Papers by Srikantan Nagarajan
Proceedings of the National Academy of Sciences of the United States of America, May 25, 1999
Magnetoencephalographic responses recorded from auditory cortex evoked by brief and rapidly succe... more Magnetoencephalographic responses recorded from auditory cortex evoked by brief and rapidly successive stimuli differed between adults with poor vs. good reading abilities in four important ways. First, the response amplitude evoked by short-duration acoustic stimuli was stronger in the post-stimulus time range of 150-200 ms in poor readers than in normal readers. Second, response amplitude to rapidly successive and brief stimuli that were identical or that differed significantly in frequency were substantially weaker in poor readers compared with controls, for interstimulus intervals of 100 or 200 ms, but not for an interstimulus interval of 500 ms. Third, this neurological deficit closely paralleled subjects' ability to distinguish between and to reconstruct the order of presentation of those stimulus sequences. Fourth, the average distributed response coherence evoked by rapidly successive stimuli was significantly weaker in the -and ␥-band frequency ranges (20-60 Hz) in poor readers, compared with controls. These results provide direct electrophysiological evidence supporting the hypothesis that reading disabilities are correlated with the abnormal neural representation of brief and rapidly successive sensory inputs, manifested in this study at the entry level of the cortical auditory/aural speech representational system(s).
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings, 1997
Determines the primary cortical evoked magnetic field responses to brief somatosensory and audito... more Determines the primary cortical evoked magnetic field responses to brief somatosensory and auditory stimuli in awake humans. These responses comprise evoked coherent low-frequency oscillations in the range of 4-15 Hz lasting for 100-300 ms. Responses to pairs of stimuli occurring at various inter-stimulus intervals interact non-linearly. Latencies between the peaks of the evoked response were linearly related to the intervals between stimuli, reflecting the high-fidelity representation of stimulus intervals in both primary cortical areas. The sources of the different cycles of these oscillations and the sources of responses to stimulus pairs both localize to the same cortical area, indicating that the observed responses reflect changes in underlying cortical excitability. The potential origins and functional role of these oscillations in the processing and representation of temporal information on this time scale are discussed.
Frontiers in Human Neuroscience, 2021
Magnetoencephalography (MEG) is increasingly used for presurgical planning in people with medical... more Magnetoencephalography (MEG) is increasingly used for presurgical planning in people with medically refractory focal epilepsy. Localization of interictal epileptiform activity, a surrogate for the seizure onset zone whose removal may prevent seizures, is challenging and depends on the use of multiple complementary techniques. Accurate and reliable localization of epileptiform activity from spontaneous MEG data has been an elusive goal. One approach toward this goal is to use a novel Bayesian inference algorithm—the Champagne algorithm with noise learning—which has shown tremendous success in source reconstruction, especially for focal brain sources. In this study, we localized sources of manually identified MEG spikes using the Champagne algorithm in a cohort of 16 patients with medically refractory epilepsy collected in two consecutive series. To evaluate the reliability of this approach, we compared the performance to equivalent current dipole (ECD) modeling, a conventional source...
Robust estimation of the number, location, and activity of multiple correlated brain sources has ... more Robust estimation of the number, location, and activity of multiple correlated brain sources has long been a challenging task in electromagnetic brain imaging from M/EEG data, one that is significantly impacted by interference from spontaneous brain activity, sensor noise, and other sources of artifacts. Recently, we introduced the Champagne algorithm, a novel Bayesian inference algorithm that has shown tremendous success in M/EEG source reconstruction. Inherent to Champagne and most other related Bayesian reconstruction algorithms is the assumption that the noise covariance in sensor data can be estimated from “baseline” or “control” measurements. However, in many scenarios, such baseline data is not available, or is unreliable, and it is unclear how best to estimate the noise covariance. In this technical note, we propose several robust methods to estimate the contributions to sensors from noise arising from outside the brain without the need for additional baseline measurements. ...
Frontiers in Neuroscience, 2020
Neurodynamic Utility Toolbox for Magnetoencephalo-and Electroencephalography (NUTMEG) is an open-... more Neurodynamic Utility Toolbox for Magnetoencephalo-and Electroencephalography (NUTMEG) is an open-source MATLAB-based toolbox for the analysis and reconstruction of magnetoencephalography/electroencephalography data in source space. NUTMEG includes a variety of options for the user in data import, preprocessing, source reconstruction, and functional connectivity. A group analysis toolbox allows the user to run a variety of inferential statistics on their data in an easy-to-use GUI-driven format. Importantly, NUTMEG features an interactive five-dimensional data visualization platform. A key feature of NUTMEG is the availability of a large menu of interference cancelation and source reconstruction algorithms. Each NUTMEG operation acts as a stand-alone MATLAB function, allowing the package to be easily adaptable and scripted for the more advanced user for interoperability with other software toolboxes. Therefore, NUTMEG enables a wide range of users access to a complete "sensor-tosource-statistics" analysis pipeline.
