Papers by Srikantan Nagarajan
Frontiers in Human Neuroscience, May 26, 2017
This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatos... more This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8-12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.
Journal of Neural Engineering, Apr 16, 2018
Objective.-Magnetoencephalography (MEG) has a well-recognized weakness at detecting deeper brain ... more Objective.-Magnetoencephalography (MEG) has a well-recognized weakness at detecting deeper brain activities. This paper proposes a novel algorithm for selective detection of deep sources by suppressing interference signals from superficial sources in MEG measurements. Approach.-The proposed algorithm combines the beamspace preprocessing method with the dual signal space projection (DSSP) interference suppression method. A prerequisite of the proposed algorithm is prior knowledge of the location of the deep sources. The proposed algorithm first derives the basis vectors that span a local region just covering the locations of the deep sources. It then estimates the time-domain signal subspace of the superficial sources by using the projector composed of these basis vectors. Signals from the deep sources are extracted by projecting the row space of the data matrix onto the direction orthogonal to the signal subspace of the superficial sources. Main results.-Compared with the previously proposed beamspace signal space separation (SSS) method, the proposed algorithm is capable of suppressing much stronger interference from superficial sources. This capability is demonstrated in our computer simulation as well as experiments using phantom data. Significance.-The proposed bDSSP algorithm can be a powerful tool in studies of physiological functions of midbrain and deep brain structures.
Consciousness and Cognition, Dec 1, 2011
We explored the neural mechanisms allowing humans to report the subjective onset times of conscio... more We explored the neural mechanisms allowing humans to report the subjective onset times of conscious events. Magnetoencephalographic recordings of neural oscillations were obtained while human subjects introspected the timing of sensory, intentional, and motor events during a forced choice task. Brain activity was reconstructed with high spatio-temporal resolution. Event-time introspection was associated with specific neural activity at the time of subjective event onset which was spatially distinct from activity induced by the event itself. Different brain regions were selectively recruited for introspection of different event types, e.g., the bilateral angular gyrus for introspection of intention. Our results suggest that event-time introspection engages specific neural networks to assess the contents of consciousness. Subjective event times should therefore be interpreted as the result of complex interactions between introspection and experience networks, rather than as direct reproduction of the individual's conscious state or as a mere posthoc interpretation.
NeuroImage, May 1, 2005
This paper discusses the location bias and the spatial resolution in the reconstruction of a sing... more This paper discusses the location bias and the spatial resolution in the reconstruction of a single dipole source by various spatial filtering techniques used for neuromagnetic imaging. We first analyze the location bias for several representative adaptive and non-adaptive spatial filters using their resolution kernels. This analysis theoretically validates previously reported empirical findings that standardized low-resolution electromagnetic tomography (sLORETA) has no location bias. We also find that the minimum-variance spatial filter does exhibit bias in the reconstructed location of a single source, but that this bias is eliminated by using the normalized lead field. We then focus on the comparison of sLORETA and the lead-field normalized minimum-variance spatial filter, and analyze the effect of noise on source location bias. We find that the signal-to-noise ratio (SNR) in the measurements determines whether the sLORETA reconstruction has source location bias, while the lead-field normalized minimum-variance spatial filter has no location bias even in the presence of noise. Finally, we compare the spatial resolution for sLORETA and the minimum-variance filter, and show that the minimum-variance filter attains much higher resolution than sLORETA does. The results of these analyses are validated by numerical experiments as well as by reconstructions based on two sets of evoked magnetic responses.
Laryngeal Dystonia is a debilitating disorder of voicing in which the laryngeal muscles are inter... more Laryngeal Dystonia is a debilitating disorder of voicing in which the laryngeal muscles are intermittently in spasm resulting in involuntary interruptions during speech. The central pathophysiology of laryngeal dystonia, underlying computational impairments in vocal motor control, remains poorly understood. Although prior imaging studies have found aberrant activity in the central nervous system during phonation in patients with laryngeal dystonia, it is not known at what timepoints during phonation these abnormalities emerge and what function may be impaired. To investigate this question, we recruited 22 adductor laryngeal dystonia patients (15 female, age range = 28.83-72.46 years) and 18 controls (8 female, age range = 27.40-71.34 years). We leveraged the fine temporal resolution of magnetoencephalography to monitor neural activity around glottal movement onset, subsequent voice onset and after the onset of pitch feedback perturbations. We examined eventrelated beta-band (12-30 Hz) and high-gamma band (65-150 Hz) neural oscillations. Prior to glottal movement onset, we observed abnormal frontoparietal motor preparatory activity. After glottal movement onset, we observed abnormal activity in somatosensory cortex persisting through voice onset. Prior to voice onset and continuing after, we also observed abnormal activity in the auditory cortex and the cerebellum. After pitch feedback perturbation onset, we observed no differences between controls and patients in their behavioural responses to the perturbation. But in patients, we did find abnormal activity in brain regions thought to be .
