Magnetoencephalography of frontotemporal dementia: spatiotemporally localized changes during semantic decisions

Behavioural variant frontotemporal dementia is a neurodegenerative disorder with dysfunction and atrophy of the frontal lobes leading to changes in personality, behaviour, empathy, social conduct and insight, with relative preservation of language and memory. As novel treatments begin to emerge, biomarkers of frontotemporal dementia will become increasingly important, including functionally relevant neuroimaging indices of the neurophysiological basis of cognition. We used magnetoencephalography to examine behavioural variant frontotemporal dementia using a semantic decision task that elicits both frontal and temporal activity in healthy people. Twelve patients with behavioural variant frontotemporal dementia (age 50-75) and 16 matched controls made categorical semantic judgements about 400 pictures during continuous magnetoencephalography. Distributed source analysis was used to compare patients and controls. The patients had normal early responses to picture confrontation, indicating intact visual processing. However, a predominantly posterior set of regions including temporoparietal cortex showed reduced source activity 250-310 ms after stimulus onset, in proportion to behavioural measures of semantic association. In contrast, a left frontoparietal network showed reduced source activity at 550-650 ms, proportional to patients' deficits in attention and orientation. This late deficit probably reflects impairment in the neural substrate of goal-oriented decision making. The results demonstrate behaviourally relevant neural correlates of semantic processing and decision making in behavioural variant frontotemporal dementia, and show for the first time that magnetoencephalography can be used to study cognitive systems in the context of frontotemporal dementia.