How the Deterioration of Hedonic Hotspots in the Brain Causes Loss of Pleasure in Dementia Patients

Many psychologists and neuroscientists argue that all human behavior can be explained by one factor — the motivation of seeking pleasure. From watching a beautiful sunset to enjoying a delicious meal to participating in your favorite hobby, humans are hard-wired to prefer and seek out pleasurable experiences, while doing our best to avoid the not-so-pleasant. However, we don’t all have these hedonic motivations — people with psychiatric disorders have shown significantly lower levels of this internal motivation to feel good. 

Also known as anhedonia, this condition refers to the decline in the ability or desire to experience and pursue pleasurable activities. While anhedonia has been widely documented in schizophrenia, Parkinson’s disease, clinical depression, and bipolar disorder, its role in dementia has largely been ignored in the research. Although apathy — a general lack of enthusiasm or interest — has been implicated in dementia and Alzheimer’s disease, researchers have yet to detail how anhedonia relates to cognitive decline. 

In a recent study published in Brain, Shaw and colleagues aim to uncover the lesser-studied relationship between anhedonia and dementia. Using neuroimaging scans, this research team from the University of Sydney in Australia finds marked levels of degeneration in areas of the brain related to pleasure- and reward-seeking, specifically in patients with frontotemporal dementia (FTD) — a less common type of dementia that typically affects middle-aged adults. This research demonstrates for the first time that a loss of pleasure-seeking motivation is implicated as a key characteristic of this form of early-onset dementia, providing a starting point for therapeutic targets to resolve this lack of pleasurable motivation that affects the quality of life in people with FTD.

Hedonic Hotspots Light Up the Brain 

There are several brain regions involved with pleasure-seeking and reward-giving — sometimes referred to as ‘hedonic hotspots.’ The ability to both think about and take action towards securing pleasure is dependent on the integrity of pathways in the brain called frontostriatal circuits. These pathways connect the frontal lobe of the brain with a group of structures called the striatum — the frontal lobe is vital for managing emotions, language, and executive functions (things like decision-making, problem-solving, and self-control), while the striatum is highly involved in movement and mediating rewarding experiences. 

The striatum can be further divided into two areas, one of which is the ventral striatum. This region contains the nucleus accumbens, which plays a significant role in our brain’s reward pathways. Both the nucleus accumbens and the ventral striatum as a whole are activated when we do something pleasurable — or even anticipate it. Together, the activities and integrity of the frontostriatal circuit prove essential to regulating the motor, cognitive, and behavioral functions that are involved with pleasure-seeking.

Detailing the Hedonic Differences in Dementia Patients

FTD involves damage to the neurons in both the frontal lobe — our behavior and emotional control center — and the temporal lobe, which is responsible for creating and preserving memories. Because of this neuronal damage in these regions, Shaw and colleagues predicted that people with FTD would show significantly more pronounced levels of anhedonia than other types of dementia. 

In this study, the research team looked at 172 adults, comparing people with FTD and Alzheimer’s disease to healthy controls and assessing anhedonia using a questionnaire designed to tease out the differences between anhedonia, apathy, and depression. They found that FTD patients did have significantly higher levels of anhedonia — both self-reported and described by their caregivers — while people with Alzheimer’s disease were not affected by this loss of pleasurable motivation. These increases in anhedonia were not associated with disease duration or severity of cognitive decline, suggesting that anhedonia is not simply an effect of more severe dementia stages, but, rather, due to the initial neuron damage seen with FTD. Additionally, the patients’ loss of hedonic motivation was significantly increased from their pre-diagnosis state, indicating that anhedonia emerges during FTD progression, rather than being an underlying trait of the patient. 

Although anhedonia is recognized as a core symptom of depression, not all depressed people have anhedonia, and not all people with anhedonia are depressed. Shaw and colleagues add to the evidence that these two conditions should be treated separately in FTD patients, stating, “Our findings have important clinical implications via novel treatment avenues that can be swiftly implemented to improve quality of life in dementia.”

Mind Over (Grey) Matter

The research team also looked at neuroimaging scans of the patients’ brains, comparing the different dementia states and hedonic activities with healthy controls. They found that, although anhedonia, apathy, and depression do share many commonalities in terms of behavior and symptoms, the conditions show divergent neural activity on their brain scans. 

When looking at the entire dementia cohort, the researchers found that anhedonia was associated with degeneration in some regions of the frontal and prefrontal cortices — the thin layers of the outer part of the brain — that are involved with cognition, learning, memory, and emotions. Specifically, these areas of neurodegeneration involved atrophy of grey matter, which contains most of the brain’s neuron cell bodies — not the projections — where information is processed within the brain. 

People with FTD were found to have significant degeneration to the grey matter in the frontal and striatal areas of the brain, which would cause the symptoms of diminished reward-seeking seen in anhedonia. Those with FTD and anhedonia also had significant losses of grey matter in regions related to decision-making, memory, and processing and evaluating future rewards. There was only a small region of overlap between those with anhedonia and apathy, while there was no neural overlap with anhedonia and depression — despite their highly similar behavioral symptoms. With these results, Shaw and colleagues uncover the neural differences between anhedonia, apathy, and depression in FTD patients, highlighting the importance of treating these conditions separately. 

The Future of Tailoring Treatments for FTD

This study is the first to tease out the anatomical changes to the brain that occur with anhedonia, apathy, and depression in FTD patients — specifically with grey matter atrophy. As it was previously unknown that the brain’s structure and function respond differently to these conditions, these results will pave the way for more individualized FTD treatments that are tailored specifically to one’s level of anhedonia.

As a loss of pleasure results in a severely diminished quality of life, Shaw and colleagues are hopeful that this research will open new therapeutic doors for treating anhedonia in dementia patients. As concluded by the authors, “As we continue to explore the cognitive neuroarchitecture of human motivation, and its vulnerability in neurodegenerative disorders, we ultimately hope to shed new light on a fundamental aspect of the human condition—the conscious experience of pleasure.”

References: 

Shaw SR, El-Omar H, Roquet D, et al. Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia [published online ahead of print, 2021 Apr 12]. Brain. 2021;awab032. doi:10.1093/brain/awab032