IEEE Transactions on Biomedical Engineering, Sep 1, 2006
This paper proposes a novel prewhitening eigenspace beamformer suitable for magnetoencephalogram ... more This paper proposes a novel prewhitening eigenspace beamformer suitable for magnetoencephalogram (MEG) source reconstruction when large background brain activities exist. The prerequisite for the method is that control-state measurements, which contain only the contributions from the background interference, be available, and that the covariance matrix of the background interference can be obtained from such control-state measurements. The proposed method then uses this interference covariance matrix to remove the influence of the interference in the reconstruction obtained from the target measurements. A numerical example, as well as applications to two types of MEG data, demonstrates the effectiveness of the proposed method.
Frontiers in Neuroscience, 2012
Uncovering brain activity from magnetoencephalography (MEG) data requires solving an illposed inv... more Uncovering brain activity from magnetoencephalography (MEG) data requires solving an illposed inverse problem, greatly confounded by noise, interference, and correlated sources. Sparse reconstruction algorithms, such as Champagne, show great promise in that they provide focal brain activations robust to these confounds. In this paper, we address the technical considerations of statistically thresholding brain images obtained from sparse reconstruction algorithms. The source power distribution of sparse algorithms makes this class of algorithms ill-suited to "conventional" techniques. We propose two non-parametric resampling methods hypothesized to be compatible with sparse algorithms.The first adapts the maximal statistic procedure to sparse reconstruction results and the second departs from the maximal statistic, putting forth a less stringent procedure that protects against spurious peaks. Simulated MEG data and three real data sets are utilized to demonstrate the efficacy of the proposed methods. Two sparse algorithms, Champagne and generalized minimum-current estimation (G-MCE), are compared to two non-sparse algorithms, a variant of minimum-norm estimation, sLORETA, and an adaptive beamformer. The results, in general, demonstrate that the already sparse images obtained from Champagne and G-MCE are further thresholded by both proposed statistical thresholding procedures. While non-sparse algorithms are thresholded by the maximal statistic procedure, they are not made sparse. The work presented here is one of the first attempts to address the problem of statistically thresholding sparse reconstructions, and aims to improve upon this already advantageous and powerful class of algorithm.
NeuroImage, 2010
The synchronous brain activity measured via MEG (or EEG) can be interpreted as arising from a col... more The synchronous brain activity measured via MEG (or EEG) can be interpreted as arising from a collection (possibly large) of current dipoles or sources located throughout the cortex. Estimating the number, location, and time course of these sources remains a challenging task, one that is significantly compounded by the effects of source correlations and unknown orientations and by the presence of interference from spontaneous brain activity, sensor noise, and other artifacts. This paper derives an empirical Bayesian method for addressing each of these issues in a principled fashion. The resulting algorithm guarantees descent of a cost function uniquely designed to handle unknown orientations and arbitrary correlations. Robust interference suppression is also easily incorporated. In a restricted setting, the proposed method is shown to produce theoretically zero reconstruction error estimating multiple dipoles even in the presence of strong correlations and unknown orientations, unlike a variety of existing Bayesian localization methods or common signal processing techniques such as beamforming and sLORETA. Empirical results on both simulated and real data sets verify the efficacy of this approach.
This paper presents an analysis on the performance of the prewhitening beamformer when applied to... more This paper presents an analysis on the performance of the prewhitening beamformer when applied to magnetoencephalography (MEG) experiments involving dual (task and control) conditions. We first analyze the method's robustness to two types of violations of the prerequisites for the prewhitening method that may arise in real-life two-condition experiments. In one type of violation, some sources exist only in the control condition but not in the task condition. In the other type of violation, some signal sources exist both in the control and the task conditions, and that they change intensity between the two conditions. Our analysis shows that the prewhitening method is very robust to these nonideal conditions. In this paper, we also present a theoretical analysis showing that the prewhitening method is considerably insensitive to overestimation of the signal-subspace dimensionality. Therefore, the prewhitening beamformer does not require accurate estimation of the signal subspace dimension. Results of our theoretical analyses are validated in numerical experiments and in experiments using a real MEG data set obtained during self-paced hand movements.
