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de Oliveira, A. R.

Publications and source records attributed to de Oliveira, A. R..

2 recordsLinked to original sources

Cross-species modeling and enhancement of cognitive control with striatal brain stimulation

Brain disorders, particularly mental disorders, might be effectively treated by direct electrical brain stimulation, but clinical progress requires understanding of therapeutic mechanisms. Animal models have not helped, because there are no direct animal models of mental illness. We show a path past this roadblock, by leveraging a common ingredient of most mental disorders: impaired cognitive control. We previously showed that deep brain stimulation (DBS) improves cognitive control in humans. We now reverse translate that result, showing that DBS-like stimulation of the mid-striatum improves cognitive control in rats. Using this model, we identify a mechanism, improvement in domain-general cognitive control, and rule out competing hypotheses such as impulsivity. The rat findings explain prior human results and have immediate implications for clinical practice and future trial design. One Sentence Summary: Developing a reliable animal model of a human brain stimulation therapy reveals that this therapy works by enhancing the brains ability to process conflicting pieces of evidence.

neuroscience↗

Lost in translation: No effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats

BACKGROUNDThe orbitofrontal cortex-ventromedial striatum (OFC-VMS) circuitry is widely believed to drive compulsive behavior. Hyperactivating this pathway in inbred mice produces excessive and persistent self-grooming, which has been considered a model for human compulsivity. We aimed to replicate these findings in outbred rats, where there are few reliable compulsivity models. METHODS27 male Long-Evans rats implanted with optical-fibers into VMS and with opsins delivered into OFC received optical stimulation at parameters that produce OFC-VMS plasticity and compulsive grooming in mice. We then evaluated rats for compulsive self-grooming at six timepoints: before, during, immediately after and one hour after each stimulation, one and two weeks after the ending of a 6-day stimulation protocol. To further test for effects of OFC-VMS hyperstimulation, we ran animals in three standard compulsivity assays: marble burying, nestlet shredding, and operant attentional setshifting. RESULTSOFC-VMS stimulation did not increase self-grooming or induce significant changes in nestlet shredding, marble burying, or set-shifting in rats. Follow-on evoked potential studies verified that the mouse protocol did alter OFC-VMS synaptic weighting. CONCLUSIONSIn sum, although physiological changes were observed in the OFC-VMS circuitry, we could not reproduce in a strongly powered study in rats a model of compulsive behavior previously reported in mice. If optogenetic effects on behavior do not reliably transfer between rodent species, this may have important implications for designing rodent-to-human translational pipelines.

neuroscience↗