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

Abstract

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.

Clinical features of sleep‐related hypermotor epilepsy in relation to the seizure‐onset zone: A review of 135 surgically treated cases

“…Of interest, the frequency of postictal confusion is considered in relation to the SP, a high proportion of postictal confusion was associated with SP4 (48%), a pattern quite different from the classic temporal lobe semiology . As suspected in TLE, involvement of subcortical regions including the thalamus and the ascending reticular activating system might explain this phenomenon . Alternately, impairment of consciousness during or after seizure might occur once impairment of associative cortices and abnormalities of long‐distance synchronization in the parietofrontal networks develop, regardless of temporal lobe involvement…”

Altered physiological brain variation in drug‐resistant epilepsy

“…The abnormal, noncoupled vasodilation may be linked to the detected VLF vasomotor pulsation increase and to the detected noise changes in the brainstem autonomous nervous system centers (Figure 3). The previous studies have also shown that connectivity of the brainstem and cortical/subcortical structures is altered in temporal lobe epilepsy (Englot et al., 2017). The LF power changes were mapped to brainstem areas in seven of 10 patients in our study indicating high probability of dysregulatory changes in these areas.…”

Impaired vigilance networks in temporal lobe epilepsy: Mechanisms and clinical implications

“…Recently, our group examined fMRI functional connectivity patterns of eight pontomesencephalic brainstem ARAS nuclei in preoperative mTLE patients versus controls. Overall, mean ARAS connectivity was significantly lower in mTLE patients than controls, and the greatest connectivity perturbations were observed in the cuneiform/subcuneiform nuclear complex, PPN, and VTA . Across the brain, the largest decreases in functional connectivity seeded from ARAS in mTLE patients were found in frontoparietal association neocortex, posterior temporal cortex, and insula (Figure ) .…”

“…In mTLE patients and rodent models of limbic seizures, our group and other collaborators previously demonstrated network alterations involving subcortical brain structures important for vigilance regulation, and have found relationships between these network changes and neuropsychological deficits . In general, these “subcortical activating structures” may refer to nuclei in the brainstem ascending reticular activating system (ARAS), the basal forebrain region including nucleus basalis, the intralaminar thalamic nuclei, the pulvinar, and the posterior hypothalamus .…”