Shalini Narayana - Academia.edu (original) (raw)

Papers by Shalini Narayana

Research paper thumbnail of TU-107. TMS is effective in localizing language cortices in a cohort of children and individuals with neurological conditions and intellectual disability

Clinical Neurophysiology, Sep 1, 2022

Research paper thumbnail of Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology

Journal of Child Neurology, Oct 23, 2014

Noninvasive brain stimulation is now an accepted technique that is used as a diagnostic aid and i... more Noninvasive brain stimulation is now an accepted technique that is used as a diagnostic aid and in the treatment of neuropsychiatric disorders in adults, and is being increasingly used in children. In this review, we will discuss the basic principles and safety of one noninvasive brain stimulation method, transcranial magnetic stimulation. Improvements in the spatial accuracy of transcranial magnetic stimulation are described in the context of image-guided transcranial magnetic stimulation. The article describes and provides examples of the current clinical applications of transcranial magnetic stimulation in children as an aid in the diagnosis and treatment of neuropsychiatric disorders and discusses future potential applications. Transcranial magnetic stimulation is a noninvasive tool that is safe for use in children and adolescents for functional mapping and treatment, and for many children it aids in the preoperative evaluation and the risk-benefit decision making.

Research paper thumbnail of Comparing methods for estimating hemispheric dominance for language using TMS: A multicenter study

Research paper thumbnail of Transcranial magnetic stimulation is sensitive and accurate in localizing motor cortices in a pediatric epilepsy cohort: Validation against invasive cortical stimulation mapping

Research paper thumbnail of Predicting postoperative language outcome using presurgical fMRI, MEG, TMS, and high gamma ECoG

Clinical Neurophysiology, Mar 1, 2018

MEG TMS High gamma electrocorticography (hgECoG) Postoperative language outcome h i g h l i g h t... more MEG TMS High gamma electrocorticography (hgECoG) Postoperative language outcome h i g h l i g h t s We predicted the postoperative language outcome using presurgical fMRI, MEG, TMS and high gamma ECoG. We compared performances of single modality and multimodality methods for prediction of the outcome. Developed multimodal method can be utilized prior to surgery for selecting an optimal surgical plan. a b s t r a c t Objective: To predict the postoperative language outcome using the support vector regression (SVR) and results of multimodal presurgical language mapping. Methods: Eleven patients with epilepsy received presurgical language mapping using functional MRI (fMRI), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and high-gamma electrocorticography (hgECoG), as well as pre-and postoperative neuropsychological evaluation of language. We constructed 15 (2 4-1) SVR models by considering the extent of resected language areas identified by all subsets of four modalities as input feature vector and the postoperative language outcome as output. We trained and cross-validated SVR models, and compared the cross-validation (CV) errors of all models for prediction of language outcome. Results: Seven patients had some level of postoperative language decline and two of them had significant postoperative decline in naming. Some parts of language areas identified by four modalities were resected in these patients. We found that an SVR model consisting of fMRI, MEG, and hgECoG provided minimum CV error, although an SVR model consisting of fMRI and MEG was the optimal model that facilitated the best trade-off between model complexity and prediction accuracy. Conclusions: A multimodal SVR can be used to predict the language outcome. Significance: The developed multimodal SVR models in this study can be utilized to calculate the language outcomes of different resection plans prior to surgery and select the optimal surgical plan.

Research paper thumbnail of WE-183. Awake TMS or MEG under sedation: Which modality is more likely to localize sensorimotor cortex in children?

Research paper thumbnail of Presurgical language mapping in bilingual children using transcranial magnetic stimulation: illustrative case

Journal of Neurosurgery: Case Lessons, 2021

BACKGROUND Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is cr... more BACKGROUND Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is critical but presents challenges unique to the pediatric population, including motion artifact, noncompliance, and sedation requirements. Furthermore, as bilingualism in children increases, functional mapping of more than one language is becoming increasingly critical. Transcranial magnetic stimulation (TMS), a noninvasive brain stimulation technique, is well suited to evaluate language areas in children since it does not require the patient to remain still during mapping. OBSERVATIONS A 13-year-old bilingual male with glioblastoma multiforme involving the left parietal lobe and deep occipital white matter underwent preoperative language mapping using magnetic resonance imaging-guided TMS. Language-specific cortices were successfully identified in both hemispheres. TMS findings aided in discussing with the family the risks of postsurgical deficits of tumor resection; postoperatively, the p...

