Noninvasive brain stimulations modulated brain modular interactions to ameliorate working memory in community-dwelling older adults.

Non-invasive brain stimulations have drawn attention in remediating memory decline in older adults. However, it remains unclear regarding the cognitive and neural mechanisms underpinning the neurostimulation effects on memory rehabilitation. We evaluated the intervention effects of 2-weeks of neurostimulations (high-definition transcranial direct current stimulation, HD-tDCS, and electroacupuncture, EA versus controls, CN) on brain activities and functional connectivity during a working memory task in normally cognitive older adults (age 60+, n = 60). Results showed that HD-tDCS and EA significantly improved the cognitive performance, potentiated the brain activities of overlapping neural substrates (i.e. hippocampus, dlPFC, and lingual gyrus) associated with explicit and implicit memory, and modulated the nodal topological properties and brain modular interactions manifesting as increased intramodular connection of the limbic-system dominated network, decreased intramodular connection of default-mode-like network, as well as stronger intermodular connection between frontal-dominated network and limbic-system-dominated network. Predictive model further identified the neuro-behavioral association between modular connections and working memory. This preliminary study provides evidence that noninvasive neurostimulations can improve older adults' working memory through potentiating the brain activity of working memory-related areas and mediating the modular interactions of related brain networks. These findings have important implication for remediating older adults' working memory and cognitive declines.

Dopamine D2 receptor antagonist modulates rTMS-induced pain experiences and corticospinal excitability dependent on stimulation targets / El antagonista del receptor de dopamina D2 modula las experiencias de dolor inducidas por rTMS y la excitabilidad corticoespinal dependiendo de los objetivos de estimulación

Both the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) rTMS have the potential to reduce certain chronic pain conditions. However, the analgesic mechanisms remain unclear, in which M1- and DLPFC-rTMS may have different impact on the release of dopamine receptor D2 neurotransmissions (DRD2). Using a double-blind, randomised, sham- and placebo-controlled design, this study investigated the influence of DRD2 antagonist on rTMS-induced analgesia and corticospinal excitability across the M1 and DLPFC. Healthy participants in each group (M1, DLPFC, or Sham) received an oral dose of chlorpromazine or placebo before the delivery of rTMS in two separate sessions. Heat pain and cortical excitability were assessed before drug administration and after rTMS intervention. DRD2 antagonist selectively abolished the increased heat pain threshold induced by DLPFC stimulation and increased pain unpleasantness. The absence of analgesic effects in DLPFC stimulation was not accompanied by plastic changes in the corticospinal pathway. In contrast, DRD2 antagonist increased corticospinal excitability and rebalanced excitation-inhibition relationship following motor cortex stimulation, although there were no clear changes in pain experiences. These novel findings together highlight the influence of dopaminergic neurotransmission on rTMS-induced analgesia and corticospinal excitability dependent on stimulation targets.(AU)

Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized controlled trial.

ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of ß-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.

Comparisons of Accelerated Continuous and Intermittent Theta Burst Stimulation for Treatment-Resistant Depression and Suicidal Ideation.

BACKGROUND: Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation. METHODS: Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period. RESULTS: Accelerated cTBS was superior to iTBS in the management of suicidal ideation (pweek 1 = .027) and anxiety symptoms (pweek 1 = .01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p < .001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups). CONCLUSIONS: These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms.

Evaluation of Relationships between Corticospinal Excitability and Somatosensory Deficits in the Acute and Subacute Phases of Stroke.

BACKGROUND: Somatosensory deficits are common symptoms post stroke. Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex is able to promote motor rehabilitation, whereby its impact on somatosensory functioning remains unknown. This study was designed to evaluate the association between somatosensory deficits and corticospinal excitability following stroke, with the purpose to provide insights on rTMS interventions for the management of somatosensory deficits. METHODS: Somatosensory functioning and corticospinal excitability (motor-evoked potential, MEP; cortical silence period, CSP) were evaluated from a group of sixteen patients with unilateral ischemic stroke in the acute or subacute phase. RESULTS: Results indicated that the uncommon presentation of larger MEPs in ipsilesional vs. contralesional motor cortex was associated with worse somatosensory function compared to those with a smaller MEP in ipsilesional motor cortex. Moreover, increased MEP ratio (ipsilesional vs. contralesional motor cortex) was associated with better somatosensory function in patients with well-preserved somatosensory function. CONCLUSIONS: In well-recovered patients, an increased MEP ratio between the ipsilesional and contralesional motor cortex could be an indicator of improved somatosensory functioning following stroke.