Scientific Reports, May 2, 2019
Reality monitoring is defined as the ability to distinguish internally self-generated information... more Reality monitoring is defined as the ability to distinguish internally self-generated information from externally-derived information. the medial prefrontal cortex (mpFC) is a key brain region subserving reality monitoring and has been shown to be activated specifically during the retrieval of self-generated information. However, it is unclear if mpFC is activated during the encoding of selfgenerated information into memory. If so, it is important to understand whether successful retrieval of self-generated information critically depends on enhanced neural activity within mpFC during initial encoding of this self-generated information. We used magnetoencephalographic imaging (MeGI) to determine the timing and location of cortical activity during a reality-monitoring task involving self generated contextual source memory encoding and retrieval. We found both during encoding and retrieval of self-generated information, when compared to externally-derived information, mpFC showed significant task induced oscillatory power modulation in the beta-band. During initial encoding of self-generated information, greater mpFC beta-band power reductions occurred within a time window of -700 ms to -500 ms prior to vocalization. This increased activity in mPFC was not observed during encoding of externally-derived information. Additionally, increased mpFC activity during encoding of self-generated information predicted subsequent retrieval accuracy of this self-generated information. Beta-band activity in mpFC was also observed during the initial retrieval of self-generated information within a time window of 300 to 500 ms following stimulus onset and correlated with accurate retrieval performance of self-generated information. together, these results further highlight the importance of mpFC in mediating the initial generation and awareness of participants' internal thoughts.
IEEE Transactions on Biomedical Engineering, Nov 1, 2009
Independent Components Analysis (ICA) has previously been used to denoise EEG/MEG signals before ... more Independent Components Analysis (ICA) has previously been used to denoise EEG/MEG signals before performing neural source localization. Source localization is then performed using a method such as beamforming or dipole fitting. Here we show how ICA can also be used as a source localization method, negating the need for beamforming and dipole fitting. This type of approach is valid whenever an estimate of the forward (mixing) model for all putative source locations is available, which includes EEG and MEG applications. The proposed method consists of estimating the forward model using the laws of physics, estimating a second forward model using ICA, and then correlating the columns of the matrices that represent the two forward models. We show that, when synthetic data are used, the proposed localization method produces a smaller localization error than several alternatives. We also show localization results for real auditory-evoked MEG data.
IEEE Transactions on Biomedical Engineering, Jul 1, 2006
Many tomographic source localization algorithms used in biomagnetic imaging assume, explicitly or... more Many tomographic source localization algorithms used in biomagnetic imaging assume, explicitly or sometimes implicitly, that the source activity at different brain locations are either independent or that the correlation structure between sources is known. Among these algorithms is a class of adaptive spatial filters known as beamformers, which have superior spatiotemporal resolution abilities. The performance of beamformers is robust to weakly coherent sources. However, these algorithms are extremely sensitive to the presence of strongly coherent sources. A frequent mode of failure in beamformers occurs with reconstruction of auditory evoked fields (AEFs), in which bilateral auditory cortices are highly coherent in their activation. Here, we present a novel beamformer that suppresses activation from regions with interfering coherent sources. First, a volume containing the interfering sources is defined. The lead field matrix for this volume is computed and reduced into a few significant columns using singular value decomposition (SVD). A vector beamformer is then constructed by rejecting the contribution of sources in the suppression region while allowing for source reconstruction at other specified regions. Performance of this algorithm was first validated with simulated data. Subsequent tests of this modified beamformer were performed on bilateral AEF data. An unmodified vector beamformer using whole head coverage misplaces the source medially. After defining a suppression region containing the temporal cortex on one side, the described method consistently results in clear focal activations at expected regions of the contralateral superior temporal plane.
Neuroreport, Sep 18, 2006
Electroencephalography and magnetoencephalography studies have shown that auditory cortical respo... more Electroencephalography and magnetoencephalography studies have shown that auditory cortical responses to self-produced speech are attenuated when compared with responses to tape-recorded speech, but that this attenuation disappears if auditory feedback is altered. These results suggest that auditory feedback during speaking is processed by comparing the feedback with its internal prediction. The present study used magnetoencephalography to investigate the precision of this matching process. Auditory responses to speech feedback were recorded under altered feedback conditions. During speech production, the M100 amplitude was maximally reduced to the participants' own unaltered voice feedback, relative to pitch-shifted and alien speech feed back. This suggests that the feedback comparison process may be very precise, allowing the auditory system to distinguish between internal and external sources of auditory information.
NeuroImage, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Journal of Neuroscience, 2019
Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including o... more Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.2 impact regional brain volume, white matter integrity, and early sensory responses in auditory cortex. Here, we test the hypothesis that abnormal cortical neurophysiology is present when genes in the 16p11.2 region are haploinsufficient, and in humans that this in turn may account for behavioral deficits specific to deletion carriers. We examine sensorimotor cortical network activity in males and females with 16p11.2 deletions compared with both typically developing individuals, and those with duplications of 16p11.2, using magnetoencephalographic imaging during preparation of overt speech or hand movements in tasks designed to be easy for all participants. In deletion carriers, modulation of beta oscillations (12-30 Hz) were increased during both movement types over effector-specific regions of motor cortices compared with typically developing individuals or duplication carriers, with no task-related performance differences between cohorts, even when corrected for their own cognitive and sensorimotor deficits. Reduced left hemispheric language specialization was observed in deletion carriers but not in duplication carriers. Neural activity over sensorimotor cortices in deletion carriers was linearly related to clinical measures of speech and motor impairment. These findings link insufficient copy number repeats at 16p11.2 to excessive neural activity (e.g., increased beta oscillations) in motor cortical networks for speech and hand motor control. These results have significant implications for understanding the neural basis of autism and related neurodevelopmental disorders.
