H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study.

Introduction: Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial. Methods: In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups. Results: We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means. Conclusion: High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05488808.

Associations of long-term clinical recovery and improved quality of life across ICD-11 chronic pain categories in a real-world registry study.

BACKGROUND: There is little knowledge of what factors are needed for successful chronic pain management. We aim to identify psychosocial and treatment predictors of clinical recovery and improved quality of life (QOL) at 12-month follow-up across three chronic pain groups, based on the International Classification of Diseases-11: neuropathic pain, secondary non-neuropathic pain, and primary pain. Furthermore, we investigate baseline differences across diagnostic groups. METHODS: The sample included baseline and 12-month follow-up data from 1056 chronic pain patients from the Oslo University Hospital's Pain Registry. Logistic regression models investigated longitudinal associations between psychosocial and treatment characteristics, and the outcome measures clinical recovery and improved QOL. Characteristics were compared across the diagnostic groups. RESULTS: Increased odds of clinical recovery and improved QOL were seen in patients receiving invasive treatment (OR = 8.04, 95% CI = 3.50-19.40; OR = 5.47, 95% CI = 2.42-12.86), while decreased odds of clinical recovery were seen for secondary non-neuropathic pain patients with pain-related disability (0.05, 95% CI = 0.01-0.29). In comparing baseline characteristics, neuropathic pain patients had lower QOL, and more severe insomnia compared to the other groups. CONCLUSION: Invasive treatment modalities were strongly associated with clinical recovery and improved QOL. Although this could be due to patient selection, it does warrant further examination as an intervention alternative for chronic pain. Intervention efficacy, risk factors and predictors of clinical recovery across diagnostic groups should be further investigated through longitudinal RCTs. SIGNIFICANCE: This observational study indicates a potential advantage in sustained recovery for pre-selected individuals with chronic pain who undergo invasive treatments. The relationship between sustained recovery and psychosocial factors differs across neuropathic, secondary non-neuropathic, and primary pain patients. This suggests that employing ICD-11 for classifying patients into mechanistically distinct pain groups could inform the evaluation and management of chronic pain. Furthermore, factors previously identified as negative indicators for long-term outcomes in chronic pain cohorts were not clinically significant in this study.

Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study.

ABSTRACT: We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. The primary outcome was the comparison of the mean change in average pain intensity over the course of the treatment (group × time interaction). Secondary outcomes included neuropathic symptoms (NPSI), pain interference, patient global impression of change (PGIC), anxiety, depression, and catastrophizing. In total, 51 patients participated in at least one session of both treatments. There was a significant interaction between "treatment" and "time" (F = 2.7; P = 0.0024), indicating that both figure-8 (F8-coil) and H-coil active stimulation induced significantly higher analgesic effects than sham stimulation. The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated ( r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.

Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans.

How and to what extent electrical brain activity reflects pharmacologically altered states and contents of consciousness, is not well understood. Therefore, we investigated whether measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective experience. High-density 62-channel EEG was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and during administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from EEG responses to TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE). Although no significant difference was found in TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all measures of spontaneous EEG signal diversity (LZc, ACE, SCE) showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine. The results suggest that PCI and spontaneous signal diversity may reflect distinct, complementary aspects of changes in brain properties related to altered states of consciousness: the brain's capacity for information integration, assessed by PCI, might be indicative of the brain's ability to sustain consciousness, while spontaneous complexity, as measured by EEG signal diversity, may be indicative of the complexity of conscious content. Thus, sub-anaesthetic ketamine may increase the complexity of the conscious content and the brain activity underlying it, while the level or general capacity for consciousness remains largely unaffected.