Reversal learning in FTD (fMRI)

Objective: Frontotemporal Dementia (FTD) is a neurodegenerative disorder
that results in disinhibition and difficulty with flexible responding when
provided feedback. Inflexible responding is observed early in the course
of the illness and contributes to the financial and social morbidities of
FTD. Reversal learning is an established cognitive paradigm that
indexes flexible responding in the face of feedback signaling a change in
reinforcement contingencies, with components of reversal learning
associated with specific neurotransmitter systems. The objective of the
study was to evaluate the neural mechanisms underlying impaired flexible
behavioural responding in FTD using a reversal learning paradigm combined
with fMRI. Methods: Twenty-two patients meeting the diagnostic criteria
for FTD and twenty-one healthy controls completed the study. Participants
completed an fMRI-adapted reversal learning task that indexes behavioural
flexibility when provided positive and negative feedback. Results:
Patients with FTD demonstrated poorer behavioural flexibility relative to
controls and abnormal BOLD responses within the left ventrolateral
prefrontal cortex to incorrect responses made during the learning phase,
and during correct responses when reward contingencies were reversed. As
well, patients showed decreased activity within the left dorsal lateral
prefrontal cortex to incorrect responses compared to controls.
Conclusions: These findings suggest that reversal learning impairments in
patients with FTD, in particular those with frontal predominant atrophy,
may be related to impaired flexible motor responding when selecting among
several choices and deficient attention to relevant stimuli during
instances of conflict (i.e. receiving negative feedback). These results
and the associated neurotransmitter systems mediating these regions may
provide targets for future pharmacological or behavioural interventions
mediating these cognitive deficits.