Cathodal transcranial direct current stimulation (tDCS) may improve hallucination susceptibility and audio-visual perceptual abnormalities by reducing right superior temporal sulcus (rSTS) activity. To assess feasibility and power requirements of this research intervention, we administered cathodal tDCS to the rSTS in a pilot sample. Outcomes included measures that engage the STS (i.e., Audio-Visual Abnormalities Questionnaire (AVAQ) and an Auditory Conditioned Hallucinations (ACH) task) to assess whether active tDCS can reduce hallucination susceptibility compared to sham. 12 participants with psychotic-spectrum disorders received 5 days of twice-daily cathodal stimulation or sham and completed the AVAQ at baseline and at 5-day follow-up. 6 individuals performed the ACH task pre- and post-stimulation using Pavlovian learning to induce false auditory perceptions. Responses were modeled on a Bayesian Hierarchical Gaussian Filter where weight of priors represented hallucination susceptibility. Stimulation-induced changes were examined with Wilcoxon tests (alpha<0.10) and correlations between AVAQ and ACH changes were conducted. AVAQ scores decreased in both groups with greater changes in the active stimulation group (ES=0.87). In the ACH task, cathodal tDCS participants had fewer conditioned hallucinations than sham. In the sham group, prior weighting (Nu) increased from baseline to 5-days, while the active stimulation group's prior weighting (Nu) remained stable or slightly decreased. Auditory detection threshold increased in active stimulation participants but not sham participants. There was also a correlation between changes in participants’ prior weighting (Nu) and auditory abnormalities in the active stimulation group (r = 0.74). NCT05165654
Autism spectrum disorder (ASD) is characterized by social communication impairments and atypical social attention, yet pharmacological interventions targeting these core symptoms remain elusive. Biomarkers such as eye tracking offer promise for improving outcome measurement in clinical trials; however, their utility may vary across autism clinical phenotypes. This pilot study examines whether eye-tracking sensitivity to treatment differs by baseline clinical characteristics in autistic adolescents and young adults enrolled in a randomized, double-blind, placebo-controlled, cross-over trial of intranasal (IN) ketamine. Twenty-one participants (ages 14–29) completed eye-tracking paradigms assessing proportion of looking to facial regions (eyes, nose, mouth) and social versus geometric scenes pre- and post-dose. Change scores from post-dose to pre-dose were correlated with parent-reported symptoms of social communication skills. Results revealed phenotype-dependent patterns: individuals with greater impairment in baseline social awareness shifted attention toward the eyes, whereas those with less impairment in their social awareness increased fixation to the nose. Fearful faces showed the broadest coupling with social communication skills, and increased geometric preference was associated with poorer social cognition. Findings underscore that biomarker informativeness is not uniform but interacts with individual clinical profiles, highlighting the need for precision measurement alongside precision medicine in autism clinical trials.
Background/Objective Methamphetamine is a potent psychostimulant associated with severe neurotoxicity mediated by oxidative stress, neuroinflammation, metabolic dysfunction, and neuronal apoptosis. Vitamin D₃ has been reported to possess antioxidant and anti-inflammatory properties that may provide neuroprotective effects. This study evaluated the potential protective effects of vitamin D₃ against methamphetamine-induced neurotoxicity in rat brain tissue. Methods Twenty male Wistar rats were randomly divided into four groups (n = 5): control, methamphetamine-treated (10mg/kg), vitamin D₃-treated (0.1μg/kg), and methamphetamine plus vitamin D₃. Treatments were administered orally for 56 days. At the end of the experimental period, brain tissues were harvested for biochemical analyses, including oxidative stress markers, antioxidant defense parameters, neurotransmitter levels, metabolic enzymes, inflammatory markers, apoptotic indicators, and histopathological examination. Results Methamphetamine administration significantly increased oxidative stress markers and inflammatory mediators while reducing antioxidant defenses, neurotransmitter levels, and metabolic enzyme activities in brain homogenates. Caspase-3 activity was significantly elevated, indicating enhanced apoptotic signaling. Histopathological examination revealed vascular congestion and structural alterations in methamphetamine-treated animals. Co-administration of vitamin D₃ attenuated several of these biochemical alterations by reducing oxidative stress and inflammatory responses and improving antioxidant status and neurotransmitter levels, although some histological changes persisted. Conclusions Methamphetamine induces neurotoxicity through mechanisms involving oxidative stress, neuroinflammation, metabolic disruption, and apoptosis in brain tissue. Vitamin D₃ supplementation partially mitigates these adverse effects, suggesting its potential role as a neuroprotective agent against methamphetamine-induced neuronal damage.
