Biology subjects

Villarreal, M. F.

Publications and source records attributed to Villarreal, M. F..

3 recordsLinked to original sources

bioRxiv2026

Dose-Dependent Effects of Low-Intensity Focused Ultrasound on Human Deep White Matter Tracts

Background: Low-intensity focused ultrasound (LIFU) is emerging as a method for anatomically specific, noninvasive, and reversible neuromodulation of deep brain structures relevant to psychopathology. A key requirement for clinical translation is evidence of graded target engagement. We examined whether LIFU applied to deep white matter tracts produces dose-dependent functional connectivity changes in healthy adults. Methods: In this preregistered, double-blind, randomized study, 35 healthy adults underwent LIFU targeting (80 s, 10% duty cycle, estimated ISPPA 2.26 W/cm2, 0.5 MHz, in a {theta}-burst pattern) of individually modeled right thalamo-prefrontal white matter tracts under two dose conditions: one and three consecutive sonications. Dose-dependent changes in resting-state functional connectivity were examined during a 30-minute poststimulation period in 31 participants. Results: One sonication acutely increased right thalamic functional connectivity with the left thalamus (28 voxels; Z = 5.48, Cohen's d = 0.61), whereas three sonications decreased connectivity with the right dorsolateral prefrontal cortex (Z = -4.05, Cohen's d = -0.45). Poststimulation time-course analysis revealed a 3-LIFU-specific linear recovery trend in the left cerebellum (Z = 4.14, d = 0.48), reflecting initial suppression followed by progressive recovery across 30 minutes. Stronger thalamo-prefrontal structural connectivity was associated with condition-specific functional connectivity changes (left frontal pole; F = 14.73, {rho}2 = 0.41). Conclusions: These findings provide initial human evidence that LIFU is well tolerated and produces dose-dependent changes in functional connectivity associated with deep white matter tract stimulation, informing parameter selection for future circuit-based mechanistic and clinical studies.

neuroscience↗

bioRxiv2026

Distinct Multimodal Imaging Correlates of Depression in Middle-Aged Adults With and Without a Family History of Alzheimer Disease

BackgroundDepression is associated with risk for late-onset Alzheimers disease (LOAD), but its underlying pathogenesis in at-risk individuals remains unclear. We examined multimodal imaging correlates of depressive symptoms in cognitively normal middle-aged offspring of patients with LOAD (O-LOAD) compared with control individuals without LOAD history up to a 4th degree of kinship (HC). MethodsParticipants (n=58; 52{+/-}3 years; 74% female) underwent assessment with the Beck Depression Inventory-II (BDI), structural MRI, resting-state fMRI, FDG-PET, and PiB-PET. Resting-state fMRI data were available for 28 O-LOAD and 24 HC; PET data for 24 O-LOAD and 22 HC. General linear models tested associations between imaging measures and BDI, including group interactions. ResultsIn O-LOAD, higher BDI scores were associated with reduced cortical thickness in the left postcentral gyrus. Resting-state fMRI revealed significant group-by-BDI interactions involving cingulate and orbitofrontal networks. In O-LOAD, greater depressive symptom severity was associated with reduced cingulate connectivity across distributed corticolimbic, prefrontal, insular, occipital, and cerebellar regions ({beta} range -0.10 to -0.18). In HC, depressive symptoms were associated with reduced right orbitofrontal and somatosensory-medial orbitofrontal connectivity ({beta}=-0.13), with divergent patterns of cingulate connectivity. FDG-PET showed no significant associations with depressive symptoms. PiB-PET demonstrated regionally specific associations between amyloid signal and BDI in HC, involving an inverse pattern in anterior and posterior insular cortices. ConclusionsDepressive symptoms in middle-aged individuals at familial risk for LOAD are associated with distinct structural and functional alterations, involving circuitry subserving salience and reward, and suggesting early network-level mechanisms linking affective symptoms with vulnerability to neurodegeneration.

neuroscience↗

bioRxiv2025

Structural Connectivity Correlates of Response to Electroconvulsive Therapy in Treatment-Resistant Depression

BackgroundElectroconvulsive therapy (ECT) is the most effective option for treatment resistant depression (TRD). In this study, we sought to explore if structural connectivity of limbic networks has an association with response to ECT. MethodsWe studied 23 patients with TRD who underwent a course of bifrontal ECT, employing probabilistic tractography at baseline to assess structural connectivity between the thalamus (THA), posterior (PCC), subgenual cingulate cortices, anterior insula (aINS), amygdala and orbitofrontal and ventrolateral prefrontal cortices, hypothesizing that these hubs participate in the formation and refractoriness of depression symptoms. We also include 21 healthy subject as controls group (HC). ResultsConnectivity between left THA and left PCC was related to both baseline depression severity (R=0.504; p= 0.017) and clinical response (R=0.452; p=0.004). Right aINS-prefrontal connectivity was associated with less clinical response. Structural connectivity was globally higher in patients than in HC (F=2.488; p=0.007). ConclusionsThe association of ECT response with stronger structural connectivity between hubs supporting self-referential bodily experience as well as autobiographical memory encoding and retrieval deserves exploration as a predictor in persons with TRD. In turn, the right aINS is a major hub for the salience network and is involved in repetitive negative mentation. Stronger structural connectivity of this region may be a heuristically valid biomarker for refractory TRD. We discuss the potential of the present findings for the design of anatomically precise neuromodulation interventions that would be useful to treat TRD while circumventing cognitive side effects of ECT.

neuroscience↗