Research paper thumbnail of Mapping typical and hypokinetic dysarthric speech production network using a connected speech paradigm in functional MRI

NeuroImage: Clinical, 2020

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.

Research paper thumbnail of Focality of the Induced E-Field Is a Contributing Factor in the Choice of TMS Parameters: Evidence from a 3D Computational Model of the Human Brain

Brain Sciences, 2020

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis an... more Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm3 between the selected nine clinically relevant coil locations. Coil orientation also changed the indu...

Research paper thumbnail of Neuroimaging and Neuropsychological Studies in Sports-Related Concussions in Adolescents: Current State and Future Directions

Frontiers in Neurology, 2019

Research paper thumbnail of Concordance of the Resting State Networks in Typically Developing, 6-to 7-Year-Old Children and Healthy Adults

Frontiers in Human Neuroscience, 2017

Though fairly well-studied in adults, less is known about the manifestation of resting state netw... more Though fairly well-studied in adults, less is known about the manifestation of resting state networks (RSN) in children. We examined the validity of RSN derived in an ethnically diverse group of typically developing 6-to 7-year-old children. We hypothesized that the RSNs in young children would be robust and would reliably show significant concordance with previously published RSN in adults. Additionally, we hypothesized that a smaller sample size using this robust technique would be comparable in quality to pediatric RSNs found in a larger cohort study. Furthermore, we posited that compared to the adult RSNs, the primary sensorimotor and the default mode networks (DMNs) in this pediatric group would demonstrate the greatest correspondence, while the executive function networks would exhibit a lesser degree of spatial overlap. Resting state functional magnetic resonance images (rs-fMRI) were acquired in 18 children between 6 and 7 years recruited from an ethnically diverse population in the Mid-South region of the United States. Twenty RSNs were derived using group independent component analysis and their spatial correspondence with previously published adult RSNs was examined. We demonstrate that the rs-fMRI in this group can be deconstructed into the fundamental RSN as all the major RSNs previously described in adults and in a large sample that included older children can be observed in our sample of young children. Further, the primary visual, auditory, and somatosensory networks, as well as the default mode, and frontoparietal networks derived in this group exhibited a greater spatial concordance with those seen in adults. The motor, temporoparietal, executive control, dorsal attention, and cerebellar networks in children had less spatial overlap with the corresponding RSNs in adults. Our findings suggest that several salient RSNs can be mapped reliably in small and diverse pediatric cohort within a narrow age range and the evolution of these RSNs can be studied reliably in such groups during early childhood and adolescence.

Research paper thumbnail of The Role of the Primary Sensory Cortices in Early Language Processing

Journal of cognitive neuroscience, Jan 30, 2017

The results of this magnetoencephalography study challenge two long-standing assumptions regardin... more The results of this magnetoencephalography study challenge two long-standing assumptions regarding the brain mechanisms of language processing: First, that linguistic processing proper follows sensory feature processing effected by bilateral activation of the primary sensory cortices that lasts about 100 msec from stimulus onset. Second, that subsequent linguistic processing is effected by left hemisphere networks outside the primary sensory areas, including Broca's and Wernicke's association cortices. Here we present evidence that linguistic analysis begins almost synchronously with sensory, prelinguistic verbal input analysis and that the primary cortices are also engaged in these linguistic analyses and become, consequently, part of the left hemisphere language network during language tasks. These findings call for extensive revision of our conception of linguistic processing in the brain.

