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Background and Objective: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this treatment currently lacks reliable biomarkers of treatment response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one of the most promising. This study investigated the association between baseline N100 amplitude and 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated rTMS (arTMS) treatment in MDD., Methods: Baseline TMS-EEG sessions were performed for 23 MDD patients. All patients then underwent 40 sessions of 1 Hz R-DLPFC (F4) arTMS over 5 days and a follow-up TMS-EEG session one week after the end of theses arTMS sessions., Results: Baseline N100 amplitude at F4 showed a strong positive association (p < .001) with treatment outcome. The association between the change in N100 amplitude (baseline to follow-up) and treatment outcome did not remain significant after Bonferroni correction (p = .06, corrected; p = .03, uncorrected). Furthermore, treatment responders had a significantly larger mean baseline F4 TEP amplitude during the N100 time frame compared to non-responders (p < .001). Topographically, after Bonferroni correction, F4 is the only electrode at which its baseline N100 amplitude showed a significant positive association (p < .001) with treatment outcome., Limitations: Lack of control group and auditory masking., Conclusion: Baseline N100 amplitude showed a strong association with treatment outcome and thus demonstrated great potential to be utilized as a cost-effective and widely adoptable biomarker of rTMS treatment in MDD., Competing Interests: Declaration of competing interest JZS, FMazza, DM, FMansouri, TR, RZ, MH, LF, HV, EBA do not report any conflict of interest. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magventure Inc. His work has been supported by the Canadian Institutes of Health Research (CIHR), the National Institute of Mental Health (NIMH), Brain Canada and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JD has received research support from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, the Canadian Institutes of Health Research (CIHR), the Klarman Family Foundation, NIH, the Ontario Brain Institute, the Toronto General and Western Hospital Foundation, and the Weston Family Foundation; he has received travel stipends from Lundbeck and ANT Neuro; he has served as an advisor for BrainCheck, Restorative Brain Clinics, and TMS Neuro Solutions, holds equity in Arc Health Partners, and is a co-founder of Ampa. JPM reports research support from the Brain & Behavior Research Foundation (BBRF), the Réseau Québécois sur le Suicide, les troubles de l'Humeur et les troubles Associés (RQSHA), the Canadian Research Initiative in Substance Misuse (CRISM), the Fonds de Recherche du Québec - Santé (FRQS), the Branch Out Neurological Foundation, and the Canadian Institutes of Health Research (CIHR). JDG has received research support from the Labatt Family Network, the CAMH Discovery Fund, the University of Toronto EMHSeed program, and the Tri-Council Canada-UK AI Initiative., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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 2  = 0.61) and LICI (F(1.68, 23.49) = 10.09, p < 0.001, η 2  = 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 2  = 0.64) and LICI (F(1.8, 25.16) = 14.29, p < 0.001, η 2  = 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., (© 2023. The Author(s).)

Background: Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the effectiveness of intermittent theta-burst stimulation (iTBS) on cognition in individuals with methamphetamine use disorder (MUD)., Methods: This was a secondary analysis of 40 MUD subjects receiving left dorsolateral prefrontal cortex (L-DLPFC) iTBS or sham iTBS for 20 times over 10 days (twice-daily). Changes in working memory (WM) accuracy, reaction time, and sensitivity index were analyzed before and after active and sham rTMS treatment. Resting-state EEG was also acquired to identify potential biological changes that may relate to any cognitive improvement., Results: The results showed that iTBS increased WM accuracy and discrimination ability, and improved reaction time relative to sham iTBS. iTBS also reduced resting-state delta power over the left prefrontal region. This reduction in resting-state delta power correlated with the changes in WM., Conclusions: Prefrontal iTBS may enhance WM performance in MUD subjects. iTBS induced resting EEG changes raising the possibility that such findings may represent a biological target of iTBS treatment response.

