TMS Intensity Research Articles

Modulation of motor cortex inhibition during manual dexterity tasks: an adaptive threshold hunting study.

Background: The ability to perform intricate movements is crucial for human motor function. The neural mechanisms underlying precision and power grips are incompletely understood. Corticospinal output from M1 is thought to be modulated by GABAA-ergic intracortical networks within M1. Objectives: To investigate the contribution of M1 intracortical inhibition to fine motor control using adaptive threshold hunting with paired-pulse TMS during pinching and grasping tasks. We hypothesised that SICI could be assessed during voluntary activation, and that corticomotor excitability and SICI modulation would be greater during pinch than grasp reflecting corticospinal control. Methods: Seventeen healthy participants performed gradual pinch and grasp tasks. Using an adaptive threshold-hunting method, paired-pulse TMS was applied in the anterior-posterior current direction to assess cortical excitability and SICI in the dominant FDI muscle. SICI and corticomotor excitability were analysed using an LMM. MEP latencies were obtained in LM, PA and AP current directions and compared using paired t-tests. Results: MEP latencies were prolonged with PA and AP coil orientations compared to LM, with AP showing the largest latency. During single-pulse TMS, there was no difference in the TMS intensity required to reach the MEP target during pinching and grasping. Greater inhibition was found during pinching compared to grasping. Conclusion: ATH with paired-pulse TMS permits investigation of intracortical inhibitory networks and their modulation during the performance of dexterous motor tasks revealing a greater modulation of GABAA-ergic inhibition contributing to SICI during pinching compared to grasping.

Meta-analysis of experimental factors influencing single-pulse TMS effects on the early visual cortex.

Single-pulse transcranial magnetic stimulation (spTMS) applied to the Early Visual Cortex (EVC) has demonstrated the ability to suppress the perception on visual targets, akin to the effect of visual masking. However, the reported spTMS suppression effects across various studies have displayed inconsistency. We aim to test if the heterogeneity of the spTMS effects can be attributable to variations in experimental factors. We conducted a meta-analysis using data collected from the PubMed and Web of Science databases spanning from 1995 to March 2024. The meta-analysis encompassed a total of 40 independent experiments drawn from 33 original articles. The findings unveiled an overall significant spTMS suppression effect on visual perception. Nevertheless, there existed substantial heterogeneity among the experiments. Univariate analysis elucidated that the spTMS effects could be significantly influenced by TMS intensity, visual angle of the stimulus, coil type, and TMS stimulators from different manufacturers. Reliable spTMS suppression effects were observed within the time windows of -80 to 0 ms and 50 to 150 ms. Multivariate linear regression analyses, which included SOA, TMS intensity, visual angle of the stimulus, and coil type, identified SOA as the key factor influencing the spTMS effects. Within the 50 to 150 ms time window, optimal SOAs were identified as 112 ms and 98 ms for objective and subjective performance, respectively. Collectively, multiple experimental factors accounted for 22.9% (r = 0.3353) and 39.9% (r = 0.3724) of the variance in objective and subjective performance, respectively. Comparing univariate and multivariate analyses, it was evident that experimental factors had different impacts on objective performance and subjective performance. The present study provided quantitative recommendations for future experiments involving the spTMS effects on visual targets, offering guidance on how to configure experimental factors to achieve the optimal masking effect.

Real-time optimization to enhance noninvasive cortical excitability assessment in the human dorsolateral prefrontal cortex.

We currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability. This closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP). In 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach. Real-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP. Enhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response.

Associative Visuomotor Learning Using Transcranial Magnetic Stimulation Induces Stimulus-Response Interference.

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by associative learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using TMS would result in stimulus-response associations that can impact future behavior. During a learning phase, we repeatedly paired the presentation of a specific color (but not other colors) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced-choice task where they had to categorize simple shapes and we studied whether the shapes' task-irrelevant color (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation. Although we were inspired by the Hebbian learning literature, future studies should investigate whether Hebbian or other learning processes were also what brought about this effect.

