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Honma, S.

Publications and source records attributed to Honma, S..

7 recordsLinked to original sources

Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

neuroscience↗

Cortical dynamics of speech feedback control in non-fluent Primary Progressive Aphasia

Primary Progressive Aphasia (PPA) is a clinical syndrome in which patients progressively lose speech and language abilities. The non-fluent variant of PPA (nfvPPA) is characterised by impaired motor speech and agrammatism. To date, no study in nfvPPA patients has either examined speech motor control behaviour or imaged the speech motor control network during vocal production. Here, we did this using a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations with voxel-based morphometry (VBM). We examined task-induced non-phase-locked neural oscillatory activity during a vocal motor control task, where participants were prompted to phonate the vowel /{square}/ for [~]2.4s while the pitch of their auditory feedback was shifted either up or down by 100 cents for a period of 400ms mid-utterance. Participants were 18 nfvPPA patients (14 female, mean age = 67.79 {+/-} 8.02 years) and 17 controls (13 female, mean age = 64.81 {+/-} 5.76 years). Patients showed a smaller compensation response to pitch perturbation than controls (p < 0.05). Task-induced neural oscillations across five frequency bands were reconstructed in source space for each subject during pitch feedback perturbation. Patients exhibited reduced task-induced alpha-band (8-12Hz) neural activity unrelated to their atrophy patterns, in the right temporal lobe and the right temporoparietal junction (p < 0.01) from 250ms to 750ms after pitch perturbation onset. Patients also showed increased task-induced beta-band (12-30Hz) activity also unrelated to cortical atrophy in the left dorsal sensorimotor cortex, left premotor cortex and the left supplementary motor area (p < 0.01) from 50ms to 150ms after pitch perturbation onset. Reduced average alpha-band power at the peak voxel in the temporoparietal cluster in the right hemisphere could predict speech motor impairment in patients ({beta} = 3.41, F = 8.31, p = 0.0128) whereas increased average beta-band power at the peak voxel in the left dorsal sensorimotor cluster could not ({beta} = -1.75, F = 1.72, p = 0.2123). Collectively, these results suggest significant disruption in sensorimotor integration during vocal production in nfvPPA patients which occurs unrelated to patterns of atrophy. These findings highlight how multimodal structure-function imaging in PPA enhances our understanding of its pathophysiological sequelae.

neuroscience↗

Temporal specificity of abnormal neural oscillations during phonatory events in Laryngeal Dystonia

Laryngeal Dystonia is a debilitating disorder of voicing in which the laryngeal muscles are intermittently in spasm resulting in involuntary interruptions during speech. The central pathophysiology of laryngeal dystonia, underlying computational impairments in vocal motor control, remains poorly understood. Although prior imaging studies have found aberrant activity in the central nervous system during phonation in patients with laryngeal dystonia, it is not known at what timepoints during phonation these abnormalities emerge and what function may be impaired. To investigate this question, we recruited 22 adductor laryngeal dystonia patients (15 female, age range = 28.83-72.46 years) and 18 controls (8 female, age range = 27.40-71.34 years). We leveraged the fine temporal resolution of magnetoencephalography to monitor neural activity around glottal movement onset, subsequent voice onset and after the onset of pitch feedback perturbations. We examined event-related beta-band (12-30 Hz) and high-gamma band (65-150 Hz) neural oscillations. Prior to glottal movement onset, we observed abnormal frontoparietal motor preparatory activity. After glottal movement onset, we observed abnormal activity in somatosensory cortex persisting through voice onset. Prior to voice onset and continuing after, we also observed abnormal activity in the auditory cortex and the cerebellum. After pitch feedback perturbation onset, we observed no differences between controls and patients in their behavioural responses to the perturbation. But in patients, we did find abnormal activity in brain regions thought to be involved in the auditory feedback control of vocal pitch (premotor, motor, somatosensory and auditory cortices). Our study results confirm the abnormal processing of somatosensory feedback that has been seen in other studies. However, there were several remarkable findings in our study. First, patients have impaired vocal motor activity even before glottal movement onset, suggesting abnormal movement preparation. These results are significant because: (i) they occur before movement onset, abnormalities in patients cannot be ascribed to deficits in vocal performance, and (ii) they show that neural abnormalities in laryngeal dystonia are more than just abnormal responses to sensory feedback during phonation as has been hypothesised in some previous studies. Second, abnormal auditory cortical activity in patients begins even before voice onset, suggesting abnormalities in setting up auditory predictions before the arrival of auditory feedback at voice onset. Generally, activation abnormalities identified in key brain regions within the speech motor network around various phonation events not only provide temporal specificity to neuroimaging phenotypes in laryngeal dystonia but also may serve as potential therapeutic targets for neuromodulation.