A randomised sham-controlled study evaluating rTMS analgesic efficacy for postherpetic neuralgia.

Context: Postherpetic neuralgia (PHN) is a refractory neuropathic pain condition in which new treatment options are being developed. Repetitive transcranial magnetic stimulation (rTMS) may have the potential to reduce pain sensations in patients with postherpetic neuralgia. Objectives: This study investigated the efficacy on postherpetic neuralgia by stimulating two potential targets, the motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC). Methods: This is a double-blind, randomised, sham-controlled study. Potential participants were recruited from Hangzhou First People's Hospital. Patients were randomly assigned to either the M1, DLPFC or Sham group. Patients received ten daily sessions of 10-Hz rTMS in 2 consecutive weeks. The primary outcome measure was visual analogue scale (VAS) assessed at baseline, first week of treatment (week 1), post-treatment (week 2), 1-week (week 4), 1-month (week 6) and 3-month (week 14) follow-up. Results: Of sixty patients enrolled, 51 received treatment and completed all outcome assessments. M1 stimulation resulted in a larger analgesia during and after treatment compared to the Sham (week 2 - week 14, p < 0.005), as well as to the DLPFC stimulation (week 1 - week 14, p < 0.05). In addition to pain, sleep disturbance was significantly improved and relieved by targeting either the M1 or the DLPFC (M1: week 4 - week 14, p < 0.01; DLPFC: week 4 - week 14, p < 0.01). Moreover, pain sensations following M1 stimulation uniquely predicted improvement in sleep quality. Conclusion: M1 rTMS is superior to DLPFC stimulation in treating PHN with excellent pain response and long-term analgesia. Meanwhile, M1 and DLPFC stimulation were equally effective in improving sleep quality in PHN. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2100051963.

Motor cortex transcranial magnetic stimulation to reduce intractable postherpetic neuralgia with poor response to other threapies: Report of two cases.

BACKGROUND: Postherpetic neuralgia (PHN) is a typical neuropathic pain condition that appears in the lesioned skin regions following the healing of shingles. The pain condition tends to persist, which is often accompanied by negative emotions (e.g., anxiety and depression) and substantially reduces the quality of life. In addition to analgesia (e.g., pregabalin and gabapentin), nerve radiofrequency technology is an effective treatment for intractable PHN. However, there is still a significant portion of patients who do not benefit from this treatment. As a non-invasive form of brain stimulation, repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex is able to reduce neuropathic pain with grade A evidence. CASE SUMMARY: Here we report two cases in which motor cortex rTMS was used to treat intractable PHN that did not respond to initial drug and radiofrequency therapies. Moreover, we specifically investigated rTMS efficacy at 3 mo following treatment. CONCLUSION: Motor cortex rTMS can treat intractable PHN that did not respond to initial drug and radiofrequency therapies.

Distinct Emotional and Cardiac Responses to Audio Erotica between Genders.

Emotional and cardiac responses to audio erotica and their gender differences are relatively unclear in the study of the human sexual response. The current study was designed to investigate gender differences regarding positive and negative emotional responses to erotica, as well as its association with cardiac response. A total of 40 healthy participants (20 women) were exposed to erotic, neutral, and happy audio segments during which emotions and heart rate changes were evaluated. Our data showed distinct emotional responses to erotica between genders, in which women reported a higher level of shame than men and rated erotic audios as less pleasant than happy audios. Meanwhile, men reported erotic and happy audios as equally pleasant. These results were independent of cardiac changes, as both sexes demonstrated comparable heart rate deceleration when exposed to erotica relative to neutral and happy stimuli. Our results highlight the role of sociocultural modulation in the emotional response to erotica.