Research paper thumbnail of Brain activation profiles during kinesthetic and visual imagery: An fMRI study

Brain research, Sep 1, 2016

The aim of this study was to identify brain regions involved in motor imagery and differentiate t... more The aim of this study was to identify brain regions involved in motor imagery and differentiate two alternative strategies in its implementation: imagining a motor act using kinesthetic or visual imagery. Fourteen adults were precisely instructed and trained on how to imagine themselves or others perform a movement sequence, with the aim of promoting kinesthetic and visual imagery, respectively, in the context of an fMRI experiment using block design. We found that neither modality of motor imagery elicits activation of the primary motor cortex and that each of the two modalities involves activation of the premotor area which is also activated during action execution and action observation conditions, as well as of the supplementary motor area. Interestingly, the visual and the posterior cingulate cortices show reduced BOLD signal during both imagery conditions. Our results indicate that the networks of regions activated in kinesthetic and visual imagery of motor sequences show a su...

Research paper thumbnail of Repetitive Transcranial Magnetic Stimulation Educes Frequency-Specific Causal Relationships in the Motor Network

Brain Stimulation, 2016

Background-Repetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain d... more Background-Repetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain disorders by modulating the activity of disease-specific brain networks, yet the rTMS frequencies used are delivered in a binary fashion-excitatory (> 1 Hz) and inhibitory (≤1 Hz). Objective-To assess the effective connectivity of the motor network at different rTMS stimulation rates during positron-emission tomography (PET) and confirm that not all excitatory rTMS frequencies act on the motor network in the same manner. Methods-We delivered image-guided, supra-threshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements. Path analysis-using structural equation modeling (SEM)-was employed to determine the effective connectivity of the motor network at all rTMS frequencies. Once determined, the final model of the motor network was used to assess any differences in effective connectivity at each rTMS frequency. Results-The exploratory SEM produced a very well fitting final network model (χ 2 = 18.04, df

Research paper thumbnail of Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons

Brain Structure and Function, 2015

The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral... more The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow (CBF) responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 15 O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 15 O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third-and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study using to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated

Research paper thumbnail of Functional PET Evaluation of the Photosensitive Baboon

The Open Neuroimaging Journal, 2011

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photo... more The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes.

Research paper thumbnail of Concurrent TMS to the primary motor cortex augments slow motor learning

NeuroImage, 2014

Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA appro... more Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up-(or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy.

Research paper thumbnail of Changes occur in resting state network of motor system during 4weeks of motor skill learning

NeuroImage, 2011

We tested whether the resting state functional connectivity of the motor system changed during 4 ... more We tested whether the resting state functional connectivity of the motor system changed during 4 weeks of motor skill learning using functional magnetic resonance imaging (fMRI). Ten healthy volunteers learned to produce a sequential finger movement by daily practice of the task over a 4 week period. Changes in the resting state motor network were examined before training (Week 0), two weeks after the onset of training (Week 2), and immediately at the end of the training (Week 4). The resting state motor system was analyzed using group independent component analysis (ICA). Statistical Parametric Mapping (SPM) second-level analysis was conducted on independent z-maps generated by the group ICA. Three regions, namely right postcentral gyrus, and bilateral supramarginal gyri were found to be sensitive to the training duration. Specifically, the strength of resting state functional connectivity in the right postcentral gyrus and right supramarginal gyrus increased from Week 0 to Week 2, during which the behavioral performance improved significantly, and decreased from Week 2 to Week 4, during which there was no more significant improvement in behavioral performance. The strength of resting state functional connectivity in left supramarginal gyrus increased throughout the training. These results confirm changes in the resting state network during slow-learning stage of motor skill learning, and support the premise that the resting state networks play a role in improving performance.

Research paper thumbnail of Long-term motor training induced changes in regional cerebral blood flow in both task and resting states

NeuroImage, 2009

Neuroimaging studies of functional activation often only reflect differentiated involvement of br... more Neuroimaging studies of functional activation often only reflect differentiated involvement of brain regions compared between task performance and control states. Signals common for both states are typically not revealed. Previous motor learning studies have shown that extensive motor skill training can induce profound changes in regional activity in both task and control states. To address the issue of brain activity changes in the resting-state, we explored long-term motor training induced neuronal and physiological changes in normal human subjects using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Ten healthy subjects performed a finger movement task daily for four weeks, during which three sessions of fMRI images and two sessions of PET images were acquired. Using a classical data analysis strategy, we found that the brain activation increased first and then returned to the pre-training, replicating previous findings. Interestingly, we also observed that motor skill training induced significant increases in regional cerebral blood flow (rCBF) in both task and resting states as the practice progressed. The apparent decrease in activation may actually result from a greater increase in activity in the resting state, rather than a decrease in the task state. By showing that training can affect the resting state, our findings have profound implications for the interpretation of functional activations in neuroimaging studies. Combining changes in resting state with activation data should greatly enhance our understanding of the mechanisms of motor-skill learning.

