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BackgroundConcurrent transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) is time-consuming because of the limited space in the MRI bore and the sophisticated placement and orientation of the TMS coil to elicit the desired brain activities and behaviors.ObjectiveWe developed a TMS coil holder capable of quick adjustment of the TMS coil position and orientation. The holder can also hold an MRI receiver coil array.MethodsA holder with one controlling knob, two omni-direction rotation joints, and two in-plane rotation joints was developed.ResultsDifferent TMS coil positions and orientations can be arranged and fixed in seconds. The holder can also accommodate two TMS coils to allow for multi-coil TMS-MRI.ConclusionOur development significantly improves the workflow of the concurrent TMS-MRI in new neuroscience studies and clinical applications.

BackgroundAccurate high-resolution EEG source reconstruction (localization) is important for several tasks, including rigorous and rapid mental health screening.ObjectiveThe present study has developed, validated, and applied a new source localization algorithm utilizing a charge-based boundary element fast multipole method (BEM-FMM) coupled with the Helmholtz reciprocity principle and the transcranial electrical stimulation (TES) forward solution.MethodsThe unknown cortical dipole density is reconstructed over the entire cortical surface by expanding into global basis functions in the form of cortical fields of active TES electrode pairs. These pairs are constructed from the reading electrodes. An analog of the minimum norm estimation (MNE) equation is obtained after substituting this expansion into the reciprocity principle written in terms of measured electrode voltages. Delaunay (geometrically balanced) triangulation of the electrode cap is introduced first. Basis functions for all electrode pairs connected by the edges of a triangular mesh are precomputed and stored in memory. A smaller set of independent basis functions is then selected and employed at every time instant. This set is based on the highest voltage differences measured.ResultsThe method is validated against the classic, yet challenging problem of median nerve stimulation and the tangential cortical sources located at the posterior wall of the central sulcus for an N20/P20 peak (2 scanned subjects). The method is further applied to perform source reconstruction of synthesized tangential cortical sources located at the posterior wall of the central sulcus (12 different subjects). In the second case, an average source reconstruction error of 7 mm is reported for the best possible noiseless scenario.ConclusionsOnce static preprocessing with TES electrodes has been done (the basis functions have been computed), our method requires fractions of a second to complete the accurate high-resolution source localization.

Background: Temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) is a common intractable epilepsy. To seek neural correlates of seizure recurrence, this study investigated aberrant int...

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (AC). Whether these influences reflect active visual processing in human ACs, which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Cross-correlation and spatiotemporal pattern similarity analyses suggested cross-sensory visual influences, which lagged auditory responses by several tens of milliseconds in ACs. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15–30-Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs.

Perception of the same narrative can vary between individuals depending on a listener’s previous experiences. We studied whether and how cultural family background may shape the processing of an audiobook in the human brain. During functional magnetic resonance imaging (fMRI), 48 healthy volunteers from two different cultural family backgrounds listened to an audiobook depicting the intercultural social life of young adults with the respective cultural backgrounds. Shared cultural family background increased inter-subject correlation of hemodynamic activity in the left-hemispheric Heschl’s gyrus, insula, superior temporal gyrus, lingual gyrus and middle temporal gyrus, in the right-hemispheric lateral occipital and posterior cingulate cortices as well as in the bilateral middle temporal gyrus, middle occipital gyrus and precuneus. Thus, cultural family background is reflected in multiple areas of speech processing in the brain and may also modulate visual imagery. After neuroimaging, the participants listened to the narrative again and, after each passage, produced a list of words that had been on their minds when they heard the audiobook during neuroimaging. Cultural family background was reflected as semantic differences in these word lists as quantified by a word2vec-generated semantic model. Our findings may depict enhanced mutual understanding between persons who share similar cultural family backgrounds.

