Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

Objective To investigate the relationship between EEG source localization and the number of scalp EEG recording channels. Methods 128 EEG channel recordings of 5 pediatric patients with medically intractable partial epilepsy were used to perform source localization of interictal spikes. The results were compared with surgical resection and intracranial recordings. Various electrode configurations were tested and a series of computer simulations based on a realistic head boundary element model were also performed in order to further validate the clinical findings. Results The improvement seen in source localization substantially decreases as the number of electrodes increases. This finding was evaluated using the surgical resection, intracranial recordings and computer simulation. It was also shown in the simulation that increasing the electrode numbers could remedy the localization error of deep sources. A plateauing effect was seen in deep and superficial sources with further increasing the electrode number. Conclusion The source localization is improved when electrode numbers increase, but the absolute improvement in accuracy decreases with increasing electrode number. Significance Increasing the electrode number helps decrease localization error and thus can more ably assist the physician to better plan for surgical procedures.

Brain networks are spatiotemporal phenomena that dynamically vary over time. Functional imaging approaches strive to noninvasively estimate these underlying processes. Here, we propose a novel source imaging approach that uses high-density EEG recordings to map brain networks. This approach objectively addresses the long-standing limitations of conventional source imaging techniques, namely, difficulty in objectively estimating the spatial extent, as well as the temporal evolution of underlying brain sources. We validate our approach by directly comparing source imaging results with the intracranial EEG (iEEG) findings and surgical resection outcomes in a cohort of 36 patients with focal epilepsy. To this end, we analyzed a total of 1,027 spikes and 86 seizures. We demonstrate the capability of our approach in imaging both the location and spatial extent of brain networks from noninvasive electrophysiological measurements, specifically for ictal and interictal brain networks. Our approach is a powerful tool for noninvasively investigating large-scale dynamic brain networks.

Estimating extended brain sources using EEG/MEG source imaging techniques is challenging. EEG and MEG have excellent temporal resolution at millisecond scale but their spatial resolution is limited due to the volume conduction effect. We have exploited sparse signal processing techniques in this study to impose sparsity on the underlying source and its transformation in other domains (mathematical domains, like spatial gradient). Using an iterative reweighting strategy to penalize locations that are less likely to contain any source, it is shown that the proposed iteratively reweighted edge sparsity minimization (IRES) strategy can provide reasonable information regarding the location and extent of the underlying sources. This approach is unique in the sense that it estimates extended sources without the need of subjectively thresholding the solution. The performance of IRES was evaluated in a series of computer simulations. Different parameters such as source location and signal-to-noise ratio were varied and the estimated results were compared to the targets using metrics such as localization error (LE), area under curve (AUC) and overlap between the estimated and simulated sources. It is shown that IRES provides extended solutions which not only localize the source but also provide estimation for the source extent. The performance of IRES was further tested in epileptic patients undergoing intracranial EEG (iEEG) recording for pre-surgical evaluation. IRES was applied to scalp EEGs during interictal spikes, and results were compared with iEEG and surgical resection outcome in the patients. The pilot clinical study results are promising and demonstrate a good concordance between noninvasive IRES source estimation with iEEG and surgical resection outcomes in the same patients. The proposed algorithm, i.e. IRES, estimates extended source solutions from scalp electromagnetic signals which provide relatively accurate information about the location and extent of the underlying source.

Objective Transcranial focused ultrasound (tFUS) has been introduced as a noninvasive neuromodulation technique with good spatial selectivity. We report an experimental investigation to detect noninvasive electrophysiological response induced by low-intensity tFUS in an in vivo animal model, and perform electrophysiological source imaging (ESI) of tFUS-induced brain activity from noninvasive scalp EEG recordings. Methods A single ultrasound transducer was used to generate low-intensity tFUS (Ispta<1 mW/cm2) and induce brain activation at multiple selected sites in an in vivo rat model. Up to 16 scalp electrodes were used to record tFUS-induced EEG. Event related potentials (ERPs) were analyzed in time, frequency, and spatial domains. Current source distributions were estimated by ESI to reconstruct spatio-temporal distributions of brain activation induced by tFUS. Results Neuronal activation was observed following low-intensity tFUS, as correlated to tFUS intensity and sonication duration. ESI revealed initial focal activation in cortical area corresponding to tFUS stimulation site, and the activation propagating to surrounding areas over time. Conclusion The present results demonstrate the feasibility of noninvasively recording brain electrophysiological response in vivo following low-intensity tFUS stimulation, and the feasibility of imaging spatio-temporal distributions of brain activation as induced by tFUS in vivo. Significance The present approach may lead to a new means of imaging brain activity using tFUS perturbation and a closed-loop ESI-guided tFUS neuromodulation modality.

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Transcranial direct current stimulation (tDCS) has been shown to affect motor and cognitive task performance and learning when applied to brain areas involved in the task. Targeted stimulation has also been found to alter connectivity within the stimulated hemisphere during rest. However, the connectivity effect of the interaction of endogenous task specific activity and targeted stimulation is unclear. This study examined the aftereffects of concurrent anodal high-definition tDCS over the left sensorimotor cortex with motor network connectivity during a one-dimensional EEG based sensorimotor rhythm brain-computer interface (SMR-BCI) task. Directed connectivity following anodal tDCS illustrates altered connections bilaterally between frontal and parietal regions, and these alterations occur in a task specific manner; connections between similar cortical regions are altered differentially during left and right imagination trials. During right-hand imagination following anodal tDCS, there was an increase in outflow from the left premotor cortex (PMC) to multiple regions bilaterally in the motor network and increased inflow to the stimulated sensorimotor cortex from the ipsilateral PMC and contralateral sensorimotor cortex. During left-hand imagination following anodal tDCS, there was increased outflow from the stimulated sensorimotor cortex to regions across the motor network. Significant correlations between connectivity and the behavioral measures of total correct trials and time-to-hit (TTH) correct trials were also found, specifically that the input to the left PMC correlated with decreased right hand imagination performance and that flow from the ipsilateral posterior parietal cortex (PPC) to midline sensorimotor cortex correlated with improved performance for both right and left hand imagination. These results indicate that tDCS interacts with task-specific endogenous activity to alter directed connectivity during SMR-BCI. In order to predict and maximize the targeted effect of tDCS, the interaction of stimulation with the dynamics of endogenous activity needs to be examined comprehensively and understood.

The aim of this study was to investigate the neurophysiological correlates of pain caused by sustained thermal stimulation. A group of 21 healthy volunteers was studied. 64-channel continuous EEG was recorded while the subject received tonic thermal stimulation. Spectral changes extracted from EEG were quantified and correlated with pain scales reported by subjects, the stimulation intensity, and the time course. Network connectivity was assessed to study the changes in connectivity patterns and strengths among brain regions that have been previously implicated in pain processing. Spectrally, a global reduction in power was observed in the lower spectral range, from delta to alpha, with the most marked changes in the alpha band. Spatially, the contralateral region of the somatosensory cortex, identified using source localization, was most responsive to stimulation status. Maximal desynchrony was observed when stimulation was present. The degree of alpha power reduction was linearly correlated to the pain rating reported by the subjects. Contralateral alpha power changes appeared to be a robust correlate of pain intensity experienced by the subjects. Granger causality analysis showed changes in network level connectivity among pain-related brain regions due to high intensity of pain stimulation versus innocuous warm stimulation. These results imply the possibility of using noninvasive EEG to predict pain intensity and to study the underlying pain processing mechanism in coping with prolonged painful experiences. Once validated in a broader population, the present EEG-based approach may provide an objective measure for better pain management in clinical applications.