Sachse, E. M. | Search bioRxiv

bioRxiv2024

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↗

bioRxiv2022

Dynamic attention signaling in V4: relation to excitatory/inhibitory cell class and population coupling

Neurons have different roles in attention processing. These roles are determined by a neurons firing properties, neurotransmitter expression, and functional connectivity. Neurons in the visual cortical area, V4, are reliably engaged by selective attention but exhibit differences in firing rate and correlated variability. It remains unclear what specific neuronal properties shape these attention effects. We identified neurons as fast-spiking (FS) (putative inhibitory) and regular-spiking (RS) (putative excitatory) and investigated their role in anticipatory attention and how this related to their functional connectivity. V4 neurons exhibited a continuum of time-varying attention effects ranging from "restless-weak" neurons at one extreme to "quiet-strong" neurons at another. We found an interdependence between neural attention effects (e.g., restless-weak or quiet-strong), neuron type (FS, RS), and functional connectivity. In particular, we found neurons with restless-weak attention effects were more likely to be RS and have greater population coupling, compared to neurons with other types of attention effects. Also, quiet-strong neurons were more likely to be FS and these FS neurons exhibited higher spike synchrony. From this we propose that time-varying attention effects in a neuronal population depends on the relative involvement of neurons that drive stimulus processing and those that are engaged by intrinsic population activity. These results add important information to our understanding of visual attention circuits at the cellular level.

neuroscience↗