In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD.

Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.

The cognitive and anatomo-functional basis of reality distortion in schizophrenia: a view from memory event-related potentials.

This study investigated the neural and cognitive correlates of reality distortion in schizophrenia by using event-related potentials (ERPs) recorded in a recognition memory task for face. This task has been chosen because previous studies have shown that it provides distinct indices related to specific cognitive processes and to the functioning of specific brain regions. ERPs have been recorded in controls and schizophrenia patients separated into high scorers (RD+) and low-scorers (RD-) according to their Reality Distortion score (hallucination and delusion SAPS subscales). The results indicate that RD+ presents abnormalities on various cognitive processes. First, RD+ are deficient at interference inhibition and knowledge integration (reduced P2a and N400 effect). The similar impairments found in RD- suggest that they represent basic traits of the illness. Second, RD+ showed inappropriate stimulus categorization and contextual integration (larger N300 and fronto-central effect). Third, RD+ showed a late index (P600 effect) not different from controls, but larger than in RD-. This result is consistent with a qualitative, rather than quantitative, impairment of mnemonic binding processes (inappropriate binding) in RD+. Since each of the ERP abnormalities observed represents associated with distinct brain dysfunction, the results are further discussed in regard of the respective contribution of the parietal, frontal and hippocampal structures to reality distortion symptoms.