Publications by authors named "Leighton B N Hinkley"

21 Publications

  • Page 1 of 1

NUTMEG: Open Source Software for M/EEG Source Reconstruction.

Front Neurosci 2020 25;14:710. Epub 2020 Aug 25.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.

Neurodynamic Utility Toolbox for Magnetoencephalo- and Electroencephalography (NUTMEG) is an open-source MATLAB-based toolbox for the analysis and reconstruction of magnetoencephalography/electroencephalography data in source space. NUTMEG includes a variety of options for the user in data import, preprocessing, source reconstruction, and functional connectivity. A group analysis toolbox allows the user to run a variety of inferential statistics on their data in an easy-to-use GUI-driven format. Importantly, NUTMEG features an interactive five-dimensional data visualization platform. A key feature of NUTMEG is the availability of a large menu of interference cancelation and source reconstruction algorithms. Each NUTMEG operation acts as a stand-alone MATLAB function, allowing the package to be easily adaptable and scripted for the more advanced user for interoperability with other software toolboxes. Therefore, NUTMEG enables a wide range of users access to a complete "sensor-to- source-statistics" analysis pipeline.
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http://dx.doi.org/10.3389/fnins.2020.00710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478146PMC
August 2020

Taking the sublexical route: brain dynamics of reading in the semantic variant of primary progressive aphasia.

Brain 2020 08;143(8):2545-2560

Department of Radiology and Biomedical Imaging, University of California San Francisco, USA.

Reading aloud requires mapping an orthographic form to a phonological one. The mapping process relies on sublexical statistical regularities (e.g. 'oo' to |uː|) or on learned lexical associations between a specific visual form and a series of sounds (e.g. yacht to/jɑt/). Computational, neuroimaging, and neuropsychological evidence suggest that sublexical, phonological and lexico-semantic processes rely on partially distinct neural substrates: a dorsal (occipito-parietal) and a ventral (occipito-temporal) route, respectively. Here, we investigated the spatiotemporal features of orthography-to-phonology mapping, capitalizing on the time resolution of magnetoencephalography and the unique clinical model offered by patients with semantic variant of primary progressive aphasia (svPPA). Behaviourally, patients with svPPA manifest marked lexico-semantic impairments including difficulties in reading words with exceptional orthographic to phonological correspondence (irregular words). Moreover, they present with focal neurodegeneration in the anterior temporal lobe, affecting primarily the ventral, occipito-temporal, lexical route. Therefore, this clinical population allows for testing of specific hypotheses on the neural implementation of the dual-route model for reading, such as whether damage to one route can be compensated by over-reliance on the other. To this end, we reconstructed and analysed time-resolved whole-brain activity in 12 svPPA patients and 12 healthy age-matched control subjects while reading irregular words (e.g. yacht) and pseudowords (e.g. pook). Consistent with previous findings that the dorsal route is involved in sublexical, phonological processes, in control participants we observed enhanced neural activity over dorsal occipito-parietal cortices for pseudowords, when compared to irregular words. This activation was manifested in the beta-band (12-30 Hz), ramping up slowly over 500 ms after stimulus onset and peaking at ∼800 ms, around response selection and production. Consistent with our prediction, svPPA patients did not exhibit this temporal pattern of neural activity observed in controls this contrast. Furthermore, a direct comparison of neural activity between patients and controls revealed a dorsal spatiotemporal cluster during irregular word reading. These findings suggest that the sublexical/phonological route is involved in processing both irregular and pseudowords in svPPA. Together these results provide further evidence supporting a dual-route model for reading aloud mediated by the interplay between lexico-semantic and sublexical/phonological neurocognitive systems. When the ventral route is damaged, as in the case of neurodegeneration affecting the anterior temporal lobe, partial compensation appears to be possible by over-recruitment of the slower, serial attention-dependent, dorsal one.
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http://dx.doi.org/10.1093/brain/awaa212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447517PMC
August 2020

Optimizing Magnetoencephalographic Imaging Estimation of Language Lateralization for Simpler Language Tasks.

