Biology subjects

Brang, D.

Publications and source records attributed to Brang, D..

4 recordsLinked to original sources

bioRxiv2021

Glioblastoma remodeling of neural circuits in the human brain decreases survival

Gliomas synaptically integrate into neural circuits. Prior work has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. In this study we wanted to know how glioma induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. We use intracranial brain recordings during lexical retrieval language tasks in awake humans in addition to site specific tumor tissue biopsies and cell biology experiments. We find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumor-infiltrated cortex, beyond cortical excitation normally recruited in the healthy brain. Site-directed biopsies from functionally connected regions within the tumor are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumor cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumor regions compared to tumor regions with less functional connectivity. The degree of functional connectivity between glioblastoma and the normal brain negatively impacts both patient survival and language task performance. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumor proliferation and impairs cognition.

cancer biology↗

bioRxiv2020

Convergence of Heteromodal Lexical Retrieval in the Lateral Prefrontal Cortex

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Prior studies investigating the neuroanatomic underpinnings of lexical retrieval used lesion models that rely on stereotyped vascular distributions, functional neuroimaging methods that lack causal certainty, or awake brain mapping that is typically limited to narrow cortical exposures. Further, few studies have probed lexical retrieval with tasks other than picture naming and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent models emerged. Because of this existing controversy, we set out to test the hypothesis that cortical and subcortical brain regions specifically involved in lexical retrieval in response to visual and auditory stimuli represent overlapping neural systems. Fifty-three patients with dysnomic aphasia due to dominant-hemisphere brain tumors performed four language tasks: picture naming, auditory naming, text reading, and describing line drawings with correct syntax. A subset of participants also underwent the Quick Aphasia Battery which provides a validated measure of lexical retrieval via the word finding subtest. Generalized linear modeling and principal components analysis revealed multicollinearity between picture naming, auditory naming, and word finding, implying redundancies between the linguistic measures. Support vector regression lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Picture naming and auditory naming survived cluster-level corrections. Specifically, lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral PFC were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC. Importance of the StudyLexical retrieval (i.e., selecting and retrieving words to convey desired concepts) is a crucial component of language processing. However, existing studies of the neuroanatomic underpinnings of lexical retrieval lack causal relationships and have provided conflicting evidence, suggesting both convergent and divergent models. In order to resolve these conflicting models, we used lesion-symptom mapping to investigate lexical retrieval in 53 patients with dominant-hemisphere brain tumors. We observed significant associations between performance on visual and auditory naming tasks. Further, performance on these tasks predicted performance on a validated neuropsychological measure of lexical retrieval. Critically, multivariate, nonparametric lesion-symptom mapping within a brain tumor framework revealed that lesions in overlapping regions of the left lateral prefrontal cortex (PFC) predict impaired visual and auditory naming. In a clinical context, this approach to identifying causal brain-behavior relationships could help to guide brain tumor therapies such as cytoreductive surgery and supportive rehabilitation services.

neuroscience↗

bioRxiv2020

Auditory-Visual Speech Behaviors are Resilient to Left pSTS Damage

The ability to understand spoken language is essential for social, vocational, and emotional health, but can be disrupted by environmental noise, injury, or hearing loss. These auditory deficits can be ameliorated by visual speech signals that convey redundant or supplemental speech information, but the brain regions critically responsible for these audiovisual (AV) interactions remain poorly understood. Previous TMS and lesion-mapping studies suggest that the left posterior superior temporal sulcus (pSTS) is causally implicated in producing the McGurk effect, an AV illusion in which auditory and visual speech are perceptually "fused." However, previous research suggests that the McGurk effect is neurally and behaviorally dissociable from other visual effects on speech perception and, therefore, may not provide a generalizable index of AV interactions in speech perception more broadly. To examine whether the left pSTS is critically responsible for AV speech integration more broadly, we measured the strength of the McGurk effect, AV facilitation effects, and AV conflict effects longitudinally over 2 years in patients undergoing surgery for intrinsic tumors in the left pSTS (n = 2) or frontal lobes (control; n = 14). Results demonstrated that left pSTS lesions impaired experience of the McGurk effect, but did not uniformly reduce visual influences on speech perception. Additionally, when multisensory behaviors were affected by a lesion, AV speech perception abilities could recover over time. Our results suggest a causal dissociation between perceptual benefits produced by congruent AV speech and perceptual modulations produced by incongruent AV speech (the McGurk effect).These data are consistent with models proposing that that the pSTS is only one of multiple critical areas necessary for AV speech interactions.

neuroscience↗

bioRxiv2020

Visual speech differentially modulates beta, theta, and high gamma bands in auditory cortex

Speech perception is a central component of social communication. While principally an auditory process, accurate speech perception in everyday settings is supported by meaningful information extracted from visual cues (e.g., speech content, timing, and speaker identity). Previous research has shown that visual speech modulates activity in cortical areas subserving auditory speech perception, including the superior temporal gyrus (STG), potentially through feedback connections from the multisensory posterior superior temporal sulcus (pSTS). However, it is unknown whether visual modulation of auditory processing in the STG is a unitary phenomenon or, rather, consists of multiple temporally, spatially, or functionally distinct processes. To explore these questions, we examined neural responses to audiovisual speech measured from intracranially implanted electrodes within the temporal cortex of 21 patients undergoing clinical monitoring for epilepsy. We found that visual speech modulates auditory processes in the STG in multiple ways, eliciting temporally and spatially distinct patterns of activity that differ across theta, beta, and high-gamma frequency bands. Before speech onset, visual information increased high-gamma power in the posterior STG and suppressed beta power in mid-STG regions, suggesting crossmodal prediction of speech signals in these areas. After sound onset, visual speech decreased theta power in the middle and posterior STG, potentially reflecting a decrease in sustained feedforward auditory activity. These results are consistent with models that posit multiple distinct mechanisms supporting audiovisual speech perception and provide a crucial map for subsequent studies to identify the types of visual features that are encoded by these separate mechanisms.

neuroscience↗