Analgesic efficacy of theta-burst stimulation for postoperative pain.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may be a relevant method to assist postoperative pain. However, studies to date have only used conventional 10 Hz rTMS and targeted the DLPFC for postoperative pain. A more recent form of rTMS, termed intermittent Theta Burst Stimulation (iTBS), enables to increase cortical excitability in a short period of time. This preliminary double-blind, randomised, sham controlled study was designed to evaluate the efficacy of iTBS in postoperative care across two distinct stimulation targets. METHODS: A group of 45 patients post laparoscopic surgery were randomised to receive a single session of iTBS over either the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), or Sham stimulation (1:1:1 ratio). Outcome measurements were number of pump attempts, total anaesthetic volume used, and self-rated pain experience, assessed at 1 hour, 6 hours, 24 hours, and 48 hours post stimulation. All randomised patients were analysed (n = 15 in each group). RESULTS: Compared to Sham stimulation, DLPFC-iTBS reduced pump attempts at 6 (DLPFC = 0.73 ± 0.88, Sham = 2.36 ± 1.65, P = 0.031), 24 (DLPFC = 1.40 ± 1.24, Sham = 5.03 ± 3.87, P = 0.008), and 48 (DLPFC = 1.47 ± 1.41, Sham = 5.87 ± 4.34, P = 0.014) hours post-surgery, whereby M1 stimulation had no effect. No group effect was observed on total anaesthetics, which was mainly provided through the continuous administration of opioids at a set speed for each group. There was also no group or interaction effect on pain ratings. Pump attempts were positively associated with pain ratings in the DLPFC (r = 0.59, P = 0.02) and M1 (r = 0.56, P = 0.03) stimulation. CONCLUSIONS: Our findings show that iTBS to the DLPFC reduces pump attempts for additional anaesthetics following a laparoscopic surgery. However, reduced pump attempts by DLPFC stimulation did not translate into a significantly smaller volume of total anaesthetic, due to the continuous administration of opioids at a set speed for each group. SIGNIFICANCE: Our findings therefore provide preliminary evidence for iTBS targeting the DLPFC to be used to improve postoperative pain management.

Concurrent TMS-EEG and EEG reveal neuroplastic and oscillatory changes associated with self-compassion and negative emotions

BacSelf-compassionSocial rejectionTheta burst stimulationTMS-EEGConnectivitykground/Objective: Self-compassion has a consensual relevance for overall mental health, but its mechanisms remain unknown. Using intermittent theta burst stimulation (iTBS) and concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG), this study investigated the causal relationship of the dorsolateral prefrontal cortex (DLPFC) with self-compassion and explored the changes in neuroplasticity and neural dynamics. Method: Thirty-two healthy participants received iTBS or sham stimulation over the DLPFC, before and after which they were instructed to either use self-compassionate strategies or to be rejected in the context of social rejection and to report the level of self-compassion or negative affect. TMS-evoked potentials were evaluated as novel neuroplastic techniques with N45, P60, N100, and P180. Results: iTBS uniquely decreased P180 amplitude measured with TMS-EEG whereby sham stimulation had no effect on neuroplasticity. In line with neuroplasticity changes, iTBS enhanced a widespread gamma band power and coherence, which correlated consistently with increased engagement in self-compassion. Meanwhile, iTBS demonstrated opposite effects on theta activity dependent on the social contexts whereby self-compassion decreased and social rejection enhanced it respectively. This unique effect of iTBS on theta activity was also supplemented by the enhancement of theta band coherence following iTBS. Conclusions: We found a causal relationship between DLPFC and self-compassion. We also provide evidence to indicate widespread gamma activity and connectivity to correlate with self-compassion as well as the critical role of the DLPFC in modulating theta activity and negative emotions. (AU)

Concurrent TMS-EEG and EEG reveal neuroplastic and oscillatory changes associated with self-compassion and negative emotions.