Physical Therapy, 1997
Background and Purpose. Jobrelated repetitive strain injuries (RSIS) are increasing, and current ... more Background and Purpose. Jobrelated repetitive strain injuries (RSIS) are increasing, and current treatment strategies often fail to return injured people to work. This study documented the neural consequences of using two different movement strategies for active, repetitive hand closing and opening. Methods. Two owl monkeys were trained for 20 weeks to repetitively close a handpiece against an 8% force (3-400 trials per day, training at 80%-90% accuracy). One monkey used a highly articulated hand-squeezing strategy, and the other monkey used a proximal armpulling strategy. Changes in motor performance were analyzed, and the electrophysiological maps of the hand representation on the trained primary sensory cortex (area 3b) were compared with those of untrained control animals and the untrained sides of the trained monkeys. Results. The monkey using the articulated hand-squeezing strategy showed motor deterioration and dedifferentiation of the normally sharply segregated areas of the hand representation in area 3b. Mild degradation of the hand representation was measured in the monkey using the proximal armpulling strategy, but there was no motor dysfunction. Conclusion and Discussion. Attended, highly articulated, repetitive finger squeezing degrades the hand representation and interferes with motor control. A proximal, more variable repetitive strategy minimized the sensory degradation and preserved motor control. Restoring the hand representation may be a critical part of treatment for patients with chronic RSI and focal hand dystonia. [Byl NN, Merzenich MM, Cheung S, et al. A primate model for studying focal dystonia and repetitive strain injury: effects on the primary somatosensory cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2016
The development of hemispheric lateralization for language is poorly understood. In one hypothesi... more The development of hemispheric lateralization for language is poorly understood. In one hypothesis, early asymmetric gene expression assigns language to the left hemisphere. In an alternate view, language is represented a priori in both hemispheres and lateralization emerges via cross-hemispheric communication through the corpus callosum. To address this second hypothesis, we capitalized on the high temporal and spatial resolution of magnetoencephalographic imaging to measure cortical activity during language processing, speech preparation, and speech execution in 25 participants with agenesis of the corpus callosum (AgCC) and 21 matched neurotypical individuals. In contrast to strongly lateralized left hemisphere activations for language in neurotypical controls, participants with complete or partial AgCC exhibited bilateral hemispheric activations in both auditory or visually driven language tasks, with complete AgCC participants showing significantly more right hemisphere activat...
Human brain mapping, Jan 25, 2016
Modulation of vocal pitch is a key speech feature that conveys important linguistic and affective... more Modulation of vocal pitch is a key speech feature that conveys important linguistic and affective information. Auditory feedback is used to monitor and maintain pitch. We examined induced neural high gamma power (HGP) (65-150 Hz) using magnetoencephalography during pitch feedback control. Participants phonated into a microphone while hearing their auditory feedback through headphones. During each phonation, a single real-time 400 ms pitch shift was applied to the auditory feedback. Participants compensated by rapidly changing their pitch to oppose the pitch shifts. This behavioral change required coordination of the neural speech motor control network, including integration of auditory and somatosensory feedback to initiate change in motor plans. We found increases in HGP across both hemispheres within 200 ms of pitch shifts, covering left sensory and right premotor, parietal, temporal, and frontal regions, involved in sensory detection and processing of the pitch shift. Later respo...
Proceedings of the 19th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 'Magnificent Milestones and Emerging Opportunities in Medical Engineering' (Cat. No.97CH36136), 1997
Determines the primary cortical evoked magnetic field responses to brief somatosensory and audito... more Determines the primary cortical evoked magnetic field responses to brief somatosensory and auditory stimuli in awake humans. These responses comprise evoked coherent low-frequency oscillations in the range of 4-15 Hz lasting for 100-300 ms. Responses to pairs of stimuli occurring at various inter-stimulus intervals interact non-linearly. Latencies between the peaks of the evoked response were linearly related to the intervals between stimuli, reflecting the high-fidelity representation of stimulus intervals in both primary cortical areas. The sources of the different cycles of these oscillations and the sources of responses to stimulus pairs both localize to the same cortical area, indicating that the observed responses reflect changes in underlying cortical excitability. The potential origins and functional role of these oscillations in the processing and representation of temporal information on this time scale are discussed.
