FROM NEUROSCIENCE LABORATORY TO NEUROLOGY CLINIC

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APATHY AND ITS NEUROBIOLOGY IN PARKINSON’S DISEASE MODEL

Ali Behram Salar

İstanbul Medipol University, International School of Medicine, Department of Physiology, İstanbul, Türkiye

Salar AB. Apathy and Its Neurobiology in Parkinson’s Disease Model. In: Hanoğlu L, editor. From Neuroscience Laboratory to Neurology Clinic. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.3-12.

ABSTRACT

Apathy is a syndrome characterized by diminished interest, emotion, and motivation, resulting in impairments in cognitive, emotional, and behavioral subdomains of goal-directed behavior. Due to its clinical presentation with anhedonia, reduced activity and reduced interest, it can easily be mistaken for depression. However, the difference between apathy and depression is that an apathetic individual has a neutral mood rather than a negative mood seen in depression.

The dysfunctions in goal-directed behavior that is seen in apathy can be categorized into three subtypes: emotional-affective impairment, cognitive dysfunction, and auto-activation deficits. Emotional-affective impairments disrupt the motivational value or the satisfaction of internal or external stimuli, while cognitive dysfunction, which is linked to Dorsolateral Prefrontal Cortex (DLPFC), affects planning in initiating the action. Auto-activation deficits, associated with the medial and lateral prefrontal cortices, describe the lack of spontaneous action without external prompts together with feeling of “nothing to do”.

The underlying pathophysiology of apathy is not yet fully understood. Studies in the literature focus mainly on a prefrontal cortex and basal ganglia centered pathologies. But more recent studies propose the involvement of lateral parietal cortex, particularly Inferior Parietal Lobule (IPL)’s role in development of apathy. In Parkinson’s disease (PD) apathy is a prevalent non-motor symptom that can appear early and usually worsens with disease progression. Because of its neurodegenerative nature, PD widely affects the functional networks of the brain. Neuroimaging studies link apathy to functional disruptions in areas like Posterior Cingulate Cortex, Precuneus, DLPFC, Subcortical areas and IPL. IPL plays a role in transforming internal states to external actions in initiating the goal-directed behavior and associating that action to self. While isolated IPL pathologies do not directly cause apathy, including the IPL in apathy models could help in understanding its complex neurobiology.

Keywords: Apathy; Parkinson’s disease; Resting state networks

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