Research paper thumbnail of Positron emission tomography during transcranial magnetic stimulation does not require μ-metal shielding

NeuroImage, 2003

Recording brain activity using positron emission tomography (PET) during the stimulation of diffe... more Recording brain activity using positron emission tomography (PET) during the stimulation of different parts of the brain by transcranial magnetic stimulation (TMS) permits the mapping of neural connections in the living human brain. However, controversy remains regarding the need for-metal shielding of the PET scanner during magnetic stimulation. The aim of this study was to test the effects of magnetic fields generated by TMS on PET data acquisition. With TMS-on and-off in the PET field of view, transmission scans with a 68 Ge/ 68 Ga pin source and emission scans with an uniform phantom filled with water and 18 F were acquired. The frequency and intensity of stimulation were set at 3-5 Hz and 70-80% of the maximum output of the stimulator, respectively. The TMS coil was placed at several locations inside the PET gantry, and the main field direction of the TMS coil was varied between parallel and perpendicular orientation to the scanner's axis. Qualitative and quantitative evaluation of the sinograms of transmission PET scans and reconstructed emission images indicated no measurable differences between TMS-on and-off and post-TMS conditions for any position or orientation. The long distance between the TMS coil and the detector block in the PET scanner, as well as the rapid reduction of the magnetic field with distance (3% of maximum field at 10 cm, in air), could explain the lack of TMS interference. The brief duration (ϳ250 s) of the TMS pulses relative to the total PET acquisition time would also explain the lack of TMS effects. The lack of TMS effects on the PET scanner, as well as PET imaging without any shielding, has been reported by other laboratories.

Research paper thumbnail of TU-107. TMS is effective in localizing language cortices in a cohort of children and individuals with neurological conditions and intellectual disability

Clinical Neurophysiology, Sep 1, 2022

Research paper thumbnail of Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology

Journal of Child Neurology, Oct 23, 2014

Noninvasive brain stimulation is now an accepted technique that is used as a diagnostic aid and i... more Noninvasive brain stimulation is now an accepted technique that is used as a diagnostic aid and in the treatment of neuropsychiatric disorders in adults, and is being increasingly used in children. In this review, we will discuss the basic principles and safety of one noninvasive brain stimulation method, transcranial magnetic stimulation. Improvements in the spatial accuracy of transcranial magnetic stimulation are described in the context of image-guided transcranial magnetic stimulation. The article describes and provides examples of the current clinical applications of transcranial magnetic stimulation in children as an aid in the diagnosis and treatment of neuropsychiatric disorders and discusses future potential applications. Transcranial magnetic stimulation is a noninvasive tool that is safe for use in children and adolescents for functional mapping and treatment, and for many children it aids in the preoperative evaluation and the risk-benefit decision making.

Research paper thumbnail of Comparing methods for estimating hemispheric dominance for language using TMS: A multicenter study

Research paper thumbnail of Transcranial magnetic stimulation is sensitive and accurate in localizing motor cortices in a pediatric epilepsy cohort: Validation against invasive cortical stimulation mapping

Research paper thumbnail of Predicting postoperative language outcome using presurgical fMRI, MEG, TMS, and high gamma ECoG

