Effects of transcutaneous auricular vagus nerve stimulation at left cymba concha on experimental pain as assessed with the nociceptive withdrawal reflex, and correlation with parasympathetic activity.

The aim of this study was to clarify the effects of transcutaneous auricular vagus nerve stimulation (taVNS) to the left cymba concha on the pain perception using nociceptive withdrawal reflex (NWR), which is known to be associated with chronic pain, and to investigate whether there is a relationship between taVNS-induced suppression of the NWR and parasympathetic activation. We applied either 3.0 mA, 100 Hz taVNS for 120 s on the left cymba concha (taVNS condition) or the left earlobe (Sham condition) for 20 healthy adults. NWR threshold was measured before (Baseline), immediately after (Post 0), 10 min (Post 10) and 30 min after (Post 30) stimulation. The NWR threshold was obtained from biceps femoris muscle by applying electrical stimulation to the sural nerve. During taVNS, electrocardiogram was recorded, and changes in autonomic nervous activity measured by heart rate variability (HRV) were analyzed. We found that the NWR thresholds at Post 10 and Post 30 increased compared with baseline in the taVNS group (10 min after: p = .008, 30 min after: p = .008). In addition, increased parasympathetic activity by taVNS correlated with a greater increase in NWR threshold at Post 10 and Post 30 (Post 10: p = .003; Post 30: p = .001). The present results of this single-blinded study demonstrate the pain-suppressing effect of taVNS on NWR threshold and suggest that the degree of parasympathetic activation during taVNS may predict the pain-suppressing effect of taVNS after its application.

Influence of postural control difficulty on changes in spatial orienting of attention after leftward prism adaptation.

Prism adaptation (PA) affects visuospatial attention such as spatial orienting in both the right and left hemifields; however, the systematic after-effects of PA on visuospatial attention remain unclear. Visuospatial attention can be affected by non-spatial attentional factors, and postural control difficulty, which delays the reaction time (RT) to external stimulation, may be one such factor. Therefore, we aimed to investigate the influence of postural control difficulty on changes in spatial orienting of attention after leftward PA. Seventeen healthy young adults underwent 15-min and 5-min PA procedures for a leftward visual shift (30 diopters). Participants underwent the Posner cueing test immediately before (pre-evaluation) and in between and after the PA procedures (post-evaluations) while standing barefoot on the floor (normal standing condition) and on a balance-disc (balance standing condition). In the pre-evaluation, RTs in the balance standing condition were significantly longer compared to those in the normal standing condition for targets appearing in both the right and left hemifields. Leftward PA improved the RT for targets appearing in the right, but no left, hemifield in the balance standing condition, such that RTs for targets in the right hemifield in the post-evaluation were not significantly different between the two standing conditions. However, leftward PA did not significantly change RTs for targets in both hemifields in the normal standing condition. Therefore, postural control difficulty may enhance sensitivity to the features of the visuospatial cognitive after-effects of leftward PA.

Beta resting-state functional connectivity predicts tactile spatial acuity.

Tactile perception is a complex phenomenon that is processed by multiple cortical regions via the primary somatosensory cortex (S1). Although somatosensory gating in the S1 using paired-pulse stimulation can predict tactile performance, the functional relevance of cortico-cortical connections to tactile perception remains unclear. We investigated the mechanisms by which corticocortical and local networks predict tactile spatial acuity in 42 adults using magnetoencephalography (MEG). Resting-state MEG was recorded with the eyes open, whereas evoked responses were assessed using single- and paired-pulse electrical stimulation. Source data were used to estimate the S1-seed resting-state functional connectivity (rs-FC) in the whole brain and the evoked response in the S1. Two-point discrimination threshold was assessed using a custom-made device. The beta rs-FC revealed a negative correlation between the discrimination threshold and S1-superior parietal lobule, S1-inferior parietal lobule, and S1-superior temporal gyrus connection (all P < 0.049); strong connectivity was associated with better performance. Somatosensory gating of N20m was also negatively correlated with the discrimination threshold (P = 0.015), with weak gating associated with better performance. This is the first study to demonstrate that specific beta corticocortical networks functionally support tactile spatial acuity as well as the local inhibitory network.

Association between somatosensory sensitivity and regional gray matter volume in healthy young volunteers: a voxel-based morphometry study.

