Roelofs, T. J. M. | Search bioRxiv

bioRxiv2019

Distinct structure-function relationships across cortical regions and connectivity scales in the rat brain

An improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in many disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Our main goal was to identify to what extent structural and functional connectivity strengths are correlated, macro- and meso-scopically, across the cortex. Correlation analyses revealed a positive correspondence between functional connectivity and macro-scale diffusion-based structural connectivity, but no correspondence between functional connectivity and meso-scale neuronal tracer-based structural connectivity. Locally, strong functional connectivity was found in two well-known resting-state networks: the sensorimotor and default mode network. Strong functional connectivity within these networks coincided with strong short-range intrahemispheric structural connectivity, but with weak heterotopic interhemispheric and long-range intrahemispheric structural connectivity. Our study indicates the importance of combining measures of connectivity at distinct hierarchical levels to accurately determine connectivity across networks in the healthy and diseased brain. Distinct structure-function relationships across the brain can explain the organization of networks and may underlie variations in the impact of structural damage on functional networks and behavior.

neuroscience↗

bioRxiv2017

A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision-making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to faulty decision-making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA-prefrontal cortex pathway promotes risky decision-making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision-making, providing a mechanistic understanding of the reckless behaviors seen in substance abuse, mania, and after dopamine replacement therapy in Parkinsons disease.

neuroscience↗