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Cortical inhibition in motor and non-motor regions: A combined TMS-EEG study

Authors:
Paul Fitzgerald at Monash University (Australia)
Paul Fitzgerald
Zafiris Daskalakis at University of California, San Diego
Zafiris Daskalakis
Kate E Hoy at Monash University (Australia)
Kate E Hoy
Faranak Farzan at Simon Fraser University
Faranak Farzan
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Abstract

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 GABA(B) 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). 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. In the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe. ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA(B) activity. ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA(B) activity.
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Cortical Inhibition in Motor and Non-Motor Regions: a Combined TMS-EEG Study
Paul B Fitzgerald; Zafiris J Daskalakis; Kate Hoy; Faranak Farzan; Daniel J U...
Clinical EEG and Neuroscience; Jul 2008; 39, 3; ProQuest Health and Medical Complete
pg. 112
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
... Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is a novel technique which allows researchers to non-invasively perturb the brain network (elicit a transient change in the network state) while EEG measures the network response within a millisecond timescale. [37][38][39][40][41][42][43] Healthy controls typically present with a globally efficient and highly integrated network in response to TMS perturbations, while disturbances in network response have been identified across a range of psychiatric populations. [44][45][46][47][48][49] By utilising this novel approach, researchers are now capable of applying a more robust and direct perturbation to regions within the mesocorticolimbic 'addiction' circuitry. ...
... [44][45][46][47][48][49] By utilising this novel approach, researchers are now capable of applying a more robust and direct perturbation to regions within the mesocorticolimbic 'addiction' circuitry. Previously, our research group delivered a paired-pulse TMS paradigm (long interval cortical inhibition [LICI] 42,50,51 ) to the frontal cortex of individuals with alcohol dependence (ALD) post-detoxification to transiently inhibit cortical activity, while EEG measured the cortical response. 52 This study provided the first direct report of altered cortical excitability (reduced cortical inhibitory [GABAergic] neurotransmission) localised within the frontal regions. ...
... 76 It has been found that application of LICI, a paired-pulse inhibitory TMS paradigm, is capable of noninvasively characterising CI of the prefrontal cortex. 41,42,77 This approach has been utilised to identify altered cortical excitability within the frontal cortex of participants with alcohol dependence post-detoxification. 52 However, as the frontal cortex is intricately interconnected with widely distributed brain regions, it was important to explore whether the compensatory response (i.e. the neurophysiology of widespread suppression of GABAergic neurotransmission) may also be identified at the network level. ...
Anomalies in global network connectivity associated with early recovery from alcohol dependence: A network transcranial magnetic stimulation and electroencephalography study
Article
Full-text available
  • Mar 2022
Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery.
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... To compare responses in different frequency bands, a 6 th order zero-shift Butterworth lter was applied where the frequency ranges were considered as delta (1-3 Hz), theta (4-7 Hz), alpha (8-13 Hz), beta (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (31-50 Hz). ...
... Perhaps the subtraction of the artifact that coincides in the single-pulse and test pulse activations (in a similar degree) makes the LICI ratio more resilient to contamination by the auditory and somatosensory artifacts as it is shown by the current ndings. The signi cant LICI over the DLPFC has been demonstrated in previous reports across both healthy and diseased states 16,17,20,30 . This nding is also in accordance with our previous results where the active paired-pulse protocol resulted in signi cant LICI, whereas auditory stimulation alone did not 10 . ...
Isolating sensory artifacts in the suprathreshold TMS-EEG signal over DLPFC
Preprint
Full-text available
  • Oct 2022
Objective 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). Method 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)). Results 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, η²=0.61) and LICI (F(1.68, 23.49)=10.09 , p<0.001, η²=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, η²=0.64) and LICI (F(1.8, 25.16)=14.29 , p<0.001, η²=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. Conclusion While previous findings of a significant somatosensory and auditory contribution to the evoked EEG signal is replicated by our study, an artifact attenuated cortical reactivity can reliably be measured in 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. Significance Our study illustrates that TMS-EEG of DLPFC remains a valid investigational tool.
