Inter-subject gamma oscillation synchronization as a biomarker of abnormal processing of social interaction in ADHD.

Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.

Distributed source modeling of stereoencephalographic measurements of ictal activity.

OBJECTIVES: Stereoelectroencephalography (SEEG) can define the epileptogenic zone (EZ). However, SEEG is susceptible to the sampling bias, where no SEEG recording is taken within a circumscribed EZ. METHODS: Nine patients with medically refractory epilepsy underwent SEEG recording, and brain resection got positive outcomes. Ictal neuronal currents were estimated by distributed source modeling using the SEEG data and individual's anatomical magnetic resonance imaging. Using a retrospective leave-one-out data sub-sampling, we evaluated the sensitivity and specificity of the current estimates using MRI after surgical resection or radio-frequency ablation. RESULTS: The sensitivity and specificity in detecting the EZ were indistinguishable from either the data from all electrodes or the sub-sampled data (rank sum test: rank sum = 23719, p = 0.13) when at least one remaining electrode contact was no more than 20 mm away. CONCLUSIONS: The distributed neuronal current estimates of ictal SEEG data can mitigate the challenge of delineating the boundary of the EZ in cases of missing an electrode implanted within the EZ and a required second SEEG exploration. SIGNIFICANCE: Distributed source modeling can be a tool for clinicians to infer the EZ by allowing for more flexible planning of the electrode implantation route and minimizing the number of electrodes.

Acoustic noise generated by TMS in typical environment and inside an MRI scanner.

BACKGROUND: 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 TMS coil. When placed in a strong magnetic field, such as inside a 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. OBJECTIVE: Our objective was to measure the sound pressure levels (SPL) of TMS "click" sounds created by commercial TMS stimulators and coils in a typical environment and inside a 3-T MRI scanner and advance the knowledge of the acoustic behaviour of TMS to safely conduct TMS alone as well as concurrently with functional MRI (fMRI). METHODS: We report SPL measurements of two commercial MRI-compatible TMS systems in the 3-T B0 field of an MRI scanner and in the earth's magnetic field. Also, we present the acoustic noise measurements of four commercial TMS stimulators and three different TMS coils in a typical operational environment without the B0 field. RESULTS: The maximum peak SPL measured was 158 dB(C) inside the 3-T MRI scanner. Outside the scanner, the maximum peak SPL was 117 dB(C). Inside the scanner, the peak SPL increased by 21-45 dB(C) depending on the stimulator and the orientation of the electric field relative to the B field. CONCLUSIONS: Hearing protection is obligatory during concurrent TMS-fMRI experiments and highly recommended during any TMS experiment. The manufacturing of quieter TMS systems is encouraged to reduce the risk of hearing damage and other unwanted effects.

Omnidirectional Monolithic Marker for Intra-Operative MR-Based Positional Sensing in Closed MRI.

We present a design of an inductively coupled radio frequency (ICRF) marker for magnetic resonance (MR)-based positional tracking, enabling the robust increase of tracking signal at all scanning orientations in quadrature-excited closed MR imaging (MRI). The marker employs three curved resonant circuits fully covering a cylindrical surface that encloses the signal source. Each resonant circuit is a planar spiral inductor with parallel plate capacitors fabricated monolithically on flexible printed circuit board (FPC) and bent to achieve the curved structure. Size of the constructed marker is Ø3-mm ×5 -mm with quality factor > 22, and its tracking performance was validated with 1.5 T MRI scanner. As result, the marker remains as a high positive contrast spot under 360° rotations in 3 axes. The marker can be accurately localized with a maximum error of 0.56 mm under a displacement of 56 mm from the isocenter, along with an inherent standard deviation of 0.1-mm. Accrediting to the high image contrast, the presented marker enables automatic and real-time tracking in 3D without dependency on its orientation with respect to the MRI scanner receive coil. In combination with its small form-factor, the presented marker would facilitate robust and wireless MR-based tracking for intervention and clinical diagnosis. This method targets applications that can involve rotational changes in all axes (X-Y-Z).

Visual Stimuli Modulate Local Field Potentials But Drive No High-Frequency Activity in Human Auditory Cortex.

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (ACs). 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 (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERPs) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. 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.

Design of coil holder for the improved maneuvering in concurrent TMS-MRI.

BACKGROUND: Concurrent 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. OBJECTIVE: We 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. METHODS: A holder with one controlling knob, two omni-direction rotation joints, and two in-plane rotation joints was developed. RESULTS: Different 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. CONCLUSION: Our development significantly improves the workflow of the concurrent TMS-MRI in new neuroscience studies and clinical applications.

Ballistocardiogram suppression in concurrent EEG-MRI by dynamic modeling of heartbeats.

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.

Processing of an Audiobook in the Human Brain Is Shaped by Cultural Family Background.

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.

Trail Making Test Performance Using a Touch-Sensitive Tablet: Behavioral Kinematics and Electroencephalography.