Two-point discrimination (2PD) test reflects somatosensory spatial discrimination ability, but evidence on the relationship between 2PD and cortical gray matter (GM) volume is limited. This study aimed to analyze the relationship between cortical GM volume and 2PD threshold in young healthy individuals and to clarify the characteristics of brain structure reflecting the individual differences in somatosensory function. 2PD was measured in 42 healthy (20 females) volunteers aged 20-32 years using a custom-made test system that can be controlled by a personal computer. The 2PD of the right index finger measured with this device has been confirmed to show good reproducibility. T1-weighted images were acquired using a 3-T magnetic resonance imaging scanner for voxel-based morphometry analysis. The mean 2PD threshold was 2.58 ± 0.54 mm. Whole-brain multiple regression analysis of the relationship between 2PD and GM volume showed that a lower 2PD threshold (i.e. better somatosensory function) significantly correlated with decreased GM volume from the middle temporal gyrus to the inferior parietal lobule (IPL) in the contralateral hemisphere. In conclusion, a lower GM volume in the middle temporal gyrus and IPL correlates with better somatosensory function. Thus, cortical GM volume may be a biomarker of somatosensory function.

Gray Matter Volume Variability in Young Healthy Adults: Influence of Gender Difference and Brain-Derived Neurotrophic Factor Genotype.

Although brain gray matter (GM) plastically changes during short-term training, it is still unclear whether brain structures are stable for short periods (several months). Therefore, this study aimed to re-test the short-term variability of GM volumes and to clarify the effect of factors (gender and BDNF-genotype) expected to contribute to such variability. The subjects comprised 41 young healthy adults. T1-weighted images were acquired twice with an interval of approximately 4 months using a 3 T-MRI scanner. Voxel-based morphometry (VBM) was used to calculate GM volumes in 47 regions. The intraclass correlation coefficient (ICC) and Test-retest variability (%TRV) were used as indices of variability. As a result, the ICCs in 43 regions were excellent (ICC > 0.90) and those in 3 regions were good (ICC > 0.80), whereas the ICC in the thalamus was moderate (ICC = 0.694). Women had a higher %TRV than men in 5 regions, and %TRV of the Val66Val group was higher than that of the Met carrier group in 2 regions. Moreover, the Female-Val66Val group had a higher %TRV than the Male-Met carrier group in 3 regions. These results indicate that although the short-term variability of GM volumes is small, it is affected by within-subject factors.

Interoceptive accuracy is related to the psychological mechanisms of the burning mouth syndrome: a cross-sectional study.

BACKGROUND: Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS. METHODS: This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared. RESULTS: The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores. CONCLUSIONS: Interoception might play a role in the pathophysiology of BMS.

The intervention of mechanical tactile stimulation modulates somatosensory evoked magnetic fields and cortical oscillations.

The different cortical activity evoked by a mechanical tactile stimulus depends on tactile stimulus patterns, which demonstrates that simple stimuli (i.e., global synchronous stimulation the stimulus area) activate the primary somatosensory cortex alone, whereas complex stimuli (i.e., stimulation while moving in the stimulus area) activate not only the primary somatosensory cortex but also the primary motor area. Here, we investigated whether the effects of a repetitive mechanical tactile stimulation (MS) on somatosensory evoked magnetic fields (SEFs) and cortical oscillations depend on MS patterns. This single-blinded study included 15 healthy participants. Two types interventions of MS lasting 20 min were used: a repetitive global tactile stimulation (RGS) was used to stimulate the finger by using 24 pins installed on a finger pad, whereas a sequential stepwise displacement tactile stimulation (SSDS) was used to stimulate the finger by moving a row of six pins between the left and right sides on the finger pad. Each parameter was measured pre- and post-intervention. The P50m amplitude of the SEF was increased by RGS and decreased by SSDS. The modulation of P50m was correlated with its amplitude before RGS and with the modulation of beta band oscillation at the resting state after SSDS. This study showed that the effects of a 20-min MS on SEFs and cortical oscillations depend on mechanical tactile stimulus patterns. Moreover, our results offer potential for the modulation of tactile functions and selection of stimulation patterns according to cortical states.

Corticospinal excitability of untrained side depends on the type of motor task and degree of improvement in motor function.