Clinical Neurophysiology, Mar 1, 2018

MEG TMS High gamma electrocorticography (hgECoG) Postoperative language outcome h i g h l i g h t... more MEG TMS High gamma electrocorticography (hgECoG) Postoperative language outcome h i g h l i g h t s We predicted the postoperative language outcome using presurgical fMRI, MEG, TMS and high gamma ECoG. We compared performances of single modality and multimodality methods for prediction of the outcome. Developed multimodal method can be utilized prior to surgery for selecting an optimal surgical plan. a b s t r a c t Objective: To predict the postoperative language outcome using the support vector regression (SVR) and results of multimodal presurgical language mapping. Methods: Eleven patients with epilepsy received presurgical language mapping using functional MRI (fMRI), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and high-gamma electrocorticography (hgECoG), as well as pre-and postoperative neuropsychological evaluation of language. We constructed 15 (2 4-1) SVR models by considering the extent of resected language areas identified by all subsets of four modalities as input feature vector and the postoperative language outcome as output. We trained and cross-validated SVR models, and compared the cross-validation (CV) errors of all models for prediction of language outcome. Results: Seven patients had some level of postoperative language decline and two of them had significant postoperative decline in naming. Some parts of language areas identified by four modalities were resected in these patients. We found that an SVR model consisting of fMRI, MEG, and hgECoG provided minimum CV error, although an SVR model consisting of fMRI and MEG was the optimal model that facilitated the best trade-off between model complexity and prediction accuracy. Conclusions: A multimodal SVR can be used to predict the language outcome. Significance: The developed multimodal SVR models in this study can be utilized to calculate the language outcomes of different resection plans prior to surgery and select the optimal surgical plan.

Research paper thumbnail of WE-183. Awake TMS or MEG under sedation: Which modality is more likely to localize sensorimotor cortex in children?

Research paper thumbnail of Presurgical language mapping in bilingual children using transcranial magnetic stimulation: illustrative case

Journal of Neurosurgery: Case Lessons, 2021

BACKGROUND Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is cr... more BACKGROUND Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is critical but presents challenges unique to the pediatric population, including motion artifact, noncompliance, and sedation requirements. Furthermore, as bilingualism in children increases, functional mapping of more than one language is becoming increasingly critical. Transcranial magnetic stimulation (TMS), a noninvasive brain stimulation technique, is well suited to evaluate language areas in children since it does not require the patient to remain still during mapping. OBSERVATIONS A 13-year-old bilingual male with glioblastoma multiforme involving the left parietal lobe and deep occipital white matter underwent preoperative language mapping using magnetic resonance imaging-guided TMS. Language-specific cortices were successfully identified in both hemispheres. TMS findings aided in discussing with the family the risks of postsurgical deficits of tumor resection; postoperatively, the p...

Research paper thumbnail of Mapping typical and hypokinetic dysarthric speech production network using a connected speech paradigm in functional MRI

NeuroImage: Clinical, 2020

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.

Research paper thumbnail of Focality of the Induced E-Field Is a Contributing Factor in the Choice of TMS Parameters: Evidence from a 3D Computational Model of the Human Brain

Brain Sciences, 2020

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis an... more Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm3 between the selected nine clinically relevant coil locations. Coil orientation also changed the indu...

Research paper thumbnail of Neuroimaging and Neuropsychological Studies in Sports-Related Concussions in Adolescents: Current State and Future Directions

Frontiers in Neurology, 2019

Research paper thumbnail of Concordance of the Resting State Networks in Typically Developing, 6-to 7-Year-Old Children and Healthy Adults

Frontiers in Human Neuroscience, 2017

Though fairly well-studied in adults, less is known about the manifestation of resting state netw... more Though fairly well-studied in adults, less is known about the manifestation of resting state networks (RSN) in children. We examined the validity of RSN derived in an ethnically diverse group of typically developing 6-to 7-year-old children. We hypothesized that the RSNs in young children would be robust and would reliably show significant concordance with previously published RSN in adults. Additionally, we hypothesized that a smaller sample size using this robust technique would be comparable in quality to pediatric RSNs found in a larger cohort study. Furthermore, we posited that compared to the adult RSNs, the primary sensorimotor and the default mode networks (DMNs) in this pediatric group would demonstrate the greatest correspondence, while the executive function networks would exhibit a lesser degree of spatial overlap. Resting state functional magnetic resonance images (rs-fMRI) were acquired in 18 children between 6 and 7 years recruited from an ethnically diverse population in the Mid-South region of the United States. Twenty RSNs were derived using group independent component analysis and their spatial correspondence with previously published adult RSNs was examined. We demonstrate that the rs-fMRI in this group can be deconstructed into the fundamental RSN as all the major RSNs previously described in adults and in a large sample that included older children can be observed in our sample of young children. Further, the primary visual, auditory, and somatosensory networks, as well as the default mode, and frontoparietal networks derived in this group exhibited a greater spatial concordance with those seen in adults. The motor, temporoparietal, executive control, dorsal attention, and cerebellar networks in children had less spatial overlap with the corresponding RSNs in adults. Our findings suggest that several salient RSNs can be mapped reliably in small and diverse pediatric cohort within a narrow age range and the evolution of these RSNs can be studied reliably in such groups during early childhood and adolescence.