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... This study in normal volunteers confirms that 1 Hz of repetitive transcranial magnetic stimulation alters rTMS-evoked EEG potential (TEP) waveforms. These waveforms can then be rendered visible with signal averaging and processing [24,26,28,30,44,56]. Numerous studies [57,58] have evaluated short-interval intracortical inhibition (SICI, typically 1-5 ms) and long-interval intracortical inhibition (LICI, typically 50-200 ms) by measuring the EEG response to paired TMS pulses. ...
... However, enhancement of inhibition was maximal at the motor cortex stimulation site. TEP changes in this study did not correlate with amplitude of the motor evoked responses, as has been noted by others [28]. We did not systematically look for changes in motor threshold or paired-pulse inhibition at various inter-stimulus intervals. ...
EEG Evoked Potentials to Repetitive Transcranial Magnetic Stimulation in Normal Volunteers: Inhibitory TMS EEG Evoked Potentials
Article
Full-text available
  • Feb 2022
  • SENSORS-BASEL
The impact of repetitive magnetic stimulation (rTMS) on cortex varies with stimulation parameters, so it would be useful to develop a biomarker to rapidly judge effects on cortical activity, including regions other than motor cortex. This study evaluated rTMS-evoked EEG potentials (TEP) after 1 Hz of motor cortex stimulation. New features are controls for baseline amplitude and comparison to control groups of sham stimulation. We delivered 200 test pulses at 0.20 Hz before and after 1500 treatment pulses at 1 Hz. Sequences comprised AAA = active stimulation with the same coil for test–treat–test phases (n = 22); PPP = realistic placebo coil stimulation for all three phases (n = 10); and APA = active coil stimulation for tests and placebo coil stimulation for treatment (n = 15). Signal processing displayed the evoked EEG waveforms, and peaks were measured by software. ANCOVA was used to measure differences in TEP peak amplitudes in post-rTMS trials while controlling for pre-rTMS TEP peak amplitude. Post hoc analysis showed reduced P60 amplitude in the active (AAA) rTMS group versus the placebo (APA) group. The N100 peak showed a treatment effect compared to the placebo groups, but no pairwise post hoc differences. N40 showed a trend toward increase. Changes were seen in widespread EEG leads, mostly ipsilaterally. TMS-evoked EEG potentials showed reduction of the P60 peak and increase of the N100 peak, both possibly reflecting increased slow inhibition after 1 Hz of rTMS. TMS-EEG may be a useful biomarker to assay brain excitability at a seizure focus and elsewhere, but individual responses are highly variable, and the difficulty of distinguishing merged peaks complicates interpretation.
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... Perhaps the subtraction of the artifact that coincides in the single-pulse and test pulse activations (in a similar degree) makes the LICI ratio more resilient to contamination by the auditory and somatosensory artifacts as it is shown by the current findings. The significant LICI over the DLPFC has been demonstrated in previous reports across both healthy and diseased states 16,17,23,34 . This finding is also in accordance with our previous results where the active paired-pulse protocol resulted in significant LICI, whereas auditory stimulation alone did not 10 . ...
Isolating sensory artifacts in the suprathreshold TMS-EEG signal over DLPFC
Article
Full-text available
  • Apr 2023
Abstract 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
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... In this process, the interplay of excitatory and inhibitory neurons is of fundamental importance, in particular of GABAergic thalamic neurons, being the main gateway of cortical projections to the thalamus. GABAergic neurons are also implicated in the origination of TMS-evoked response, in particular between 30 and 150 ms after TMS, as shown by TMS-EEG investigations using GABA-agonists [75,76] or by measuring GABA-ergic dependent MEP measures [77,78]. In this view, it could be hypothesized that modulation of cerebellar output could have affected the excitability of GABA-ergic interneurons at thalamic and/or cortical level, and in turn the natural frequency of oscillation of M1 and surrounding cortex [20,79]. ...