The ballistocardiogram (BCG), the induced electric potentials by the head motion originating from heartbeats, is a prominent source of noise in electroencephalography (EEG) data during magnetic resonance imaging (MRI). Although methods have been proposed to suppress the BCG artifact, more work considering the variability of cardiac cycles and head motion across time and subjects is needed to provide highly robust correction. Here, a method called "dynamic modeling of heartbeats" (DMH) is proposed to reduce BCG artifacts in EEG data recorded inside an MRI system. The DMH method models BCG artifacts by combining EEG points at time instants with similar dynamics. The modeled BCG artifact is then subtracted from the EEG recording to suppress the BCG artifact. Performance of DMH was tested and specifically compared with the Optimal Basis Set (OBS) method on EEG data recorded inside a 3T MRI system with either no MRI acquisition (Inside-MRI), echo-planar imaging (EPI-EEG), or fast MRI acquisition using simultaneous multi-slice and inverse imaging methods (SMS-InI-EEG). In a steady-state visual evoked response (SSVEP) paradigm, the 15-Hz oscillatory neuronal activity at the visual cortex after DMH processing was about 130% of that achieved by OBS processing for Inside-MRI, SMS-InI-EEG, and EPI-EEG conditions. The DMH method is computationally efficient for suppressing BCG artifacts and in the future may help to improve the quality of EEG data recorded in high-field MRI systems for neuroscientific and clinical applications.

The functional connectivity of the default-mode network (DMN) monitored by functional magnetic resonance imaging (fMRI) in Alzheimer's disease (AD) patients has been found weaker than that in healthy participants. Since breathing and heart beating can cause fluctuations in the fMRI signal, these physiological activities may affect the fMRI data differently between AD patients and healthy participants. We collected resting-state fMRI data from AD patients and age-matched healthy participants. With concurrent cardiac and respiratory recordings, we estimated both physiological responses phase-locked and non-phase-locked to heart beating and breathing. We found that the cardiac and respiratory physiological responses in AD patients were 3.00 ± 0.51 s and 3.96 ± 0.52 s later (both p < 0.0001) than those in healthy participants, respectively. After correcting the physiological noise in the resting-state fMRI data by population-specific physiological response functions, the DMN estimated by seed-correlation was more localized to the seed region. The DMN difference between AD patients and healthy controls became insignificant after suppressing physiological noise. Our results indicate the importance of controlling physiological noise in the resting-state fMRI analysis to obtain clinically related characterizations in AD.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, functional mapping of brain functions has been limited because the implantations have sparse coverage and differ greatly across individuals. Here, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. Our novel approach accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈−3.6). The signa-to-noise ratio and sensitivity in the thalamus and brain stem were comparable to those locations at the vicinity of electrode contact implantation. The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized functional mapping of human brain using both iERP and HBBG data.

Transcranial magnetic stimulation (TMS) can non-invasively induce both excitatory and inhibitory neuronal activity. However, the neurophysiological basis for both kinds of modulation remains elusive. In this study, with a controlled dosage over the 30-s interval, we elicited excitatory and inhibitory TMS modulations over the human primary motor cortex (M1) with TMS bursts of high (10-Hz and 30-Hz) and low frequency (0.5-Hz), respectively, and took functional magnetic resonance images (fMRI). Excitatory and inhibitory modulations were evidenced by changes in motor evoked potentials (MEP). Significantly increased fMRI signal at M1 was only detected under excitatory high-frequency TMS but not during inhibitory low-frequency TMS. The supplementary motor area (SMA) had significant fMRI signal changes after both excitatory and inhibitory TMS. The topology of the activated M1 and SMA matched the activated sensorimotor network during voluntary movement. The precuneus was selectively activated with bursts of five TMS pulses. These findings demonstrated the asymmetric hemodynamic responses to excitatory and inhibitory TMS modulations with region-dependent relationships between the local fMRI signal changes and TMS dosage over different time scales.