Frontiers in human neuroscience, 2017
This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatos... more This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8-12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M20...
We examine the relative timing of numerous brain regions involved in human decisions that are bas... more We examine the relative timing of numerous brain regions involved in human decisions that are based on external criteria, learned information, personal preferences, or unconstrained internal considerations. Using magnetoencephalography (MEG) and advanced signal analysis techniques, we were able to non-invasively reconstruct oscillations of distributed neural networks in the high-gamma frequency band (60-150 Hz). The time course of the observed neural activity suggested that two-alternative forced choice tasks are processed in four overlapping stages: processing of sensory input, option evaluation, intention formation, and action execution. Visual areas are activated fi rst, and show recurring activations throughout the entire decision process. The temporo-occipital junction and the intraparietal sulcus are active during evaluation of external values of the options, 250-500 ms after stimulus presentation. Simultaneously, personal preference is mediated by cortical midline structures. Subsequently, the posterior parietal and superior occipital cortices appear to encode intention, with different subregions being responsible for different types of choice. The cerebellum and inferior parietal cortex are recruited for internal generation of decisions and actions, when all options have the same value. Action execution was accompanied by activation peaks in the contralateral motor cortex. These results suggest that high-gamma oscillations as recorded by MEG allow a reliable reconstruction of decision processes with excellent spatiotemporal resolution.
The Journal of Neuroscience, 2007
The discrimination of temporal information in acoustic inputs is a crucial aspect of auditory per... more The discrimination of temporal information in acoustic inputs is a crucial aspect of auditory perception, yet very few studies have focused on auditory perceptual learning of timing properties and associated plasticity in adult auditory cortex. Here, we trained participants on a temporal discrimination task. The main task used a base stimulus (four tones separated by intervals of 200 ms) that had to be distinguished from a target stimulus (four tones with intervals down to ∼180 ms). We show that participants' auditory temporal sensitivity improves with a short amount of training (3 d, 1 h/d). Learning to discriminate temporal modulation rates was accompanied by a systematic amplitude increase of the early auditory evoked responses to trained stimuli, as measured by magnetoencephalography. Additionally, learning and auditory cortex plasticity partially generalized to interval discrimination but not to frequency discrimination. Auditory cortex plasticity associated with short-term...
Proceedings of the National Academy of Sciences, 2013
The control of vocalization is critically dependent on auditory feedback. Here, we determined the... more The control of vocalization is critically dependent on auditory feedback. Here, we determined the human peri-Sylvian speech network that mediates feedback control of pitch using direct cortical recordings. Subjects phonated while a real-time signal processor briefly perturbed their output pitch (speak condition). Subjects later heard the same recordings of their auditory feedback (listen condition). In posterior superior temporal gyrus, a proportion of sites had suppressed responses to normal feedback, whereas other spatially independent sites had enhanced responses to altered feedback. Behaviorally, speakers compensated for perturbations by changing their pitch. Single-trial analyses revealed that compensatory vocal changes were predicted by the magnitude of both auditory and subsequent ventral premotor responses to perturbations. Furthermore, sites whose responses to perturbation were enhanced in the speaking condition exhibited stronger correlations with behavior. This sensorimot...
NeuroImage, 2009
We explored the neural mechanisms allowing humans to report the subjective onset times of conscio... more We explored the neural mechanisms allowing humans to report the subjective onset times of conscious events. Magnetoencephalographic recordings of neural oscillations were obtained while human subjects introspected the timing of sensory, intentional, and motor events during a forced choice task. Brain activity was reconstructed with high spatiotemporal resolution. Event-time introspection was associated with specific neural activity at the time of subjective event onset which was spatially distinct from activity induced by the event itself. Different brain regions were selectively recruited for introspection of different event types, e.g., the bilateral angular gyrus for introspection of intention. Our results suggest that event-time introspection engages specific neural networks to assess the contents of consciousness. Subjective event times should therefore be interpreted as the result of complex interactions between introspection and experience networks, rather than as direct reproduction of the individual's conscious state or as a mere post-hoc interpretation.
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Papers by Srikantan Nagarajan