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

Abstract

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.

Grey and white matter brain network changes in frontotemporal dementia subtypes

“…VMPFC changes, in particular in orbitofrontal and anterior cingulate cortices in bvFTD [42,43], that have been associated with many of the classical behavioural features in the disease, notably disinhibition, apathy, loss of insight and reduced empathy [44][45][46]. The striatal contributions to bvFTD symptomology are less well established, although this region is consistently affected in this FTD subtype [47]. Recent findings suggest that the striatal changes in bvFTD might be related to inhibitory and apathy processes [48].…”

Copy number deletion burden is associated with cognitive, structural, and resting-state network differences in patients with schizophrenia

“…There was a negative correlation between connectivity between the mPFC M a n u s c r i p t 18 and the left iPFC and performance IQ. Prefrontal striatal connectivity has been linked with cognitive functioning in schizophrenia [71,72] as well as in other populations [73][74][75]. The striatum and cortex are anatomically and functionally linked through several cortico-striatal-thalamic-cortical circuits [76] and pathologies of the striatum affect cognition in a similar manner to pathologies of the prefrontal cortex [77].…”

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

“…These diseases are known to have extremely high morbidity rates, reinforcing the importance of their timely diagnosis and treatment. Unfortunately, none of these diseases are known to be completely curable [265]. Hence, the only strategy is symptomatic treatment.…”

“…Hence, the only strategy is symptomatic treatment. The management of symptoms largely depends upon the mode of neurodegeneration as well as other associated physiological changes [265,266].…”

“…Repeated engagement in sexual activities inspite of the negative consequences is the major hallmark of CSB [256][257][258][259][260][261][262][263][264][265][266][267][268][269][270][271]. Hypersexuality can manifest itself in a variety of ways with differing degrees of severity and further divided into paraphilic and nonparaphilic types.…”