Transcranial magnetic stimulation (TMS) can non-invasively induce both excitatory and inhibitory neuronal activity. However, the neurophysiological basis for both kinds of modulation remains elusive. In this study, with a controlled dosage over the 30-s interval, we elicited excitatory and inhibitory TMS modulations over the human primary motor cortex (M1) with TMS bursts of high (10-Hz and 30-Hz) and low frequency (0.5-Hz), respectively, and took functional magnetic resonance images (fMRI). Excitatory and inhibitory modulations were evidenced by changes in motor evoked potentials (MEP). Significantly increased fMRI signal at M1 was only detected under excitatory high-frequency TMS but not during inhibitory low-frequency TMS. The supplementary motor area (SMA) had significant fMRI signal changes after both excitatory and inhibitory TMS. The topology of the activated M1 and SMA matched the activated sensorimotor network during voluntary movement. The precuneus was selectively activated with bursts of five TMS pulses. These findings demonstrated the asymmetric hemodynamic responses to excitatory and inhibitory TMS modulations with region-dependent relationships between the local fMRI signal changes and TMS dosage over different time scales.

Intracranial stereoelectroencephalography (sEEG) provides unsurpassed sensitivity and specificity for human neurophysiology. However, sEEG group analyses are complicated because the electrode implantations differ greatly across individuals. Here, using an auditory experiment as the test case, we developed a distributed, anatomically realistic sEEG source-modeling approach for within- and between-subject analyses. In addition to intracranial event-related potentials (iERP), we also estimated the sources of high broadband gamma activity (HBBG), a putative correlate of local neural firing. The source models accounted for a significant portion of the variance of the sEEG measurements in leave-one-out cross-validation. After logarithmic transformations, the sensitivity and signal-to-noise ratio were linearly inversely related to the minimal distance between the brain location and electrode contacts (slope≈-3.6). The HGGB source estimates were remarkably consistent with analyses of intracranial-contact data. In conclusion, distributed sEEG source modeling provides a powerful neuroimaging tool, which facilitates anatomically-normalized group analyses of both iERP and HBBG.

Magnetoencephalography (MEG) is directly sensitive to postsynaptic neuronal activity with the millisecond temporal resolution. MEG is ideally to complement functional MRI (fMRI), which measures hemodynamic responses secondary to neuronal activity with the millimeter spatial resolution, for noninvasive imaging of human brain function. Here, using the Minimum-Norm Estimate as an example, we review how fMRI can be integrated with MEG (and electroencephalography, EEG) source modeling and summarize potential advantages and pitfalls of this data fusion technique. Neurovascular coupling as the physiological basis for MEG/EEG/fMRI integration is also discussed. Ultimately, we expect to develop multimodal MEG/EEG/fMRI neuroimaging methodology for characterizing spatiotemporal functional connectivity in large-scale neural networks of the human brain with high sensitivity and accuracy.

Electroencephalography (EEG) concurrently collected with functional magnetic resonance imaging (fMRI) is heavily distorted by the repetitive gradient coil switching during the fMRI acquisition. The performance of the typical template-based gradient artifact suppression method can be suboptimal because the artifact changes over time. Gradient artifact residuals also impede the subsequent suppression of ballistocardiography artifacts. Here we propose recording continuous EEG with temporally sparse fast fMRI (fast fMRI-EEG) to minimize the EEG artifacts caused by MRI gradient coil switching without significantly compromising the field-of-view and spatiotemporal resolution of fMRI. Using simultaneous multi-slice inverse imaging to achieve whole-brain fMRI with isotropic 5-mm resolution in 0.1 ​s, and performing these acquisitions once every 2 ​s, we have 95% of the duty cycle available to record EEG with substantially less gradient artifact. We found that the standard deviation of EEG signals over the entire acquisition period in fast fMRI-EEG was reduced to 54% of that in conventional concurrent echo-planar imaging (EPI) and EEG recordings (EPI-EEG) across participants. When measuring 15-Hz steady-state visual evoked potentials (SSVEPs), the baseline-normalized oscillatory neural response in fast fMRI-EEG was 2.5-fold of that in EPI-EEG. The functional MRI responses associated with the SSVEP delineated by EPI and fast fMRI were similar in the spatial distribution, the elicited waveform, and detection power. Sparsely interleaved fast fMRI-EEG provides high-quality EEG without substantially compromising the quality of fMRI in evoked response measurements, and has the potential utility for applications where the onset of the target stimulus cannot be precisely determined, such as epilepsy.