Front Hum Neurosci 2020 15;14:105. Epub 2020 May 15.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task - auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12-30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650-850 ms (stimulus-locked) and -350 to -150 ms (response-locked) and for PN -450 to -250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort ( = 30 for NWR, = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort ( = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI.
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http://dx.doi.org/10.3389/fnhum.2020.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242765PMC
May 2020

Intervention-specific patterns of cortical function plasticity during auditory encoding in people with schizophrenia.

Schizophr Res 2020 01 21;215:241-249. Epub 2019 Oct 21.

Department of Radiology and Biomedical Imaging, University of California San Francisco, United States; UCB-UCSF Graduate Program in Bioengineering, University of California, Berkeley, United States.

Schizophrenia is a neurocognitive illness characterized by behavioral and neural impairments in both early auditory processing and higher order verbal working memory. Previously we have shown intervention-specific cognitive performance improvements with computerized, targeted training of auditory processing (AT) when compared to a computer games (CG) control intervention that emphasized visual processing. To investigate spatiotemporal changes in patterns of neural activity specific to the AT intervention, the current study used magnetoencephalography (MEG) imaging to derive induced high gamma band oscillations (HGO) during auditory encoding, before and after 50 h (∼10 weeks) of exposure to either the AT or CG intervention. During stimulus encoding, AT intervention-specific changes in high gamma activity occurred in left middle frontal and left middle-superior temporal cortices. In contrast, CG intervention-specific changes were observed in right medial frontal and supramarginal gyri during stimulus encoding, and in bilateral temporal cortices during response preparation. These data reveal that, in schizophrenia, intensive exposure to either training of auditory processing or exposure to visuospatial activities produces significant but complementary patterns of cortical function plasticity within a distributed fronto-temporal network. These results underscore the importance of delineating the specific neuroplastic effects of targeted behavioral interventions to ensure desired neurophysiological changes and avoid unintended consequences on neural system functioning.
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http://dx.doi.org/10.1016/j.schres.2019.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035971PMC
January 2020

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

J Neurosci 2019 09 3;39(37):7321-7331. Epub 2019 Jul 3.

Departments of Radiology and Biomedical Imaging,

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. The recurrent ∼600 kb deletion at 16p11.2 (BP4-BP5) is one of the most common genetic etiologies of ASD and, more generally, of neurodevelopmental disorders. Here, we use high-resolution magnetoencephalographic imaging (MEG-I) to define with millisecond precision the underlying neurophysiological signature of motor impairments for individuals with 16p11.2 deletions. We identify significant increases in beta (12-30 Hz) suppression in sensorimotor cortices related to performance during speech and hand movement tasks. These findings not only provide a neurophysiological phenotype for the clinical presentation of this genetic deletion, but also guide our understanding of how genetic variation encodes for neural oscillatory dynamics.
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http://dx.doi.org/10.1523/JNEUROSCI.3001-17.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759026PMC
September 2019

Beta-band activity in medial prefrontal cortex predicts source memory encoding and retrieval accuracy.

Sci Rep 2019 05 2;9(1):6814. Epub 2019 May 2.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA-94143, USA.

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 self-generated 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.
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http://dx.doi.org/10.1038/s41598-019-43291-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497659PMC
May 2019

The Contribution of the Corpus Callosum to Language Lateralization.

J Neurosci 2016 Apr;36(16):4522-33

Department of Radiology and Biomedical Imaging,

Unlabelled: The development of hemispheric lateralization for language is poorly understood. In one hypothesis, early asymmetric gene expression assigns language to the left hemisphere. In an alternate view, language is represented a priori in both hemispheres and lateralization emerges via cross-hemispheric communication through the corpus callosum. To address this second hypothesis, we capitalized on the high temporal and spatial resolution of magnetoencephalographic imaging to measure cortical activity during language processing, speech preparation, and speech execution in 25 participants with agenesis of the corpus callosum (AgCC) and 21 matched neurotypical individuals. In contrast to strongly lateralized left hemisphere activations for language in neurotypical controls, participants with complete or partial AgCC exhibited bilateral hemispheric activations in both auditory or visually driven language tasks, with complete AgCC participants showing significantly more right hemisphere activations than controls or than individuals with partial AgCC. In AgCC individuals, language laterality positively correlated with verbal IQ. These findings suggest that the corpus callosum helps to drive language lateralization.