Cerebellar noninvasive neuromodulation influences the reactivity of the contralateral primary motor cortex and surrounding areas: a TMS-EMG-EEG study
Article
Full-text available
  • Mar 2022
  • CEREBELLUM
Understanding cerebellar–cortical physiological interactions is of fundamental importance to advance the efficacy of neurorehabilitation strategies for patients with cerebellar damage. Previous works have aimed to modulate this pathway by applying transcranial electrical or magnetic stimulation (TMS) over the cerebellum and probing the resulting changes in the primary motor cortex (M1) excitability with motor-evoked potentials (MEPs). While these protocols produce changes in cerebellar excitability, their ability to modulate MEPs has produced inconsistent results, mainly due to the MEP being a highly variable outcome measure that is susceptible to fluctuations in the excitability of M1 neurons and spinal interneurons. To overcome this limitation, we combined TMS with electroencephalography (EEG) to directly record TMS-evoked potentials (TEPs) and oscillations from the scalp. In three sessions, we applied intermittent theta-burst stimulation (iTBS), cathodal direct current stimulation (c-DC) or sham stimulation to modulate cerebellar activity. To assess the effects on M1 and nearby cortex, we recorded TMS-EEG and MEPs before, immediately after (T1) and 15 min (T2) following cerebellar neuromodulation. We found that cerebellar iTBS immediately increased TMS-induced alpha oscillations and produced lasting facilitatory effects on TEPs, whereas c-DC immediately decreased TMS-induced alpha oscillations and reduced TEPs. We also found increased MEP following iTBS but not after c-DC. All of the TMS-EEG measures showed high test–retest repeatability. Overall, this work importantly shows that cerebellar neuromodulation influences both cortical and corticospinal physiological measures; however, they are more pronounced and detailed when utilizing TMS-EEG outcome measures. These findings highlight the advantage of using TMS-EEG over MEPs when assessing the effects of neuromodulation.
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... In addition to the top-down mechanisms, cortical excitability is a promising mechanism as repeated sessions of rTMS restored defective intracortical inhibition in chronic pain (Lefaucheur et al. 2006). Concurrent TMS and electroencephalogram (TMS-EEG) is able to evaluate neuroplastic effects of rTMS delivered over nonmotor regions, such as the prefrontal cortex (Fitzgerald et al. 2008;Cash et al. 2017). TMS-evoked potentials (TEPs) are believed to ref lect the shifts in the inhibitionexcitation balance in cortical circuits following a single TMS pulse (Premoli, Castellanos, et al. 2014;, which have been demonstrated to be stable and reproducible cortical responses Ozdemir, Tadayon, et al. 2021). ...
Concurrent TMS-EEG to Reveal the Neuroplastic Changes in the Prefrontal and Insular Cortices in the Analgesic Effects of DLPFC-rTMS
Article
  • Feb 2022
The dorsolateral prefrontal cortex (DLPFC) is an important target for repetitive transcranial magnetic stimulation (rTMS) to reduce pain. However, the analgesic efficacy of DLPFC-rTMS needs to be optimized, in which the mechanisms of action remain unclear. Concurrent TMS and electroencephalogram (TMS-EEG) is able to evaluate neuroplastic changes beyond the motor cortex. Using TMS-EEG, this study was designed to investigate the local and distributed neuroplastic changes associated with DLPFC analgesia. Thirty-four healthy adults received DLPFC or sham stimulation in a randomized, crossover design. In each session, participants underwent cold pain and TMS-EEG assessment both before and after 10-Hz rTMS. We provide novel findings that DLPFC analgesia is associated with a smaller N120 amplitude in the contralateral prefrontal cortex as well as with a larger N120 peak in the ipsilateral insular cortex. Furthermore, there was a strong negative correlation between N120 changes of these two regions whereby the amplitude changes of this dyad were associated with increased pain threshold. In addition, DLPFC stimulation enhanced coherence between the prefrontal and somatosensory cortices oscillating in the gamma frequency. Overall, our data present novel evidence on local and distributed neuroplastic changes associated with DLPFC analgesia.