PURPOSE: We designed and implemented an orthogonal shim array consisting of shim coils with their planes perpendicular to the planes of neighboring radio-frequency (RF) coils. This shim coil improves the magnetic field homogeneity with the minimal interference to RF coils. METHODS: Using realistic off resonance maps of the human brain, we first evaluated the performance of shim coils in different orientations. Based on simulations, we developed a 7-channel orthogonal shim array, whose coil plan was perpendicular to neighboring RF coils, at the forehead. A programmable open-source current driver supplied shim currents. RESULTS: The 7-channel orthogonal shim array caused only marginal SNR loss to the integrated 32-channel RF-shim array. The 7-channel orthogonal shim array itself improved the magnetic field homogeneity by 30% in slice-optimized shimming, comparable to the baseline shimming offered by the scanner’s second order spherical harmonic shimming. CONCLUSION: Orthogonal shim coils can improve the field homogeneity while maintaining good image SNR.

Supplemental material, JCB897442 Supplemental material for Impact of physiological noise in characterizing the functional MRI default-mode network in Alzheimer’s disease by Yi-Tien Li, Chun-Yuan Chang, Yi-Cheng Hsu, Jong-Ling Fuh, Wen-Jui Kuo, Jhy-Neng Tasso Yeh and Fa-Hsuan Lin in Journal of Cerebral Blood Flow & Metabolism

Variability in neuronal response latency has been typically considered caused by random noise. Previous studies of single cells and large neuronal populations have shown that the temporal variability tends to increase along the visual pathway. Inspired by these previous studies, we hypothesized that functional areas at later stages in the visual pathway of face processing would have larger variability in the response latency. To test this hypothesis, we used magnetoencephalographic data collected when subjects were presented with images of human faces. Faces are known to elicit a sequence of activity from the primary visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus showed larger variability in the response latency compared to the calcarine fissure. Dynamic and spectral analyses of the latency variability indicated that the response latency in the fusiform gyrus was more variable than in the calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4 Hz and 40 Hz, respectively. The sequential processing of face information from the calcarine sulcus to the fusiform sulcus was more reliably detected based on sizes of the response variability than instants of the maximal response peaks. With two areas in the ventral visual pathway, we show that the variability in response latency across brain areas can be used to infer the sequence of cortical activity.

We propose a flexible form-fittingMRI receiver coil array assembledby individualcoilmodules. This design targetsMRI applications requiring a receiver array conforming to the anatomy of various shapes or sizes. Coil modules in our proposed array were arranged with gaps between them. Each coil module had a circumferential shielding structure stacked on top of the coil. Together they achieve robust decoupling when the array was bent differently. Two types of the circumferential shielding structure were investigatedby using full-wave electromagnetic simulations and imaging experiments. Results showed that our flexible coil array had good decoupling between coils whether they were on a flat or curved surface with the S21 magnitude ranged between −18.1 dB and −19.9 dB in simulations, and with the average of off-diagonal entries of the noise correlationmatrix less than 0.047 in experimentalmeasurements. Anatomical images of human brain, calf, and knee were acquired by our seven-channel prototype on a 3T MRI system. The maximal and the average SNR within 50 mm from our array surpassed those from the commercial 32-channel head and 4-channel flexible coil arrays by 2.63/1.35-fold and 3.89/1.50-fold, respectively.

BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = −0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Previous evaluation of brain function in schizophrenia has focused on standard experimental tasks, with cerebral response to natural stimuli less clear. This study employed inter-subject correlation (ISC) analysis to investigate the neural basis of humor processing during free viewing of comedy movies in patients with schizophrenia. We recruited 29 patients diagnosed with schizophrenia and 29 healthy, age- and sex-matched controls. Each participant underwent fMRI scanning during two viewings of three comedy movie clips. The ISC map from each participant pair within each population group and each movie viewing was separately derived. The significance of ISC within a group and between two groups were assessed by bootstrapping. The ISC map from each patient pair were also correlated with the product of Positive and Negative Syndrome Scale (PANSS) rating between the same participant pair in schizophrenia patients. Schizophrenia patients showed significant ISC in bilateral lateraloccipital, bilateral superior frontal, left supramarginal, and right lateralorbiofrontal cortices. Compared with the controls, the schizophrenia group exhibited significantly lower ISC in the left superior temporal sulcus, bilateral supramarginal, and bilateral inferiorparietal cortices. Higher clinical severity (higher total PANSS rating) was associated with lower ISC in the middle frontal and middle temporal regions, and also higher ISC in the visual cortex, inferior temporal gyrus, and anterior cingulate. The findings indicated that patients with schizophrenia are characterized by lower ISC in a frontal parietal network while viewing comedy film clips, which implicated a deficit in the cognitive component of humor processing. The lower synchronization in parts of the frontal parietal network also correlated with symptom severity.