Auditory Fine-Tuned Suppressor of TMS-Clicks (TMS-Click AFTS): A Novel, Perceptually Driven/Tuned Approach for the Reduction in AEP Artifacts in TMS-EEG Studies

TMS contaminates concurrent EEG recordings with Auditory Evoked Potentials (AEPs), which are caused by the perceived impulsive acoustic noise of the TMS coils. We hereby introduce a novel and perceptually motivated/tuned method for the suppression of auditory evoked EEG artifacts of rTMS under the name of “Auditory Fine-Tuned Suppressor of TMS-Clicks” (TMS-click AFTS). The proposed method is based on the deployment of a psychophysically-matched wide-band noise (WBN) masking stimulus, whose parametric synthesis and presentation are based upon adaptive psychophysical optimization. The masking stimulus is constructed individually for each patient/subject, thus facilitating aspects of precision medicine. A specially designed automation software is used for the realization of an adaptive procedure for optimal parameterization of masking noise level, optimizing both the subject’s comfort and the degree of AEP reduction. The proposed adaptive procedure also takes into account the combined effect of TMS intensity level and can as well account for any possibly available subject’s hearing acuity data. To assess the efficacy of the proposed method in reducing the acoustic effects of TMS, we performed TMS-EEG recordings with a 60 channel TMS-compatible EEG system in a cohort of healthy subjects (n = 10) and patients with epilepsy (n = 10) under four conditions (i.e., resting EEG with and without acoustic mask and sham TMS-EEG with and without acoustic mask at various stimulus intensity levels). The proposed approach shows promising results in terms of efficiency of AEP suppression and subject’s comfort and warrants further investigation in research and clinical settings.

Effect of head positioning on TMS intensity: E-field modeling with BEM-FMM and modeling validation

Effect of head positioning on TMS intensity: E-field modeling with BEM-FMM and modeling validation

Short latency afferent inhibition: comparison between threshold-tracking and conventional amplitude recording methods.

Short-latency afferent inhibition (SAI), which is conventionally measured as a reduction in motor evoked potential amplitude (A-SAI), is of clinical interest as a potential biomarker for cognitive impairment. Since threshold-tracking has some advantages for clinical studies of short-interval cortical inhibition, we have compared A-SAI with a threshold-tracking alternative method (T-SAI). In the T-SAI method, inhibition was calculated by tracking the required TMS intensity for the targeted MEP amplitude (200 uV) both for the test (TMS only) and paired (TMS and peripheral stimulation) stimuli. A-SAI and T-SAI were recorded from 31 healthy subjects using ten stimuli at each of 12 inter-stimulus intervals, once in the morning and again in the afternoon. There were no differences between morning and afternoon recordings. When A-SAI was normalized by log conversion it was closely related to T-SAI. Between subjects, variability was similar for the two techniques, but within-subject variability was significantly smaller for normalized A-SAI. Conventional amplitude measurements appear more sensitive for detecting changes within-subjects, such as in interventional studies, but threshold-tracking may be as sensitive as detecting abnormal SAI in a patient.

Using diffusion tensor imaging to effectively target TMS to deep brain structures

TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

BackgroundPrefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia. Objective/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity. MethodsWe enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition. ResultsOf the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004). ConclusionsSubjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

Сomparative efficiency of rTMS in combined treatment of pharmaco-resistant depression

Objective The aim of the study was comparative assessment of efficiency of combined TMS included treatment of pharmaco-resistant depression upon reduction of clinical symptoms and neurocognitive deficits. Methods 50 female patients aged 18 to 56 years (mean age 36.3 ± 13.1) with pharmaco-resistant depression (F31.3, F33.0, F33.1 by ICD-10) were enrolled in the study. 23 patients (control group) were treated with SSRI antidepressants, while 27 patients (TMS group) received the same pharmacotherapy together with the course of TMS. Both groups did not differ statistically in demographics parameters and depression severity (mean HDRS-17 scores were 21.0 and 23.2, respectively). High frequency rTMS (25 Hz, intensity of 60–80% of motor threshold, 40 series by 2 s with 14 s intervals–that may be called “beta-bursts” mode, total 1600 pulses, 15 daily sessions) was applied to the projection of the left dorsolateral prefrontal cortex. Relatively low TMS intensity was chosen to prevent facial muscles jerks and to make the procedure more comfortable for patients. Results After 3 weeks of treatment both previously resistant groups demonstrated highly significant (P Conclusions Even low intensity high frequency rTMS of the left dorsolateral prefrontal cortex appeared to be useful method for overcoming the pharmaco-resistance and for improvement of decision-making functions in depressive patients.