Research paper thumbnail of The Role of the Primary Sensory Cortices in Early Language Processing

Journal of cognitive neuroscience, Jan 30, 2017

The results of this magnetoencephalography study challenge two long-standing assumptions regardin... more The results of this magnetoencephalography study challenge two long-standing assumptions regarding the brain mechanisms of language processing: First, that linguistic processing proper follows sensory feature processing effected by bilateral activation of the primary sensory cortices that lasts about 100 msec from stimulus onset. Second, that subsequent linguistic processing is effected by left hemisphere networks outside the primary sensory areas, including Broca's and Wernicke's association cortices. Here we present evidence that linguistic analysis begins almost synchronously with sensory, prelinguistic verbal input analysis and that the primary cortices are also engaged in these linguistic analyses and become, consequently, part of the left hemisphere language network during language tasks. These findings call for extensive revision of our conception of linguistic processing in the brain.

Research paper thumbnail of Brain activation profiles during kinesthetic and visual imagery: An fMRI study

Brain research, Sep 1, 2016

The aim of this study was to identify brain regions involved in motor imagery and differentiate t... more The aim of this study was to identify brain regions involved in motor imagery and differentiate two alternative strategies in its implementation: imagining a motor act using kinesthetic or visual imagery. Fourteen adults were precisely instructed and trained on how to imagine themselves or others perform a movement sequence, with the aim of promoting kinesthetic and visual imagery, respectively, in the context of an fMRI experiment using block design. We found that neither modality of motor imagery elicits activation of the primary motor cortex and that each of the two modalities involves activation of the premotor area which is also activated during action execution and action observation conditions, as well as of the supplementary motor area. Interestingly, the visual and the posterior cingulate cortices show reduced BOLD signal during both imagery conditions. Our results indicate that the networks of regions activated in kinesthetic and visual imagery of motor sequences show a su...

Research paper thumbnail of Repetitive Transcranial Magnetic Stimulation Educes Frequency-Specific Causal Relationships in the Motor Network

Brain Stimulation, 2016

Background-Repetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain d... more Background-Repetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain disorders by modulating the activity of disease-specific brain networks, yet the rTMS frequencies used are delivered in a binary fashion-excitatory (> 1 Hz) and inhibitory (≤1 Hz). Objective-To assess the effective connectivity of the motor network at different rTMS stimulation rates during positron-emission tomography (PET) and confirm that not all excitatory rTMS frequencies act on the motor network in the same manner. Methods-We delivered image-guided, supra-threshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements. Path analysis-using structural equation modeling (SEM)-was employed to determine the effective connectivity of the motor network at all rTMS frequencies. Once determined, the final model of the motor network was used to assess any differences in effective connectivity at each rTMS frequency. Results-The exploratory SEM produced a very well fitting final network model (χ 2 = 18.04, df

Research paper thumbnail of Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons

Brain Structure and Function, 2015

The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral... more The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow (CBF) responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 15 O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 15 O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third-and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study using to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated

Research paper thumbnail of Functional PET Evaluation of the Photosensitive Baboon

The Open Neuroimaging Journal, 2011

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photo... more The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes.

Research paper thumbnail of Concurrent TMS to the primary motor cortex augments slow motor learning

NeuroImage, 2014

Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA appro... more Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up-(or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy.

