FAST functional connectivity implicates P300 connectivity in working memory deficits in Alzheimer’s disease

Measuring transient functional connectivity is an important challenge in electroencephalogram (EEG) research. Here, the rich potential for insightful, discriminative information of brain activity offered by high-temporal resolution is confounded by the inherent noise of the medium and the spurious nature of correlations computed over short temporal windows. We propose a methodology to overcome these problems called filter average short-term (FAST) functional connectivity. First, a long-term, stable, functional connectivity is averaged across an entire study cohort for a given pair of visual short-term memory (VSTM) tasks. The resulting average connectivity matrix, containing information on the strongest general connections for the tasks, is used as a filter to analyze the transient high-temporal resolution functional connectivity of individual subjects. In simulations, we show that this method accurately discriminates differences in noisy event-related potentials (ERPs) between two conditions where standard connectivity and other comparable methods fail. We then apply this to analyze an activity related to visual short-term memory binding deficits in two cohorts of familial and sporadic Alzheimer’s disease (AD)-related mild cognitive impairment (MCI). Reproducible significant differences were found in the binding task with no significant difference in the shape task in the P300 ERP range. This allows new sensitive measurements of transient functional connectivity, which can be implemented to obtain results of clinical significance.