The effect of shoulder position on motor evoked and maximal muscle compound action potentials of the biceps brachii.

The purpose of the study was to assess the effect of shoulder position, 0° versus 90° shoulder flexion, on stimulation intensity and maximal muscle compound action potentials (Mmax) and motor evoked potentials (MEP) of the biceps brachii during both rest and 10% maximum voluntary contraction (MVC). Nine participants completed two experimental sessions with four conditions. During each condition, transcranial magnetic (TMS) and Erb's point stimulation were used to elicit MEPs and Mmax, respectively. During rest, the TMS intensity to elicit a MEP response (p<0.001), was significantly lower by 28.6±6.8%, in the 90° compared to the 0° position, but the stimulation intensity to elicit a Mmax was not different. MEP (p<0.001) and Mmax (p<0.001) amplitudes were significantly higher by 212.4±43.3% and 86.5±38.0%, respectively in the 90° compared to the 0° position. During 10% MVC the Mmax stimulation intensity (p=0.022), but not TMS intensity, was significantly lower by 7.4±3.8% in the 90° compared to the 0° position. Mmax (p<0.001) amplitudes were significantly higher by 92.2±20.2% in the 90° compared to the 0° position whereas MEP (p<0.001) amplitudes were significantly lower by 24.5±6.0% in the 90° compared to the 0° position. In conclusion, TMS intensity and Mmax intensity were both shoulder-position and state-dependent, whereas MEP and Mmax amplitudes were only shoulder position-dependent.

The effect of TMS intensity on contrast sensitivity

The effect of TMS intensity on contrast sensitivity

P156 Ongoing EEG oscillations modulate MEP amplitudes: A possible mechanism of MEP variability

Objective Although the resting motor threshold (RMT) is relatively stable, the variability of MEPs produced by TMS over the primary motor cortex (M1) is well known, and its precise mechanism is still unclear. We hypothesized that EEG oscillations just before TMS could modulate the MEP amplitudes that underlie the MEP variability. Thus, we evaluated the relationship between EEG oscillations and MEP amplitudes. Methods Two experiments were conducted in this study. EEGs were obtained at 19 locations (international 10–20 system) and MEPs were recorded from right FDI in Exp. 1 (n = 12). Left M1 hotspot was stimulated by TMS with the intensity to obtain about 1 mV MEP amplitudes (S-1 mV). MEPs and EEGs were recorded for 200 times in total for each subject under the eyes-open (EO) and eyes-close (EC) conditions. EEGs were segmented between −500 and 0 ms of the TMS onset, and the power values (8–30 Hz) were calculated by wavelet analysis. EEG powers were compared between the epochs of higher and lower amplitude MEPs. In Exp. 2 (n = 9), the effect of low TMS intensity was evaluated under the EO condition. EEG oscillations were compared between the high (S-1 mV) and low intensity (RMT) TMS conditions. Results EEG powers of α and β range were significantly increased (synchronization) at C3 when MEP amplitudes were larger in both EO and EC conditions. When the EEG power difference of higher/lower MEPs was compared between the EO and EC conditions, these differences under EO were more pronounced than that of EC at frontal and parietal leads. In contrast, EEG powers were reduced (desynchronization) at C3 when MEP amplitudes were larger in the low TMS condition (Exp. 2). Discussion We found that EEG synchronization of α / β bands prior to TMS was a determinant factor for the MEP amplitudes at S-1 mV (Exp. 1). Distributed networks over the frontal areas may modulate MEPs differently under EO and EC conditions. However, desynchronization of α / β bands produced MEPs at RMT (Exp. 2). From this complex interaction between EEG synchronization/desynchronization and TMS intensity, we assume that ongoing EEG oscillations of α / β bands performs the dual functions of gateway and gatekeeper. Like a push–pull system, that depends on the ongoing EEG state and TMS intensity, the dual system may allow the TMS impulses to M1 by which the MEP variability occurs.

