Concurrent TMS-fMRI Research Articles

Subgenual cingulate connectivity as a treatment predictor during low-frequency right dorsolateral prefrontal rTMS: A concurrent TMS-fMRI study

IntroductionRepetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) is effective in alleviating treatment-resistant depression (TRD). It has been proposed that regions within the left DLPFC that are anti-correlated with the right subgenual anterior cingulate cortex (sgACC) may represent optimal individualized target sites for high-frequency left rTMS (HFL). Objective/hypothesisThis study aimed to explore the effects of low-frequency right rTMS (LFR) on left sgACC connectivity during concurrent TMS-fMRI. Methods34 TRD patients underwent an imaging session that included both a resting-state fMRI run (rs-fMRI0) and a run during which LFR was applied to the right DLPFC (TMS-fMRI). Participants subsequently completed four weeks of LFR treatment. The left sgACC functional connectivity was compared between the rs-fMRI0 run and TMS-fMRI run. Personalized e-fields and a region-of-interest approach were used to calculate overlap of left sgACC functional connectivity at the TMS target and to assess for a relationship with treatment effects. ResultsTMS-fMRI increased left sgACC functional connectivity to parietal regions within the ventral attention network; differences were not significantly associated with clinical improvements. Personalized e-fields were not significant in predicting treatment outcomes (p = 0.18). ConclusionThis was the first study to examine left sgACC anti-correlation with the right DLPFC during an LFR rTMS protocol. In contrast to studies that targeted the left DLPFC, we did not find that higher anti-correlation was associated with clinical outcomes. Our results suggest that the antidepressant mechanism of action of LFR to the right DLPFC may be different than for HFL.

Within-subject reliability of concurrent TMS-fMRI during a single session.

Concurrent transcranial magnetic stimulation with functional MRI (concurrent TMS-fMRI) allows real-time causative probing of brain connectivity. However, technical challenges, safety, and tolerability may limit the number of trials employed during a concurrent TMS-fMRI experiment. We leveraged an existing data set with 100 trials of active TMS compared to a sub-threshold control condition to assess the reliability of the evoked BOLD response during concurrent TMS-fMRI. This data will permit an analysis of the minimum number of trials that should be employed in a concurrent TMS-fMRI protocol in order to achieve reliable spatial changes in activity. Single-subject maps of brain activity were created by splitting the trials within the same experimental session into groups of 50, 40, 30, 25, 20, 15, or 10 trials, correlations (R) between t-maps derived from paired subsets of trials within the same individual were calculated as reliability. R was moderate-high for 50 trials (mean R=.695) and decreased as the number of trials decreased. Consistent with previous findings of high individual variability in the spatial patterns of evoked neuronal changes following a TMS pulse, the spatial pattern of Rs differed across participants, but regional R was correlated with the magnitude of TMS-evoked activity. These results demonstrate concurrent TMS-fMRI produces a reliable pattern of activity at the individual level at higher trial numbers, particularly within localized regions. The spatial pattern of reliability is individually idiosyncratic and related to the individual pattern of evoked changes.

Downstream hippocampal memory response during concurrent theta-burst TMS-fMRI

Downstream hippocampal memory response during concurrent theta-burst TMS-fMRI

Optimal transducer for concurrent TMS-fMRI

Optimal transducer for concurrent TMS-fMRI

Functional connectivity- and E-field-optimized TMS targeting: method development and concurrent TMS-fMRI validation

Functional connectivity- and E-field-optimized TMS targeting: method development and concurrent TMS-fMRI validation

A guide for concurrent TMS-fMRI to investigate functional brain networks.

Transcranial Magnetic Stimulation (TMS) allows for the direct activation of neurons in the human neocortex and has proven to be fundamental for causal hypothesis testing in cognitive neuroscience. By administering TMS concurrently with functional Magnetic Resonance Imaging (fMRI), the effect of cortical TMS on activity in distant cortical and subcortical structures can be quantified by varying the levels of TMS output intensity. However, TMS generates significant fluctuations in the fMRI time series, and their complex interaction warrants caution before interpreting findings. We present the methodological challenges of concurrent TMS-fMRI and a guide to minimize induced artifacts in experimental design and post-processing. Our study targeted two frontal-striatal circuits: primary motor cortex (M1) projections to the putamen and lateral prefrontal cortex (PFC) projections to the caudate in healthy human participants. We found that TMS parametrically increased the BOLD signal in the targeted region and subcortical projections as a function of stimulation intensity. Together, this work provides practical steps to overcome common challenges with concurrent TMS-fMRI and demonstrates how TMS-fMRI can be used to investigate functional brain networks.

Developments in Transcranial Magnetic Stimulation to Study Human Cognition.

Developments in Transcranial Magnetic Stimulation to Study Human Cognition.

TU-122. Adaptive brain changes to TMS Over V1 and V5 determined by concurrent TMS-fMRI

TU-122. Adaptive brain changes to TMS Over V1 and V5 determined by concurrent TMS-fMRI

TU-121. Disentangling the transcranially evoked BOLD response from re-afferent feedback during concurrent TMS-fMRI of the motor cortex using ischemic nerve blockade

TU-121. Disentangling the transcranially evoked BOLD response from re-afferent feedback during concurrent TMS-fMRI of the motor cortex using ischemic nerve blockade

TMS Does Not Increase BOLD Activity at the Site of Stimulation: A Review of All Concurrent TMS-fMRI Studies.

