Orbitofrontal Dysfunction Related to Both Apathy and Disinhibition in Frontotemporal Dementia

Abstract

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD.

Can Molecular Gradients Wire the Brain?

“…reported that orbitofrontal dysfunction is related to both apathy and disinhibition in FTD patients (Peters et al, 2006). In accordance with this we noted increased tau immuno-reactivity and NFT formation by silver staining in 12 month-old Tg animals.…”

Neurobiology of apathy in Alzheimer's disease

“…More recently, Marshall and colleagues, employing PeT in Ad patients with mild to moderate dementia, showed that apathy was related to hypometabolism in ventromedial PFc, including the ventral Acc and medial oFc 61 , as predicted and described below in our proposed account for neurobiology of apathy in Ad. PeT data from frontal variant of frontotemporal dementia (fvFTd) has also shown a significant relationship between apathy and oFc hypometabolism 62 . It should be stressed that given decision-making is a dynamic process, resting PeT or sPecT may lack the optimal spatio-temporal resolution to infer the underlying behavioral neurophysiology 63 , and may have higher sensitivity in more advanced stages of dementia.…”

Cognitive disinhibition and socioemotional functioning in Alzheimer's disease

“…Converging evidence now suggests that the self-perspective is the cognitive "default mode," and therefore, to evaluate another's perspective, some form of active inhibitory mechanism must regulate the prepotent self-perspective. However, although loss of empathy is a common feature of neurodegenerative disease, the only studies that have assessed the relationship between cognitive inhibition and empathy in relation to dementia have focused on frontotemporal dementia (Lough et al, 2006;Peters et al, 2006), and thus the relationship between cognitive disinhibition and empathy in individuals with AD remains to be established. ular importance has been attributed to the processes of reappraisal and suppression.…”