Up to 50% of youth with depression do not respond to conventional first-line treatments. However, little research has been conducted on the pathophysiology of youth depression, hindering the identification of more effective treatments. Our goal was to identify neurophysiological markers that differentiate youth with depression from healthy youth and could serve as targets of novel treatments. We hypothesized that youth with depression would exhibit network-specific cortical reactivity and connectivity abnormalities compared with healthy youth. Transcranial magnetic stimulation combined with electroencephalography and magnetic resonance imaging was employed in combination with clinical and behavioral assessments to study cortical reactivity and connectivity in bilateral dorsolateral prefrontal cortex (DLPFC), motor cortex, and inferior parietal lobule, sites linked to the frontoparietal network, sensorimotor network, and default mode network, respectively. In youth depression, greater cortical reactivity was observed specific to the left and right DLPFC stimulation only, which correlated with anhedonia scores. Additionally, the connectivity of the right DLPFC was significantly higher in youth depression. Source reconstruction attributed the observed connectivity dysregulation to regions belonging to the default mode network. The neurophysiological signatures identified in this study have high potential to inform the development of more effective and targeted interventions for the youth depression population., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Repetitive transcranial magnetic stimulation (rTMS) is entering wider use as a therapeutic intervention for many psychiatric illnesses. The efficacy of this therapeutic intervention may depend on accurately localizing target brain regions. Recent work investigating whole-brain maps of circuits associated with depression and its successful treatment has identified foci of interest within the dorsolateral prefrontal cortex (DLPFC). To create an updated scalp heuristic for localizing the DLPFC based on convergent evidence of lesion and brain stimulation studies in depression. Using the standard MNI ICBM152 anatomical template, we localized the scalp sites at minimum Euclidean distance from target MNI coordinates and performed nasion-inion, tragus-tragus, and head-circumference measurements on the anatomical template. We then derived equations to localize these scalp sites. The derived equations to calculate the arc length X and Y for these new targets are as follows: [ Y = ((N I + T r T r) / 2) × 0.3167 ; X = H C × 0.1359 ] for the left anterior DLPFC[ Y = ((N I + T r T r) / 2) × 0.2884 ; X = H C × 0.1352 ] for the right anterior DLPFC[ Y = ((N I + T r T r) / 2) × 0.2480 ; X = H C × 0.1847 ] for the left posterior DLPFC[ Y = ((N I + T r T r) / 2) × 0.2316 ; X = H C × 0.1968 ] for the right posterior DLPFC This heuristic may help localize DLPFC targets identified in previous lesion-/stimulation-mapping work. A spreadsheet calculation tool is offered to support use of this heuristic. • Targets from convergent maps of lesion and brain stimulation studies in depression. • Updated scalp-based heuristic for localizing the dorsolateral prefrontal cortex. • Calculation tool for locating targets with the input of cardinal scalp measurements. [ABSTRACT FROM AUTHOR]

There has been a distinct shift in neuroimaging from localization of function into a more network based approach focused on connectivity. While fMRI has proven very fruitful for this, the hemodynamic signal is inherently slow which limits the temporal resolution of fMRI-only connectivity measures. The brain, however, works on a time scale of milliseconds. This study utilized concurrent transcranial magnetic stimulation (TMS)-fMRI in a novel way to obtain measures of dynamic connectivity by measuring changes in fMRI signal amplitude in regions distal to the site of stimulation following differing TMS onset times. Seventeen healthy subjects completed an associative memory encoding task known to involve the DLPFC, viewing pairs of objects which could be semantically related or unrelated. Three pulses of 10 Hz repetitive TMS were applied over the left DLPFC starting either at 200, 600, or 1000 ms after stimulus onset. Associations for related pairs were better remembered than unrelated pairs in a post-scan cued recall test. Differences in neural activity were assessed across different TMS onsets, separately for related and unrelated pairs. Time specific TMS effects were observed in several regions, including those associated with higher-level processing (lateral frontal, anterior cingulate), visual areas (occipital), and regions involved in semantic processing (e.g., left mid-temporal and medial frontal). Activity in the frontal cortex was decreased at 200 ms post-stimulus for unrelated pairs, and 1000 ms post-stimulus for related pairs. This suggests differences in the timing across conditions in which the DLFPC interacts with other PFC regions, consistent with the notion that the DLPFC is facilitating extended semantic processing for related items. This study demonstrates that time-varying TMS onset inside the MRI can be used to reliably measure fast dynamic connectivity with a temporal resolution in the hundreds of milliseconds. [ABSTRACT FROM AUTHOR]

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for the assessment of various neurophysiological processes in the human cortex. One of these paradigms, short-latency afferent inhibition (SAI), is thought to be a sensitive measure of cholinergic activity. In a previous study, we demonstrated the temporal pattern of this paradigm from both the motor (M1) and dorsolateral prefrontal cortex (DLPFC) using simultaneous TMS-EEG recording. The SAI paradigm led to marked modulations at N100. In this study, we aimed to investigate the age-related effects on TMS-evoked potentials (TEPs) with the SAI from M1 and the DLPFC in younger (18-59 years old) and older (≥60 years old) participants. Older participants showed significantly lower N100 modulation in M1-SAI as well as DLPFC-SAI compared to the younger participants. Furthermore, the modulation of N100 by DLPFC-SAI in the older participants correlated with executive function as measured with the Trail making test. This paradigm has the potential to non-invasively identify cholinergic changes in cortical regions related to cognition in older participants. [ABSTRACT FROM AUTHOR]