Transcranial magnetic stimulation (TMS) is widely used for understanding brain function in neurologically intact subjects and for the treatment of various disorders. However, the precise neurophysiological effects of TMS at the site of stimulation remain poorly understood. The local effects of TMS can be studied using concurrent TMS-functional magnetic resonance imaging (fMRI), a technique where TMS is delivered during fMRI scanning. However, although concurrent TMS-fMRI was developed over 20 years ago and dozens of studies have used this technique, there is still no consensus on whether TMS increases blood oxygen level-dependent (BOLD) activity at the site of stimulation. To address this question, here we review all previous concurrent TMS-fMRI studies that reported analyses of BOLD activity at the target location. We find evidence that TMS increases local BOLD activity when stimulating the primary motor (M1) and visual (V1) cortices but that these effects are likely driven by the downstream consequences of TMS (finger twitches and phosphenes). However, TMS does not appear to increase BOLD activity at the site of stimulation for areas outside of the M1 and V1 when conducted at rest. We examine the possible reasons for such lack of BOLD signal increase based on recent work in nonhuman animals. We argue that the current evidence points to TMS inducing periods of increased and decreased neuronal firing that mostly cancel each other out and therefore lead to no change in the overall BOLD signal.

Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies.

Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base.

A guide for concurrent TMS-fMRI to investigate functional brain networks

A guide for concurrent TMS-fMRI to investigate functional brain networks

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.

The impulse noise of TMS inside a 3 T and 9.4 T MRI

Abstract The operation of a transcranial magnetic stimulation (TMS) coil produces high-intensity impulse sounds. In TMS, a magnetic field is generated by a short-duration pulse in the range of thousands of amperes in the coil. When placed in a strong magnetic field, such as inside an magnetic resonance imaging (MRI) bore, the interaction of the magnetic field and the current in the TMS coil can cause strong forces on the coil casing. The strengths of these forces depend on the coil orientation in the main magnetic field (B0). Part of the energy in this process is dissipated in the form of acoustic noise. To conduct concurrent TMS and functional MRI (fMRI) safely, the sound pressure levels (SPLs) generated by the TMS coil must be quantitatively characterized. Measuring the SPLs of fast and loud impulse sounds accurately in the presence of static and gradient magnetic fields is challenging. In this study, we present a method for such measurements and report the SPLs of two commercial MRI-compatible TMS systems inside a 3T MRI scanner and of a prototype multi-channel TMS (mTMS) system inside a 9.4T small-animal MRI scanner. The mTMS coil allows for changing the direction of the electric field (E-field) without physically moving the TMS coil. We measured the acoustic noise generated by the TMS coils with different E-field orientations relative to the B0 field at different stimulation intensities and locations. The measurements were compared to the sound level measured outside the MRI room. SPLs and spectrum of the click sounds changed depending on coil and induced E-field orientation compared to the B0 field. SPLs exceeding the safety limit of 140 dB(C) was measured with all the devices. Our study provide is an important step towards the safety operation of concurrent TMS-fMRI respecting the auditory limits of small animals and humans. Keywords: TMS, mTMS, fMRI, acoustic noise

Disentangling the transcranially evoked BOLD response from re-afferent sensory feedback during concurrent TMS-fMRI of the human motor cortex using an ischemic nerve block

Disentangling the transcranially evoked BOLD response from re-afferent sensory feedback during concurrent TMS-fMRI of the human motor cortex using an ischemic nerve block

Resting-state functional connectivity in the attention networks is not altered by offline theta-burst stimulation of the posterior parietal cortex or the temporo-parietal junction as compared to a vertex control site

Disruption of resting-state functional connectivity (RSFC) between core regions of the dorsal attention network (DAN), including the bilateral superior parietal lobule (SPL), and structural damage of the right-lateralized ventral attention network (VAN), including the temporo-parietal junction (TPJ), have been described as neural basis for hemispatial neglect.Pursuing a virtual lesion model, we aimed to perturbate the attention networks of 22 healthy subjects by applying continuous theta burst stimulation (cTBS) to the right SPL or TPJ. We first created network masks of the DAN and VAN based on RSFC analyses from a RS-fMRI baseline session and determined the SPL and TPJ stimulation site within the respective mask. We then performed RS-fMRI immediately after cTBS of the SPL, TPJ (active sites) or vertex (control site). RSFC between SPL/TPJ and whole brain as well as between predefined regions of interest (ROI) in the attention networks was analyzed in a within-subject design.Contrary to our hypothesis, seed-based RSFC did not differ between the four experimental conditions. The individual change in ROI-to-ROI RSFC from baseline to post-stimulation did also not differ between active (SPL, TPJ) and control (vertex) cTBS.In our study, a single session offline cTBS over the right SPL or TPJ could not alter RSFC in the attention networks as compared to a control stimulation, maybe because effects wore off too early. Future studies should consider a modified cTBS protocol, concurrent TMS-fMRI or transcranial direct current stimulation.