Unimanual motor tasks change the corticospinal excitability of the trained and untrained side. However, whether the motor task type influences the modulation of the corticospinal excitability of the untrained side remains unclear. This study aimed to clarify the effects of motor tasks on the corticospinal excitability of the untrained side and the relationship between the excitability and motor function. In Experiment I, we measured the corticospinal excitability of the untrained side and motor function after 10 min of motor training in two conditions (gripping task and ball rotation task). The gripping task decreased the excitability. In contrast, excitability remained unchanged after the ball rotation task; further, the modulation of excitability and motor function showed a correlation. In Experiment II, we measured the corticospinal excitability of the untrained side and motor function after two sessions of the ball rotation task. The excitability increased, but motor function remained unchanged after the first session, whereas the excitability decreased to the level observed before training, and motor function improved after the second session. We suggest that the training condition modulates the corticospinal excitability of the untrained side and that this is related to the modulation of motor function.

Brain changes associated with impaired attention function in chronic pain.

Attention function is thought to be important in chronic pain, with the pathology of chronic pain closely associated with cognitive-emotional components. However, there have been few neuroimaging studies of the relationship between attention function and chronic pain. We used the method of functional connectivity analysis for resting-state fMRI (rs-fMRI) data and the Attention Network Test-Revision (ANT-R) to clarify the attention-related pathology of chronic pain. We performed rs-fMRI and ANT-R on a group of 26 chronic pain (somatoform pain disorder) patients and 28 age-matched healthy controls. A significant group difference in validity effects, a component of ANT-R, emerged (F1,46 = 5.91, p = 0.019), and the chronic pain group exhibited slower reaction times. Decreased brain connectivity of the left insula and left frontal regions was confirmed in chronic pain patients (pFWE < 0.05), and connectivity was negatively correlated with validity effects (r = -0.29, permutation test p = 0.033). Further, decreased functional connectivity strength of the right insula and left temporal gyrus in the chronic pain group were confirmed (pFWE < 0.05). We conclude that poor control of attention function results from deficits of functional connectivity in the left insula and left frontal regions in chronic pain.

Change-Driven M100 Component in the Bilateral Secondary Somatosensory Cortex: A Magnetoencephalographic Study.

Our previous demonstration that the M100 somatosensory evoked magnetic field (SEF) has a similar temporal profile, dipole orientation and source location whether induced by activation (ON-M100) or deactivation (OFF-M100) of electrical stimulation suggests a common cortical system to detect sensory change. While we have not recorded such change-driven components earlier than M100 using electrical stimulation, clear M50 responses were reported using both ON and OFF mechanical stimulation (Onishi et al. in Clin Neurophysiol 121:588-593, 2010). To examine the significance of M50 and M100 in reflecting the detection of somatosensory changes, we recorded these waveforms in 12 healthy subjects (9 males and 3 females) by magnetoencephalography in response to mechanical stimulation from a piezoelectric actuator. Onset and offset (ON and OFF) stimuli were randomly presented with three preceding steady state (PSS) durations (0.5, 1.5 and 3 s) in one consecutive session. Results revealed that (i) onset and offset somatosensory events elicited clear M50 and M100 components; (ii) M50 and M100 components had distinct origins, with M50 localised to the contralateral primary somatosensory cortex (cS1) and M100 to the bilateral secondary somatosensory cortex (iS2, cS2); and (iii) the amplitude of M50 in cS1 was independent of the PSS durations, whereas that of M100 in S2 was dependent on the PSS durations for both ON and OFF events. These findings suggest that the M50 amplitude in cS1 reflects the number of activated mechanoreceptors during Onset and Offset, whereas the M100 amplitude in S2 reflects change detection based on sensory memory for Onset and Offset stimuli at least in part. We demonstrated that the M50 in cS1 and M100 in S2 plays different roles in the change detection system in somatosensory modality.

Variability and Reliability of Paired-Pulse Depression and Cortical Oscillation Induced by Median Nerve Stimulation.

