Insertable inductively coupled volumetric coils for MR microscopy in a human 7T MR system.

PURPOSE: To demonstrate the capability of insertable inductively coupled volumetric coils for MR microscopy in a human 7T MR system. METHODS: Insertable inductively coupled volume coils with diameters of 26 and 64 mm (D26 and D64 coils) targeted for monkey and mouse brain specimen sizes were designed and fabricated. These coils were placed inside the imaging volume of a transmit/receive knee coil without wired connections to the main system. Signal-to-noise ratio (SNR) evaluations were conducted with and without the insertable coils, and the g-factor maps of parallel imaging (PI) were also calculated for the D64 coil. Brain specimens were imaged using 3D T2∗ -weighted images with spatial resolution of isotropic 50 and 160 µm using D26 and D64 coils, respectively. RESULTS: Relative average (SD) SNRs compared with knee coil alone were 12.54 (0.30) and 2.37 (0.05) at the center for the D26 and D64 coils, respectively. The mean g-factors of PI with the D64 coil for the factor of 2 were less than 1.1 in the left-right and anterior-posterior directions, and around 1.5 in the superior-inferior direction or when the PI factor of 3 was used. Acceleration in two directions showed lower g-factors but suffered from intrinsic low SNR. Representative T2∗ -weighted images of the specimen showed structural details. CONCLUSION: Inductively coupled small diameter coils insertable to the knee coil demonstrated high SNR and modest PI capability. The concept was successfully used to visualize fine structures of the brain specimen. The insertable coils are easy to handle and enable MR microscopy in a human whole-body 7T MRI system.

Optimal Model Mapping for Intravoxel Incoherent Motion MRI.

In general, only one diffusion model would be applied to whole field-of-view voxels in the intravoxel incoherent motion-magnetic resonance imaging (IVIM-MRI) study. However, the choice of the applied diffusion model can significantly influence the estimated diffusion parameters. The quality of the diffusion analysis can influence the reliability of the perfusion analysis. This study proposed an optimal model mapping method to improve the reliability of the perfusion parameter estimation in the IVIM study. Six healthy volunteers (five males and one female; average age of 38.3 ± 7.5 years). Volunteers were examined using a 3.0 Tesla scanner. IVIM-MRI of the brain was applied at 17 b-values ranging from 0 to 2,500 s/mm2. The Gaussian model, the Kurtosis model, and the Gamma model were found to be optimal for the CSF, white matter (WM), and gray matter (GM), respectively. In the mean perfusion fraction (fp) analysis, the GM/WM ratios were 1.16 (Gaussian model), 1.80 (Kurtosis model), 1.94 (Gamma model), and 1.54 (Optimal model mapping); in the mean pseudo diffusion coefficient (D*) analysis, the GM/WM ratios were 1.18 (Gaussian model), 1.19 (Kurtosis model), 1.56 (Gamma model), and 1.24 (Optimal model mapping). With the optimal model mapping method, the estimated fp and D* were reliable compared with the conventional methods. In addition, the optimal model maps, the associated products of this method, may provide additional information for clinical diagnosis.

A venous mechanism of ventriculomegaly shared between traumatic brain injury and normal ageing.

Recently, age-related timing dissociation between the superficial and deep venous systems has been observed; this was particularly pronounced in patients with normal pressure hydrocephalus, suggesting a common mechanism of ventriculomegaly. Establishing the relationship between venous drainage and ventricular enlargement would be clinically relevant and could provide insight into the mechanisms underlying brain ageing. To investigate a possible link between venous drainage and ventriculomegaly in both normal ageing and pathological conditions, we compared 225 healthy subjects (137 males and 88 females) and 71 traumatic brain injury patients of varying ages (53 males and 18 females) using MRI-based volumetry and a novel perfusion-timing analysis. Volumetry, focusing on the CSF space, revealed that the sulcal space and ventricular size presented different lifespan profiles with age; the latter presented a quadratic, rather than linear, pattern of increase. The venous timing shift slightly preceded this change, supporting a role for venous drainage in ventriculomegaly. In traumatic brain injury, a small but significant disease effect, similar to idiopathic normal pressure hydrocephalus, was found in venous timing, but it tended to decrease with age at injury, suggesting an overlapping mechanism with normal ageing. Structural bias due to, or a direct causative role of ventriculomegaly was unlikely to play a dominant role, because of the low correlation between venous timing and ventricular size after adjustment for age in both patients and controls. Since post-traumatic hydrocephalus can be asymptomatic and occasionally overlooked, the observation suggested a link between venous drainage and CSF accumulation. Thus, hydrocephalus, involving venous insufficiency, may be a part of normal ageing, can be detected non-invasively, and is potentially treatable. Further investigation into the clinical application of this new marker of venous function is therefore warranted.