neuroscience↗

Phase Gradients and Anisotropy of the Suprachiasmatic Network

Biological neural networks operate at several levels of granularity, from the individual neuron to local neural circuits to networks of thousands of cells. The daily oscillation of the brains master clock in the suprachiasmatic nucleus (SCN) rests on a yet to be identified network of connectivity among its ~20,000 neurons. The SCN provides an accessible model to explore neural organization at several levels of organization. To relate cellular to local and global network behaviors, we explore network topology by examining SCN slices in three orientations using immunochemistry, light and confocal microscopy, real-time imaging, and mathematical modeling. Importantly, the results reveal small local groupings of neurons that form intermediate structures, here termed "phaseomes" which can be identified through stable local phase differences of varying magnitude among neighboring cells. These local differences in phase are distinct from the global phase relationship - that between individual cells and the mean oscillation of the overall SCN. The magnitude of the phaseomes local phase differences are associated with a global phase gradient observed in the SCNs rostral-caudal extent. Modeling results show that a gradient in connectivity strength can explain the observed gradient of phaseome strength, an extremely parsimonious explanation for the heterogeneous oscillatory structure of the SCN. Significance statementOscillation is a fundamental property of information sensing and encoding in the brain. Using real time imaging and modeling, we explore encoding of time by examining circadian oscillation in single neurons, small groups of neurons, and the entire nucleus, in the brains master: the suprachiasmatic nucleus (SCN). New insights into the network organization underlying circadian rhythmicity include the discovery of intermediate structures, termed phaseomes, characterized by neurons which are stably out of phase with their neighbors. Modeling indicates that the pattern of phaseomes across the tissue encompasses a gradient in connectivity strength from the rostral to caudal aspects of the nucleus. Anisotropy in network organization emerges from comparisons of phaseomes and connectivity gradients in sagittal, horizontal and coronal slices.

neuroscience↗

Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia.

Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g., it has eight legs) to conceptual (e.g., venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing. Impact StatementFollowing anterior temporal lobe neurodegeneration, defective semantic representations are compensated via enhanced perceptual processing and associated with a dysregulation of the semantic control system.

neuroscience↗

Taking the sub-lexical route: brain dynamics of reading in the semantic variant of Primary Progressive Aphasia.

Reading aloud requires mapping an orthographic form to a phonological one. The mapping process relies on sub-lexical statistical regularities (e.g., "oo" to |u{square}|) or on learned lexical associations between a specific visual form and a series of sounds (e.g., yacht to /j{square}t/). Computational, neuroimaging, and neuropsychological evidence suggest that sub-lexical, 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). Behaviorally, svPPA patients 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 (ATL), affecting primarily the ventral, occipito-temporal, lexical route. Therefore, this clinical population allows for testing of specific hypotheses on the neural implementation of the dualroute 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 analyzed time-resolved whole-brain activity in 12 svPPA patients and 12 healthy age-matched controls while reading irregular words (e.g., yacht) and pseudowords (e.g., pook). Consistent with previous findings that the dorsal route is involved in sub-lexical, 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 sub-lexical/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 sub-lexical/phonological neuro-cognitive systems. When the ventral route is damaged, as in the case of neurodegeneration affecting the ATL, partial compensation appears to be possible by over-recruitment of the slower, serial attention-dependent, dorsal one. Abbreviated SummaryBorghesani et al. investigate brain dynamics during irregular word reading using magnetoencephalographic imaging in patients with semantic variant of primary progressive aphasia. Due to ventral anterior temporal lobe neurodegeneration, patients show greater reliance of dorsal, occipito-parietal brain regions - providing novel evidence for the interplay between ventral and dorsal routes for reading.

neuroscience↗

Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this \"presumably transient\" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

systems biology↗