Parkinson's disease (PD) is often accompanied by sleep disturbances, impacting patients' quality of life. While repetitive transcranial magnetic stimulation (rTMS) shows promise in improving ...self-reported sleep quality, its effects on objective sleep architecture in PD remain understudied. Sleep disturbances, including rapid eye movement (REM) and slow-wave sleep disturbances, correlate with cognitive decline and motor symptoms. This study investigated the effect of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) modifying objective sleep architecture and explored symptom improvement mechanisms in PD patients.
In this randomized, double-blind, sham-controlled trial, 67 PD patients received 10 consecutive days of 1-Hz rTMS over the right DLPFC. Polysomnography assessed sleep microstructure, while electroencephalogram recordings evaluated power spectral density and sleep spindle activity. Clinical scales measured sleep quality, motor symptoms, and cognition at baseline, post-treatment, and 3 months post-rTMS.
The rTMS group exhibited improvements in sleep quality, motor symptoms, and cognition post-treatment, persisting at the 3-month follow-up. There was a notable increase in the REM sleep proportion post-rTMS. The rTMS group exhibited elevated low-frequency (0.5–2 Hz) slow-wave electroencephalogram spectral density during non-REM sleep. Cognitive enhancement correlated with increased lower delta power, while motor symptom progression correlated with spindle frequency and slow-wave sleep percentage changes.
Low-frequency rTMS targeting the right DLPFC holds promise for improving clinical symptoms and modulating sleep architecture in PD. These findings suggest a link between symptom improvement and sleep structure enhancement, highlighting the need for further investigation into the therapeutic potential of rTMS in PD management.
•Low frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex can improve sleep quality, and adjust sleep structure reflected on the change of rapid eye movement sleep and low-frequency slow wave during non-rapid eye movement sleep.•The increase of lower delta power during non-rapid eye movement sleep was found to correlate with the improvement of cognition in the active group.•The progress of motor symptoms was significantly correlated with the increase in spindle frequency and percentage of slow-wave sleep.
The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled ...trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3+ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = -1.40, 95%CIs = -2.67 to -0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.
•Efficacy and acceptability of fourteen active non-invasive brain stimulation (NIBS) treatments were analyzed.•Most NIBS were transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS).•Only anodal tDCS over F3 plus cathodal tDCS over an extracephalic location significantly improved autistic symptoms.•No NIBS markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants.•There was no difference in dropout or side effect rates between any active NIBS and sham controls.
This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number ...of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.
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•Any of the six parameters significantly predicted variance in efficacy.•Frequency as a potential parameter interacts with the other five parameters.•RCTs using frequency > 10 Hz showed better dose-effect relationships compared to those using the FDA-recommended 10 Hz.
Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although ...abnormalities in two hippocampal networks, the anterior–temporal (AT) and posterior–medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI.
Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response.
Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group.
Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.
The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional ...brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.
•Non-invasive brain stimulation protocols induce variable plasticity-like after-effects in the human brain.•Many factors produce variability; some are unavoidable; some can be controlled.•EEG ...feedback, pulse shape modification and spaced protocols may enhance reliability.
Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. Non-invasive transcranial brain stimulation may modulate cortical excitability outlasting the period of non-invasive transcranial brain stimulation itself from several minutes to more than one hour. Quite a few lines of evidence, including pharmacological, physiological and behavioral studies in humans and animals, suggest that the effects of non-invasive transcranial brain stimulation are produced through effects on synaptic plasticity. However, there is still a need for more direct and conclusive evidence. The fragility and variability of the effects are the major challenges that non-invasive transcranial brain stimulation currently faces. A variety of factors, including biological variation, measurement reproducibility and the neuronal state of the stimulated area, which can be affected by factors such as past and present physical activity, may influence the response to non-invasive transcranial brain stimulation. Work is ongoing to test whether the reliability and consistency of non-invasive transcranial brain stimulation can be improved by controlling or monitoring neuronal state and by optimizing the protocol and timing of stimulation.
Rapidly changing excitability states in an oscillating neuronal network can explain response variability to external stimulation, but if repetitive stimulation of always the same high- or ...low-excitability state results in long-term plasticity of opposite direction has never been explored in vivo.
Different phases of the endogenous sensorimotor μ-rhythm represent different states of corticospinal excitability, and repetitive transcranial magnetic stimulation (rTMS) of always the same high- vs. low-excitability state results in long-term plasticity of different direction.
State-dependent electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS) was applied to target the EEG negative vs. positive peak of the sensorimotor μ-rhythm in healthy subjects using a millisecond resolution real-time digital signal processing system. Corticospinal excitability was indexed by motor evoked potential amplitude in a hand muscle.
EEG negative vs. positive peak of the endogenous sensorimotor μ-rhythm represent high- vs. low-excitability states of corticospinal neurons. More importantly, otherwise identical rTMS (200 triple-pulses at 100 Hz burst frequency and ∼1 Hz repetition rate), triggered consistently at this high-excitability vs. low-excitability state, leads to long-term potentiation (LTP)-like vs. no change in corticospinal excitability.
Findings raise the intriguing possibility that real-time information of instantaneous brain state can be utilized to control efficacy of plasticity induction in humans.
•Millisecond-resolved real-time EEG-TMS allows targeting phases of ongoing μ-rhythm.•Negative (positive) μ-rhythm phase represent high (low) corticospinal excitability.•RTMS of negative but not positive μ-rhythm phase induces LTP-like motor plasticity.•Real-time information of brain state allows controlling efficacy of plasticity induction.
Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that ...rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double‐blind RCT in 262 chronic smokers meeting DSM‐5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilateral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue‐induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four‐week continuous quit rate (CQR) until Week 18 in the intent‐to‐treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent‐to‐treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X2=5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2=7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smoking cessation for adults.
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