Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy

Abstract

Depression is a common comorbidity in temporal lobe epilepsy (TLE) that is thought to have a neurobiological basis. This study investigated the functional connectivity (FC) of medial temporal networks in depression symptomatology of TLE and the relative contribution of structural versus FC measures. Volumetric and functional connectivity MRI (fcMRI) were performed on nineteen patients with TLE and 20 controls. The hippocampi and amygdalae were selected as seeds, and five prefrontal and five cingulate regions of interest (ROIs) were selected as targets. Low-frequency blood-oxygen-level-dependent signals were isolated from fcMRI data, and ROIs with synchronous signal fluctuations with the seeds were identified. Depressive symptoms were measured by the Beck Depression Inventory-II. Patients with TLE showed greater ipsilateral hippocampal atrophy (HA) and reduced FC between the ipsilateral hippocampus and ventral posterior cingulate cortex (vPCC). Neither HA nor hippocampal-vPCC FC asymmetry was a robust contributor to depressive symptoms. Rather, hippocampal-anterior prefrontal FC was a stronger contributor to depressive symptoms in left TLE (LTLE). Conversely, right amygdala FC was correlated with depressive symptoms in both patient groups, with a positive and negative correlation in LTLE and right TLE (RTLE), respectively. Frontolimbic network dysfunction is a strong contributor to levels of depressive symptoms in TLE and a better contributor than HA in LTLE. In addition, the right amygdala may play a role in depression symptomatology regardless of side of the epileptogenic focus. These findings may inform the treatment of depressive symptoms in TLE and inspire future research to help guide surgical planning.

Resting-state functional connectivity in epilepsy

“…Chen et al [58] described decreased functional connectivity within a prefrontal-limbic system in TLE patients who were depressed, but increased functional connectivity within the limbic system and angular gyrus, indicating that interactions among networks may be crucial to the appearance of depressive symptoms. Kemmotsu et al [56,59] demonstrated that hippocampalanterior prefrontal functional connectivity was a stronger contributor to depressive symptoms in left compared with right TLE, and right amygdala functional connectivity correlated with depressive symptoms in both the groups (a positive correlation in the left and negative in the right TLE).…”

“…The amygdala has been described as hyperactive in left TLE patients with mood disturbance [53,54]. RsFC studies have provided evidence of connectivity abnormalities with the amygdala contralateral to the epileptogenic zone [5,[55][56][57]. Chen et al [58] described decreased functional connectivity within a prefrontal-limbic system in TLE patients who were depressed, but increased functional connectivity within the limbic system and angular gyrus, indicating that interactions among networks may be crucial to the appearance of depressive symptoms.…”

Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy

“…Several studies have suggested an effect of connectivity disruptions on cognition, particularly with respect to memory impairments [95,96]. Furthermore, connectivity disruptions may also be associated with socioaffective difficulties seen in some patient subgroups with TLE [97][98][99].…”

“…Based on neuroimaging analysis without graph theory, multiple studies in TLE have shown associations between diffusion anomalies in fiber tracts and memory and language deficits [153], between gray matter alterations and general cognitive functioning [154], and between functional connectivity disruptions and cognitive as well as affective impairments [95][96][97][98][99]. On the other hand, studies relating cognitive deficits or affective challenges in TLE to topological parameters are sparse.…”

Frontolimbic brain networks predict depressive symptoms in temporal lobe epilepsy

“…Although hippocampal atrophy has long been associated with depression in TLE (Valente and Busatto Filho, 2013), there are recent data to suggest that functional connectivity (FC) between medial temporal (MT) lobe structures and the prefrontal cortex (PFC) is a stronger predictor of depressive symptoms in patients with TLE (Kemmotsu et al, 2013). These data provide support for the notion that both TLE and depression are network disorders that may arise from disruption within multiple frontolimbic regions or to the white matter pathways connecting them.…”