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... The LICI protocol has been studied over various cortical regions and has been shown to suppress the cortical response over the DLPFC Fitzgerald et al., 2008;Rogasch et al., 2015;Sun et al., 2016). Significant inhibition across all frequency bands of neural oscillation over this region was shown by Farzan and colleagues (2009). ...
Differentiating Transcranial Magnetic Stimulation Cortical and Auditory Responses via Single Pulse and Paired Pulse protocols: A TMS-EEG study
Article
  • May 2021
  • CLIN NEUROPHYSIOL
Objective 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). Methods 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. Results 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. Conclusion 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. Significance Our study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.
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... The use of TMS along with EEG (termed TMS-EEG) allows us to externally examine brain states, including their phase dynamics across motor and non-motor cortical areas [7,8]. The approach is capable of recording the time taken to resolve cortico-cortical interactions to within ms [9] in both normal and pathological brains [10] and has provided insights into excitatory and inhibitory human brain mechanisms [11,12]. It is also a powerful tool for assessing cortical dynamics at rest and during tasks [13,14]. ...
Real-Time Artifacts Reduction during TMS-EEG Co-Registration: A Comprehensive Review on Technologies and Procedures
Article
Full-text available
  • Jan 2021
  • SENSORS-BASEL
Transcranial magnetic stimulation (TMS) excites neurons in the cortex, and neural activity can be simultaneously recorded using electroencephalography (EEG). However, TMS-evoked EEG potentials (TEPs) do not only reflect transcranial neural stimulation as they can be contaminated by artifacts. Over the last two decades, significant developments in EEG amplifiers, TMS-compatible technology, customized hardware and open source software have enabled researchers to develop approaches which can substantially reduce TMS-induced artifacts. In TMS-EEG experiments, various physiological and external occurrences have been identified and attempts have been made to minimize or remove them using online techniques. Despite these advances, technological issues and methodological constraints prevent straightforward recordings of early TEPs components. To the best of our knowledge, there is no review on both TMS-EEG artifacts and EEG technologies in the literature to-date. Our survey aims to provide an overview of research studies in this field over the last 40 years. We review TMS-EEG artifacts, their sources and their waveforms and present the state-of-the-art in EEG technologies and front-end characteristics. We also propose a synchronization toolbox for TMS-EEG laboratories. We then review subject preparation frameworks and online artifacts reduction maneuvers for improving data acquisition and conclude by outlining open challenges and future research directions in the field.
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Methodological choices matter: A systematic comparison of TMS-EEG studies targeting the primary motor cortex
Preprint
Full-text available
  • Mar 2024
Background Transcranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Methods Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared total cortical activation and specific TEP peaks and components. Results Reporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and pre-processing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the ’prototypical’ TEP waveform of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude and latencies were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long-latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP amplitudes. Conclusion Some aspects of reporting practices could be improved in TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted.
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NIBS as a Research Tool in Clinical and Translational Neuroscience
Chapter
  • Aug 2020
Since the introduction of noninvasive transcranial brain stimulation techniques decades ago, these tools have been applied in both basic and clinical research, with the aims to enhance knowledge about the pathophysiology as well as to develop new treatment options for neurological and psychiatric diseases. In this chapter, we describe the implementation of these techniques to monitor and modulate neurophysiological processes in the human brain, which enables a better understanding of disease-related pathophysiology, and the development of therapeutic interventions.
