“Much of human experience is motivated by the drive to experience pleasure but we often take this capacity for granted,” says Muireann Irish, PhD, professor at the University of Sydney’s Brain and Mind Centre and School of Psychology.

The ability to feel pleasure depends on the activity of hedonic hotspots in the brain. Scientists at the University of Sydney, led by Irish, show loss of the ability to experience pleasure is unique to early-onset dementia, also known as frontotemporal dementia (FTD), but not Alzheimer’s disease. This is the first study the researchers claim, that links FTD to the loss of the ability to experience pleasure—clinically called anhedonia.

The study presents neuroimaging results that show grey matter deterioration in the pleasure centers of the brain that are distinct from brain regions linked to depression or apathy.

These findings are published in an article titled “Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia” in the journal, Brain.

morphometry
Neuroimaging findings show grey matter intensity decreases related to anhedonia, apathy and depression. Anhedonia in FTD was related to degeneration of the regions circled in green, which are ‘hedonic hotspots’ (related to reward-seeking) in the brain [University of Sydney].
Patients with early-onset dementia are often misdiagnosed with depression and other neuropsychiatric disorders.  This is potentially because anhedonia is also common in people with depression, bipolar disorder and obsessive-compulsive disorder and can be particularly disabling for the individual. The uniqueness of brain regions associated with early-onset dementia that this study reveals may lead to targeting these regions to develop specific therapeutics.

“Consider what it might be like to lose the capacity to enjoy the simple pleasures of life. This has stark implications for the wellbeing of people affected by these neurodegenerative disorders,” says Irish, senior author on the study.

The study reveals marked degeneration in the reward-seeing centers of the brain including the frontal and striatal areas, in FTD patients. In the study, patients with FTD displayed a dramatic decline from pre-disease onset, in contrast to patients with Alzheimer’s disease, who did not exhibit clinically significant anhedonia.

Despite increasing evidence of motivational disturbances, earlier studies have not investigated the capacity to experience pleasure in people with FTD, says Irish, senior author on the study. “Our findings point to the importance of considering anhedonia as a primary presenting feature of behavioral variant FTD and semantic dementia, with distinct neural drivers to that of apathy or depression,” the authors note.

The study includes 172 participants, including 87 with FTD, 34 with Alzheimer’s disease, and 51 healthy older control participants. Of the 87 participants with FTD, 55 were diagnosed with a behavioral variant FTD, 24 with semantic dementia characterized by loss of semantic memory in both the verbal and non-verbal domains, and eight cases had progressive non-fluent aphasia (PNFA) with specific verbal deficits.

The researchers used whole-brain voxel-based morphometry analysis to examine associations between grey matter atrophy and levels of anhedonia, apathy, and depression in patients.

“Our findings also reflect the workings of a complex network of regions in the brain, signaling potential treatments,” says Irish. His earlier paper in Brain focuses on moral reasoning in FTD.

Future studies will be essential to address the impact of anhedonia on daily life, and to inform the development of targeted interventions to improve quality of life in FTD patients and their families.

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