Research paper thumbnail of Changes occur in resting state network of motor system during 4weeks of motor skill learning

NeuroImage, 2011

We tested whether the resting state functional connectivity of the motor system changed during 4 ... more We tested whether the resting state functional connectivity of the motor system changed during 4 weeks of motor skill learning using functional magnetic resonance imaging (fMRI). Ten healthy volunteers learned to produce a sequential finger movement by daily practice of the task over a 4 week period. Changes in the resting state motor network were examined before training (Week 0), two weeks after the onset of training (Week 2), and immediately at the end of the training (Week 4). The resting state motor system was analyzed using group independent component analysis (ICA). Statistical Parametric Mapping (SPM) second-level analysis was conducted on independent z-maps generated by the group ICA. Three regions, namely right postcentral gyrus, and bilateral supramarginal gyri were found to be sensitive to the training duration. Specifically, the strength of resting state functional connectivity in the right postcentral gyrus and right supramarginal gyrus increased from Week 0 to Week 2, during which the behavioral performance improved significantly, and decreased from Week 2 to Week 4, during which there was no more significant improvement in behavioral performance. The strength of resting state functional connectivity in left supramarginal gyrus increased throughout the training. These results confirm changes in the resting state network during slow-learning stage of motor skill learning, and support the premise that the resting state networks play a role in improving performance.

Research paper thumbnail of Long-term motor training induced changes in regional cerebral blood flow in both task and resting states

NeuroImage, 2009

Neuroimaging studies of functional activation often only reflect differentiated involvement of br... more Neuroimaging studies of functional activation often only reflect differentiated involvement of brain regions compared between task performance and control states. Signals common for both states are typically not revealed. Previous motor learning studies have shown that extensive motor skill training can induce profound changes in regional activity in both task and control states. To address the issue of brain activity changes in the resting-state, we explored long-term motor training induced neuronal and physiological changes in normal human subjects using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Ten healthy subjects performed a finger movement task daily for four weeks, during which three sessions of fMRI images and two sessions of PET images were acquired. Using a classical data analysis strategy, we found that the brain activation increased first and then returned to the pre-training, replicating previous findings. Interestingly, we also observed that motor skill training induced significant increases in regional cerebral blood flow (rCBF) in both task and resting states as the practice progressed. The apparent decrease in activation may actually result from a greater increase in activity in the resting state, rather than a decrease in the task state. By showing that training can affect the resting state, our findings have profound implications for the interpretation of functional activations in neuroimaging studies. Combining changes in resting state with activation data should greatly enhance our understanding of the mechanisms of motor-skill learning.

Research paper thumbnail of Positron emission tomography during transcranial magnetic stimulation does not require μ-metal shielding

NeuroImage, 2003

Recording brain activity using positron emission tomography (PET) during the stimulation of diffe... more Recording brain activity using positron emission tomography (PET) during the stimulation of different parts of the brain by transcranial magnetic stimulation (TMS) permits the mapping of neural connections in the living human brain. However, controversy remains regarding the need for-metal shielding of the PET scanner during magnetic stimulation. The aim of this study was to test the effects of magnetic fields generated by TMS on PET data acquisition. With TMS-on and-off in the PET field of view, transmission scans with a 68 Ge/ 68 Ga pin source and emission scans with an uniform phantom filled with water and 18 F were acquired. The frequency and intensity of stimulation were set at 3-5 Hz and 70-80% of the maximum output of the stimulator, respectively. The TMS coil was placed at several locations inside the PET gantry, and the main field direction of the TMS coil was varied between parallel and perpendicular orientation to the scanner's axis. Qualitative and quantitative evaluation of the sinograms of transmission PET scans and reconstructed emission images indicated no measurable differences between TMS-on and-off and post-TMS conditions for any position or orientation. The long distance between the TMS coil and the detector block in the PET scanner, as well as the rapid reduction of the magnetic field with distance (3% of maximum field at 10 cm, in air), could explain the lack of TMS interference. The brief duration (ϳ250 s) of the TMS pulses relative to the total PET acquisition time would also explain the lack of TMS effects. The lack of TMS effects on the PET scanner, as well as PET imaging without any shielding, has been reported by other laboratories.