P154 Probing the sensitivity of a novel MR head coil array for TMS/fMRI studies of the motor cortex

Question The typical setup used in online TMS/fMRI experiments presents some limitations, most importantly the poor sensitivity of the MR coil (Fig. 1a) Download : Download high-res image (262KB) Download : Download full-size image . In addition, new imaging techniques like parallel imaging and multiband excitation are not available. To get over these limitations, a dedicated MR coil array (Fig. 1b) for combining TMS with fMRI was developed (Navarro de et al., 2015) . We present results of an online TMS/fMRI experiment over the motor cortex to show the advantages of the new setup. Methods The experiment was performed at 3T (Siemens, Germany). The TMS system included a MagProX100 stimulator and an MRi-B91 MR-compatible TMS coil (MagVenture, Denmark). Six healthy subjects participated in the study. Functional images were acquired using a multiband EPI sequence (TR/TE = 1000/33 ms), 14 slices, 1.5 × 1.5 × 3 mm3. Slices were aligned parallel to the TMS coil and covered primary motor cortex. The stimulation protocol comprised 20 stimulation blocks, with five blocks of each of the following stimulation intensities: 80, 90, 100 and 110% of the individual’s motor threshold distributed randomly over the experiment. A finger tapping task was also conducted. Data analysis was performed using SPM12. The design matrix comprised four task regressors representing the 4 stimulation amplitudes. For each subject, two regions were defined based on fMRI activation maps: (i) the global maximum, and (ii) the maximum within M1. Results Fig. 2a,b Download : Download high-res image (632KB) Download : Download full-size image shows group results as the mean of the BOLD signal intensity change in percent for the two voxels defined above with indicator of statistical significance. In addition, averaged time courses were calculated for global maximum (2c) and the M1 maximum (2d). Conclusions In both regions, a monotonic ascending relationship of signal change amplitude with TMS intensity was observed. While activations at the global maxima were statistically significant for all intensities, results on the M1 maximum are only significant for the 100% and 110% intensities. These results on M1 are consistent with results obtained before (Bestmann et al., 2004) . Contrary to the standard setup, the new one didn’t suffer of any artefacts under the TMS coil, where the global maximal activation was always found. The obtained time courses demonstrated the efficiency of the new setup to acquire the signal with high accuracy.

P161 Robot-guided approach to the correlation of TMS intensity and focality in man

Introduction Strength and extension of the TMS-induced electromagnetic field increase with stimulation intensity at the expense of spatial accuracy.The concept of focality has not been investigated systematically in vivo yet. Objective To determine the focality of a given TMS coil we developed a linear mapping approach that assesses the correlation of intensity and spatial accuracy. Methods A line of 21 targets was placed in anterior–posterior direction through the center of gravity (COG) of the FDI hotspot with 2 mm spacing (N = 8, Magstim 2002, 70 mm figure-8 coil).Recruitment curves were measured at each target with 15 pulses per intensity (threshold intensity + 1, 2 and 3% of maximum stimulator output (MSO)) with a randomized order over all targets and intensities.The probability was calculated as the ratio of pulses resulting in an MEP ⩾ 50 μV to the total number of pulses for each stimulation point and intensity.The intensities were categorized by the lowest intensity with a probability of 1 (P1) and lower (P1-1%, P1-2% and P1-3%).The bilateral data was centered on the COG, a logistic function (P = A/(1+(x/x0)p) was fitted to the unilateral data to describe the relation of coil position, stimulation intensity and probability (MEP ⩾ 50 μV). The extent of FDI representation in relation to intensity was determined as two times the difference between the COG and the minimum of the 2nd derivative.Additionally, we calculated the slope width between the minimum and maximum of the 2nd derivative to determine the range at which the effective electric field leaves the hotspot, resulting in the highest decrease of probability.The extent of FDI and the slope width were plotted against the intensities to describe their correlation. Results A sigmoid relation between response rate and stimulation intensity was observed for all intensities.The plateau width (FDI extent) increased linear by 6.4 ± 1.3 mm/%MSO. In contrast, the slope width was 6.1 ± 0.2 mm across all intensities. Conclusion The results prove a linear relation of near threshold TMS intensities and focality with a decrease of spatial accuracy by 6.5 mm/%MSO when using a standard figure-8 coil.By calculating the slope widths of the intensity curves (6.1 mm) we propose a novel approach to determine the extent of a motor cortical representation that is not influenced by intensity. Download : Download high-res image (211KB) Download : Download full-size image Download : Download high-res image (274KB) Download : Download full-size image