Significance Statement: The role that corpus callosum development has on the hemispheric specialization of language is poorly understood. Here, we used magnetoencephalographic imaging during linguistic tests (verb generation, picture naming) to test for hemispheric dominance in patients with agenesis of the corpus callosum (AgCC) and found reduced laterality (i.e., greater likelihood of bilaterality or right hemisphere dominance) in this cohort compared with controls, especially in patients with complete agenesis. Laterality was positively correlated with behavioral measures of verbal intelligence. These findings provide support for the hypothesis that the callosum aids in functional specialization throughout neural development and that the loss of this mechanism correlates with impairments in verbal performance.
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http://dx.doi.org/10.1523/JNEUROSCI.3850-14.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837685PMC
April 2016

Complex-value coherence mapping reveals novel abnormal resting-state functional connectivity networks in task-specific focal hand dystonia.

Front Neurol 2013 10;4:149. Epub 2013 Oct 10.

Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA , USA.

Resting-state imaging designs are powerful in modeling functional networks in movement disorders because they eliminate task performance related confounds. However, the most common metric for quantifying functional connectivity, i.e., bivariate magnitude coherence (Coh), can sometimes be contaminated by spurious correlations in blood-oxygen level dependent (BOLD) signal due to smoothing and seed blur, thereby limiting the identification of true interactions between neighboring neural populations. Here, we apply a novel functional connectivity metric., i.e., imaginary coherence (ICoh), to BOLD fMRI data in healthy individuals and patients with task-specific focal hand dystonia (tspFHD), in addition to the traditional magnitude Coh metric. We reconstructed resting-state sensorimotor, basal ganglia, and default-mode networks using both Coh and ICoh. We demonstrate that indeed the ICoh metric eliminates spatial blur around seed placement and reflects slightly different networks from Coh. We then identified significant reductions in resting-state connectivity within both the sensorimotor and basal ganglia networks in patients with tspFHD, primarily in the hemisphere contralateral to the affected hand. Collectively, these findings direct our attention to the fact that multiple networks are decoupled in tspFHD that can be unraveled by different functional connectivity metrics, and that this aberrant communication contributes to clinical deficits in the disorder.
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http://dx.doi.org/10.3389/fneur.2013.00149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794296PMC
October 2013

Resting-state networks and the functional connectome of the human brain in agenesis of the corpus callosum.

Brain Connect 2013 16;3(6):547-62. Epub 2013 Nov 16.

1 Department of Radiology and Biomedical Imaging, University of California , San Francisco, California.

The corpus callosum is the largest white matter fiber bundle connecting the two cerebral hemispheres. In this work, we investigate the effect of callosal dysgenesis on functional magnetic resonance imaging (fMRI) resting-state networks and the functional connectome. Since alternate commissural routes between the cerebral hemispheres exist, we hypothesize that bilateral cortical networks can still be maintained in partial or even complete agenesis of the corpus callosum (AgCC). However, since these commissural routes are frequently indirect, requiring polysynaptic pathways, we hypothesize that quantitative measurements of interhemispheric functional connectivity in bilateral networks will be reduced in AgCC compared with matched controls, especially in the most highly interconnected cortical regions that are the hubs of the connectome. Seventeen resting-state networks were extracted from fMRI of 11 subjects with partial or complete AgCC and 11 matched controls. The results show that the qualitative organization of resting-state networks is very similar between controls and AgCC. However, interhemispheric functional connectivity of precuneus, posterior cingulate cortex, and insular-opercular regions was significantly reduced in AgCC. The preserved network organization was confirmed with a connectomic analysis of the resting-state fMRI data, showing five functional modules that are largely consistent across the control and AgCC groups. Hence, the reduction or even complete absence of callosal connectivity does not affect the qualitative organization of bilateral resting-state networks or the modular organization of the functional connectome, although quantitatively reduced functional connectivity can be demonstrated by measurements within bilateral cortical hubs, supporting the hypothesis that indirect polysynaptic pathways are utilized to preserve interhemispheric temporal synchrony.
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http://dx.doi.org/10.1089/brain.2013.0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868398PMC
August 2014

Aberrant Oscillatory Activity during Simple Movement in Task-Specific Focal Hand Dystonia.