Objectives.Preclinical studies suggest that cortical alterations within the prefrontal cortex (PFC) are critical to the pathophysiology of alcohol dependence. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows direct assessment of cortical excitability and inhibition within the PFC of human subjects. We report the first application of TMS-EEG to measure these indices within the PFC of alcohol-dependent (ALD) patients post-detoxification.Methods.Cortical inhibition was assessed in 12 ALD patients and 14 healthy controls through single and paired-pulse TMS paradigms. Long-interval cortical inhibition indexed cortical inhibition in the PFC. In the motor cortex (MC), short- interval intracortical inhibition and cortical silent period determined inhibition, while intracortical facilitation measured facilitation, resting and active motor threshold indexed cortical excitability.Results.ALD patients demonstrated altered cortical inhibition across the bilateral frontal cortices relative to controls. There was evidence of altered cortical excitability in ALD patients; however, no significant differences in MC inhibition.Conclusions.Our study provides first direct evidence of reduced cortical inhibition in the PFC of ALD patients post-detoxification. Altered cortical excitability in the MC may reflect hyper-excitability within the cortex associated with chronic alcohol consumption. These findings provide initial neurophysiological evidence of disrupted cortical excitability within the PFC of ALD patients. [ABSTRACT FROM AUTHOR]

Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) enables noninvasive neurophysiological investigation of the human cortex. A TMS paradigm of short-latency afferent inhibition (SAI) is characterized by attenuation of the motor-evoked potential (MEP) and modulation of N100 of the TMS-evoked potential (TEP) when TMS is delivered to motor cortex (M1) following median nerve stimulation. SAI is a marker of cholinergic activity in the motor cortex; however, the SAI has not been tested from the prefrontal cortex. We aimed to explore the effect of SAI in dorsolateral prefrontal cortex (DLPFC). SAI was examined in 12 healthy subjects with median nerve stimulation and TMS delivered to M1 and DLPFC at interstimulus intervals (ISIs) relative to the individual N20 latency. SAI in M1 was tested at the optimal ISI of N20 + 2 ms. SAI in DLPFC was investigated at a range of ISI from N20 + 2 to N20 + 20 ms to explore its temporal profile. For SAI in M1, the attenuation of MEP amplitude was correlated with an increase of TEP N100 from the left central area. A similar spatiotemporal neural signature of SAI in DLPFC was observed with a marked increase of N100 amplitude. SAI in DLPFC was maximal at ISI N20 + 4 ms at the left frontal area. These findings establish the neural signature of SAI in DLPFC. Future studies could explore whether DLPFC-SAI is neurophysiological marker of cholinergic dysfunction in cognitive disorders. [ABSTRACT FROM AUTHOR]

Using TMS and EEG, Radhu et al. reveal reductions in long-interval cortical inhibition specific to the dorsolateral prefrontal cortex in patients with schizophrenia compared to healthy subjects and individuals with obsessive-compulsive disorder (OCD). The absence of such changes in OCD confirms that reductions in inhibition are not a generalized deficit associated with severe psychopathology.Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology. [ABSTRACT FROM AUTHOR]

Background: Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder. Methods: T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18–55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored. Results: Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance. Conclusions: We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia. [ABSTRACT FROM PUBLISHER]

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Background: Transcranial direct current stimulation (tDCS), applied to the left dorsolateral prefrontal cortex (DLPFC) has been found to improve working memory (WM) performance in both healthy and clinical participants. However, whether this effect can be enhanced by cognitive activity undertaken during tDCS has not yet been explored. Objective: This study aimed to explore whether tDCS applied to the left DLPFC during the persistent performance of one WM task would improve performance on a subsequent WM task, to a greater extent than either tDCS or cognitive activity alone. Methods: Ten healthy participants took part in three counterbalanced conditions. The conditions involved 10 minutes of either anodal tDCS while completing an n-back task, anodal tDCS while at rest, or sham tDCS while completing an n-back task. The n-back that was used in this study was a computer-based letter WM task that involved 5 minutes of two-back, followed by 5 minutes of three-back. Digit span forward and backward was administered immediately before and after each treatment, and performance change (pre- to posttreatment) calculated and compared across conditions. The digit span tasks involved a series of numbers being read to the participant, and the participant was required to repeat them back, either in the same order (Digits forward) or in the reverse order (Digits backward). Results: tDCS applied during completion of the n-back task was found to result in greater improvement in performance on digit span forward, compared with tDCS applied while at rest and sham tDCS during the n-back task. This finding was not evident with digit span backward. Conclusions: These results indicate that there may be potential for the use of adjunctive cognitive remediation techniques to enhance the effects of tDCS. However, further research needs to be undertaken in this area to replicate and extend this finding. [Copyright &y& Elsevier]