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Suppression of -Oscillations in the Dorsolateral Prefrontal Cortex following Long Interval Cortical Inhibition: A TMS–EEG Study
Article
Full-text available
  • Dec 2008
  • NEUROPSYCHOPHARMACOL
Gamma (gamma)-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 gamma-oscillations have been associated with various neuropsychiatric disorders including schizophrenia. Animal research suggests that suppression of gamma-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 gamma-oscillations by combining TMS with EEG. Long interval cortical inhibition (LICI), a paired TMS paradigm, was used to index GABA(B) receptor mediated inhibitory neurotransmission in the motor cortex and DLPFC of healthy individuals. Gamma-oscillations were significantly inhibited by LICI (38.1+/-26.5%; p< or =0.013) in the DLPFC but not in the motor cortex. These results provide neurophysiological evidence to demonstrate gamma-oscillations are inhibited by LICI in the DLPFC but not in the motor cortex. Such specificity suggests that the modulation of gamma-oscillations may represent an important neurophysiological process that may, in part, be responsible for optimal DLPFC functioning in healthy human subjects.
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Ziemann U, L??nnecker S, Steinhoff BJ, Paulus W. The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109: 127-135
Article
  • Apr 1996
The effect of the short-acting benzodiazepine lorazepam on motor cortex excitability was investigated in 11 healthy volunteers using the technique of focal transcranial magnetic stimulation. The threshold intensity for evoking an electromyographic response in the resting and active abductor digiti minimi muscle, the size of the motor evoked potential, the duration of the cortical and peripheral silent periods, the corticocortical inhibition and facilitation after paired magnetic stimuli, and the transcallosal inhibition were used as parameters to assess various aspects of motor system excitability. Baseline values were compared with data obtained 2, 5 and 24 h after a single oral dose of 2.5 mg lorazepam. Resting and active motor thresholds and the size of the motor evoked potential remained unchanged. The duration of the cortical silent period was prolonged with a maximum effect 5 h after drug intake, while the peripheral silent period did not show any lengthening at that time. The corticocortical inhibition showed a tendency toward more inhibition, while the corticocortical facilitation was almost completely suppressed. The transcallosal inhibition showed an inconsistent trend to less inhibition. In parallel to the pharmacokinetics of lorazepam, all effects peaked at 2 h and 5 h, and were (partially) reversible after 24 h. It is hypothesized that most of these findings are due to the reinforcement of GABA action by lorazepam at the level of the motor cortex. The lack of effect on motor threshold and on the size of the motor evoked potential may indicate that these parameters are physiologically distinct from corticocortical excitability and the cortical silent period. The relevance of the present data in clinical epileptology is discussed.
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Valls-Sole J, Pascual-Leone A, Wassermann EM, Hallett M. Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85: 355-364
Article
  • Jan 1993
  • Electroencephalogr Clin Neurophysiol
We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5–40 msec, followed by facilitation at ISIs of 50–90 msec. At a high intensity, there was facilitation at ISIs of 25–50 msec, followed by inhibition at ISIs of 60–150 msec and, occassionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms.
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Off-line removal of TMS-induced artifacts on human electroencephalography by Kalman filter
Article
  • May 2007
  • J NEUROSCI METH
In this paper we present an off-line Kalman filter approach to remove transcranial magnetic stimulation (TMS)-induced artifacts from electroencephalographic (EEG) recordings. Two dynamic models describing EEG and TMS signals generation are identified from data and the Kalman filter is applied to the linear system arising from their combination. The keystone of the approach is the use of time-varying covariance matrices suitably tuned on the physical parameters of the problem that allow to model the nonstationary components of the EEG-TMS signal. This guarantees an efficient deletion of TMS-induced artifacts while preserving the integrity of EEG signals around TMS impulses. Experimental results show that the Kalman filter is more effective than stationary filters (Wiener filter) for the problem under investigation.