Background/Objective: Self-compassion has a consensual relevance for overall mental health, but its mechanisms remain unknown. Using intermittent theta burst stimulation (iTBS) and concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG), this study investigated the causal relationship of the dorsolateral prefrontal cortex (DLPFC) with self-compassion and explored the changes in neuroplasticity and neural dynamics. Method: Thirty-two healthy participants received iTBS or sham stimulation over the DLPFC, before and after which they were instructed to either use self-compassionate strategies or to be rejected in the context of social rejection and to report the level of self-compassion or negative affect. TMS-evoked potentials were evaluated as novel neuroplastic techniques with N45, P60, N100, and P180. Results: iTBS uniquely decreased P180 amplitude measured with TMS-EEG whereby sham stimulation had no effect on neuroplasticity. In line with neuroplasticity changes, iTBS enhanced a widespread gamma band power and coherence, which correlated consistently with increased engagement in self-compassion. Meanwhile, iTBS demonstrated opposite effects on theta activity dependent on the social contexts whereby self-compassion decreased and social rejection enhanced it respectively. This unique effect of iTBS on theta activity was also supplemented by the enhancement of theta band coherence following iTBS. Conclusions: We found a causal relationship between DLPFC and self-compassion. We also provide evidence to indicate widespread gamma activity and connectivity to correlate with self-compassion as well as the critical role of the DLPFC in modulating theta activity and negative emotions.

Concurrent TMS-EEG to reveal the neuroplastic changes in the prefrontal and insular cortices in the analgesic effects of DLPFC-rTMS.

The dorsolateral prefrontal cortex (DLPFC) is an important target for repetitive transcranial magnetic stimulation (rTMS) to reduce pain. However, the analgesic efficacy of DLPFC-rTMS needs to be optimized, in which the mechanisms of action remain unclear. Concurrent TMS and electroencephalogram (TMS-EEG) is able to evaluate neuroplastic changes beyond the motor cortex. Using TMS-EEG, this study was designed to investigate the local and distributed neuroplastic changes associated with DLPFC analgesia. Thirty-four healthy adults received DLPFC or sham stimulation in a randomized, crossover design. In each session, participants underwent cold pain and TMS-EEG assessment both before and after 10-Hz rTMS. We provide novel findings that DLPFC analgesia is associated with a smaller N120 amplitude in the contralateral prefrontal cortex as well as with a larger N120 peak in the ipsilateral insular cortex. Furthermore, there was a strong negative correlation between N120 changes of these two regions whereby the amplitude changes of this dyad were associated with increased pain threshold. In addition, DLPFC stimulation enhanced coherence between the prefrontal and somatosensory cortices oscillating in the gamma frequency. Overall, our data present novel evidence on local and distributed neuroplastic changes associated with DLPFC analgesia.

Investigating the Influence of Self-Compassion-Focused Interventions on Posttraumatic Stress: A Systematic Review and Meta-Analysis.

OBJECTIVES: Self-compassion-focused interventions may be able to decrease posttraumatic stress symptoms. However, previous studies demonstrated mixed effects in which a series of confounders were not systematically quantified. In this study, a systematic review with meta-analysis was conducted to quantify the effects of self-compassion-focused therapies on posttraumatic stress disorder. METHODS: Twelve eligible studies were included after a systematic search of databases. Outcome measures were extracted for posttraumatic stress disorder. RESULTS: Our data indicated a medium protective effect on posttraumatic stress symptoms (SMD = - 0.65), with most of the studies (8/12) coming from clinical settings. More importantly, longer interventions were associated with better posttraumatic stress outcomes (p < 0.001). Baseline or changes in self-compassion scores were not associated with posttraumatic stress outcomes post-interventions. CONCLUSIONS: Overall, findings from this meta-analysis quantified the complex influence of self-compassion-focused interventions on posttraumatic stress symptoms and may provide insights for optimizing intervention strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01732-3.

High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: A systematic review and meta-analysis.

BACKGROUND: High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain. OBJECTIVES/METHODS: In this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain. RESULTS: A total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = -0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = -0.53, 24.6 days average) and long term (SMD = -0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = -0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions. CONCLUSIONS: Overall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.

Corrigendum to "Self-Compassion Demonstrating a Dual Relationship with Pain Dependent on High-Frequency Heart Rate Variability".

[This corrects the article DOI: 10.1155/2020/3126036.].

