Beyond and below the cortex: the contribution of striatal dysfunction to cognition and behaviour in neurodegeneration.

Investigations of cognitive and behavioural changes in neurodegeneration have been mostly focussed on how cortical changes can explain these symptoms. In the proposed review, we will argue that the striatum has been overlooked as a critical nexus in understanding the generation of such symptoms. Although the striatum is historically more associated with motor dysfunction, there is increasing evidence from functional neuroimaging studies in the healthy that striatal regions modulate behaviour and cognition. This should not be surprising, as the striatum has strong anatomical connections to many cortical regions including the frontal, temporal and insula lobes, as well as some subcortical regions (amygdala, hippocampus). To date, however, it is largely unclear to what extent striatal regions are affected in many neurodegenerative conditions-and if so, how striatal dysfunction can potentially influence cognition and behaviour. The proposed review will examine the existing evidence of striatal changes across selected neurodegenerative conditions (Parkinson's disease, progressive supranuclear palsy, Huntington's disease, motor neuron disease, frontotemporal dementia and Alzheimer's disease), and will document their link with the cognitive and behavioural impairments observed. Thus, by reviewing the varying degrees of cortical and striatal changes in these conditions, we can start outlining the contributions of the striatal nexus to cognitive and behavioural symptoms. In turn, this knowledge will inform future studies investigating corticostriatal networks and also diagnostic strategies, disease management and future therapeutics of neurodegenerative conditions.