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Evaluating the Relationship between Long Interval Cortical Inhibition, Working Memory and Gamma Band Activity in the Dorsolateral Prefrontal Cortex
Article
  • Aug 2008
Recent reports have demonstrated that long interval cortical inhibition (LICI) can be indexed in the dorsolateral prefrontal cortex (DLPFC) in healthy controls. LICI is a neurophysiology process indexed using transcranial magnetic stimulation and is closely associated with cortical GABA B receptor mediated inhibitory neurotransmission. Several previous studies have also reported that gamma band activity represents a neurophysiological process that is mediated, in part, through GABAergic inhibitory neurotransmission and may subserve several cognitive operations including working memory (WM) in the DLPFC. The intension of the current study, therefore, was to directly evaluate the relationship between these neurophysiological processes in healthy subjects. Eleven right-handed healthy subjects participated in this experiment in which gamma band activity was measured through simultaneous recording of electroencephalography (EEG) during the N-back task, a cognitive task designed to index WM. LICI was recorded through EEG from the left DLFPC, left motor cortex and through EMG of peripheral hand muscles in a separate session according to previously published methods. There was no evidence for a relationship in the DLPFC between LICI and gamma band activity elicited during the N-back task, though there was a significant relationship between LICI and performance on the 3-back condition, the N-back condition of greatest difficulty. In conclusion these data provide evidence to suggest that in the DLPFC, there is no direct relationship between GABA B receptor mediated inhibitory neurotransmission and gamma band activity. However, our data does suggest that LICI was related to 3-back performance providing evidence implicating DLPFC GABAergic inhibitory neurotransmission in WM performance.
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Spinal motor neuron excitability during silent period after cortical stimulation
Article
  • Sep 1991
  • Electroencephalogr Clin Neurophysiol
During tonic voluntary muscle contraction, a period of electromyographic silence follows the motor evoked potential produced by transcranial stimulation of the contralateral motor cortex. We studied the silent period in the wrist flexors of 3 normal volunteers and a deafferented patient during 20% of maximal contraction. To test the excitability of the spinal motor neuron pool during the period of silence, the H-reflex was evoked in the normal subjects at different intervals after cortical stimulation. The amplitude of the H-reflex in the silent period was expressed as a percentage of the amplitude during complete muscle relaxation. The H-reflex was profoundly depressed at the beginning of the silent period (13.5-27% of the control measurement), but showed a clear tendency to recover toward the end of the silent period despite continued absence of muscle activation (71-84% of the control). Moreover, the silent period in the deafferented patient was of longer duration than can be accounted for by segmental mechanisms. These findings imply, at least in the late part of the silent period, that a reduction in the excitability of the spinal motor neuron pool plays only a minor role in determining the phenomenon and that it is probably caused by lack of cortical drive.
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GABA as an Inhibitory Neurotransmitter in Human Cerebral Cortex
Article
  • Dec 1989
1. The possible role of gamma-aminobutyric acid (GABA) as an inhibitory neurotransmitter in the human cerebral cortex was investigated with the use of intracellular recordings from neocortical slices maintained in vitro. 2. Electrical stimulation of afferents to presumed pyramidal cells resulted in an initial excitatory postsynaptic potential (EPSP) followed by fast and slow inhibitory postsynaptic potentials (IPSPs). The early IPSP had an average reversal potential of -68 mV, was associated with a mean 67-nS increase in membrane conductance, was reduced by the GABAA antagonist bicuculline, was sensitive to the intracellular injection of Cl-, and was mimicked by the GABAA agonist muscimol. 3. The late IPSP, in contrast, had an average reversal potential of -95 mV, was associated with a mean 12-nS increase in membrane conductance, was reduced by the GABAB antagonist phaclofen, and was mimicked by the GABAB agonist baclofen. 4. Block of the early IPSP by bicuculline or picrotoxin led to the generation of paroxysmal epileptiform activity, which could be further enhanced by reduction of the late IPSP. 5. These data strongly support the hypothesis that GABA is a major inhibitory neurotransmitter in the human cerebral cortex and that GABAergic IPSPs play an important role in controlling the excitability and responsiveness of cortical neurons.
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