Anterior cingulate integrity: Executive and neuropsychiatric features in Parkinson's disease

Patients with advanced Parkinson's disease (PD) commonly suffer with significant executive dysfunction and concomitant visual hallucinations. Although the underlying pathophysiology remains poorly understood, numerous studies have highlighted the strong association between these neuropsychiatric features, suggesting common neural pathways. Although previous neuroimaging studies have identified widespread volume loss across a number of cortical regions, to date, no studies have utilized proton magnetic resonance spectroscopy to provide insights into how neurometabolic changes may relate to such symptoms. Twenty patients with PD and 20 healthy controls underwent spectroscopy to determine the N-acetyl aspartate/creatine (NAA/Cr) ratio, which reflects the degree of neuronal integrity in neurodegenerative diseases. Voxels were obtained from the anterior cingulate cortex (ACC), an area critical for a wide range of executive mechanisms as well as from a control volume in the posterior cingulate cortex (PCC). Compared to controls, patients with PD had lower NAA/Cr ratios in the ACC. In turn, lower NAA/Cr ratios significantly correlated with poorer executive function on tasks of attentional set-shifting and response inhibition, as well as more-severe psychotic symptoms and poorer performance on the Bistable Percept Paradigm, a neuropsychological probe of visual hallucinations. NAA/Cr ratios were significantly lower in hallucinators, compared to nonhallucinators, within the ACC, but did not differ in the PCC. These results suggest that loss of neuronal integrity within the ACC plays an important role in the pathophysiology underlying executive functioning and visual hallucinations in PD.