Neurology & clinical neurophysiology : NCN, Jan 30, 2004
We have developed an analysis toolbox called NUTMEG (Neurodynamic Utility Toolbox for Magnetoence... more We have developed an analysis toolbox called NUTMEG (Neurodynamic Utility Toolbox for Magnetoencephalography) for reconstructing the spatiotemporal dynamics of neural activations and overlaying them onto structural MR images. The toolbox runs under MATLAB in conjunction with SPM2 and can be used with the Linux/UNIX, Mac OS X, and even Windows platforms. Currently, evoked magnetic field data from 4-D Neuroimaging, CTF, and KIT systems can be imported to the toolbox for analysis. NUTMEG uses an eigenspace vector beamforming algorithm to generate a tomographic reconstruction of spatiotemporal magnetic source activity over selected time intervals and spatial regions. The MEG coordinate frame is coregistered with an anatomical MR image using fiducial locations and, optionally, head shape information. This allows the reconstruction to be superimposed onto an MRI to provide a convenient visual correspondence to neuroanatomy. Navigating through the MR volume automatically updates the displa...
Frontiers in human neuroscience, 2010
The cognitive dysfunction present in patients with schizophrenia is thought to be driven in part ... more The cognitive dysfunction present in patients with schizophrenia is thought to be driven in part by disorganized connections between higher-order cortical fields. Although studies utilizing electroencephalography (EEG), PET and fMRI have contributed significantly to our understanding of these mechanisms, magnetoencephalography (MEG) possesses great potential to answer long-standing questions linking brain interactions to cognitive operations in the disorder. Many experimental paradigms employed in EEG and fMRI are readily extendible to MEG and have expanded our understanding of the neurophysiological architecture present in schizophrenia. Source reconstruction techniques, such as adaptive spatial filtering, take advantage of the spatial localization abilities of MEG, allowing us to evaluate which specific structures contribute to atypical cognition in schizophrenia. Finally, both bivariate and multivariate functional connectivity metrics of MEG data are useful for understanding how ...
Neural Plasticity, 2002
Focal hand dystonia (FHd) is a recalcitrant, disabling movement disorder, characterized by involu... more Focal hand dystonia (FHd) is a recalcitrant, disabling movement disorder, characterized by involuntary co-contractions of agonists and antagonists, that can develop in patients who overuse or misuse their hands. The aim of this study was to document clinical neuromusculoskeletal performance and somatosensory responses (magnetoencephalography) in healthy controls and in FHd subjects withmildversusseverehand dystonia. The performance of healthy subjects (n = 17) was significantly better than that of FHd subjects (n = 17) on all clinical parameters. Those withmild dystonia(n = 10) demonstrated better musculoskeletal skills, task-specific motor performance, and sensory discrimination, but the performance of sensory and fine motor tasks was slower than that of patients withsevere dystonia. In terms of somatosensory evoked field responses (SEFs), FHd subjects demonstrated a significant difference in the location of the hand representation on the x and y axes, lower amplitude of SEFs integ...
The Journal of Neuroscience, 2013
Despite significant research and important clinical correlates, direct neural evidence for a phon... more Despite significant research and important clinical correlates, direct neural evidence for a phonological loop linking speech perception, short-term memory and production remains elusive. To investigate these processes, we acquired whole-head magnetoencephalographic (MEG) recordings from human subjects performing a variable-length syllable sequence reproduction task. The MEG sensor data were source localized using a time–frequency optimized spatially adaptive filter, and we examined the time courses of cortical oscillatory power and the correlations of oscillatory power with behavior between onset of the audio stimulus and the overt speech response. We found dissociations between time courses of behaviorally relevant activations in a network of regions falling primarily within the dorsal speech stream. In particular, verbal working memory load modulated high gamma power in both Sylvian–parietal–temporal and Broca's areas. The time courses of the correlations between high gamma p...
