Biology subjects

Carney, A. F.

Publications and source records attributed to Carney, A. F..

4 recordsLinked to original sources

bioRxiv2026

AI-guided analysis of human pancreatic islet sociology reveals distinct cell compositional changes in type 1 diabetes

Human pancreatic islets exhibit greater anatomic and cellular heterogeneity than previously appreciated, raising fundamental questions about how their composition varies with age, sex, region, and islet size and how type 1 diabetes (T1D) alters these relationships. Yet these questions remained largely unresolved due to the bottleneck of manual tissue inspection. Here, we developed an integrated artificial intelligence (AI)-guided imaging, processing, and statistical pipeline enabling unbiased, high-throughput analysis of more than 2 million candidate islets from 106 non-diabetic (ND) and T1D donors. We identified age-, region-, sex-, and islet size-dependent differences in islet distribution and composition between ND and T1D donors. Profound {beta}-cell loss in T1D was accompanied by reciprocal -cell expansion, whereas {delta}-cells and pancreatic polypeptide cells were largely resilient. Cell area and pseudotime analyses uncovered regional and age-dependent trajectories of islet remodeling across T1D progression, along with distinct patterns of cytoarchitectural reorganization of the endocrine pancreas.

pathology↗

bioRxiv2026

Targeted medial prefrontal cortex stimulation prevents incubation of cocaine craving and restores functional connectivity

BackgroundRelapse remains a central obstacle in the treatment of cocaine use disorder (CUD), for which no medications have received approval from the U.S. Food and Drug Administration. Transcranial magnetic stimulation (TMS) has shown promise as a potential therapeutic intervention. However, current clinical trials often rely on a "trial-and-error" approach in target selection and experimental design. We previously developed a novel TMS platform and high-density theta burst stimulation (hdTBS) technology, enabling precise, focal stimulation of the rat medial prefrontal cortex (mPFC), including the prelimbic and anterior cingulate cortices. MethodsWe applied hdTBS intervention to a well-established rat model of cocaine relapse and craving after cessation of extended access intravenous drug self-administration and assessed brain response using resting-state functional magnetic resonance imaging (fMRI). ResultsAs expected, we observed robust time-dependent increases in cocaine seeking (incubation of cocaine craving) in control rats receiving sham stimulation over 3 weeks of abstinence accompanied by a reduction in prefrontal functional connectivity. In contrast, daily sessions of hdTBS for 7 days delivered on abstinence days 14-20 prevented the emergence of the incubation effect and restored prefrontal network functional connectivity. ConclusionsThis study provides strong preclinical evidence demonstrating that precise circuit modulation of medial prefrontal subregions causally reverses both behavioral and network-level adaptations associated with relapse vulnerability. Given the clinical accessibility and established safety profile of TMS, this work provides a mechanistically grounded framework for target selection and supports the translation of focal TMS of the mPFC for relapse prevention in CUD patient. One Sentence SummaryFocal transcranial magnetic stimulation (TMS) of the mPFC using the hdTBS procedure prevents incubation of cocaine craving and restores functional connectivity.

neuroscience↗

bioRxiv2026

Focal Transcranial Magnetic Stimulation of the Rat Anterior Cingulate Cortex Inhibits Incubation of Opioid Craving after Voluntary Abstinence

Relapse remains a major challenge in opioid addiction treatment, underscoring the need for innovative therapies. Progress in neuromodulation therapies has been limited by insufficient mechanistic understanding of stimulation engagement and disease-related changes in the brain. We used a novel, focal transcranial magnetic stimulation (TMS) system to deliver high-density theta burst stimulation (hdTBS) combined with resting-state fMRI to test whether anterior cingulate cortex (ACC) stimulation reduces relapse-like behavior and alters functional circuitry in a rodent model of opiate dependence. The coil focality and stimulation parameters approximate human TMS protocols, and the targeted region represents a functional homolog of the human ACC. We trained rats to self-administer oxycodone intravenously for 14 days. We then introduced an electric barrier for 13 days, which caused cessation of drug self-administration. We assessed relapse to oxycodone seeking immediately after training (early abstinence) and after electric-barrier exposure (late abstinence). We administered daily hdTBS or sham stimulation for 7 days before the late-abstinence test. Sham-treated rats showed a time-dependent increase in oxycodone seeking during abstinence (incubation of oxycodone craving) and reduced ACC functional connectivity. In contrast, hdTBS prevented the incubation of oxycodone craving and restored ACC connectivity with the dorsal and ventral striatum. Tracer-based axonal-projection data further showed that stimulation-induced effects aligned with regions receiving dense projections from the stimulation site, suggesting that the projection architecture is critical to the propagation of focal stimulation across distributed networks. These findings identify ACC-centered circuits as mechanistically informed targets for TMS-based interventions that aim to reduce opioid relapse during abstinence. One sentence SummaryPrefrontal TMS stimulation reduced relapse-like behavior and restored corticostriatal circuits, highlighting translational targets for addiction treatment.

neuroscience↗

bioRxiv2025

High-density theta burst stimulation (hdTBS) at 100 Hz triples the aftereffects of the conventional intermittent TBS

Slice electrophysiological studies have experimentally demonstrated that theta burst stimulation, consisting of electrical pulses delivered at 10 ms (100 Hz) inter-pulse intervals, optimally induces long-term potentiation in the hippocampus. Inspired by this observation, a novel transcranial magnetic stimulation (TMS) paradigm, 100 Hz high-density theta burst stimulation (100 Hz hdTBS), is presented. This paradigm delivers 6 pulses per burst with an inter-pulse interval of 10 ms - doubling the pulse frequency and total pulse count of the conventional intermittent TBS (iTBS). The effect of this new paradigm was studied in the motor cortex of awake rats using a rat-specific focal TMS coil and a hdTBS stimulator developed in house. Results reveal that 100 Hz hdTBS triples the after-effects of conventional iTBS. In a separate group of animals that received two consecutive iTBS session back-to-back (prolonged iTBS), we observed an inhibitory effect. Since that prolonged iTBS matches the total pulse count of 100 Hz hdTBS but produced opposite after-effects, our results underscore the critical roles of the temporal structure of TMS pulses--not merely the total number of pulses--in driving neuroplasticity. This new paradigm has the potential to significantly enhance therapeutic efficacy if confirmed to be safe and effective in humans.

neuroscience↗