Clinical Neurophysiology最新文献

Objective

Transcranial magnetic stimulation (TMS) can efficiently and robustly modulate synaptic plasticity, but little is known about how TMS affects functional connectivity (rs-fMRI). Accordingly, this project characterized TMS-induced rsFC changes in depressed patients who received 3 days of left prefrontal intermittent theta burst stimulation (iTBS).

Methods

rs-fMRI was collected from 16 subjects before and after iTBS. Correlation matrices were constructed from the cleaned rs-fMRI data. Electric-field models were conducted and used to predict pre-post changes in rs-fMRI. Site by orientation heatmaps were created for vectors centered on the stimulation site and a control site (contralateral motor cortex).

Results

For the stimulation site, there was a clear relationship between both site and coil orientation, and connectivity changes. As distance from the stimulation site increased, prediction accuracy decreased. Similarly, as eccentricity from the optimal orientation increased, prediction accuracy decreased. The systematic effects described above were not apparent in the heatmap centered on the control site.

Conclusions

These results suggest that rs-fMRI following iTBS changes systematically as a function of the distribution of electrical energy delivered from the TMS pulse, as represented by the e-field model.

Significance

This finding lays the groundwork for future studies to individualize TMS targeting based on how predicted rs-fMRI changes might impact psychiatric symptoms.

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.

Objective

Persistent fatigue is a major symptom of the so-called ’long-COVID syndrome’, but the pathophysiological processes that cause it remain unclear.

We hypothesized that fatigue after COVID-19 would be associated with altered cortical activity in premotor and motor regions.

Methods

We used transcranial magnetic stimulation combined with EEG (TMS-EEG) to explore the neural oscillatory activity of the left primary motor area (l-M1) and supplementary motor area (SMA) in a group of sixteen post-COVID patients complaining of lingering fatigue as compared to a sample of age-matched healthy controls. Perceived fatigue was assessed with the Fatigue Severity Scale (FSS) and Fatigue Rating Scale (FRS).

Results

Post-COVID patients showed a remarkable reduction of beta frequency in both areas. Correlation analysis exploring linear relation between neurophysiological and clinical measures revealed a significant inverse correlation between the individual level of beta oscillations evoked by TMS of SMA with the individual scores in the FRS (r(15) = -0.596; p = 0.012).

Conclusions

Post-COVID fatigue is associated with a reduction of TMS-evoked beta oscillatory activity in SMA.

Significance

TMS-EEG could be used to identify early alterations of cortical oscillatory activity that could be related to the COVID impact in central fatigue.

Objective

This study aimed to evaluate whether auditory brainstem response (ABR) using a paired-click stimulation paradigm could serve as a tool for detecting cochlear synaptopathy (CS).

Methods

The ABRs to single-clicks and paired-clicks with various inter-click intervals (ICIs) and scores for word intelligibility in degraded listening conditions were obtained from 57 adults with normal hearing. The wave I peak amplitude and root mean square values for the post-wave I response within a range delayed from the wave I peak (referred to as the RMS_post-w1) were calculated for the single- and second-click responses.

Results

The wave I peak amplitudes did not correlate with age except for the second-click responses at an ICI of 7 ms, and the word intelligibility scores. However, we found that the RMS_post-w1 values for the second-click responses significantly decreased with increasing age. Moreover, the RMS_post-w1 values for the second-click responses at an ICI of 5 ms correlated significantly with the scores for word intelligibility in degraded listening conditions.

Conclusions

The magnitude of the post-wave I response for the second-click response could serve as a tool for detecting CS in humans.

Significance

Our findings shed new light on the analytical methods of ABR for quantifying CS.

Objective

We aimed to establish specific biomarkers of Parkinson’s disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry.

Methods

We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed.

Results

We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12–15 Hz.

Conclusions

Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both.

Significance

Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology.

Objective

Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application.

Methods

In this study, seven patients with idiopathic Parkinson’s disease and one with familial Parkinson’s disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations.

Results

While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block).

Conclusion

We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson’s disease to rapidly control pathological subthalamic beta oscillations.

Significance

Fully-implanted DBS electrode-guided neurofeedback is feasible and can now be explored over extended timespans.

Objective

Parkinson’s disease (PD) patients exhibit changes in mechanisms underlying movement preparation, particularly the suppression of corticospinal excitability – termed “preparatory suppression” – which is thought to facilitate movement execution in healthy individuals. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to study the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics.