The Trail Making Test (TMT) is widely used to probe brain function and is performed with pen and paper, involving Parts A (linking numbers) and B (alternating between linking numbers and letters). The relationship between TMT performance and the underlying brain activity remains to be characterized in detail. Accordingly, sixteen healthy young adults performed the TMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed of linking movements, during simultaneous electroencephalography (EEG). Linking and non-linking periods were derived as estimates of the time spent executing and preparing movements, respectively. The seconds per link (SPL) was also used to quantify TMT performance. A strong effect of TMT Part A and B was observed on the SPL value as expected (Part B showing increased SPL value); whereas the EEG results indicated robust effects of linking and non-linking periods in multiple frequency bands, and effects consistent with the underlying cognitive demands of the test.

Distributed source modeling of intracranial stereoelectro-encephalographic measurements.

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.

Seizure Frequency Is Associated with Effective Connectivity of the Hippocampal-Diencephalic-Cingulate in Epilepsy with Unilateral Mesial Temporal Sclerosis.

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 intrinsic effective connectivity (iEC) in TLE with unilateral MTS and their associations with seizure frequency. Methods: Thirty patients with unilateral MTS (left/right MTS = 14/16) and 37 age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rsfMRI) on a 3-Tesla magnetic resonance imaging (MRI) system. The structural equation modeling was employed to estimate the iEC of the three candidate epilepsy models, including the Papez circuit, hippocampal-diencephalic-cingulate (HDC) model, and simplified HDC model. After comparing the performance of model fitting, the best model was selected to compare iEC among the study groups. The linear regression analysis was performed to associate abnormal iEC with seizure frequency. Results: The simplified HDC model was the best model to estimate iEC across the three study groups (p < 0.05), and it composed of the 26 interconnected pathway between the mesial temporal lobe, thalamus, and cingulate cortices. The linear regression analysis revealed a significant relationship between the shared iEC alterations in both patient groups and seizure frequency (adjusted-R2 = 0.350; p = 0.037), including the three paths of mammillary body (MB) → bilateral anterior thalamic nuclei (left: standardized ß-value = 0.580, p = 0.013; right: standardized ß-value = -0.711, p = 0.006) and right hippocampus → MB (standardized ß-value = 0.541, p = 0.045). Conclusions: Our findings provide new insights into neurophysiological significance relevant to seizure recurrence. Aberrant iEC on the neural paths connected to the MB can be a potential imaging marker, aiding the therapeutic management in TLE with unilateral MTS. Impact statement Within the simplified hippocampal-diencephalic-cingulate model, we identified that altered intrinsic effective connectivity (iEC) on the three paths connecting to the mammillary body was common in temporal lobe epilepsy (TLE) with left and right mesial temporal sclerosis (MTS) and was associated with seizure frequency. Therefore, these common iEC alterations could be a potential imaging marker, aiding the therapeutic management in patients with TLE with unilateral MTS.

Impact of physiological noise in characterizing the functional MRI default-mode network in Alzheimer's disease.

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.

Concurrent electrophysiological and hemodynamic measurements of evoked neural oscillations in human visual cortex using sparsely interleaved fast fMRI and EEG.

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 â€‹s, and performing these acquisitions once every 2 â€‹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.

Multivariate Identification of Functional Neural Networks Underpinning Humorous Movie Viewing.

While univariate functional magnetic resonance imaging (fMRI) data analysis methods have been utilized successfully to map brain areas associated with cognitive and emotional functions during viewing of naturalistic stimuli such as movies, multivariate methods might provide the means to study how brain structures act in concert as networks during free viewing of movie clips. Here, to achieve this, we generalized the partial least squares (PLS) analysis, based on correlations between voxels, experimental conditions, and behavioral measures, to identify large-scale neuronal networks activated during the first time and repeated watching of three ∼5-min comedy clips. We identified networks that were similarly activated across subjects during free viewing of the movies, including the ones associated with self-rated experienced humorousness that were composed of the frontal, parietal, and temporal areas acting in concert. In conclusion, the PLS method seems to be well suited for the joint analysis of multi-subject neuroimaging and behavioral data to quantify a functionally relevant brain network activity without the need for explicit temporal models.

An orthogonal shim coil for 3T brain imaging.

PURPOSE: We designed and implemented an orthogonal shim array consisting of shim coils with their planes perpendicular to the planes of neighboring RF coils. This shim coil improves the magnetic field homogeneity by minimizing the 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 2nd order spherical harmonic shimming. CONCLUSION: Orthogonal shim coils can improve the field homogeneity while maintaining high image SNR.

Premature white matter aging in patients with right mesial temporal lobe epilepsy: A machine learning approach based on diffusion MRI data.

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 < 0.05 against left MTLE; p < 0.001 against control]; PAD of left MTLE = 2.2 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.

Differential brain mechanisms during reading human vs. machine translated fiction and news texts.

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.

Reduced synchronized brain activity in schizophrenia during viewing of comedy movies.

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.