Concurrent TMS-fMRI for causal network perturbation and proof of target engagement

The experimental manipulation of neural activity by neurostimulation techniques overcomes the inherent limitations of correlative recordings, enabling the researcher to investigate causal brain-behavior relationships. But only when stimulation and recordings are combined, the direct impact of the stimulation on neural activity can be evaluated. In humans, this can be achieved non-invasively through the concurrent combination of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Concurrent TMS-fMRI allows the assessment of the neurovascular responses evoked by TMS with excellent spatial resolution and full-brain coverage. This enables the functional mapping of both local and remote network effects of TMS in cortical as well as deep subcortical structures, offering unique opportunities for basic research and clinical applications. The purpose of this review is to introduce the reader to this powerful tool. We will introduce the technical challenges and state-of-the art solutions and provide a comprehensive overview of the existing literature and the available experimental approaches. We will highlight the unique insights that can be gained from concurrent TMS-fMRI, including the state-dependent assessment of neural responsiveness and inter-regional effective connectivity, the demonstration of functional target engagement, and the systematic evaluation of stimulation parameters. We will also discuss how concurrent TMS-fMRI during a behavioral task can help to link behavioral TMS effects to changes in neural network activity and to identify peripheral co-stimulation confounds. Finally, we will review the use of concurrent TMS-fMRI for developing TMS treatments of psychiatric and neurological disorders and suggest future improvements for further advancing the application of concurrent TMS-fMRI.

Design of TMS coils with reduced Lorentz forces: application to concurrent TMS-fMRI

Objective. Interleaving TMS (transcranial magnetic stimulation) with fMRI (functional Magnetic Resonance Imaging) is a promising technique to study functional connectivity in the human brain, but its development is being restricted by technical limitations, such as that due to the interaction of the TMS current pulses with the magnetic fields of an MRI scanner. In this work, a TMS coil design method capable of controlling Lorentz forces experienced by the coil in the presence of static magnetic fields is presented. Approach. The suggested approach is based on an existing inverse boundary element method (IBEM) for TMS coil design, in which new electromagnetic computational models of the Lorentz forces have been included to be controlled in the design process. Main results. To demonstrate the validity of this technique, it has been used for the design and simulation of TMS coils wound on rectangular flat, spherical and hemispherical surfaces with improved mechanical stability. The obtained results confirm that TMS coils with reduced Lorentz forces inside the static main field of an MRI scanner can be produced, which is achieved to the detriment of other coil performance parameters. Significance. The proposed approach provides an efficient tool to design TMS stimulators of a wide range of coil geometries with improved mechanical stability, which can be extremely useful to overcome current limitations for interleaved TMS-fMRI.

EPI distortion correction for concurrent human brain stimulation and imaging at 3T

BackgroundTranscranial magnetic stimulation (TMS) can be paired with functional magnetic resonance imaging (fMRI) in concurrent TMS-fMRI experiments. These multimodal experiments enable causal probing of network architecture in the human brain which can complement alternative network mapping approaches. Critically, merely introducing the TMS coil into the scanner environment can sometimes produce substantial magnetic field inhomogeneities and spatial distortions which limit the utility of concurrent TMS-fMRI. Method and resultsWe assessed the efficacy of point spread function corrected echo planar imaging (PSF-EPI) in correcting for the field inhomogeneities associated with a TMS coil at 3 T. In phantom and brain scans, we quantitatively compared the coil-induced distortion artifacts measured in EPI scans with and without PSF correction. We found that the application of PSF corrections to the EPI data significantly improved signal-to-noise and reduced distortions. In phantom scans with the PSF-EPI sequence, we also characterized the temporal profile of dynamic artifacts associated with TMS delivery and found that image quality remained high as long as the TMS pulse preceded the RF excitation pulses by at least 50 ms. Lastly, we validated the PSF-EPI sequence in human brain scans involving TMS and motor behavior as well as resting state fMRI scans. ConclusionsOur collective results demonstrate the potential benefits of PSF-EPI for concurrent TMS-fMRI when coil-related artifacts are a concern. The ability to collect high quality resting state fMRI data in the same session as the concurrent TMS-fMRI experiment offers a unique opportunity to interrogate network architecture in the human brain.

Radio-Frequency Coil Array for Improved Concurrent Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging.

To perform concurrent TMS-fMRI on difficult targets, such as the occipital lobe. a 3-channel flexible, thin RF coil was constructed that allows for whole head image coverage without impeding TMS placement. A custom MR-safe patient table which mates with typical 3T MR scanners was constructed for the purpose of face-down subject positioning to allow for access to posterior TMS targets. To counterbalance the loading effect of the TMS coil on the RF coil circuits "Dummy Loads" are introduced, which mimic the loading conditions of the TMS coil when it is not present. the designed RF coil performed as expected, achieving acceptable SNR values at depths equal to the center of the average human head, and high SNR values near the surface. The system allows for concurrent TMS-fMRI, targeting any area of the being while imaging the entire volume.