Biology subjects

Hinkley, L. B.

Publications and source records attributed to Hinkley, L. B..

3 recordsLinked to original sources

bioRxiv2022

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↗

bioRxiv2022

Multi-tasking Deep Network for Tinnitus Classification and Severity Prediction from Multimodal Structural Images

Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Fast and efficient diagnostic tools will advance clinical practice by detecting or confirming the condition, tracking change in severity, and monitoring treatment response. Motivated by evidence of subtle anatomical or functional morphological information in magnetic resonance images (MRI) of the brain, we examined data-driven machine learning methods for joint tinnitus classification (tinnitus or no tinnitus) and tinnitus severity prediction. We propose a deep multi-task multi-modal framework for joint functionalities using structural MRI (sMRI) data. To leverage cross-information multimodal neuroimaging data, we integrated two modalities of 3-dimensional sMRI - T1 weighted (T1w) and T2 weighted (T2w) images. To explore the key components in the MR images that drove task performance, we segmented both T1w and T2w images into three different components - cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM), and examined performance of each segmented image. Results demonstrate that our multimodal framework capitalizes on the information across both modalities (T1w and T2w) for the joint task of tinnitus classification and severity prediction. Our model outperforms existing learning-based and conventional methods in terms of accuracy, sensitivity, specificity, and negative predictive value.

neuroscience↗

bioRxiv2019

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↗