Previous studies have shown that patients with schizophrenia and bipolar disorder have deficits in cortical inhibition. Through the combination of interleaved transcranial magnetic stimulation and electroencephalography, we have recently reported on methods in which cortical inhibition can be measured from the dorsolateral prefrontal cortex, a cortical region that is more closely associated with the pathophysiology of schizophrenia. Furthermore, it is possible to index cortical inhibition of specific oscillatory frequencies including the gamma band (30–50 Hz) whose modulation has been related to higher order cortical processing. In this study, we show that patients with schizophrenia have significant deficits of cortical inhibition of gamma oscillations in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder, while no deficits are demonstrated in the motor cortex. These results suggest that the lack of inhibition of gamma oscillations in the dorsolateral prefrontal cortex may represent an important frontal neurophysiological deficit, which may be responsible for the spectrum of deficits commonly found in schizophrenia. [ABSTRACT FROM PUBLISHER]

Gamma (γ)-oscillations (30–50 Hz) represent important electrophysiological measures, which are generated through the execution of higher order cognitive tasks (eg, working memory) in the dorsolateral prefrontal cortex (DLPFC). By contrast, cortical inhibition (CI) refers to a neurophysiological process in which GABAergic inhibitory interneurons selectively suppress the activation of other neurons in the cortex. Recently, abnormalities in both CI and γ-oscillations have been associated with various neuropsychiatric disorders including schizophrenia. Animal research suggests that suppression of γ-oscillations is, in part, mediated through GABAergic inhibitory neurotransmission. However, no such evidence has been demonstrated in human, largely because of technological limitations. Recently, we reported on novel methods permitting the recording of CI from the DLPFC through transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). The aim of this study was to examine the effects of GABAergic inhibitory neurotransmission on γ-oscillations by combining TMS with EEG. Long interval cortical inhibition (LICI), a paired TMS paradigm, was used to index GABAB receptor mediated inhibitory neurotransmission in the motor cortex and DLPFC of healthy individuals. γ-Oscillations were significantly inhibited by LICI (38.1±26.5%; p0.013) in the DLPFC but not in the motor cortex. These results provide neurophysiological evidence to demonstrate γ-oscillations are inhibited by LICI in the DLPFC but not in the motor cortex. Such specificity suggests that the modulation of γ-oscillations may represent an important neurophysiological process that may, in part, be responsible for optimal DLPFC functioning in healthy human subjects.Neuropsychopharmacology (2009) 34, 1543–1551; doi:10.1038/npp.2008.211; published online 26 November 2008 [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8±30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1±26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.Neuropsychopharmacology (2008) 33, 2860–2869; doi:10.1038/npp.2008.22; published online 5 March 2008 [ABSTRACT FROM AUTHOR]

Abstract: High and low frequency repetitive transcranial magnetic stimulation (rTMS) are both used to treat major depressive disorder(MDD). However, the physiological mechanisms underlying the therapeutic benefit and the effect of the stimulation frequency are unclear. Twelve healthy participants received 1Hz, 2Hz, and 5Hz active rTMS. Twenty 5 second trains were delivered at left dorsolateral prefrontal cortex at 110% of resting motor threshold with a 25 second inter-train interval. Blood oxygenation (HbO) was significantly reduced following the 1Hz trains compared to the HbO increases observed in both the 2Hz and 5Hz conditions. There was no significant inter-hemispheric difference in response. These results suggest that short trains of high and low frequency rTMS delivered to prefrontal cortex evoke a differential HbO response and provide additional evidence that high frequency trains result in increased neural activity. The findings may provide further explanation for the improved symptoms observed in MDD patients treated with high frequency rTMS. [Copyright &y& Elsevier]

