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Biomedical subjects

Srikantan S Nagarajan

Publications and source records attributed to Srikantan S Nagarajan.

At least 19 recordsLinked to original sources

Sensorimotor integration in S2, PV, and parietal rostroventral areas of the human sylvian fissure.

We explored cortical fields on the upper bank of the Sylvian fissure using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to measure responses to two stimulus conditions: a tactile stimulus applied to the right hand and a tactile stimulus with an additional movement component. fMRI data revealed bilateral activation in S2/PV in response to tactile stimulation alone and source localization of MEG data identified a peak latency of 122 ms in a similar location. During the tactile and movement condition, fMRI revealed bilateral activation of S2/PV and an anterior field, while MEG data contained one source at a location identical to the tactile-only condition with a latency of 96 ms and a second rostral source with a longer latency (136 ms). Furthermore, Region-of-interest analysis of fMRI data identified increased bilateral activation in S2/PV and the rostral area in the tactile and movement condition compared with the tactile only condition. An area of cortex immediately rostral to S2/PV in monkeys has been called the parietal rostroventral area (PR). Based on location, latency, and conditions under which this field was active, we have termed the rostral area of human cortex PR as well. These findings indicate that humans, like non-human primates, have a cortical field rostral to PV that processes proprioceptive inputs, both S2/PV and PR play a role in somatomotor integration necessary for manual exploration and object discrimination, and there is a temporal hierarchy of processing with S2/PV active prior to PR.

Adult↗

Magnetoencephalographic evidence for a precise forward model in speech production.

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 feedback. 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.

Acoustic Stimulation↗

Controlled Support MEG imaging.

In this paper, we present a novel approach to imaging sparse and focal neural current sources from MEG (magnetoencephalography) data. Using the framework of Tikhonov regularization theory, we introduce a new stabilizer that uses the concept of controlled support to incorporate a priori assumptions about the area occupied by focal sources. The paper discusses the underlying Tikhonov theory and its relationship to a Bayesian formulation which in turn allows us to interpret and better understand other related algorithms.

Algorithms↗

Modified beamformers for coherent source region suppression.

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.

Adult↗

A novel adaptive beamformer for MEG source reconstruction effective when large background brain activities exist.

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.

Algorithms↗

Motor field sensitivity for preoperative localization of motor cortex.

OBJECT: In this study the role of magnetic source imaging for preoperative motor mapping was evaluated by using a single-dipole localization method to analyze motor field data in 41 patients. METHODS: Data from affected and unaffected hemispheres were collected in patients performing voluntary finger flexion movements. Somatosensory evoked field (SSEF) data were also obtained using tactile stimulation. Dipole localization using motor field (MF) data was successful in only 49% of patients, whereas localization with movement-evoked field (MEF) data was successful in 66% of patients. When the spatial distribution of MF and MEF dipoles in relation to SSEF dipoles was analyzed, the motor dipoles were not spatially distinct from somatosensory dipoles. CONCLUSIONS: The findings in this study suggest that single-dipole localization for the analysis of motor data is not sufficiently sensitive and is nonspecific, and thus not clinically useful.

Brain Mapping↗

A graphical model for estimating stimulus-evoked brain responses from magnetoencephalography data with large background brain activity.

This paper formulates a novel probabilistic graphical model for noisy stimulus-evoked MEG and EEG sensor data obtained in the presence of large background brain activity. The model describes the observed data in terms of unobserved evoked and background factors with additive sensor noise. We present an expectation maximization (EM) algorithm that estimates the model parameters from data. Using the model, the algorithm cleans the stimulus-evoked data by removing interference from background factors and noise artifacts and separates those data into contributions from independent factors. We demonstrate on real and simulated data that the algorithm outperforms benchmark methods for denoising and separation. We also show that the algorithm improves the performance of localization with beamforming algorithms.

Algorithms↗

A simple nonparametric statistical thresholding for MEG spatial-filter source reconstruction images.

This paper proposes a simple statistical method for extracting target source activities from spatio-temporal source activities reconstructed from MEG measurements. The method requires measurements in a control condition, which contains only non-target source activities. The method derives, at each pixel location, an empirical probability distribution of the non-target source activity using the time course reconstruction obtained from the control period. The statistical threshold that can extract the target source activities is derived from the empirical distributions obtained from all pixel locations. Here, the multiple comparison problem is addressed with a two-step procedure involving standardizing these empirical distributions and deriving an empirical distribution of the maximum pseudo T value at each pixel location. The results of applying the proposed method to auditory-evoked measurements are presented to demonstrate the method's effectiveness.