Overlapping but Asymmetrical Relationships Between Schizophrenia and Autism Revealed by Brain Connectivity.

Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. The authors quantified and visualized the relationship between ASD and SSD using dual classifiers that discriminate patients from healthy controls (HCs) based on resting-state functional connectivity magnetic resonance imaging. To develop a reliable SSD classifier, sophisticated machine-learning algorithms that automatically selected SSD-specific functional connections were applied to Japanese datasets from Kyoto University Hospital (N = 170) including patients with chronic-stage SSD. The generalizability of the SSD classifier was tested by 2 independent validation cohorts, and 1 cohort including first-episode schizophrenia. The specificity of the SSD classifier was tested by 2 Japanese cohorts of ASD and major depressive disorder. The weighted linear summation of the classifier's functional connections constituted the biological dimensions representing neural classification certainty for the disorders. Our previously developed ASD classifier was used as ASD dimension. Distributions of individuals with SSD, ASD, and HCs s were examined on the SSD and ASD biological dimensions. We found that the SSD and ASD populations exhibited overlapping but asymmetrical patterns in the 2 biological dimensions. That is, the SSD population showed increased classification certainty for the ASD dimension but not vice versa. Furthermore, the 2 dimensions were correlated within the ASD population but not the SSD population. In conclusion, using the 2 biological dimensions based on resting-state functional connectivity enabled us to discover the quantified relationships between SSD and ASD.

A Resilient, Non-neuronal Source of the Spatiotemporal Lag Structure Detected by BOLD Signal-Based Blood Flow Tracking.

Recent evidence has suggested that blood oxygenation level-dependent (BOLD) signals convey information about brain circulation via low frequency oscillation of systemic origin (sLFO) that travels through the vascular structure ("lag mapping"). Prompted by its promising application in both physiology and pathology, we examined this signal component using multiple approaches. A total of 30 healthy volunteers were recruited to perform two reproducibility experiments at 3 Tesla using multiband echo planar imaging. The first experiment investigated the effect of denoising and the second was designed to study the effect of subject behavior on lag mapping. The lag map's intersession test-retest reproducibility and image contrast were both diminished by removal of either the neuronal or the non-neuronal (e.g., cardiac, respiratory) components by independent component analysis-based denoising, suggesting that the neurovascular coupling also comprises a part of the BOLD lag structure. The lag maps were, at the same time, robust against local perfusion increases due to visuomotor task and global changes in perfusion induced by breath-holding at the same level as the intrasession reliability. The lag structure was preserved after time-locked averaging to the visuomotor task and breath-holding events, while any preceding signal changes were canceled out for the visuomotor task, consistent with the passive effect of neurovascular coupling in the venous side of the vasculature. These findings support the current assumption that lag mapping primarily reflects vascular structure despite the presence of sLFO perturbation of neuronal or non-neuronal origin and, thus, emphasize the vascular origin of the lag map, encouraging application of BOLD-based blood flow tracking.

Common and differential brain abnormalities in gambling disorder subtypes based on risk attitude.

Studying brain abnormalities in behavioral addiction including GD enables us to exclude possible confounding effects of exposure to neurotoxic substances, which should provide important insight that can lead to a better understanding of addiction per se. There have been a few brain structural magnetic resonance imaging studies for GD, although the results have been inconsistent. On the other hand, GD was suggested to be a heterogeneous disorder in terms of risk attitude. We aimed to examine the heterogeneity of GD by combining a behavioral economics task and voxel-based morphometry. Thirty-six male GD patients and 36 healthy male control subjects underwent a task for estimation of loss aversion, which can assess risk attitude in real-life decision-making. The GD patients were divided into two groups based on their level of loss aversion, low and high. While both groups showed common gray matter volume reduction in the left supramarginal gyrus and bilateral posterior cerebellum, high loss-aversion GD showed pronounced reduction in the left posterior cerebellum and additional reduction in the bilateral medial orbitofrontal cortex. Our study suggests that the heterogeneity of GD is underpinned at the brain structural level. This result might be useful for understanding neurobiological mechanisms and for the establishment of precise treatment strategies for GD.

