Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy.

Englot DJ, D'Haese PF, Konrad PE, Jacobs ML, Gore JC, Abou-Khalil BW, Morgan VL
J Neurol Neurosurg Psychiatry. 2017 88 (11): 925-932

PMID: 28630376 · PMCID: PMC5634927 · DOI:10.1136/jnnp-2017-315732

OBJECTIVE - Seizures in temporal lobe epilepsy (TLE) disturb brain networks and lead to connectivity disturbances. We previously hypothesised that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no studies of ARAS connectivity have been previously reported in patients with epilepsy.

METHODS - We used resting-state functional MRI recordings in 27 patients with TLE (67% right sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pedunculopontine and ventral tegmental area. Connectivity patterns were related to disease and neuropsychological parameters.

RESULTS - In control subjects, regions showing highest connectivity to ARAS structures included limbic structures, thalamus and certain neocortical areas, which is consistent with prior studies of ARAS projections. Overall, ARAS connectivity was significantly lower in patients with TLE than controls (p<0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p<0.01, Pearson's correlation) and was associated with impairments in verbal IQ, attention, executive function, language and visuospatial memory on neuropsychological evaluation (p<0.05, Spearman's rho or Kendell's tau-b).

CONCLUSIONS - Recurrent seizures in TLE are associated with disturbances in ARAS connectivity, which are part of the widespread network dysfunction that may be related to neurocognitive problems in this devastating disorder.

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MeSH Terms (18)

Adult Brain Brain Mapping Brain Stem Case-Control Studies Cerebral Cortex Epilepsy, Temporal Lobe Female Humans Limbic System Magnetic Resonance Imaging Male Middle Aged Neocortex Neural Inhibition Neural Pathways Neurocognitive Disorders Synaptic Transmission

Connections (3)

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