Front Neurol 2012 28;3:165. Epub 2012 Nov 28.

Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA.

In task-specific focal hand dystonia (tspFHD), the temporal dynamics of cortical activity in the motor system and how these processes are related to impairments in sensory and motor function are poorly understood. Here, we use time-frequency reconstructions of magnetoencephalographic (MEG) data to elaborate the temporal and spatial characteristics of cortical activity during movement. A self-paced finger tapping task during MEG recording was performed by 11 patients with tspFHD and 11 matched healthy controls. In both groups robust changes in beta (12-30 Hz) and high gamma (65-90 Hz) oscillatory activity were identified over sensory and motor cortices during button press. A significant decrease [p < 0.05, 1% False Discovery Rate (FDR) corrected] in high gamma power during movements of the affected hand was identified over ipsilateral sensorimotor cortex in the period prior to (-575 ms) and following (725 ms) button press. Furthermore, an increase (p < 0.05, 1% FDR corrected) in beta power suppression following movement of the affected hand was identified over visual cortex in patients with tspFHD. For movements of the unaffected hand, a significant (p < 0.05, 1% FDR corrected) increase in beta power suppression was identified over secondary somatosensory cortex (S2) in the period following button press in patients with tspFHD. Oscillatory activity within in the tspFHD group was however not correlated with clinical measures. Understanding these aberrant oscillatory dynamics can provide the groundwork for interventions that focus on modulating the timing of this activity.
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http://dx.doi.org/10.3389/fneur.2012.00165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508423PMC
December 2012

Autism traits in individuals with agenesis of the corpus callosum.

J Autism Dev Disord 2013 May;43(5):1106-18

School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n = 106) with the Autism Spectrum Quotient (AQ) and found that 45 % of children, 35 % of adolescents, and 18 % of adults exceeded the predetermined autism-screening cut-off. Interestingly, performance on the AQ's imagination domain was inversely correlated with magnetoencephalography measures of resting-state functional connectivity in the right superior temporal gyrus. Individuals with AgCC should be screened for ASD and disorders of the corpus callosum should be considered in autism diagnostic evaluations as well.
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http://dx.doi.org/10.1007/s10803-012-1653-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625480PMC
May 2013

The role of corpus callosum development in functional connectivity and cognitive processing.

PLoS One 2012 3;7(8):e39804. Epub 2012 Aug 3.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039804PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411722PMC
February 2013

Dynamics of hemispheric dominance for language assessed by magnetoencephalographic imaging.

Ann Neurol 2012 May;71(5):668-86

Department of Radiology and Biomedical Imaging, University of California at San Francisco, USA.

Objective: The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG imaging, and to determine whether MEG imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold standard for preoperative language lateralization in neurosurgical candidates.

Methods: MEG was recorded during an auditory verb generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time windows and brain regions of interest that best discriminated between IAP-determined left or right dominance for language were identified. Parameters derived in the retrospective analysis were applied to a prospective cohort of 14 patients and healthy controls.

Results: Power decreases in the beta frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%.

Interpretation: Our results demonstrate excellent correlation between MEG imaging findings and the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing.
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http://dx.doi.org/10.1002/ana.23530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380661PMC
May 2012

Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment.

Biol Psychiatry 2011 Dec 8;70(12):1134-42. Epub 2011 Sep 8.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94143, USA.

Background: Schizophrenia (SZ) is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants.

Methods: Thirty patients with SZ and 15 healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEG source data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain.

Results: In patients, decreased connectivity was observed in left prefrontal cortex (PFC) and right superior temporal cortex, whereas increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms.

Conclusions: This study demonstrates direct functional disconnection in SZ between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in SZ.
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http://dx.doi.org/10.1016/j.biopsych.2011.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327723PMC
December 2011

Amplitude and timing of somatosensory cortex activity in task-specific focal hand dystonia.

Clin Neurophysiol 2011 Dec 28;122(12):2441-51. Epub 2011 Jul 28.

Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, School of Medicine, CA 94143-0628, USA.

Objective: Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear.