Personal relative deprivation impairs ability to filter out threat-related distractors from visual working memory.

The literature has indicated that personal relative deprivation (PRD) results in anxiety disorders. Given that some cognitive models propose that attention bias toward a threat causes and maintains anxiety, relatively deprived individuals may have difficulty gating threat from working memory. To test this hypothesis, this study investigated the influence of PRD on the filtering ability of happy, angry, and neutral facial distractors from visual working memory using electroencephalography (EEG). Participants were randomly assigned to a PRD (n = 24) or a non-PRD group (n = 24). Filtering ability was reflected by comparing the contralateral delay activity (CDA) amplitude for one-target, one-target-one-distractor, and two-targets conditions. The CDA was measured as the difference in mean amplitudes between activity in the hemispheres contralateral and ipsilateral to the to-be-remembered information. Results indicated that individuals in the PRD group showed a reduced ability to filter out neutral and angry facial distractors, as reflected by similar CDA amplitudes for one-target-one-distractor and two-targets conditions for both angry and neutral distractors in the PRD group. However, PRD did not impair the ability to filter out happy facial distractors, as reflected by similar CDA amplitudes for one-target-one-distractor and one-target conditions for happy distractors in the PRD group. As neutral faces might then be taken as potentially threatening information by relatively deprived individuals, these results support the hypothesis that relatively deprived individuals might have difficulty filtering out threat-related information.

Prolonged Continuous Theta Burst Stimulation to Demonstrate a Larger Analgesia as Well as Cortical Excitability Changes Dependent on the Context of a Pain Episode.

A series of neuropathic pain conditions have a prevalence in older adults potentially associated with declined functioning of the peripheral and/or central nervous system. Neuropathic pain conditions demonstrate defective cortical excitability and intermissions, which raises questions of the impact of pain on cortical excitability changes and when to deliver repetitive transcranial magnetic stimulation (rTMS) to maximize the analgesic effects. Using prolonged continuous theta-burst stimulation (pcTBS), a relatively new rTMS protocol to increase excitability, this study was designed to investigate pcTBS analgesia and cortical excitability in the context of pain. With capsaicin application, twenty-nine healthy participants received pcTBS or Sham stimulation either in the phase of pain initialization (capsaicin applied) or pain ascending (20 min after capsaicin application). Pain intensity was measured with a visual-analogic scale (VAS). Cortical excitability was assessed by motor-evoked potential (MEP) and cortical silent period (CSP) which evaluates corticospinal excitability and GABAergic intracortical inhibition, respectively. Our data on pain dynamics demonstrated that pcTBS produced a consistent analgesic effect regardless of the time frame of pcTBS. More importantly, pcTBS delivered at pain initialization induced a larger pain reduction and a higher response rate compared to the stimulation during pain ascending. We further provide novel findings indicating distinct mechanisms of pcTBS analgesia dependent on the context of pain, in which pcTBS delivered at pain initialization was able to reverse depressed MEP, whereby pcTBS during pain ascending was associated with increased CSP. Overall, our data indicate pcTBS to be a potential protocol in pain management that could be delivered before the initialization of a pain episode to improve rTMS analgesia, potentially through inducing early corticospinal excitability changes that would be suppressed by nociceptive transmission.

Self-Compassion Demonstrating a Dual Relationship with Pain Dependent on High-Frequency Heart Rate Variability.

One previous study indicated the significance of trait self-compassion in psychological well-being and adjustment in people with chronic pain. Higher-frequency heart rate variability (HF-HRV) was found to be closely associated with self-compassion and pain coping. The current study was therefore designed to investigate the relationship between self-compassion and experimental pain as well as the impact of HF-HRV. Sixty healthy participants provided self-reported self-compassion and underwent a cold pain protocol during which HF-HRV was evaluated. Results demonstrated a dual relationship between self-compassion and pain, dependent on the level of HF-HRV during pain exposure. Specifically, self-compassion was associated with lower pain in the condition of higher HF-HRV, while there was an inverse relationship between self-compassion and pain when HF-HRV was lower. Our data indicate the significance of HF-HRV in moderating the association between self-compassion and experimental pain.