Few neuroimaigng studies on reading comprehension have been conducted under natural reading settings. In this study, we showed texts presented in a natural way during functional MRI (fMRI) measurements to reveal brain areas sensitive to reading comprehension. Specifically, this paradigm independently manipulated two holistic features of article style: text genre and translation style, a qualitative index of how typical word choices and arrangements are made in daily use of the language. Specifically, articles from The New York Times (news) and Reader’s Digest (fiction) translated from English to Mandarin Chinese either by human experts or machine (Google Translate) were used to investigate the correlation of brain activity across participants during article reading. We found that bi-hemispheric visual cortex, precuneus, and occipito-parietal junction show significantly correlated hemodynamics across participants regardless of translation style and article genre. Compared to machine translation, reading human expert translation elicited more reliable fMRI signals across participants at precuneus, potentially because narrative representations and contents can be coherently presented over tens of seconds. We also found significantly stronger inter-subject correlated fMRI signals at temporal poles and fusiform gyri in fiction reading than in news reading. This may be attributed to more stable empathy processing across participants in fiction reading. The degree of stability of brain responses across subjects at extra-linguistic areas was found correlated with subjective rating on the text fluency. The functional connectivity between these areas was modulated by text genre and translation style. Taken together, our imaging results suggested stable and selective neural substrates associated with comprehending holistic features of written narratives.

Highlights • A brain age prediction model was developed based on diffusion MRI data. • Patients with right MTLE exhibited older brain age than those with left MTLE. • Predicted age difference (PAD) was correlated with seizure frequency in right MTLE. • Right uncinate fasciculus had highest contribution to the observed PAD in right MTLE., Brain age prediction based on machine learning has been applied to various neurological diseases to discover its clinical values. By this innovative approach, it has been reported that the patients with refractory epilepsy had premature brain aging. Of refractory epilepsy, right and left subtypes of mesial temporal lobe epilepsy (MTLE) are the most common forms and exhibit distinct patterns in white matter alterations. So far, it is unclear whether these two subtypes of MTLE would have difference in white matter aging due to distinct white matter alterations. To address this issue, a machine learning based brain age model using diffusion MRI data was established to investigate biological age of white matter tracts. All diffusion MRI datasets were obtained from the same 3-Tesla MRI scanner. To build the brain age prediction model, diffusion MRI datasets of 300 healthy participants were processed to extract age-relevant diffusion indices from 76 major white matter tracts. The extracted diffusion indices underwent Gaussian process regression to build the prediction model for white matter brain age. The model was validated in an independent testing set (N = 40) to ensure no overfitting of the model. The model was then applied to patients with right and left MTLE and matched controls (right MTLE: N = 17, left MTLE: N = 18, controls: N = 37), and predicted age difference (PAD) was obtained by calculating the difference between each individual's predicted brain age and chronological age. The higher PAD score indicated older brain age. The results showed that right MTLE exhibited older predicted brain age than the other two groups (PAD of right MTLE = 10.9 years [p 0.1 against control]; PAD of controls = 0.82 years). Patients with right and left MTLE showed strong correlations of the PAD scores with age of onset and duration of illness, but both groups showed opposite directions of correlations. In right MTLE, positive correlation of PAD with seizure frequency was found, and the right uncinate fasciculus was the most attributable tract to the increase in PAD. In conclusion, the present study found that patients with right MTLE exhibited premature white matter brain aging and their PAD scores were correlated with seizure frequency. Therefore, PAD is a potentially useful indicator of white matter impairment and disease severity in patients with right MTLE.