Proceedings of the National Academy of Sciences, 2000
The biological basis for developmental dyslexia remains unknown. Research has suggested that a fu... more The biological basis for developmental dyslexia remains unknown. Research has suggested that a fundamental deficit in dyslexia is the inability to process sensory input that enters the nervous system rapidly and that deficits in processing rapid acoustic information are associated with impaired reading. Functional magnetic resonance imaging (fMRI) was used to identify the brain basis of rapid acoustic processing in normal readers and to discover the status of that response in dyslexic readers. Normal readers showed left prefrontal activity in response to rapidly changing, relative to slowly changing, nonlinguistic acoustic stimuli. Dyslexic readers showed no differential left frontal response. Two dyslexic readers participated in a remediation program and showed increased activity in left prefrontal cortex after training. These fMRI results identify left prefrontal regions as normally being sensitive to rapid relative to slow acoustic stimulation, insensitive to the difference betwe...
NeuroImage, 2012
In this paper, we present an extensive performance evaluation of a novel source localization algo... more In this paper, we present an extensive performance evaluation of a novel source localization algorithm, Champagne. It is derived in an empirical Bayesian framework that yields sparse solutions to the inverse problem. It is robust to correlated sources and learn the statistics of nonstimulus-evoked activity to suppress the effect of noise and interfering brain activity. We tested Champagne on both simulated and real M/EEG data. The source locations used for the simulated data were chosen to test performance on challenging source configurations. In simulations, we found that Champagne outperforms the benchmark algorithms in terms of both the accuracy of the source localizations and the correct estimation of source time courses. We also demonstrate that Champagne is more robust to correlated brain activity present in real MEG data and is able to resolve many distinct and functionally relevant brain areas with real MEG and EEG data.
Journal of Neurosurgery, 2008
Object The goal of this study was to examine the sensitivity and specificity in preoperative loca... more Object The goal of this study was to examine the sensitivity and specificity in preoperative localization of hand motor cortex by imaging regional event-related desynchronization (ERD) of brainwaves in the β frequency band (15–25 Hz) involved in self-paced movement. Methods Using magnetoencephalography (MEG), the authors measured ERD that occurred before self-paced unilateral index finger flexion in 66 patients with brain tumors, epilepsy, and arteriovenous malformations. Results The authors applied an adaptive spatial filtering algorithm to MEG data and found that peaks of the tomographic distribution of β-band ERD sources reliably localized hand motor cortex compared with electrical cortical stimulation. They also observed high specificity in estimating contralateral hand motor cortical representations relative to somatosensory cortex. Neither presence nor location of tumor changed the qualitative or quantitative location of motor cortex relative to somatosensory cortex. Conclusio...
Experimental Neurology, 2012
After cerebral ischemia, disruption and subsequent reorganization of functional connections occur... more After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential
Computational Intelligence and Neuroscience, 2011
NUTMEG is a source analysis toolbox geared towards cognitive neuroscience researchers using MEG a... more NUTMEG is a source analysis toolbox geared towards cognitive neuroscience researchers using MEG and EEG, including intracranial recordings. Evoked and unaveraged data can be imported to the toolbox for source analysis in either the time or time-frequency domains. NUTMEG offers several variants of adaptive beamformers, probabilistic reconstruction algorithms, as well as minimum-norm techniques to generate functional maps of spatiotemporal neural source activity. Lead fields can be calculated from single and overlapping sphere head models or imported from other software. Group averages and statistics can be calculated as well. In addition to data analysis tools, NUTMEG provides a unique and intuitive graphical interface for visualization of results. Source analyses can be superimposed onto a structural MRI or headshape to provide a convenient visual correspondence to anatomy. These results can also be navigated interactively, with the spatial maps and source time series or spectrogram...
Cerebral Cortex, 2010
Little is known about the temporal dynamics of cortical activation during visually guided behavio... more Little is known about the temporal dynamics of cortical activation during visually guided behavior. We measured changes in brain activity in human posterior parietal cortex (PPC) and premotor cortex (PMC) during saccades and visually guided reaching using magnetoencephalography (MEG) and novel time-frequency reconstructions of MEG (tfMEG) data. Results indicate that early highgamma activity over the frontal eye fields (FEFs) was present during saccade preparation, and high-gamma activity progressed from the supplementary and FEFs to visual cortex during saccade execution. In contrast, early high-gamma activity over dorsal PMC and late beta activity in primary motor cortex and PPC were unique to reach preparation. During reaching, high-gamma activity progressed from sensorimotor cortex and PMC to parietooccipital cortex. These unique spatial-temporal processing patterns reflect the known connectivity of 2 different sensorimotor networks in macaques. The onset and duration of activity in these areas provides direct evidence for concurrent serial and parallel processing in the human brain during the integration of the sensorimotor inputs necessary for visually guided performance.
Uploads
Papers by Srikantan Nagarajan