Aspects of Frontal and Medial Temporal Brain Functions. Neuropsychological and functional imaging studies in normals and in frontotemporal dementia

Sammanfattning: The thesis is based on five investigations. In the first study the nature and the degree of cognitive impairment of patients with frontotemporal dementia (FTD) is explored. The results from neuropsychological assessment are described as three levels of cognitive impairment. These levels of functional disturbance corresponded to increased severity of abnormality of the regional cerebral blood flow measurements (rCBF). In the second study a close coupling between reduced rCBF and specific neuropsychological deficits in FTD is demonstrated. Significant correlations were found between a global impairment score and relative blood flow in frontal areas. The global impairment scale might be useful in detecting and following the progress of frontal deficiencies in FTD patients. The results of the third investigation indicate that for differential diagnosis of FTD versus dementia of Alzheimer type (DAT) the scores on cognitive tests measuring verbal ability, visuospatial ability and verbal episodic memory are of value, especially when evaluated in combination. The fourth study investigates the functional involvement of the frontal lobes during performance of verbal (VFT) and design fluency tasks (DFT), and the influence of different strategies utilised when solving the fluency tasks. The results from measurements of rCBF in normal subjects demonstrate a left-sided frontal activation during the VFT and bilateral flow augmentations during the DFT. Furthermore, the findings suggest that patterns of cortical activity vary according to the chosen cognitive strategy when performing a task. In the fifth investigation the involvement of the medial temporal lobes (MTL) in retrieval of declarative memories (abstract visuospatial designs) is studied by measuring rCBF with positron emission tomography (PET). In the recall of abstract designs a less practised memory state (novel recall) was compared to a well practised (trained recall) memory state. The MTL was more activated during retrieval in the less practised memory state compared to the well practised memory state, indicating a changing role of the MTL during recall in the earlier stages of acquisition of declarative knowledge compared to the well encoded declarative memory state.