Methods: In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls.

Results: Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength.

Conclusions: There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD.

Significance: Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions.
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http://dx.doi.org/10.1016/j.clinph.2011.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327722PMC
December 2011

Sensory processing in autism: a review of neurophysiologic findings.

Pediatr Res 2011 May;69(5 Pt 2):48R-54R

Department of Neurology, University of California, San Francisco, California 94143, USA.

Atypical sensory-based behaviors are a ubiquitous feature of autism spectrum disorders (ASDs). In this article, we review the neural underpinnings of sensory processing in autism by reviewing the literature on neurophysiological responses to auditory, tactile, and visual stimuli in autistic individuals. We review studies of unimodal sensory processing and multisensory integration that use a variety of neuroimaging techniques, including electroencephalography (EEG), magnetoencephalography (MEG), and functional MRI. We then explore the impact of covert and overt attention on sensory processing. With additional characterization, neurophysiologic profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions for autism and reveal potential strategies and target brain regions for therapeutic interventions.
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http://dx.doi.org/10.1203/PDR.0b013e3182130c54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086654PMC
May 2011

Cognitive Impairments in Schizophrenia as Assessed Through Activation and Connectivity Measures of Magnetoencephalography (MEG) Data.

Front Hum Neurosci 2010 11;3:73. Epub 2010 Nov 11.

Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA.

The cognitive dysfunction present in patients with schizophrenia is thought to be driven in part by disorganized connections between higher-order cortical fields. Although studies utilizing electroencephalography (EEG), PET and fMRI have contributed significantly to our understanding of these mechanisms, magnetoencephalography (MEG) possesses great potential to answer long-standing questions linking brain interactions to cognitive operations in the disorder. Many experimental paradigms employed in EEG and fMRI are readily extendible to MEG and have expanded our understanding of the neurophysiological architecture present in schizophrenia. Source reconstruction techniques, such as adaptive spatial filtering, take advantage of the spatial localization abilities of MEG, allowing us to evaluate which specific structures contribute to atypical cognition in schizophrenia. Finally, both bivariate and multivariate functional connectivity metrics of MEG data are useful for understanding how these interactions in the brain are impaired in schizophrenia, and how cognitive and clinical outcomes are affected as a result. We also present here data from our own laboratory that illustrates how some of these novel functional connectivity measures, specifically imaginary coherence (IC), are quite powerful in relating disconnectivity in the brain to characteristic behavioral findings in the disorder.
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http://dx.doi.org/10.3389/neuro.09.073.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991173PMC
July 2011

Cortical temporal dynamics of visually guided behavior.

Cereb Cortex 2011 Mar 2;21(3):519-29. Epub 2010 Jul 2.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA.

Little is known about the temporal dynamics of cortical activation during visually guided behavior. We measured changes in brain activity in human posterior parietal cortex (PPC) and premotor cortex (PMC) during saccades and visually guided reaching using magnetoencephalography (MEG) and novel time-frequency reconstructions of MEG (tfMEG) data. Results indicate that early high-gamma activity over the frontal eye fields (FEFs) was present during saccade preparation, and high-gamma activity progressed from the supplementary and FEFs to visual cortex during saccade execution. In contrast, early high-gamma activity over dorsal PMC and late beta activity in primary motor cortex and PPC were unique to reach preparation. During reaching, high-gamma activity progressed from sensorimotor cortex and PMC to parietooccipital cortex. These unique spatial-temporal processing patterns reflect the known connectivity of 2 different sensorimotor networks in macaques. The onset and duration of activity in these areas provides direct evidence for concurrent serial and parallel processing in the human brain during the integration of the sensorimotor inputs necessary for visually guided performance.
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http://dx.doi.org/10.1093/cercor/bhq102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041007PMC
March 2011

Visual-manual exploration and posterior parietal cortex in humans.

J Neurophysiol 2009 Dec 7;102(6):3433-46. Epub 2009 Oct 7.

Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA.

