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Abstract: Objective: Concentration changes in hemoglobin following single and paired pulse (2 and 15ms inter-stimulus interval) transcranial magnetic stimulation (TMS) was investigated using near infra-red spectroscopy (NIRS). Methods: TMS was delivered to left pre-frontal cortex at typical intensities used in neuroscience research and concentrations of deoxyhemoglobin (Hb), oxyhemoglobin (HbO) and total hemoglobin (HbT) were measured. Results: Significant drops in concentration of HbO and HbT were observed and while there was no effect of the different pulse types on amplitude, there was a difference in the time taken to return to baseline. Conclusions: The changes observed imply that in pre-frontal cortex, the different TMS pulse types result in differential effects on oxygen consumption. Significance: This study aids our understanding of the physiological effects of single and paired pulse TMS. [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]

Abstract: Repetitive transcranial magnetic stimulation (rTMS) procedures are being widely applied in therapeutic and investigative studies. Numerous studies have investigated the effects of rTMS on cortical excitability and inhibition, yielding somewhat contradictory results. The purpose of this study was to comprehensively review this literature to guide the selection of methodology in therapeutic studies. We conducted a comprehensive review of all identified studies that investigated effects of low and/or high frequency rTMS on motor cortical excitability or inhibition. Low frequency rTMS appears to produce a transient reduction in cortical excitability as assessed by motor evoked potential (MEP) size and produces no substantial effect on cortical inhibition. High frequency rTMS appears to produce a persistent increase in MEP size and a reduction in cortical inhibition measured with paired pulse methods although few studies have investigated frequencies greater than 5Hz. A number of novel stimulation paradigms have significant potential for altering cortical excitability but require further investigation. Although commonly applied forms of rTMS have effects on cortical excitability, more substantial effects may be obtained through the use of novel stimulation paradigms or innovative approaches to the stimulation of areas connected to a potential target site. Further research is required, however, before these paradigms can be more widely adopted. [Copyright &y& Elsevier]

• The N100, associated with GABA B receptor mediated inhibition, decreased in amplitude after rTMS in association with improvement in depressive symptoms. • Cortical activity in the DLPFC (the site of rTMS stimulation) decreased after active rTMS. • TMS-EEG markers of cortical inhibition and excitation demonstrate high potential as biomarkers of response to rTMS. Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS' effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS. TMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral):sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest. The N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability. Our results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability. These findings uncover potentially important neurophysiological mechanisms of rTMS action. [ABSTRACT FROM AUTHOR]

• Active single-pulse TMS generates similar waveform as auditory response but with larger amplitude. • Only active paired-pulse protocol induced significant cortical inhibition in dorsolateral prefrontal cortex. • Cortical inhibition is observed over all frequency bands in active long interval cortical inhibition. We measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography). Nineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS. Cortical excitability indexed by area under the curve (AUC (25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η2 = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η2 = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition. The significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation. Our study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity. [ABSTRACT FROM AUTHOR]

• Interhemispheric signal propagation was elevated in schizophrenia and depression patients relative to healthy controls. • Interhemispheric signal propagation did not differ between patient groups. • There were no medication effects on interhemispheric signaling from inter-individual comparisons and no significant correlation with symptom severity. Altered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls. We evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls. ISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method. Altered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations. These findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients. [ABSTRACT FROM AUTHOR]

• rTMS treatment outcome is quadratically related to the individual alpha peak frequency (IAF) in depression. • Absolute distance of IAF to 10 Hz is linearly related to clinical outcome. • These results strengthen the theory that 10 Hz rTMS entrains brain oscillations. The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome. Correlations were performed to investigate the relationship between IAF-prox and percentage symptom improvement in a sample of 153 patients with major depressive disorder treated with 10 Hz (N = 59) to the left dorsolateral prefrontal cortex (DLPFC) or 1 Hz (N = 94) to the right DLPFC repetitive Transcranial Magnetic Stimulation (rTMS). There was a significant negative correlation between IAF-prox and the percentage of symptom improvement only for the 10 Hz group. Curve fitting models revealed that there was a quadratic association between IAF and treatment response in the 10 Hz group, with a peak at 10 Hz IAF. The main result of Corlier and colleagues was replicated, and the findings suggest that the distance between 10 Hz stimulation frequency and the IAF may influence clinical outcome in a non-linear manner. rTMS is often administered at a frequency of 10 Hz, which is the center of the EEG alpha frequency band. The results can make a significant contribution to optimizing the clinical application of rTMS. [ABSTRACT FROM AUTHOR]

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]