Background: The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for non-invasive investigation of cortical response and connectivity in human cortex. This study aimed to examine the amplitudes and latencies of each TMS-evoked potential (TEP) component induced by single-pulse TMS (spTMS) to the left motor (M1) and dorsolateral prefrontal cortex (DLPFC) among healthy young participants (YNG), older participants (OLD), and patients with schizophrenia (SCZ). Methods: We compared the spatiotemporal characteristics of TEPs induced by spTMS among the groups. Results: Compared to YNG, M1-spTMS induced lower amplitudes of N45 and P180 in OLD and a lower amplitude of P180 in SCZ, whereas the DLPFC-spTMS induced a lower N45 in OLD. Further, OLD demonstrated latency delays in P60 after M1-spTMS and in N45-P60 over the right central region after left DLPFC-spTMS, whereas SCZ demonstrated latency delays in N45-P60 over the midline and right central regions after DLPFC-spTMS. Conclusions: These findings suggest that inhibitory and excitatory mechanisms mediating TEPs may be altered in OLD and SCZ. The amplitude and latency changes of TEPs with spTMS may reflect underlying neurophysiological changes in OLD and SCZ, respectively. The spTMS administered to M1 and the DLPFC can probe cortical functions by examining TEPs. Thus, TMS-EEG can be used to study changes in cortical connectivity and signal propagation from healthy to pathological brains. [ABSTRACT FROM AUTHOR]

• The effects of 600, 1200 and 1800 pulses of intermittent theta burst stimulation were compared in healthy volunteers. • None of the three doses was superior in modulating prefrontal evoked activity and oscillatory activity. • iTBS may act on dorsolateral prefrontal cortex activity via the modulation of excitation/inhibition balance. Using concurrent transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG), this study aims to compare the effect of three intermittent theta-burst stimulation (iTBS) doses on cortical activity in the left dorsolateral prefrontal (DLPFC) cortex. Fourteen neurotypical participants took part in the following three experimental conditions: 600, 1200 and 1800 pulses. TMS-EEG recordings were conducted on the left DLPFC pre/post iTBS, including single-pulse TMS and short- and long-interval intracortical inhibition (SICI, LICI). TMS-evoked potentials (TEP) and event-related spectral perturbation (ERSP) were quantified. Linear mixed models were used to assess the effect of iTBS on brain activity. The effects of iTBS on DLPFC activity did not significantly differ between the three doses. Specifically, regardless of dose, iTBS modulated the amplitude of most TEP components (P30, N45, P60, P200), reduced SICI and LICI ratios of P30 and P200, and decreased ERSP power of theta oscillations. In neurotypical individuals, doubling or tripling the number of iTBS pulses does not result in stronger potentiation of prefrontal activity. However, all iTBS conditions induced significant modulations of DLPFC activity. Replicating the study in clinical populations could help define optimal parameters for clinical applications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham. Methods: Ten participants undertook three experimental sessions in which they received 10min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task. Results: There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding. Conclusions: The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed. Significance: Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia. [Copyright &y& Elsevier]

There is some evidence of cortical hyper-excitability in Alzheimer's Dementia (AD) but its relationship with cognition is not clear. In this study, we assessed dorsolateral prefrontal cortex (DLPFC) excitability and its relationship with cognition in AD. Twenty-four participants with AD (mean [SD] age = 74.1 [7.2] years) and eleven elderly healthy controls (HC) (mean [SD] age = 68.8 [7.3] years) were recruited. Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) was used to assess cortical excitability. Cortical evoked activity (CEA) between 25 and 80 ms post-TMS stimulus was calculated as the primary measure of cortical excitability. TMS-evoked potential peak (TEP) amplitudes (P30, N45 and P60) were also calculated. Cognition was assessed using Montreal Cognitive Assessment (MoCA), Executive Interview (EXIT) and Cambridge Neuropsychological Test Automated Battery Stockings of Cambridge (SOC). There was no difference in TMS stimulus intensity between the groups. DLPFC-CEA was higher in the AD (mean [SD] = 134.64 [90.22] μV) than the HC group (mean [SD] = 82.65 [40.28] μV; t 33 = 2.357, p = 0.025). There were no differences in TEP peak amplitudes between the groups. Further, DLPFC-CEA was inversely associated with MoCA and SOC, and positively associated with EXIT scores in AD. These results suggest increased DLPFC excitability in AD, and its inverse associations with global cognition and executive function. Future studies should examine these findings in larger samples and longitudinally, and could also assess these markers of cortical excitability in relation to other established markers of AD and in response to interventions. • We compared frontal cortex excitability in Alzheimer's Dementia and healthy controls. • There was higher cortical excitability in Alzheimer's Dementia as compared to healthy controls. • Cortical excitability was inversely associated with global cognition and executive function. [ABSTRACT FROM AUTHOR]

