Biology subjects

Leff, A.

Publications and source records attributed to Leff, A..

4 recordsLinked to original sources

bioRxiv2026

Neurotransmitter circuits of the human language network and their disruption in post-stroke aphasia

Language depends on distributed brain networks whose neurochemical organisation remains largely unknown. Here, we combine large-scale functional MRI, positron-emission tomography-derived receptor and transporter maps, and structural connectomics to characterise the neurotransmitter architecture of the human language network and its disruption in post-stroke aphasia. We show that language circuits are organised by connection class: cortico-cortical pathways are dominated by serotonergic and glutamatergic signalling, thalamo-cortical projections are predominantly cholinergic, and anterior temporal connections show GABAergic circuit enrichment. In 239 stroke patients, aphasia was associated with distinct neurochemical disruption profiles, with lobar lesions showing postsynaptic serotonergic injury and subcortical aphasia showing preferential presynaptic cholinergic or serotonergic disruption. These findings map the neurochemical architecture of the language network and establish a neurotransmitter circuit-level framework for post-stroke aphasia. The post-hoc analysis of four pharmacological trials revealed an association between treatment-to-neurotransmitter matching and aphasia improvement, suggesting that personalised pharmacological strategies may enhance behavioural intervention responsiveness.

neuroscience↗

bioRxiv2023

Neural patterns of conscious visual awareness in the Riddoch syndrome

The Riddoch syndrome is one in which patients blinded by lesions to their primary visual cortex can consciously perceive visual motion in their blind field, an ability that correlates with activity in motion area V5. Our assessment of the characteristics of this syndrome in patient ST, using multimodal MRI, showed that: 1. STs V5 is intact, receives direct subcortical input, and decodable neural patterns emerge in it only during the conscious perception of visual motion; 2. moving stimuli activate medial visual areas but, unless associated with decodable V5 activity, they remain unperceived; 3. STs high confidence ratings when discriminating motion at chance levels, is associated with inferior frontal gyrus activity. Finally, we report that STs Riddoch Syndrome results in hallucinatory motion with hippocampal activity as a correlate. Our results shed new light on perceptual experiences associated with this syndrome and on the neural determinants of conscious visual experience.

neuroscience↗

bioRxiv2021

Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study

BACKGROUNDStroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some patients than others. Here, we asked whether that variation might be more systematic, and even predictable, than previously thought. METHODS18 patients, each at least 6 months after left hemisphere stroke, engaged in a computerised treatment for their anomia over a 6 week period. Using only: (a) the patients initial accuracy when naming (to-be) trained items; (b) the hours of therapy that they devoted to the therapy; and (c) whole-brain lesion location data, derived from structural MRI; we developed Partial Least Squares regression models to predict the patients improvements on treated items, and tested them in cross-validation. RESULTSSomewhat surprisingly, the best model included only lesion location data and the hours of therapy undertaken. In cross-validation, this model significantly out-performed the null model, in which the prediction for each patient was simply the mean treatment effect of the group. This model also made promisingly accurate predictions in absolute terms: the correlation between empirical and predicted treatment response was 0.62 (95%CI: 0.27, 0.95). DISCUSSIONOur results indicate that individuals variation in response to anomia treatment are, at least somewhat, systematic and predictable, from the interaction between where and how much lesion damage they have suffered, and the time they devoted to the therapy.

neuroscience↗

bioRxiv2021

Modulating the left inferior frontal cortex by task domain, cognitive challenge and tDCS

The left inferior frontal cortex (LIFC) is a key region for spoken language processing, but its neurocognitive architecture remains controversial. Here we assess the domain-generality vs. domain-specificity of the LIFC from behavioural, functional neuroimaging and neuromodulation data. Using concurrent fMRI and transcranial direct current stimulation (tDCS) delivered to the LIFC, we investigated how brain activity and behavioural performance are modulated by task domain (naming vs. non-naming), cognitive challenge (low vs. high), and tDCS (anodal vs. sham). The data revealed: (1) co-existence of neural signatures both common and distinct across tasks within the LIFC; (2) domain-preferential effects of task (naming); (3) significant tDCS modulations of activity in a LIFC sub-region selectively during high-challenge naming. The presence of both domain-specific and domain-general signals, and the existence of a gradient of activation where naming relied more on sub-regions within the LIFC, may help reconcile both perspectives on spoken language processing.

neuroscience↗