Algorithms↗

Functional organization and hemispheric comparison of primary auditory cortex in the common marmoset (Callithrix jacchus).

Hemispheric fine-grain maps of primary auditory cortex (AI) were derived from microelectrode penetrations in the temporal gyrus of the common marmoset (Callithrix jacchus) to 1) compare the functional organization of AI in the marmoset with other mammalian species and 2) compare the right and left AI maps in individual monkeys. Frequency receptive fields (FRFs) were recorded with pure tones. Five FRF parameters were analyzed: characteristic frequency, threshold, sharpness of tuning 10 dB and 40 dB above threshold, and minimum response latency. The present study confirms that the functional organization of AI is characterized by a robust tonotopic frequency gradient overlaid with spatially clustered distributions of other FRF parameters. Globally, this functional organization of AI in the common marmoset is similar to that in other mammalian species. With respect to within-subject hemispheric comparisons of the five FRF parameters, a coherent pattern of asymmetry is not evident in marmoset AI. The overall results indicate that the basic functional organization between hemispheres is similar but not identical.

Acoustic Stimulation↗

Localization bias and spatial resolution of adaptive and non-adaptive spatial filters for MEG source reconstruction.

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.

Algorithms↗

Plasticity in primary auditory cortex of monkeys with altered vocal production.

Response properties of primary auditory cortical neurons in the adult common marmoset monkey (Callithrix jacchus) were modified by extensive exposure to altered vocalizations that were self-generated and rehearsed frequently. A laryngeal apparatus modification procedure permanently lowered the frequency content of the native twitter call, a complex communication vocalization consisting of a series of frequency modulation (FM) sweeps. Monkeys vocalized shortly after this procedure and maintained voicing efforts until physiological evaluation 5-15 months later. The altered twitter calls improved over time, with FM sweeps approaching but never reaching the normal spectral range. Neurons with characteristic frequencies <4.3 kHz that had been weakly activated by native twitter calls were recruited to encode self-uttered altered twitter vocalizations. These neurons showed a decrease in response magnitude and an increase in temporal dispersion of response timing to twitter call and parametric FM stimuli but a normal response profile to pure tone stimuli. Tonotopic maps in voice-modified monkeys were not distorted. These findings suggest a previously unrecognized form of cortical plasticity that is specific to higher-order processes involved in the discrimination of more complex sounds, such as species-specific vocalizations.

Acoustic Stimulation↗

Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping.

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.

Adult↗

Performance of an MEG adaptive-beamformer source reconstruction technique in the presence of additive low-rank interference.

The influence of external interference on neuromagnetic source reconstruction by adaptive beamformer techniques was investigated. In our analysis, we assume that the interference has the following two properties: First, it is additive and uncorrelated with brain activity. Second, its temporal behavior can be characterized by a few distinct activities, and as a result, the spatio-temporal matrix of the interference has a few distinctly large singular values. Namely, the interference can be modeled as a low-rank signal. Under these assumptions, our analysis shows that the adaptive beamformer techniques are insensitive to interference when its spatial singular vectors are so different from a lead field vector of a brain source that the generalized cosine between these two vectors is much smaller than unity. Four types of numerical examples verifying this conclusion are presented.

Algorithms↗

Asymptotic SNR of scalar and vector minimum-variance beamformers for neuromagnetic source reconstruction.

To reconstruct neuromagnetic sources, the minimum-variance beamformer has been extended to incorporate the three-dimensional vector nature of the sources, and two types of extensions-the scalar- and vector-type extensions-have been proposed. This paper discusses the asymptotic signal-to-noise ratio (SNR) of the outputs of these two types of beamformers. We first show that these two types of beamformers give exactly the same output power and output SNR if the beamformer pointing direction is optimized. We then compare the output SNR of the beamformer with optimum direction to that of the conventional vector beamformer formulation where the beamformer pointing direction is not optimized. The comparison shows that the beamformer with optimum direction gives an output SNR superior to that of the conventional vector beamformer. Numerical examples validating the results of the analysis are presented.

Action Potentials↗

Preliminary results of a functional MRI study of brain activation patterns in stuttering and nonstuttering speakers during a lexical access task.

