title: Compensating for thalamocortical synaptic loss in Alzheimer's disease.
abstract: The study presents a thalamocortical network model which oscillates within the alpha frequency band (8-13 Hz) as recorded in the wakeful relaxed state with closed eyes to study the neural causes of abnormal oscillatory activity in Alzheimer's disease (AD). Incorporated within the model are various types of cortical excitatory and inhibitory neurons, recurrently connected to thalamic and reticular thalamic regions with the ratios and distances derived from the mammalian thalamocortical system. The model is utilized to study the impacts of four types of connectivity loss on the model's spectral dynamics. The study focuses on investigating degeneration of corticocortical, thalamocortical, corticothalamic, and corticoreticular couplings, with an emphasis on the influence of each modeled case on the spectral output of the model. Synaptic compensation has been included in each model to examine the interplay between synaptic deletion and compensation mechanisms, and the oscillatory activity of the network. The results of power spectra and event related desynchronization/synchronization (ERD/S) analyses show that the dynamics of the thalamic and cortical oscillations are significantly influenced by corticocortical synaptic loss. Interestingly, the patterns of changes in thalamic spectral activity are correlated with those in the cortical model. Similarly, the thalamic oscillatory activity is diminished after partial corticothalamic denervation. The results suggest that thalamic atrophy is a secondary pathology to cortical shrinkage in Alzheimer's disease. In addition, this study finds that the inhibition from neurons in the thalamic reticular nucleus (RTN) to thalamic relay (TCR) neurons plays a key role in regulating thalamic oscillations; disinhibition disrupts thalamic oscillatory activity even though TCR neurons are more depolarized after being released from RTN inhibition. This study provides information that can be explored experimentally to further our understanding on the neurodegeneration associated with AD pathology.
authors.affiliation: Department of Biology, University of Leicester Leicester, UK.
authors.forename: Kamal
authors.initials: K
authors.lastname: Abuhassan
authors.affiliation: Intelligent Systems Research Centre, School of Computing and Intelligent Systems, University of Ulster Derry, UK.
authors.forename: Damien
authors.initials: D
authors.lastname: Coyle
authors.affiliation: Intelligent Systems Research Centre, School of Computing and Intelligent Systems, University of Ulster Derry, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Maguire
keywords: Alzheimer's disease; Electroencephalography; connectivity loss; synaptic compensation mechanisms; thalamic atrophy; thalamocortical network model; thalamocortical oscillations