Paired-pulse depression (PPD) has been widely used to investigate the functional profiles of somatosensory cortical inhibition. However, PPD induced by somatosensory stimulation is variable, and the reasons for between- and within-subject PPD variability remains unclear. Therefore, the purpose of this study was to clarify the factors influencing PPD variability induced by somatosensory stimulation. The study participants were 19 healthy volunteers. First, we investigated the relationship between the PPD ratio of each component (N20m, P35m, and P60m) of the somatosensory magnetic field, and the alpha, beta, and gamma band changes in power [event-related desynchronization (ERD) and event-related synchronization (ERS)] induced by median nerve stimulation. Second, because brain-derived neurotrophic factor (BDNF) gene polymorphisms reportedly influence the PPD ratio, we assessed whether BDNF genotype influences PPD ratio variability. Finally, we evaluated the test-retest reliability of PPD and the alpha, beta, and gamma ERD/ERS induced by somatosensory stimulation. Significant positive correlations were observed between the P60m_PPD ratio and beta power change, and the P60m_PPD ratio was significantly smaller for the beta ERD group than for the beta ERS group. P35m_PPD was found to be robust and highly reproducible; however, P60m_PPD reproducibility was poor. In addition, the ICC values for alpha, beta, and gamma ERD/ERS were 0.680, 0.760, and 0.552 respectively. These results suggest that the variability of PPD for the P60m deflection may be influenced by the ERD/ERS magnitude, which is induced by median nerve stimulation.

Effect of noisy galvanic vestibular stimulation in community-dwelling elderly people: a randomised controlled trial.

BACKGROUND: Balance disorders are a risk factor for falls in the elderly. Although noisy galvanic vestibular stimulation (nGVS) has been reported to improve balance in young people, randomised control trials targeting community-dwelling elderly people have not been conducted to date. We aimed to assess the influence of nGVS on COP sway in the open-eye standing posture among community-dwelling elderly people in a randomised controlled trial. METHODS: A randomised controlled trial of 32 community-dwelling elderly people randomly assigned to control (sham stimulation) and an nGVS groups. All participants underwent centre of pressure (COP) sway measurements while standing with open eyes at baseline and during stimulation. The control group underwent sham stimulation and the nGVS group underwent noise stimulation (0.4 mA; 0.1-640 Hz). RESULTS: In the nGVS group, sway path length, mediolateral mean velocity and anteroposterior mean velocity decreased during stimulation compared with baseline (P < 0.01). The effect of nGVS was large in participants with a high COP sway path length at baseline, but there was no significant difference in COP sway in the control group. CONCLUSIONS: We conclude that nGVS decreases the COP sway path length and mean velocity of community-dwelling elderly people when standing with open eyes. This suggests that nGVS could be effective for treating balance dysfunction in the elderly.

Effectiveness of group cognitive behavioral therapy for somatoform pain disorder patients in Japan: A preliminary non-case-control study.

AIMS: Somatoform pain disorder is associated with psychosocial dysfunction, and psychotherapies, such as cognitive behavioral therapy (CBT), are thought to provide useful interventions to address such dysfunction as well as the pain itself. However, little is known about whether CBT for somatoform pain disorder is effective, including the long-term course of the illness, in non-Western populations. We therefore tailored such a program based on an existing CBT protocol and examined its effectiveness in Japan. METHODS: Thirty-four Japanese participants (22 women; mean age = 52.5 years) enrolled in a weekly 12-session group treatment, with 32 completing both wait-list and treatment conditions. The primary outcome measure was pain intensity. Secondary outcome measures included pain characteristics, as measured by pain catastrophizing and psychometric evaluations, including depression, anxiety, and quality of life. The patients were followed up for 12 months after treatment. RESULTS: We found that pain intensity, anxiety, depressive symptoms, and social functioning all significantly improved after treatment compared with the wait-list period, and the improvements in pain intensity, depressive symptoms, and social functioning were sustained at 12 months following the completion of CBT. There were strong positive correlations (P < 0.01) among pre- and post-treatment changes in the affective dimension of pain, depression, anxiety, and pain catastrophizing. CONCLUSIONS: These results show that the present CBT program was effective for Japanese patients with somatoform pain disorder and that gains were maintained over the long term. More work is needed to further clarify the effects of CBT interventions on somatoform symptoms, particularly in Japan.

Change-related auditory P50: a MEG study.