UNLABELLED: An fMRI study examining lexical access and lexical generation in nine non-stuttering and seven stuttering speakers is presented. Lexical access was examined during a word description task that was presented auditorily while subjects "silently" thought of the target words. Participants alternated between four 30-s rest blocks and four 30-s "active" blocks. Activation patterns were assessed utilizing a standard subtraction paradigm, where the activation during the rest blocks was subtracted from the activation during the active blocks. High levels of variability characterized activation patterns within both speaker groups. Group comparisons using random effects statistical analyses did not identify significant differences between the groups when corrected for multiple comparisons. Analyses were subsequently conducted by comparing the trends in the group activation patterns between the speaker groups using fixed (corrected) and random effects (uncorrected) analyses. Non-stuttering control speakers activated primarily left hemisphere cortical speech and language areas while the stuttering speakers appeared to produce more bilateral activation. Discussion of these results focuses on the specific within- and between-hemispheric activation patterns and possible interpretations of these patterns. EDUCATIONAL OBJECTIVES: The reader will learn about: (1) issues related to interpreting brain activation findings in stuttering speakers; (2) the role and neurological substrates of lexical access during speech production in non-stuttering and stuttering speakers; (3) the basics of functional MRI; and (4) the brain activation areas involved during a silent lexical retrieval task in non-stuttering and stuttering speakers.

Adult↗

Analysis of efficiency of magnetic stimulation.

Magnetic stimulation can activate excitable tissues noninvasively. However, this method requires high energy to operate and can produce equipment heat that leads to inefficient stimulation. In this study, a comprehensive optimization of efficiency for magnetic stimulation has been conducted. A total of 16 781 coil designs were tested in order to determine the optimal coil geometry and inductance for neural excitation. Induced electric fields were calculated to find the optimal stimulation site (OSS) of a given coil. The threshold energy of a magnetic pulse for neural excitation was then calculated based on the transmembrane responses of a nerve model. Simulation results show that there exists an optimal inductance, as a consequence of an optimal pulse duration, corresponding to a minimum threshold energy. A longer pulse width is required to obtain the maximum efficiency for axons with slower membrane dynamics, a longer coil-to-fiber distance, and greater values of resistance (R) and capacitance (C) of the resistance-inductance-capacitance circuit. The optimal geometry features a minimum coil height, suggesting a flat coil design for optimal efficiency. The dimension of the optimal coil design increases with the coil-to-fiber distance. Moreover, the cloverleaf design achieves the highest efficiency for infinitely long fibers whereas the butterfly design is optimal for terminating or bending fibers.

Animals↗

Modulation of the auditory cortex during speech: an MEG study.

Several behavioral and brain imaging studies have demonstrated a significant interaction between speech perception and speech production. In this study, auditory cortical responses to speech were examined during self-production and feedback alteration. Magnetic field recordings were obtained from both hemispheres in subjects who spoke while hearing controlled acoustic versions of their speech feedback via earphones. These responses were compared to recordings made while subjects listened to a tape playback of their production. The amplitude of tape playback was adjusted to match the amplitude of self-produced speech. Recordings of evoked responses to both self-produced and tape-recorded speech were obtained free of movement-related artifacts. Responses to self-produced speech were weaker than were responses to tape-recorded speech. Responses to tones were also weaker during speech production, when compared with responses to tones recorded in the presence of speech from tape playback. However, responses evoked by gated noise stimuli did not differ for recordings made during self-produced speech versus recordings made during tape-recorded speech playback. These data suggest that during speech production, the auditory cortex (1) attenuates its sensitivity and (2) modulates its activity as a function of the expected acoustic feedback.

Adult↗

Application of an MEG eigenspace beamformer to reconstructing spatio-temporal activities of neural sources.

We have applied the eigenspace-based beamformer to reconstruct spatio-temporal activities of neural sources from MEG data. The weight vector of the eigenspace-based beamformer is obtained by projecting the weight vector of the minimum-variance beamformer onto the signal subspace of a measurement covariance matrix. This projection removes the residual noise-subspace component that considerably degrades the signal-to-noise ratio (SNR) of the beamformer output when errors in estimating the sensor lead field exist. Therefore, the eigenspace-based beamformer produces a SNR considerably higher than that of the minimum-variance beamformer in practical situations. The effectiveness of the eigenspace-based beamformer was validated in our numerical experiments and experiments using auditory responses. We further extended the eigenspace-based beamformer so that it incorporates the information regarding the noise covariance matrix. Such a prewhitened eigenspace beamformer was experimentally demonstrated to be useful when large background activity exists.

Evoked Potentials, Auditory↗