Lateralization of intrinsic frontoparietal network connectivity and symptoms in schizophrenia.

It has been frequently reported that schizophrenia patients have reduced functional lateralization in the areas related to language processing. Furthermore, there is evidence supporting that schizophrenia patients have disrupted functional connectivity in the bilateral frontoparietal networks (FPNs), of which the left is strongly associated with a cognition-language paradigm, using resting-state functional magnetic resonance imaging (rsfMRI). To examine the laterality of resting-state functional connectivity in schizophrenia, we investigated the bilateral FPNs. We investigated 41 schizophrenia and 35 healthy participants using independent component analysis for rsfMRI. We extracted mean connectivity values of both left and right FPNs and calculated their laterality index by (left - right)/(left + right). Subsequently, we investigated group differences of these values and the correlation between these values and symptoms. In schizophrenia, mean connectivity values of both left and right FPNs were significantly lower than in healthy controls, whereas their laterality indices were not significantly different. However, correlation analyses revealed that the laterality index was negatively correlated with positive symptoms, and that mean connectivity of left FPN was negatively correlated with depressive symptoms in schizophrenia. Our results suggest that language-related networks and their laterality might be one of the neural correlates of schizophrenia symptoms.

Creativity and positive symptoms in schizophrenia revisited: Structural connectivity analysis with diffusion tensor imaging.

Both creativity and schizotypy are suggested to be manifestations of the hyperactivation of unusual or remote concepts/words. However, the results of studies on creativity in schizophrenia are diverse, possibly due to the multifaceted aspects of creativity and difficulties of differentiating adaptive creativity from pathological schizotypy/positive symptoms. To date, there have been no detailed studies comprehensively investigating creativity, positive symptoms including delusions, and their neural bases in schizophrenia. In this study, we investigated 43 schizophrenia and 36 healthy participants using diffusion tensor imaging. We used idea, design, and verbal (semantic and phonological) fluency tests as creativity scores and Peters Delusions Inventory as delusion scores. Subsequently, we investigated group differences in every psychological score, correlations between fluency and delusions, and relationships between these scores and white matter integrity using tract-based spatial statistics (TBSS). In schizophrenia, idea and verbal fluency were significantly lower in general, and delusion score was higher than in healthy controls, whereas there were no group differences in design fluency. We also found positive correlation between phonological fluency and delusions in schizophrenia. By correlation analyses using TBSS, we found that the anterior part of corpus callosum was the substantially overlapped area, negatively correlated with both phonological fluency and delusion severity. Our results suggest that the anterior interhemispheric dysconnectivity might be associated with executive dysfunction, and disinhibited automatic spreading activation in the semantic network was manifested as uncontrollable phonological fluency or delusions. This dysconnectivity could be one possible neural basis that differentiates pathological positive symptoms from adaptive creativity.

Network hyperexcitability in a patient with partial reading epilepsy: converging evidence from magnetoencephalography, diffusion tractography, and functional magnetic resonance imaging.

OBJECTIVE: The pathophysiological mechanisms of partial reading epilepsy are still unclear. We delineated the spatial-temporal characteristics of reading-induced epileptic spikes and hemodynamic activation in a patient with partial reading epilepsy. METHODS: Magnetoencephalography (MEG) was recorded during silent letter-by-letter reading, and the source of reading-induced spikes was estimated using equivalent current dipole (ECD) analysis. Diffusion tractography was employed to determine if the white matter pathway connected spike initiation and termination sites. Functional magnetic resonance imaging (fMRI) was employed to determine the spatial pattern of hemodynamic activation elicited by reading. RESULTS: In 91 spike events, ECDs were clustered in the left posterior basal temporal area (pBTA) during Katakana reading. In 8 of these 91 events, when the patient continued to read >30 min, another ECD cluster appeared in the left ventral precentral gyrus/frontal operculum with a time-difference of ∼24 ms. Probabilistic diffusion tractography revealed that the long segment of the arcuate fasciculus connected these two regions. fMRI conjunction analysis indicated that both Katakana and Kanji reading activated the left pBTA, but Katakana activated the left lateral frontal areas more extensively than Kanji. CONCLUSIONS: Prolonged reading of Katakana induced hyper-activation of the cortical network involved in normal language function, concurrently serving as the seizure onset and symptomatogenic zones. SIGNIFICANCE: Reflex epilepsy is believed to result from intrinsic hyper-excitability in the cortical regions recruited during behavioral states that trigger seizures. Our case shows that reading epilepsy can arise from a hyperexcitable network of cortical regions. Physiological activation of this network can have cumulative effects, resulting in greater reciprocal network propagation and electroclinical seizures. These effects, in turn, may give insights into the brain networks recruited by reading.

