Biology subjects

Weissman, D. H.

Publications and source records attributed to Weissman, D. H..

4 recordsLinked to original sources

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↗

bioRxiv2019

GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

Age-related neural dedifferentiation - a decline in the distinctiveness of neural representations in the aging brain-has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults positively predicted individual differences in neural distinctiveness. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.

neuroscience↗

bioRxiv2018

Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.\n\nSignificance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.

neuroscience↗

bioRxiv2018

Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation

BackgroundAging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).\n\nMethods/DesignThe MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI) sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.\n\nDiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.

neuroscience↗