A choice disinhibition paradigm to reveal neural correlates of behavioral disinhibition in Frontotemporal dementia

Frontotemporal dementia (bvFTD) is characterized by behavioral disinhibition, a symptom without a cure or method to slow its progression. Researchers have struggled to understand the mechanisms behind this disinhibition and how self-control is affected. Until recently, no disinhibition had been demonstrated in a FTD model. To address this, a new paradigm was created to assess disinhibition, distinguishing between general cognitive capacity and behavioral disinhibition.

The study found that aged mutant mice exhibited increased impulsive choice but maintained intact cognition, indicating early-mid stage bvFTD-associated symptoms. Importantly, the researchers discovered that the neural mechanisms underlying self-control are distinct from impulsive choice. During self-control tasks, CaMKIIlower case Greek alpha and somatostatin-expressing neurons in the medial prefrontal cortex were activated, while the classical anterior cingulate cortex was not involved.

This research demonstrates the presence of behavioral disinhibition in mutant mice and identifies specific regions and cell types that play a role in self-control. This new paradigm opens up possibilities for future studies to explore the neural circuits underlying impulsive choice and self-control behavior in bvFTD and other neurological conditions.