fMRI evidence of improved visual function in patients with progressive retinitis pigmentosa by eye-movement training.

To evaluate changes in the visual processing of patients with progressive retinitis pigmentosa (RP) who acquired improved reading capability by eye-movement training (EMT), we performed functional magnetic resonance imaging (fMRI) before and after EMT. Six patients with bilateral concentric contraction caused by pigmentary degeneration of the retina and 6 normal volunteers were recruited. Patients were given EMT for 5 min every day for 8-10 months. fMRI data were acquired on a 3.0-Tesla scanner while subjects were performing reading tasks. In separate experiments (before fMRI scanning), visual performances for readings were measured by the number of letters read correctly in 5 min. Before EMT, activation areas of the primary visual cortex of patients were 48.8% of those of the controls. The number of letters read correctly in 5 min was 36.6% of those by the normal volunteers. After EMT, the activation areas of patients were not changed or slightly decreased; however, reading performance increased in 5 of 6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After EMT, increased activity was observed in the frontal eye fields (FEFs) of all patients; however, increases in the activity of the parietal eye fields (PEFs) were observed only in patients who showed greater improvement in reading capability. The improvement in reading ability of the patients after EMT is regarded as an effect of the increased activity of FEF and PEF, which play important roles in attention and working memory as well as the regulation of eye movements.

Topographic representation of an occluded object and the effects of spatiotemporal context in human early visual areas.

Occlusion is a primary challenge facing the visual system in perceiving object shapes in intricate natural scenes. Although behavior, neurophysiological, and modeling studies have shown that occluded portions of objects may be completed at the early stage of visual processing, we have little knowledge on how and where in the human brain the completion is realized. Here, we provide functional magnetic resonance imaging (fMRI) evidence that the occluded portion of an object is indeed represented topographically in human V1 and V2. Specifically, we find the topographic cortical responses corresponding to the invisible object rotation in V1 and V2. Furthermore, by investigating neural responses for the occluded target rotation within precisely defined cortical subregions, we could dissociate the topographic neural representation of the occluded portion from other types of neural processing such as object edge processing. We further demonstrate that the early topographic representation in V1 can be modulated by prior knowledge of a whole appearance of an object obtained before partial occlusion. These findings suggest that primary "visual" area V1 has the ability to process not only visible or virtually (illusorily) perceived objects but also "invisible" portions of objects without concurrent visual sensation such as luminance enhancement to these portions. The results also suggest that low-level image features and higher preceding cognitive context are integrated into a unified topographic representation of occluded portion in early areas.

Overlapping connections within the motor cortico-basal ganglia circuit: fMRI-tractography analysis.

Contribution of the subcortical nuclei to the coordination of human behavior is dependent on the existence of appropriate anatomical architecture. Interpretations of available data have led to opposing 'information funneling' and 'parallel processing' hypotheses. Using motor circuit as a model, we examined whether cortico-subcortical circuits, especially cortico-basal ganglia circuits, are funneled or parallel in the control of volitional movement. Twenty-five healthy subjects underwent functional magnetic resonance imaging (fMRI). Activated clusters during self-initiated, sequential finger-to-thumb opposition movements of the left hand were identified in the bilateral supplementary motor area (SMA), right lateral premotor cortex (PM) and primary motor cortex (M1), and in the right striatum and thalamus. These functionally defined clusters were applied to probabilistic tractography based on diffusion-weighted MRI to examine patterns of connectivity. Striatal and thalamic sub-regions with high probabilities of connection to the motor cortices partially overlapped, with connection to the two premotor areas outspreading rostrally relative to M1. We suggest that, on a macroscopic anatomical level, there is overlap as well as segregation among connections of the motor cortices with the striatum and thalamus. This supports the notion that neuronal information of the motor cortices is funneled, and parallel processing is not an exclusive principle in the basal ganglia.