Abstract Repetitive transcranial magnetic stimulation (rTMS) is an effective clinical intervention for various neuropsychiatric diseases. However, it is still unclear whether rTMS has an effect on cognitive functioning. In this review, we aimed to systematically evaluate the cognitive effects of rTMS in depression, schizophrenia, and Alzheimer's disease. We searched PubMed (1996–2018) under the set terms to review randomized controlled trials (RCT) to examine the effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC) and evaluated cognitive functions in patients with depression, schizophrenia, and Alzheimer's disease. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. The search identified 579 articles, 31 of which met inclusion and exclusion criteria. Among them, 15 were conducted in patients with depression, 11 in patients with schizophrenia, and 5 in patients with Alzheimer's disease. Specifically, 6 studies demonstrated a significant improvement of executive function across these diseases. Further, no evidence for cognitive adverse effects was found in these included rTMS studies. Although the heterogeneity between studies in terms of cognitive measures applied, stimulation parameters, and participants limits the ability to generalize conclusions, this review demonstrated that prefrontal rTMS could exert pro-cognitive effects on executive function and attention in some patients with depression but inconsistent cognitive impacts in any of the examined domains especially in patients with schizophrenia and Alzheimer's disease. The results warrant further rTMS studies that include systematic assessment of cognition across various neuropsychiatric diseases. Highlights • Prefrontal rTMS could exert partial pro-cognitive effects in depression. • rTMS has inconsistent cognitive impacts in schizophrenia and Alzheimer's disease. • rTMS studies with comprehensive cognitive assessment in these diseases are needed. [ABSTRACT FROM AUTHOR]

Introduction The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful tool for causally investigating cortical mechanisms and networks. However, various artefacts contaminate TMS-EEG recordings, particularly over regions such as the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC and motor cortex using independent component analysis (ICA). Methods 36 healthy volunteers (30.8 ± 9 years, 9 female) received 75 single TMS pulses to the left DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of 9 volunteers also received 50 sham pulses. The large TMS artefact and early muscle activity (− 2 to ~ 15 ms) were removed using interpolation and the remaining EEG signal was processed in two separate ICA runs using the FastICA algorithm. Five sub-types of TMS-related artefacts were manually identified: remaining muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials and other noise-related artefacts. The cause of proposed blink and auditory-evoked potentials was assessed by concatenating known artefacts (i.e. voluntary blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials before ICA and evaluating grouping of resultant independent components (ICs). Finally, we assessed the effect of removing specific artefact types on TMS-evoked potentials (TEPs) and TMS-evoked oscillations. Results Over DLPFC, ICs from proposed muscle and decay artefacts correlated with TMS-evoked muscle activity size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact sub-types characteristically distorted each measure of DLPFC function across the scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured following DLPFC stimulation. Importantly, characteristic TEPs following motor cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual data, corroborating the reliability of ICA-based artefact correction. Conclusions Various different artefacts contaminate TMS-EEG recordings over the DLPFC and motor cortex. However, these artefacts can be removed with apparent minimal impact on neural activity using ICA, allowing the study of TMS-evoked cortical network properties. [ABSTRACT FROM AUTHOR]

Abstract: Cognitive deficits in schizophrenia underlie more functional disability than any other symptom of the illness and existing treatments are largely inadequate. Non-invasive brain stimulation has been shown to enhance aspects of cognition in both healthy controls and patient populations; however there has been very little research into the use of tDCS for enhancing cognitive performance in schizophrenia. We conducted an initial investigation into the post stimulation effects of tDCS on cognitive performance in a repeated measures design in 18 patients with schizophrenia; in particular looking at dose of stimulation. Specifically, we provided a single 20-minute session of anodal left dorsolateral prefrontal tDCS (1mA, 2mA, sham) and measured performance on a working memory task across three time points post-stimulation (0, 20 and 40min). Our results revealed a significant improvement in performance over time following 2mA stimulation only. These findings speak to the feasibility of tDCS for enhancing cognitive performance in schizophrenia, as well as the importance of dose of stimulation. [Copyright &y& Elsevier]

Abstract: Objective: The induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABAB receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG). Methods: ppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. Results: In the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250ms in DLPFC, and between 50 and 175ms in the parietal lobe. Conclusions: ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABAB activity. Significance: ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABAB activity. [Copyright &y& Elsevier]