Biology subjects

McKenna, F.

Publications and source records attributed to McKenna, F..

4 recordsLinked to original sources

bioRxiv2026

Multimodal MRI Clustering Reveals an Elevated Free-Water Biotype in Autism with Increased Social Symptoms

Background: Autism spectrum disorder (ASD) is neurobiologically heterogeneous, and group comparisons may mask effects confined to subgroups. We tested whether distinct biotypes exist within ASD using unsupervised clustering of multimodal MRI. Methods: We analyzed 149 participants with ASD and 129 typically developing (TD) controls from the Autism Brain Imaging Data Exchange II (6 sites; age 5 to 64 years). Site-harmonized features comprised free water (FW), tissue anisotropy and diffusivity, diffusion tensor image analysis along the perivascular space (DTI-ALPS), cerebrospinal fluid (CSF) volumes and exploratory resting-state regional homogeneity. ASD participants were clustered with k-means using global (7 features) and regional (17 features) sets, with robustness tested by permutation and two further algorithms. TD participants were projected post hoc to test specificity. A composite imaging score was related to Social Responsiveness Scale (SRS) subscales, symptom severity and IQ using partial correlations with false discovery rate correction. Results: Clustering identified an elevated free-water (EFW) biotype comprising approximately 10% of ASD participants, defined by markedly increased FW (d = +4.91 versus remaining ASD participants), reduced tissue anisotropy, reduced DTI-ALPS and enlarged ventricles. It was recovered across feature sets and algorithms (permutation p < .0001) and departed from TD norms, unlike the remaining ASD participants. The composite score correlated with social-perceptual and communicative SRS subscales, most strongly social awareness (r = +0.253, q = .026), but not with symptom severity or IQ. FW related to social motivation in children and adolescents (r = +0.287, q = .037) but not adults. Limitations: Each person was scanned once, so we cannot tell whether these brain differences cause social difficulties or how they change with age. The subgroup was small, clinical data were incomplete, the sample was mostly male with a wide age range, and the findings await confirmation in an independent group. Free water can reflect inflammation, swelling or tissue loss, so its biological meaning remains uncertain. Conclusions: We identify an ASD subgroup defined by extracellular fluid excess and altered white matter that is associated with greater social difficulties. If replicated, this signature may help stratify autistic individuals in mechanistic studies and clinical trials.

neuroscience↗

bioRxiv2026

White matter cognition mapping in pediatric cancer survivors: a two-cohort NODDI-Bingham study

Childhood cancer survivors (CS) treated with chemotherapy frequently experience long-term cognitive impairments, commonly referred to as CRCI. Whether these deficits reflect disrupted white matter microstructure, altered relationships between microstructure and cognition, or both remains unclear. Here, we applied the NODDI-Bingham model, which quantifies neurite density (NDI), isotropic free water (ISO), and orientation dispersion along primary (ODIp), secondary (ODIs), and total (ODIt) fiber axes, to characterize biophysically specific white matter microstructure in CS and examine its relationship to cognition. Twenty-one pediatric cancer survivors and 21 age-matched healthy controls (HC) underwent multi-shell diffusion MRI. Voxel-wise NODDI-Bingham analyses were performed within JHU atlas regions. Group differences were tested by ANCOVA, and associations between microstructure and cognition were examined with the NIH Toolbox Crystallized, Fluid, and Early Childhood composites using group-specific regressions. Confirmatory analyses were performed in an age-matched subsample of the HCP (n = 679). Notably, CS showed reduced NDI in the corona radiata, cerebral peduncles, and corpus callosum, with elevated ODIt and ODIp in the middle cerebellar peduncle, pathways that subserve processing speed and interhemispheric integration, cognitive domains among the most vulnerable in CRCI. Group-specific regressions revealed qualitatively different relationships between microstructure and cognition: HC exhibited mixed positive and negative relationships across four of five metrics (138 clusters spanning approximately 305,000 voxels; peak Cohen's d up to 3.00), whereas CS showed a predominantly uniformly negative pattern (67 clusters across 57,000 voxels), with no positive clusters for ISO, ODIt, ODIp, or ODIs, thus highlighting that reduced dispersion and extracellular free water are linked to better cognitive performance in CS. HCP analyses reproduced the HC pattern across all five metrics at proportionally smaller effect sizes, ruling out sample-size effects. NODDI-Bingham identifies two aspects of chemotherapy-related white matter pathology that standard diffusion metrics cannot resolve. First, pediatric cancer survivors show selective elevation of ODIp and ODIt in the cerebellar peduncles and reduced NDI in the corona radiata and corpus callosum, localizing group-level injury to specific fanning and neurite density signatures. Second, whereas in healthy controls white matter shows mixed positive and negative relationships between microstructure and cognition, survivors retain only negative relationships for ODIp and ODIt and a diminished mixed pattern for NDI, such that in the chemotherapy-exposed brain, only reduced neurite density and increased primary-axis fanning relate to cognitive impairment. These findings implicate a biophysically specific restructuring of the relationships between white matter and cognition as a candidate mechanism for CRCI and support NODDI-Bingham as a targeted biomarker panel for monitoring and intervention trials.

neuroscience↗

bioRxiv2026

Cognitive Control in Pediatric Cancer Survivors: A task-fMRI study

BackgroundChemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. MethodsParticipants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. ResultsCompared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. ConclusionsChemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

neuroscience↗

bioRxiv2024

Association between loneliness and hippocampal responses to dynamic social stimuli in psychotic disorders

BackgroundThe incidence of loneliness has increased over the past several decades worldwide and is particularly common among people with serious mental illnesses. However, this public health problem has been difficult to address, in part because the neurocognitive mechanisms underlying loneliness are poorly understood. MethodsTo investigate these mechanisms, a functional magnetic resonance imaging (fMRI) study was conducted which accounted for known cognitive biases associated with loneliness. Participants with (n = 40) and without (n = 60) psychotic disorders (PD) viewed images of faces that appeared to approach or withdraw from the participants, while fMRI data were collected. Following the scanning, participants rated the trustworthiness of the faces, and these ratings were included as weights in the fMRI analyses. Neural responses to approaching versus withdrawing faces were measured, and whole brain regression analyses, with loneliness as the regressor, were performed. ResultsIn the PD and full samples, a higher level of loneliness was significantly associated with greater responses of the hippocampus and areas of the basal ganglia to withdrawing (versus approaching) face stimuli. Moreover, the effects in the hippocampus, but not the basal ganglia, remained significant after controlling for potential confounds such as social activity levels, depression and social anhedonia. Lastly, in a subset of the sample (n = 66), greater hippocampal responses to withdrawing faces predicted greater loneliness one year later. ConclusionsHeightened responses of the hippocampus to withdrawing faces may represent a candidate objective marker of loneliness that could be modified by interventions targeting loneliness.

neuroscience↗