Changes in continuous sounds elicit a preattentive component that peaks at around 100ms (Change-N1m) on electroencephalograms or magnetoencephalograms (MEG). Change-N1m is thought to reflect brain activity relating to the automatic detection of changes, which facilitate processes for the execution of appropriate behavior in response to new environmental events. The aim of the present MEG study was to elucidate whether a component relating to auditory changes existed earlier than N1m. Change-related cortical responses were evoked by abrupt sound movement in a train of clicks at 100Hz. Sound movement was created by inserting an interaural time delay (ITD) of 0.15, 0.25, 0.35, and 0.45ms into the right ear. Ten out of 12 participants exhibited clear change-related cortical responses earlier than Change-N1m at around 60ms (Change-P50m). The results of source analysis showed that Change-P50m originated from the superior temporal gyrus of both hemispheres and that its location did not differ significantly from dipoles for the response to the sound onset. The magnitude of Change-P50m increased and the peak latency shortened with an increase in the ITD, similar to those of Change-N1m. These results suggest that change-related cortical activity is present as early as its onset latency at around 50ms.

Individual and group-level optimization of electric field in deep brain region during multichannel transcranial electrical stimulation.

Electrode montage optimization for transcranial electric stimulation (tES) is a challenging topic for targeting a specific brain region. Targeting the deep brain region is difficult due to tissue inhomogeneity, resulting in complex current flow. In this study, a simplified protocol for montage optimization is proposed for multichannel tES (mc-tES). The purpose of this study was to reduce the computational cost for mc-tES optimization and to evaluate the mc-tES for deep brain regions. Optimization was performed using a simplified protocol for montages under safety constraints with 20 anatomical head models. The optimization procedure is simplified using the surface EF of the deep brain target region, considering its small volume and non-concentric distribution of the electrodes. Our proposal demonstrated that the computational cost was reduced by >90%. A total of six-ten electrodes were necessary for robust EF in the target region. The optimization with surface EF is comparable to or marginally better than using conventional volumetric EF for deep brain tissues. An electrode montage with a mean injection current amplitude derived from individual analysis was demonstrated to be useful for targeting the deep region at the group level. The optimized montage and injection current were derived at the group level. Our proposal at individual and group levels showed great potential for clinical application.

Region-specific Effects of Transcranial Direct Current Stimulation Over Posterior Parietal Cortex and Cerebellum on Standing Postural Displacement After Prism Adaptation.

Prism adaptation (PA) induces the after-effects of adapted tasks and transfers after-effects of non-adapted tasks, in which PA with pointing movements transfers to postural displacement during eyes-closed standing. However, the neural mechanisms underlying the transfer of PA after-effects on standing postural displacement remain unclear. The present study investigated the region-specific effects of transcranial direct current stimulation (tDCS) over the posterior parietal cortex (PPC) and cerebellum during prism exposure (PE) on standing postural displacement in healthy adults. Forty-two healthy young adults were grouped into pointing during PE with cathodal tDCS over the right PPC, anodal tDCS over the right cerebellum, and sham tDCS groups. They received 20 min of tDCS, during which they pointed to the visual targets while wearing prism lenses with a leftward visual shift (30 diopters) for 15 min. During the early PE, the pointing errors in the cerebellum group were significantly displaced more accurately toward the targets than those in the PPC group. However, after leftward PE, all groups had similar rightward displacements of the straight-ahead pointing with eyes closed. The PPC group only exhibited significant rightward center-of-pressure displacement during eyes-closed standing with feet-closed after leftward PE. The perception of longitudinal body axis rotation, as an indicator of the subjective body vertical axis, did not differ significantly between the pre- and post-evaluations in all groups. These results show that the PPC during PE could make an important neural contribution to inducing transfer of PA after-effect on standing postural displacement.

Transcranial alternating current stimulation does not affect microscale learning.