Areas of human posterior parietal cortex (PPC) specialized for processing sensorimotor information associated with visually locating an object, reaching to grasp, and manually exploring that object were examined using functional MRI. Cortical activation was observed in response to three tasks: 1) saccadic eye movements, 2) visually guided reaching to grasp, and 3) manual shape discrimination. During saccadic eye movements, cortical fields within the lateral and rostral superior parietal lobe (SPL) and the caudal SPL and parieto-occipital boundary were active. During visually guided reaching to grasp, regions of cortex within the postcentral sulcus (PoCS) and rostral intraparietal sulcus (IPS) were active, as well as the caudal SPL of the left hemisphere and the medial and caudal IPS of the right hemisphere. Cortical regions at the junction of the IPS and PoCS and an area in the medial SPL were active bilaterally during shape manipulation. Only a few regions were most active during a single motor behavior, whereas several areas were highly active during two or more tasks. Hemispheric asymmetries in activation patterns were observed during visually guided reaching to grasp. The gross areal organization of human PPC is likely similar to the pattern previously described in nonhuman primates, including multifunctional regions and asymmetric processing of some manual abilities.
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http://dx.doi.org/10.1152/jn.90785.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804435PMC
December 2009

Neuroimaging characteristics of patients with focal hand dystonia.

J Hand Ther 2009 Apr-Jun;22(2):125-34; quiz 135. Epub 2009 Feb 12.

Department of Radiology, University of California, San Francisco, San Francisco, California 94143-0628, USA.

NARRATIVE REVIEW: Advances in structural and functional imaging have provided both scientists and clinicians with information about the neural mechanisms underlying focal hand dystonia (FHd), a motor disorder associated with aberrant posturing and patterns of muscle contraction specific to movements of the hand. Consistent with the hypothesis that FHd is the result of reorganization in cortical fields, studies in neuroimaging have confirmed alterations in the topography and response properties of somatosensory and motor areas of the brain. Noninvasive stimulation of these regions also demonstrates that FHd may be due to reductions in inhibition between competing sensory and motor representations. Compromises in neuroanatomical structure, such as white matter density and gray matter volume, have also been identified through neuroimaging methods. These advances in neuroimaging have provided clinicians with an expanded understanding of the changes in the brain that contribute to FHd. These findings should provide a foundation for the development of retraining paradigms focused on reversing overlapping sensory representations and interactions between brain regions in patients with FHd. Continued collaborations between health professionals who treat FHd and research scientists who examine the brain using neuroimaging tools are imperative for answering difficult questions about patients with specific movement disorders.
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http://dx.doi.org/10.1016/j.jht.2008.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287964PMC
August 2009

Ipsilateral representation of oral structures in human anterior parietal somatosensory cortex and integration of inputs across the midline.

J Comp Neurol 2003 Dec;467(4):487-95

Department of Neurology, Center for Neuroscience, University of California, Davis, Davis, California 95616, USA.

Anterior parietal somatosensory areas 3a, 3b, 1, and 2 generally contain cells with receptive fields that are on the contralateral body. However, inputs from midline structures such as the mouth must be uniquely integrated across the midline. This hypothesis is supported by studies of these fields from nonhuman primates that demonstrate ipsilateral representations of oral structures. We used magnetoencephalography (MEG) to examine the cortical representations of the lips and tongue in humans and to examine the time course of interaction of bilateral inputs from these structures. Ipsilateral activation was observed in response to tactile stimulation of the upper lip in 69% of cases, the lower lip in 85% of cases, and the tongue in 88% of cases. In the contralateral hemisphere, the map of oral structures tended to be in agreement with that from nonhuman primates, although variation was large and source locations were not statistically significantly different from each other. There were no differences in latency of activation for ipsi-vs. contralateral responses (about 30 msec), and cortical sources from ipsi-and contralateral stimulation tended to be located together. Differential activation for bilateral vs. unilateral stimulation occurred later than activation in S1, around 110 msec, and was localized to the upper bank of the Sylvian sulcus. Our findings indicate that, unlike nonhuman primates, humans have an ipsilateral representation of the lips in 3b/1, possibly related to the precise manipulation necessary for the articulation of speech. The distinct pattern of differential activation for uni-vs. bilateral stimulation suggests a unique neural mechanism of integration across the midline for inputs from the mouth.
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http://dx.doi.org/10.1002/cne.10935DOI Listing
December 2003