P236 The effect of intermittent theta burst stimulation over the prefrontal cortex on resting-state fronto-striatal connectivity

Fronto-striatal loops play a role in various cognitive and emotional processes. Intermittent theta burst stimulation (iTBS) has been shown to increase regional excitability and functional connectivity of connected areas ( Huang et al., 2005 ). The choice of an optimal TMS intensity, which is interlinked with ethical and practical issues such as pain and muscle twitches, has not been explored in detail. Also, the role of white matter tracts in functional connectivity has often not been taken into account. We therefore applied iTBS with different intensities and methods of determining the exact stimulation sites to systematically test optimal parameters combining strong fronto-striatal activity with minimal adverse effects. Healthy subjects underwent excitatory iTBS at different intensities (90% and 120% of individual resting motor threshold). The protocol consisted of 600 pulses (3.33 min) and was applied over the left prefrontal cortex (lPFC). Directly before and 7 min after stimulation a task-free resting state functional MRI scan was conducted. The stimulation site was determined anatomically, taking into account white matter tracts. This was done by finding individual tracts connecting the left caudate with the lPFC using DSI studio ( Yeh et al., 2013 ). Resting state data was denoised using FSL’s MELODIC ( Jenkinson et al., 2012 ) and analysed using DPABI ( Chao-Gan, 2014 ); with the caudate and the stimulation sites as seed regions. Our findings suggest that a sub-threshold stimulation intensity of 90% is sufficient to induce changes in functional connectivity of the fronto-striatal network, when stimulation is applied over the lPFC. Furthermore, stimulation effects might be increased by determining an individual stimulation site based on DTI-tracts, rather than using only macro-anatomical landmarks. By using sub-threshold intensities adverse effects such as pain and head movements due to muscle twitches can be reduced or avoided.

P006 Effects of Zonisamide on human motor cortical plasticity: A TMS study

Introduction Zonisamide (ZNS) was reported to be effective for patients with Parkinson’s disease (PD). However, anti-Parkinsonian mechanisms of ZNS remain unclear. Some reports suggest that abnormal cortical plasticity is related to pathophysiology of PD. Previous study revealed that Levodopa, which is a crucial drug for PD treatment, enhances plasticity-like effects induced by rTMS in normal subjects, or restores LTP-like effects in PD patients. Objectives We studied the influence of ZNS on the motor cortical LTP-like effect induced by Quadripulse Transcranial Magnetic Stimulation (QPS) in normal subjects. Materials and methods 24 healthy volunteers (12 men and 12 women; 65.8 ± 2.4 years old) participated in this study. The study design was a double-blinded, complete crossover and placebo-controlled form. The subject took either ZNS (25 mg) or a placebo in each session. Two hours after a capsule intake, QPS was given over the left M1 after measuring the motor thresholds (RMT/AMT) and the baseline MEP size. QPS consists of bursts of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms, which is the best interval for LTP induction, and was repeated every 5 s for 30 min. We measured the MEP amplitude at 0, 5, 10, 15, 20, and 25 min after the end of the QPS. We divided the subjects into “responders” and “non-responders” according to a previously reported definition and compared the time courses between the experimental conditions in each group of subjects separately. Results 14 participants were defined as a responder, and the other 10 were as a non-responder. There were no significant differences in the RMT, AMT, baseline MEP, or the single pulse TMS intensity that was used between responders and non-responders. ZNS significantly enhanced the LTP in non-responders ( p = 0.008), but not in responders ( p = 0.48). Conclusion ZNS significantly enhanced LTP in non-responders, but had no influence in responders. The mild LTP enhancement by ZNS shown here may partly explain its anti-Parkinsonian mechanisms.

Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex.

Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep–wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans.

EP 71. The effect of intermittent theta burst stimulation over the dorsolateral prefrontal cortex on cortico-striatal connectivity

Aim Fronto-striatal loops play an important role in various cognitive and emotional processes. Intermittent theta burst transcranial magnetic stimulation has been shown to increase regional excitability as well as functional connectivity of connected areas ( Huang et al., 2005 ). The issue of choosing an optimal TMS intensity, which is interlinked with ethical and practical issues such as pain and muscle twitches, has not been explored in detail yet. Furthermore, the role of purely anatomical white matter tracts on functional connectivity has often not been taken into account when studying TMS effects. We therefore applied intermittent theta burst stimulation (iTBS) with different intensities and methods of determining the exact stimulation sites to systematically test optimal parameters combining strong fronto-striatal activity with minimal adverse effects. Methods Healthy subjects underwent iTBS at different intensities (90% and 120% of individual resting motor threshold). The excitatory iTBS protocol consisted of 600 pulses (2 s trains and 8 s pauses for 3.33 min) and was applied over the left dorsolateral prefrontal cortex (lDLPFC). Directly before and 7 min after stimulation a task-free resting state functional magnetic resonance imaging scan was conducted. The exact stimulation site was either determined using a lDLPFC standard coordinate or by extracting an individual lDLPFC coordinate from diffusion tensor imaging (DTI) data. The latter was done by analysing DTI data with FSL ( Smith et al., 2004 ) and finding individual tracts connecting the left caudate with the lDLPFC. Resting state data was analysed using the Data Processing Assistant for Resting-State fMRI (DPARSF; Chao-Gan, 2012 ) SPM toolbox, with the caudate and the stimulation sites as seed regions. Results and conclusion Our preliminary findings suggest that a sub-threshold stimulation intensity of 90% is sufficient to induce changes in functional connectivity of the fronto-striatal network when stimulation is applied over the lDLPFC. Furthermore, stimulation effects might be increased by determining an individual stimulation site based on DTI tracts, rather than using a standardised mean coordinate for all participants. By using sub-threshold intensities adverse effects such as pain and head movements due to muscle twitches can be reduced or avoided.

Gamma-band connectivity is reduced in schizophrenia following prefrontal TMS and during working memory

s / Brain Stimulation 8 (2015) 360e377 365 NIBS is large interand intra-subject variability in NIBS-induced neuroplastic responses. We investigated (1) the reproducibility of neuroplastic responses induced by continuous theta-burst stimulation (cTBS) and (2) factors that can influence an individual’s neuroplasticity response to cTBS. In 18 subjects, motor evoked potential (MEP) input-output (I/O) curves were obtained before and after cTBS (3 stimuli at 50 Hz every 200 msec for 40 sec) and measures of physical activity levels, stress levels, and sleep patterns were obtained in three separate experimental sessions. MEP suppression was observed following cTBS at the upper end of the IO curve (150 e 180% RMT). Significant linear relationships were evident between (1) cTBS-induced MEP suppression (probed at 150% RMT) and perceived stress and (2) cTBS-induced MEP suppression (probed at the stimulus intensity that evoked a MEPw50% of the maximal MEP; SI50) and the interval between experimental sessions (in days). The current data suggest (1) the most reliable TMS intensity to probe cTBS-induced neuroplastic responses is 150% RMT; (2) the perceived stress scale is sufficiently sensitive to show the positive relationship between stress and long-term depression-like plasticity; (3) short intervals between experimental sessions administering NIBS protocols is associated with increased NIBS-induced plasticity responses.