A theory has been posited that microscale learning, which involves short intervals of a few seconds during explicit motor skill learning, considerably enhances performance. This phenomenon correlates with diminished beta-band activity in the frontal and parietal regions. However, there is a lack of neurophysiological studies regarding the relationship between microscale learning and implicit motor skill learning. In the present study, we aimed to determine the effects of transcranial alternating current stimulation (tACS) during short rest periods on microscale learning in an implicit motor task. We investigated the effects of 20-Hz ß-tACS delivered during short rest periods while participants performed an implicit motor task. In Experiments 1 and 2, ß-tACS targeted the right dorsolateral prefrontal cortex and the right frontoparietal network, respectively. The participants performed a finger-tapping task using their nondominant left hand, and microscale learning was separately analyzed for micro-online gains (MOnGs) and micro-offline gains (MOffGs). Contrary to our expectations, ß-tACS exhibited no statistically significant effects on MOnGs or MOffGs in either Experiment 1 or Experiment 2. In addition, microscale learning during the performance of the implicit motor task was improved by MOffGs in the early learning phase and by MOnGs in the late learning phase. These results revealed that the stimulation protocol employed in this study did not affect microscale learning, indicating a novel aspect of microscale learning in implicit motor tasks. This is the first study to examine microscale learning in implicit motor tasks and may provide baseline information that will be useful in future studies.

Effects of transcranial alternating current stimulation to the supplementary motor area on motor learning.

Transcranial alternating current stimulation (tACS) is a noninvasive method for brain stimulation that artificially modulates oscillatory brain activity in the cortical region directly beneath the electrodes by applying a weak alternating current. Beta (ß) oscillatory activity in the supplementary motor area (SMA) is involved in motor planning and maintenance, whereas gamma (γ) oscillatory activity is involved in the updating of motor plans. However, the effect of applying tACS to the SMA on motor learning has not yet been investigated. This study assessed the effects of applying tACS to the SMA on motor learning. Forty-two right-handed healthy adults (age 20.6 ± 0.5 years, 24 men and 18 women) were included. Motor learning was assessed using a visuomotor tracking task with pinch tension of the right thumb and right forefinger. Each trial lasted 60 s, and the error rates were measured. Conductive rubber electrodes were attached to the SMA and the left shoulder for tACS. Stimulation was applied at an intensity of 1.0 mA and frequencies of 70 and 20 Hz in the γ-tACS and ß-tACS treatment groups, respectively. The sham group was only administered a fade-in/out. The visuomotor tracking task was performed for 10 trials before tACS and 10 trials after tACS. Two trials were conducted on the following day to determine motor skill retention. The average deviation measured during 60 s was considered the error value. Pre-stimulation learning rate was calculated as the change in error rate. Post-stimulation learning rate and retention rate were calculated as the change in error rate after stimulation and on the day after stimulation, respectively. In both the stimulation groups, differences in pre-stimulation learning, post-stimulation learning, and retention rates were not significant. However, in the γ-tACS group, baseline performance and pre-stimulation learning rate were positively correlated with post-stimulation learning rate. Therefore, applying γ-tACS to the SMA can increase post-stimulation learning rate in participants exhibiting low baseline performance and high pre-stimulation learning rate. Our findings suggest that motor learning can be effectively enhanced by applying γ-tACS to the SMA based on an individual's motor and learning abilities.

Electric field envelope focality in superficial brain areas with linear alignment montage in temporal interference stimulation.

Temporal interference stimulation (TIS) uses two pairs of conventional transcranial alternating current stimulation (tACS) electrodes, each with a different frequency, to generate a time-varying electric field (EF) envelope (EFE). The EFE focality in primary somatosensory and motor cortex areas of a standard human brain was computed using newly defined linear alignment montages. Sixty head volume conductor models constructed from magnetic resonance images were considered to evaluate interindividual variability. Six TIS and two tACS electrode montages were considered, including linear and rectangular alignments. EFEs were computed using the scalar-potential finite-difference method. The computed EFE was projected onto the standard brain space for each montage. Computational results showed that TIS and tACS generated different EFE and EF distributions in postcentral and precentral gyri regions. For TIS, the EFE amplitude in the target areas had lower variability than the EF strength of tACS. However, bipolar tACS montages showed higher focality in the superficial postcentral and precentral gyri regions than in TIS. TIS generated greater EFE penetration than bipolar tACS at depths <5-10 mm below the brain surface. From group-level analysis, tACS with a bipolar montage was preferred for targets <5-10 mm in depth (gyral crowns) and TIS for deeper targets. TIS with a linear alignment montage could be an effective method for deep structures and sulcal walls. These findings provide valuable insights into the choice of TIS and tACS for stimulating specific brain regions.

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study.

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors' and others' prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61-90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PERSPECTIVE: We conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.