Disruptions to mind-wandering are common across neuropsychiatric disorders. Whilst the large-scale brain networks associated with mind-wandering are increasingly well understood, we know very little about what neurobiological mechanisms trigger a mind-wandering episode and sustain the mind-wandering brain state. From a clinical perspective, we aimed to understand dysfunctional mind-wandering in neuropsychiatric diseases of ageing: frontotemporal dementia, Alzheimer’s disease and Parkinson’s disease. We also tested the hypothesis that mind-wandering relates to visual hallucinations in Parkinson’s disease. From a theoretical perspective, we advance the hypothesis that the hippocampal sharp wave-ripple is a compelling candidate for a brain state that can trigger mind-wandering episodes. The occurrence of the sharp wave-ripple is heavily dependent on hippocampal neuromodulatory tone. Neuromodulatory systems that regulate the sharp wave-ripple may be crucial for understanding the disruption to mind-wandering in neuropsychiatric disease.

We developed a thought-sampling task to probe mind-wandering in neuropsychiatric diseases of ageing. To explore brain patterns related to mind-wandering, we used multi-modal neuroimaging (i.e., resting state and structural scans). In separate studies, we applied these techniques in frontotemporal dementia and Alzheimer’s disease; and in Parkinson’s patients with and without visual hallucinations.

We showed reduced mind-wandering in frontotemporal dementia, associated with functional and structural changes across the default network. In Parkinson’s disease, we also found a reduction in mind-wandering compared with healthy controls. However, in patients with visual hallucinations, mind-wandering was preserved and associated with increased connectivity between the default network and early visual regions.

Together, disrupted mind-wandering occurs in neuropsychiatric diseases of ageing. It may contribute to some of the more recognisable symptoms in these conditions, including apathy and hallucinations. These findings also provide a unique clinical validation of current brain network models of mind-wandering that have been developed in healthy populations. Neuromodulatory influences over mind-wandering have implications for treating impairments in this process across neuropsychiatric conditions.