Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy

Abstract

ObjectiveTo determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses.MethodsWe acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing.ResultsWe observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = −0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%).ConclusionsThese results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.

Epilepsy and brain network hubs

“…69 Moreover, there are findings showing increased fMRI functional connectivity within limbic mesiotemporal regions co-occurring with decreased connectivity in remote cortical networks. 70 These findings are compatible with network "regularization" in TLE patients, showing an increased emergence of local connections together with disruption of long-range connections associated with increased local segregation and reductions in overall network integration. 66 A similar finding was recently highlighted by an analysis that profiled the distance of functional connectivity patterns (Figure 2C), 71 pointing to reductions in long-range connections of distributed cortical networks, together with local increases in connectivity in temporolimbic circuits proximal to the seizure focus.…”

Correlation Between the Functional Connectivity of Basal Forebrain Subregions and Vigilance Dysfunction in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizure

“…Fourth, we cannot rule out the effect of interictal discharges on patient alertness because a synchronous electroencephalogram was not performed during the acquisition of imaging data. Finally, we defined BF subregions using a probabilistic map extracted from the SPM Anatomy Toolbox, which has been extensively used in previous research ( 1 , 17 ). However, the BF subregions are segregated in additional ways ( 52 ).…”

“…Temporal lobe epilepsy (TLE), the most frequent form of focal epilepsy in humans, is characterized by sclerosis of the medial temporal lobe and recurring seizures that mainly occur in the hippocampus and amygdala ( 1 ). In general, TLE can be classified into three categories: focal awareness seizures (FAS), focal impaired awareness seizures (FIAS), and focal to bilateral tonic-clonic seizures (FBTCS) ( 2 ).…”

“…Recent studies have proven that significant BF neuron degeneration and loss of cortical cholinergic innervation promote cognitive decline in Alzheimer's disease, Parkinson's disease, Wilson's disease, and multiple sclerosis ( 22 – 25 ). Hern'an et al observed aberrant functional connectivity and community between the nucleus basalis of Meynert (NBM) and cerebral hemisphere, related to cognitive impairments in TLE( 1 ).…”

Network dysfunction in pre and postsurgical epilepsy: connectomics as a tool and not a destination

“…More broadly, Fadaie et al outline that abnormal hierarchical organization in sensory-petal streams exhibited widespread cognitive deficits that were more pronounced in patients with long epilepsy duration and seizure free outcomes [17]. Additionally, in individuals with TLE, Gonza ´lez et al outlined abnormal connectivity involving the nucleus basalis of Meynert (NBM), a subcortical cholinergic arousal structure, which was associated with certain neurocognitive deficits [18]. The NBM is an actively researched stimulation target in Parkinson and Alzheimer disease, but this work suggests striking NBM dysfunction in epilepsy and possibly a future target of DBS to improve cognitive function.…”