•TMS combined with EMG permits the generation of key neurophysiological indices in the cortex.•AD patients had increased motor cortical excitability and decreased cholinergic and GABAergic functions ...compared with HC.•MCI patients had increased motor cortical excitability and decreased cholinergic function compared with HC.•TMS neurophysiology are useful measure to understand the pathophysiology of AD and MCI.
Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with AD, mild cognitive impairment (MCI), and healthy controls (HC). Our meta-analyses indicated that RMT, SAI, SICI, and LICI were significantly lower in patients with AD, while ICF did not show a difference in patients with AD compared with HC. In patients with MCI, RMT and SAI were significantly lower than in HC. In conclusion, motor cortical excitability was increased, while cholinergic function was decreased in AD and MCI in comparison with HC and patients with AD had decreased GABAergic and glutamatergic functions compared with HC. Our results warrant further studies to differentiate AD, MCI, and HC, employing multimodal TMS neurophysiology.
Structured care pathways (SCPs) consist of treatment algorithms that patients advance through with the goal of achieving remission or response. These SCPs facilitate the application of current ...evidence and adequate treatment, which potentially benefit patients with mood disorders. The aim of this systematic review was to provide an updated synthesis of SCPs for the treatment of depressive disorders and bipolar disorder (BD).
PubMed, PsycINFO, and Embase were searched through June 2022 for peer-reviewed studies examining outcomes of SCPs. Eligibility criteria included being published in a peer-reviewed journal in the English language, reporting of intervention used in the SCP, and having quantitative outcomes. Studies Cochrane risk of bias tool was used to assess quality of RCTs.
Thirty-six studies including 15,032 patients were identified for qualitative synthesis. Six studies included patients with BD. The studies were highly heterogeneous in design, outcome measures, and algorithms. More than half of the studies reported superiority of SCPs over treatment as usual, suggesting that the standardized structure and consistent monitoring inherent in SCPs may be contributing to their effectiveness. We also found accumulating evidence supporting feasibility of SCPs in different settings, although dropout rates were generally higher in SCPs. The studies included were limited to being published in peer-reviewed journals in English language. The heterogeneity of studies did not allow quantitative evaluation.
The findings of our study suggest that SCPs are equally or more effective than treatment as usual in depression and BD. Further studies are required to ascertain their effectiveness, particularly for BD, and to identify factors that influence their feasibility and success.
Application of magnetic or electrical stimulation to the motor cortex can result in a period of electromyography (EMG) silence in a tonically active peripheral muscle. This period of EMG silence is ...referred to as the silent period (SP). The duration of SP shows intersubject variability and reflects the integrity of cortical and corticospinal pathways. A non-invasive technique for assessing the duration of SP is the combination of Transcranial Magnetic Stimulation (TMS) with EMG. Utilizing TMS–EMG, several studies have reported on the shortening or lengthening of SP in neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, obsessive compulsive disorder, epilepsy, Parkinson's disease, and stroke. However, cortical, corticospinal and peripheral components are difficult to disentangle from EMG alone. Here, we use the multimodal neuroimaging technique of TMS–EMG combined with concurrent electroencephalography (EEG) recording to further examine the cortical origin of SP and the cortical oscillatory activity that underlies SP genesis. We demonstrate that the duration of SP is related to the temporal characteristics of the cortical reactivity and the power of delta to alpha oscillations in both local and remote areas ipsilateral and contralateral to the stimulation site, and beta oscillations locally. We illustrate that, compared to EMG, the EEG indices of the SP provide additional information about the brain dynamics and propose that the EEG measures of SP may be used in future clinical and research investigations to more precisely delineate the mechanisms underlying inhibitory impairments.
•We examined the EEG characteristics during the TMS-induced EMG silent period.•Silent period is related to EEG duration, peaks, and amplitude of N100 component.•Silent period may be mediated by local and distributed slow oscillations (1-12Hz).
It has been recognized that the efficacy of TMS-based modulation may depend on the network profile of the stimulated regions throughout the brain. However, what profile of this stimulation network ...optimally benefits treatment outcomes is yet to be addressed. The answer to the question is crucial for informing network-based optimization of stimulation parameters, such as coil placement, in TMS treatments. In this study, we aimed to investigate the feasibility of taking a disease-specific network as the target of stimulation network for guiding individualized coil placement in TMS treatments. We present here a novel network-based model for TMS targeting of the pathological network. First, combining E-field modeling and resting-state functional connectivity, stimulation networks were modeled from locations and orientations of the TMS coil. Second, the spatial anti-correlation between the stimulation network and the pathological network of a given disease was hypothesized to predict the treatment outcome. The proposed model was validated to predict treatment efficacy from the position and orientation of TMS coils in two depression cohorts and one schizophrenia cohort with auditory verbal hallucinations. We further demonstrate the utility of the proposed model in guiding individualized TMS treatment for psychiatric disorders. In this proof-of-concept study, we demonstrated the feasibility of the novel network-based targeting strategy that uses the whole-brain, system-level abnormity of a specific psychiatric disease as a target. Results based on empirical data suggest that the strategy may potentially be utilized to identify individualized coil parameters for maximal therapeutic effects.