Methods

On two consecutive days, we applied single-pulse transcranial magnetic stimulation to the primary motor cortex of 20 advanced PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials (MEPs) were elicited at rest or during movement preparation in an instructed-delay choice reaction time task including left- or right-hand responses. Preparatory suppression was assessed by expressing MEPs during movement preparation relative to rest.

Results

PD patients exhibited a deficit in preparatory suppression when it was probed on the responding hand side, particularly when this corresponded to their most-affected hand, regardless of their STN-DBS status.

Conclusions

Advanced PD patients displayed a reduction in preparatory suppression which was not restored by STN-DBS.

Significance

The current findings confirm that PD patients lack preparatory suppression, as previously reported. Yet, the fact that this deficit was not responsive to STN-DBS calls for future studies on the neural source of this regulatory mechanism during movement preparation.

Objective

This study investigated the efficacy of combining at-home anodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) with mindfulness meditation (MM) in fibromyalgia patients trained in mindfulness.

Methods

Thirty-seven patients were allocated to receive ten daily sessions of MM paired with either anodal or sham tDCS over the primary motor cortex. Primary outcomes were pain intensity and quality of life. Secondary outcomes were psychological impairment, sleep quality, mood, affective pain, mindfulness level, and transcranial magnetic stimulation (TMS) measures of cortical excitability. Outcomes were analyzed pre- and post-treatment, with a one-month follow-up.

Results

We found post-tDCS improvement in all clinical outcomes, including mindfulness level, except for positive affect and stress, in both groups without significant difference between active and sham conditions. No significant group*time interaction was found for all clinical and TMS outcomes.

Conclusions

Our findings demonstrate no synergistic or add-on efffect of anodal tDCS of the left M1 compared to the proper effect of MM in patients with fibromyalgia.

Significance

Our findings challenge the potential of combining anodal tDCS of the left M1 and MM in fibromyalgia.

Objective

Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism.

Methods

We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6–11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Evoked and induced gamma (30–90 Hz) responses were separately quantified using a wavelet-based time–frequency analysis, and group differences were evaluated using a permutation-based clustering procedure.

Results

Autistic children exhibited reduced evoked gamma power but increased induced gamma power compared to TD peers. Group differences in induced responses showed the most prominent effect size and remained statistically significant after excluding outliers.

Conclusions

Our study corroborates recent research indicating diminished evoked gamma responses in children with autism. Additionally, we observed a pronounced increase in induced power. Building upon existing ABC-CT findings, these results highlight the potential to detect variations in gamma-related neural activity, despite the absence of significant group differences in time-domain VEP components.

Significance

The contrasting patterns of decreased evoked and increased induced gamma activity in autistic children suggest that a combination of different EEG metrics may provide a clearer characterization of autism-related circuitry than individual markers alone.

Objectives

Strength-duration time constant (SDTC) may now be determined for cortical motor neurones, with activity mediated by transient Na⁺ conductances. The present study determined whether cortical SDTC is abnormal and linked to the pathogenesis of amyotrophic lateral sclerosis.

Methods

Cortical SDTC and rheobase were estimated from 17 ALS patients using a controllable pulse parameter transcranial magnetic stimulation (cTMS) device. Resting motor thresholds (RMTs) were determined at pulse widths (PW) of 30, 45, 60, 90 and 120 µs and M−ratio of 0.1, using a figure-of-eight coil applied to the primary motor cortex.

Results

SDTC was significantly reduced in ALS patients (150.58 ± 9.98 µs; controls 205.94 ± 13.7 µs, P < 0.01). The reduced SDTC correlated with a rate of disease progression (Rho = -0.440, P < 0.05), ALS functional rating score (ALSFRS-R) score (Rho = 0.446, P < 0.05), and disease duration (R = 0.428, P < 0.05). The degree of change in SDTC was greater in patients with cognitive abnormalities as manifested by an abnormal total Edinburgh Cognitive ALS Screen score (140.5 ± 28.7 µs, P < 0.001) and ALS-specific subscore (141.7 ± 33.2 µs, P = 0.003).

Conclusions

Cortical SDTC reduction was associated with a more aggressive ALS phenotype, or with more prominent cognitive impairment.

Significance

An increase in transient Na⁺ conductances may account for the reduction in SDTC, linked to the pathogenesis of ALS.