who had high risk for MDD before bereavement. However, considering the study's small sample size, further research is needed.

Development of an Advanced Sham Coil for Transcranial Magnetic Stimulation and Examination of Its Specifications.

Transcranial magnetic stimulation (TMS) neurophysiology has been widely applied worldwide, but it is often contaminated by confounders other than cortical stimulus-evoked activities. Although advanced sham coils that elaborately mimic active stimulation have recently been developed, their performance is not examined in detail. Developing such sham coils is crucial to improve the accuracy of TMS neurophysiology. Herein, we examined the specifications of the sham coil by comparison with the active coil. The magnetic flux and click sound pressure changes were measured when the stimulus intensity was varied from 10% to 100% maximum stimulator output (MSO), and the changes in coil surface temperature over time with continuous stimulation at 50% MSO for each coil. The magnetic flux change at the center of the coil showed a peak of 12.51 (kT/s) for the active coil, whereas it was 0.41 (kT/s) for the sham coil. Although both coils showed a linear change in magnetic flux as the stimulus intensity increased, due to the difference in coil winding structure, the sham coil took less than half the time to overheat and had 5 dB louder coil click sounds than the active coil. The sham coil showed a sufficiently small flux change at the center of the coil, but the flux change from the periphery of the coil was comparable to that of the active coil. Future use of high-quality sham coil will extend our understanding of the TMS neurophysiology of the cortex at the stimulation site.

Photobiological Neuromodulation of Resting-State EEG and Steady-State Visual-Evoked Potentials by 40 Hz Violet Light Optical Stimulation in Healthy Individuals.

Photobiological neuromodulation and its clinical application has been investigated in recent years. The response of the gamma-oscillation to human visual stimuli is known to be both burst and resonant in nature, and the coupling between alpha and gamma oscillations may play a functional role in visual processing. To date, there is no study that examined the effects of gamma-frequency violet light (VL) stimulation on human electroencephalography (EEG). In this study, we investigated the neurophysiological changes induced by light stimulation using EEG. The purpose of this study was to evaluate the specific effects of 40 Hz gamma-frequency VL stimulation on EEG activity by comparing the effects of white light (WL) with the same condition. Twenty healthy participants (10 females: 37.5 ± 14.3 years; 10 males: 38.0 ± 13.3 years) participated in this study and the following results were observed. First, when compared with the power spectrum density (PSD) of baseline EEG, 40 Hz-WL induced significant increase of PSD in theta band. Second, compared the PSDs between EEG with 40 Hz-VL and EEG with 40 Hz-WL, 40 Hz-VL induced significantly lower enhancement in delta and theta bands than 40 Hz-WL. Third, when focused on the occipital area, negative peak of VEP with 40 Hz-VL was smaller than that of 40 Hz-WL. Fourth, 40 Hz-VL induced an increase of alpha-gamma coupling during the VEP at the F5 electrode site as well as post-EEG at the C4 electrode site, compared with baseline EEG. Thus, the present study suggested that 40 Hz-VL stimulation may induce unique photobiological neuromodulations on human EEG activity.

Noncontact In-Bed Measurements of Physiological and Behavioral Signals Using an Integrated Fabric-Sheet Sensing Scheme.

Home monitoring requires measuring the physiological and behavioral signals without impairing a subject's everyday life. This paper presents an integrated and noncontact approach for obtaining simultaneous physiological and behavioral signals of recumbent humans in beds using a home-monitoring application. In the proposed approach, a fabric-sheet unified sensing electrode (FUSE) obtains physiological signals by recording the electrocardiogram (ECG), chest and abdominal respiratory movements (RMs), and ballistocardiogram (BCG). The FUSE also detects the behavioral signals of body proximity (BPx) and lateral/supine lying postures. A prototype system with FUSE was validated in a short-term experiment and 6-h overnight measurements on two different groups composed of seven lying subjects. The results confirmed that the approach senses each signal independently and records the ECG, RMs, BCG, and BPx signals simultaneously. The mean sensitivities of the R and T waves of the ECG during sleep were 86.1% and 88.0%, respectively, whereas those of the chest and abdominal RMs were 90.7% and 90.1%, respectively. Although our prototype system has room for improvement, the results suggest that our approach enables the unconstrained, nocturnal monitoring of the physiological and behavioral signals in recumbent humans. The at-home monitoring of the physiological and behavioral signals is expected to contribute to cost-effective personalized healthcare in the future. This noncontact and easy-to-install system for in-bed measurements can facilitate a new era of home monitoring.

The effect of B vitamin supplementation on wound healing in type 2 diabetic mice.

The aim of this study was to test the effects of B-group vitamin supplements on wound healing in diabetic mice. The mice in the experimental group were treated daily with 1 g/L B6, 1.25 mg/L B12, and 62.5 mg/L folic acid in their drinking water. Full-thickness excision wounds were created with 6-mm skin biopsy punches. Each wound closure was digitally photographed. Beginning on day 3 after wounding, the wound area in the diabetic mice was statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 42.8 ± 11.3%, p<0.05). On day 9 after wounding, the wound area in the diabetic mice was also statistically larger than that of normal mice (p<0.05 vs diabetic mice). The diabetic mice treated with B vitamins displayed accelerated wound closure on day 3 (wound area 13.2 ± 16.8%, p<0.05). In addition, the high glucose level in the diabetic animals decreased significantly in response to B vitamin treatment. In conclusion, the results of this study indicate that B vitamin supplementation may improve wound healing in diabetic mice.

The effect of systemic anti-tumor necrosis factor-alpha treatment on Porphyromonas gingivalis infection in type 2 diabetic mice.

OBJECTIVE: Diabetes mellitus and periodontal disease are two common chronic diseases that have long been thought to be biologically linked. Overexpression of tumor necrosis factor alpha (TNF-alpha) is thought to contribute to this bidirectional inter-relationship. This study examined the effect of anti-TNF-alpha antibody treatment on Porphyromonas gingivalis infection in diabetic mice. METHODS: In C57BL/6 (normal) and KKAy (diabetic) mice, the area adjacent to the periosteum at a point on the skull midway between the ears was inoculated with P. gingivalis. At 24h after the inoculation, the mice in the test group were treated with rat anti-murine TNF-alpha intravenously, while the control group received non-immunized rat IgG. TNF-alpha, IL-6, and fasting blood glucose levels in the mice were measured on day 3. RESULTS: Anti-TNF-alpha antibody treatment improved the host response to P. gingivalis and was associated with reduced serum TNF-alpha, IL-6, and fasting blood glucose levels in the KKAy mice. Anti-TNF-alpha antibody treatment also decreased the lesion size at the P. gingivalis inoculation. CONCLUSIONS: Our results suggest that TNF-alpha plays a role in the two-way relationship between P. gingivalis infection and diabetes mellitus. Anti-TNF-alpha antibody treatment may improve the host response to P. gingivalis infection and glycemic control in diabetes mellitus.