Highlights • TMS measures of motor cortical excitation, inhibition and plasticity were assessed in young vs older adults. • Age-related motor cortical hypo-excitability and a trending decrease in ...LTP-like plasticity observed. • Older adults showed deficits in sensorimotor integration in comparison to young adults.
Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an effective way to evaluate neurophysiological processes at the level of the cortex. To further characterize the ...TMS-evoked potential (TEP) generated with TMS-EEG, beyond the motor cortex, we aimed to distinguish between cortical reactivity to TMS versus non-specific somatosensory and auditory co-activations using both single-pulse and paired-pulse protocols at suprathreshold stimulation intensities over the left dorsolateral prefrontal cortex (DLPFC). Fifteen right-handed healthy participants received six blocks of stimulation including single and paired TMS delivered as active-masked (i.e., TMS-EEG with auditory masking and foam spacing), active-unmasked (TMS-EEG without auditory masking and foam spacing) and sham (sham TMS coil). We evaluated cortical excitability following single-pulse TMS, and cortical inhibition following a paired-pulse paradigm (long-interval cortical inhibition (LICI)). Repeated measure ANOVAs revealed significant differences in mean cortical evoked activity (CEA) of active-masked, active-unmasked, and sham conditions for both the single-pulse (F(1.76, 24.63) = 21.88, p < 0.001, η
= 0.61) and LICI (F(1.68, 23.49) = 10.09, p < 0.001, η
= 0.42) protocols. Furthermore, global mean field amplitude (GMFA) differed significantly across the three conditions for both single-pulse (F(1.85, 25.89) = 24.68, p < 0.001, η
= 0.64) and LICI (F(1.8, 25.16) = 14.29, p < 0.001, η
= 0.5). Finally, only active LICI protocols but not sham stimulation (active-masked (0.78 ± 0.16, P < 0.0001), active-unmasked (0.83 ± 0.25, P < 0.01)) resulted in significant signal inhibition. While previous findings of a significant somatosensory and auditory contribution to the evoked EEG signal are replicated by our study, an artifact attenuated cortical reactivity can reliably be measured in the TMS-EEG signal with suprathreshold stimulation of DLPFC. Artifact attenuation can be accomplished using standard procedures, and even when masked, the level of cortical reactivity is still far above what is produced by sham stimulation. Our study illustrates that TMS-EEG of DLPFC remains a valid investigational tool.
Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAA receptor-mediated inhibition and ...glutamatergic excitatory transmission, respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from the dorsolateral prefrontal cortex (DLPFC) using combined TMS and electroencephalography (TMS-EEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS-evoked potentials (TEPs) and spectral power modulation. Subsequently, these paradigms were applied in the DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation, respectively) of P30 and P60 TEP amplitude, which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, whereas P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long-interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall, the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing noninvasive measures of glutamatergic and GABAA receptor-mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders.
Repetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4–6 weeks for maximal effect. Recent studies suggest that ...multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions.
This open-label study reviewed clinical outcomes over a 20–30 session course of high-frequency bilateral dorsomedial prefrontal cortex (DMPFC)-rTMS among patients receiving 6000 pulses/day delivered either in twice-daily sessions 80 min apart (at 20 Hz) or single, longer, once-daily sessions (at 10 Hz).
A retrospective chart review identified 130 MDD patients who underwent 20–30 daily sessions of bilateral DMPFC-rTMS (Once-daily, n = 65; Twice-daily, n = 65) at a single Canadian clinic.
Mixed-effects modeling revealed significantly faster improvement (group-by-time interaction) for twice-daily versus once-daily DMPFC-rTMS. Across both groups, the pace of improvement showed a consistent relationship with number of cumulative sessions, but not with cumulative number of pulses. Although the twice-daily group completed treatment in half as many days, final clinical outcomes did not differ significantly between groups on dichotomous measures (response/remission rates: once-daily, 35.4%/33.8%; twice-daily, 41.5%/35.4%), or continuous measures, or on overall response distribution.
Twice-daily rTMS appears feasible, tolerable, and capable of achieving comparable results to once-daily rTMS, while also reducing course length approximately twofold. Therapeutic gains tracked the cumulative number of sessions, not pulses. Future randomized studies comparing once-daily to multiple-daily rTMS sessions, while controlling for number of pulses, may be warranted.
•Case series: 130 MDD patients once-daily 10 Hz vs. twice-daily 20 Hz DMPFC-rTMS.•Same number of pulses per day (6000) in each group, divided into 1 vs 2 fractions.•Safety, tolerability, and degree of final improvement did not differ between groups.•Response trajectories tracked number of sessions, and not number of pulses.
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