Kinetics of neurodegeneration based on a risk-related biomarker in animal model of glaucoma.

BACKGROUND: Neurodegenerative diseases including Parkinson's and Alzheimer's diseases progress slowly and steadily over years or decades. They show significant between-subject variation in progress and clinical symptoms, which makes it difficult to predict the course of long-term disease progression with or without treatments. Recent technical advances in biomarkers have facilitated earlier, preclinical diagnoses of neurodegeneration by measuring or imaging molecules linked to pathogenesis. However, there is no established "biomarker model" by which one can quantitatively predict the progress of neurodegeneration. Here, we show predictability of a model with risk-based kinetics of neurodegeneration, whereby neurodegeneration proceeds as probabilistic events depending on the risk. RESULTS: We used five experimental glaucomatous animals, known for causality between the increased intraocular pressure (IOP) and neurodegeneration of visual pathways, and repeatedly measured IOP as well as white matter integrity by diffusion tensor imaging (DTI) as a biomarker of axonal degeneration. The IOP in the glaucomatous eye was significantly increased than in normal and was varied across time and animals; thus we tested whether this measurement is useful to predict kinetics of the integrity. Among four kinds of models of neurodegeneration, constant-rate, constant-risk, variable-risk and heterogeneity models, goodness of fit of the model and F-test for model selection showed that the time course of optic nerve integrity was best explained by the variable-risk model, wherein neurodegeneration kinetics is expressed in an exponential function across cumulative risk based on measured IOP. The heterogeneity model with stretched exponential decay function also fit well to the data, but without statistical superiority to the variable-risk model. The variable-risk model also predicted the number of viable axons in the optic nerve, as assessed by immunohistochemistry, which was also confirmed to be correlated with the pre-mortem integrity of the optic nerve. In addition, the variable-risk model identified the disintegrity in the higher-order visual pathways, known to underlie the transsynaptic degeneration in this disease. CONCLUSIONS: These findings indicate that the variable-risk model, using a risk-related biomarker, could predict the spatiotemporal progression of neurodegeneration. This model, virtually equivalent to survival analysis, may allow us to estimate possible effect of neuroprotection in delaying progress of neurodegeneration.

Comparison of diffusion-weighted fMRI and BOLD fMRI responses in a verbal working memory task.

Diffusion-weighted functional MRI (DfMRI) has been reported to have a different response pattern in the visual cortex than that of BOLD-fMRI. Especially, the DfMRI signal shows a constantly faster response at both onset and offset of the stimulus, suggesting that the DfMRI signal might be more directly linked to neuronal events than the hemodynamic response. However, because the DfMRI response also contains a residual sensitivity to BOLD this hypothesis has been challenged. Using a verbal working memory task we show that the DfMRI time-course features are preserved outside visual cortices, but also less liable to between-subject/between-regional variation than the BOLD response. The overall findings not only support the feasibility of DfMRI as an approach for functional brain imaging, but also strengthen the uniqueness of the DfMRI signal origin.

Signal changes in the brain on susceptibility-weighted imaging under reduced cerebral blood flow: a preliminary study.

OBJECTIVES: To reveal the characteristics of susceptibility-weighted imaging (SWI) under low cerebral blood flow (CBF) induced by hyperventilation (HV). MATERIALS AND METHODS: This study was approved by the institutional review board. Informed consent was obtained. Six healthy volunteers (5 men, 1 woman; mean age, 29 years; range, 24-33 years) underwent SWI and arterial spin labeling perfusion imaging under normal ventilation (NV) and HV at 3.0 T. Regions of interest (ROIs) were placed on gray matter (GM) and white matter (WM) of the frontal lobe (FL) and occipital lobe (OL). Intensities of ROIs were compared between NV and HV. Contrast of veins compared with adjacent cerebral parenchyma (CV) was also compared between NV and HV. RESULTS: CBF during HV (CBF(HV)) was decreased compared with CBF during NV (CBF(NV)) (29.1 +/- 4.6%). FL-GM(HV) and OL-GM(HV) showed significant signal decreases compared with FL-GM(NV) and OL-GM(NV), respectively (P= .018, .017). CV(HV) was significantly increased compared with CV(NV) (164.1 +/- 29.9%) (P= .00019). CONCLUSIONS: SWI sensitively reflects HV-induced decreases in CBF. The present results might assist in the interpretation of SWI in clinical practice, since CBF decreases might also influence signal changes on SWI.

An intrinsic diffusion response function for analyzing diffusion functional MRI time series.

To disentangle the temporal profiles of the diffusion and BOLD components of diffusion-weighted functional MRI (DfMRI) during visual activation, we extracted the raw signal from an anatomically defined volume of interest encompassing the visual cortex of 16 subjects. Under the assumption of a linear, time invariant system we were able to define an intrinsic diffusion response function (DRF) from neural tissue, as a counterpart to the hemodynamic response function (HRF) commonly used in BOLD-fMRI. The shape of the DRF response was found to be very similar to the time courses of optical imaging transmittance signals, thought to originate from local geometric changes in brain tissue at the microscopic scale. The overall DfMRI signal response was modeled as the convolution of the stimulation paradigm time course with a DhRF, which is the sum of the DRF and a fractional HRF resulting from residual tissue T2-BOLD contrast. The contribution of the HRF to the DfMRI signal was found to be 26% at peak amplitude, but the DRF component which has a much steeper onset contributed solely at beginning of the response onset. The suitability of this model over the canonical HRF to process DfMRI data was then demonstrated on datasets acquired in 5 other subjects using a rapid event-related design. Some non-linearities in the responses were observed, mainly after the end of the stimulation.

Water-diffusion slowdown in the human visual cortex on visual stimulation precedes vascular responses.

We used magnetic resonance imaging (MRI) to investigate the temporal dynamics of changes in water diffusion and blood oxygenation level-dependent (BOLD) responses in the brain cortex of eight subjects undergoing visual stimulation, and compared them with changes of the vascular hemoglobin content (oxygenated, deoxygenated, and total hemoglobin) acquired simultaneously from intrinsic optical recordings (near infrared spectroscopy). The group average rise time for the diffusion MRI signal was statistically significantly shorter than those of the BOLD signal and total hemoglobin content optical signal, which is assumed to be the fastest observable vascular signal. In addition, the group average decay time for the diffusion MRI also was shortest. The overall time courses of the BOLD and optical signals were strongly correlated, but the covariance was weaker with the diffusion MRI response. These results suggest that the observed decrease in water diffusion reflects early events that precede the vascular responses, which could originate from changes in the extravascular tissue.

Spin-echo T1-weighted imaging of the brain with interleaved acquisition and presaturation pulse at 3 T: a feasibility study before clinical use.

RATIONALE AND OBJECTIVES: Although spin-echo (SE) sequence has some advantages over gradient-echo sequence in brain imaging, gradient-echo sequence is commonly used for T1-weighted imaging (T1WI) at 3 T because contrast on SE T1WI is widely believed to be poor at 3 T. Recently, gray-white matter contrast on single-slice and multi-slice SE imaging with interslice gap was reported as better at 3 T than at 1.5 T. This study examined the feasibility of interleaved SE T1WI of the brain at 3 T. This study also examined whether presaturation pulse (PP) sufficiently suppresses intra-arterial signals because these signals tend to be hyperintense due to longer T1 at 3 T. MATERIALS AND METHODS: Subjects consisted of 18 healthy volunteers. Two sets of T1WI were performed using SE sequence. One set consisted of imaging without PP, and the other consisted of imaging with PP. Each set contained three types of gapless imaging as follows; sequential, 100% interleaved, and 200% interleaved imaging. In each subject, contrast-to-noise ratio between gray-matter and white-matter (CNR(GM-WM)) and intra-arterial signals were evaluated. RESULTS: CNR(GM-WM) was significantly higher on interleaved images than on sequential images, regardless of PP (P < .0001). PP sufficiently suppressed intra-arterial signals (P < .0001). CONCLUSION: CNR(GM-WM) on SE T1WI at 3 T can be improved by interleaved acquisition, and PP sufficiently suppressed intra-arterial signals. Interleaved SE T1WI with PP appears clinically feasible at 3 T.

Stimulus-response profile during single-pulse transcranial magnetic stimulation to the primary motor cortex.

We examined the stimulus-response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus-response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.