Genevieve Rayner

Profiling the evolution of depression after epilepsy surgery.

Purpose:  Both neurobiologic and psychosocial factors have been proposed to account for the high prevalence of depression surrounding epilepsy surgery. Using a prospective longitudinal approach, this study aimed to profile the evolution of depression after epilepsy surgery at multiple time points, including early and longer‐term follow‐up. We also sought to identify neurobiologic and psychosocial predictors of depression before and after surgery, including whether patients undergoing mesial temporal lobe resection (MTR) were at greater risk of depression than patients undergoing nonmesial temporal lobe resection (NMTR).

Cognition-related brain networks underpin the symptoms of unipolar depression: Evidence from a systematic review

This systematic review sources the latest neuroimaging evidence for the role of cognition-related brain networks in depression, and relates their abnormal functioning to symptoms of the disorder. Using theoretically informed and rigorous inclusion criteria, we integrate findings from 59 functional neuroimaging studies of adults with unipolar depression using a narrative approach. Results demonstrate that two distinct neurocognitive networks, the autobiographic memory network (AMN) and the cognitive control network (CCN), are central to the symptomatology of depression. Specifically, hyperactivity of the introspective AMN is linked to pathological brooding, self-blame, rumination. Anticorrelated under-engagement of the CCN is associated with indecisiveness, negative automatic thoughts, poor concentration, distorted cognitive processing. Downstream effects of this imbalance include reduced regulation of networks linked to the vegetative and affective symptoms of depression. The configurations of these networks can change between individuals and over time, plausibly accounting for both the variable presentation of depressive disorders and their fluctuating course. Framing depression as a disorder of neurocognitive networks directly links neurobiology to psychiatric practice, aiding researchers and clinicians alike.

Differential contributions of objective memory and mood to subjective memory complaints in refractory focal epilepsy

People with epilepsy frequently present with bitter memory complaints. Previous research variously attributes this to symptoms of mood disturbance or objective memory deficits. To investigate the influence of the epileptogenic region on this variability, we examined interrelationships between mood, objective memory, and memory complaints in a sample of patients with refractory focal epilepsy and controls (N = 96). Patients had either mesial temporal (MT, n = 39) or non mesial-temporal (NMT, n = 21) foci. In contrast to controls (n = 36), both patient groups were highly concerned about their memory (P<0.001) and were more likely to have a history of depression (P = 0.005). Multiple regression showed that objective memory dysfunction and current depressive symptoms predicted the memory complaints of patients with MT epilepsy (P = 0.005), whereas a history of depression predicted the complaints of patients with NMT epilepsy (P = 0.008). These findings suggest that patients have concerns about their memory underpinned by distinct psychological and neurobiological factors depending on the location of their epileptogenic focus.

MRI-negative temporal lobe epilepsy A network disorder of neocortical connectivity

Objective: To define the functional network changes that characterize MRI-negative temporal lobe epilepsy (TLE) and TLE with hippocampal sclerosis (HS-TLE). Methods: We studied 36 patients with medically refractory unilateral TLE, having either a normal clinical MRI (n = 18) or unilateral hippocampal sclerosis (n = 18). Patients were compared to healthy controls of equivalent age and sex (n = 27). Functional connectivity in 10 minutes of task-free functional MRI was assessed using a voxel-resolution graph theoretic analysis, using the metrics of degree, clustering coefficient, eigenvector, and betweenness centrality. Significant clusters were further explored with a seed-based analysis. Results: MRI-negative TLE showed decreased connectivity at the ipsilateral superior and middle temporal gyri compared to controls (decreased eigenvector centrality). No functional abnormality was detected within mesial temporal structures. In contrast, HS-TLE showed increased connectivity within the affected hippocampus and anterior thalamus (increased clustering coefficient) and decreased connectivity of the ventromesial prefrontal cortex (decreased betweenness centrality). Using the detected clusters as seed regions revealed decreased connectivity from the sclerotic hippocampus to both the contralateral temporal lobe and regions of the default mode network. Conclusion: MRI-negative TLE is associated with impaired interictal connectivity of the temporal neocortex, lateralized to the epileptic side. HS-TLE shows a different pattern, with functional segregation of the sclerotic hippocampus and impairment of its long-range connectivity. This suggests that MRI-negative TLE is not merely a subtle version of hippocampal sclerosis, but is rather a separate condition that involves distinct brain networks.

Developmental outcomes of childhood‐onset temporal lobe epilepsy: A community‐based study

Purpose:  To assess the impact of childhood‐onset temporal lobe epilepsy (TLE) on the attainment of normative developmental tasks and identify predictors of long‐term developmental outcomes.

Psychiatric care in epilepsy surgery: who needs it?

At present there is considerable variability in the psychiatric evaluation and follow-up of patients in epilepsy surgery programs globally. There is a large body of research now demonstrating heightened risk for psychological disturbance in surgically remedial patients before and after surgery. This evidence provides a compelling case for the routine provision of psychiatric and psychological treatment to optimize the benefits of epilepsy surgery and patient outcomes. In a comprehensive model of care, presurgical psychiatric and psychosocial evaluation plays an integral role in shaping the teams understanding of surgical candidacy and the patients capacity for informed consent. After surgery, efficacious treatment of psychiatric comorbidity increases the likelihood of seizure freedom as well as optimizes psychosocial functioning and quality of life. By contrast, failure to treat can allow psychiatric comorbidity to persist or psychological difficulties to develop as the patient adjusts to life after surgery.

Mechanisms of memory impairment in epilepsy depend on age at disease onset.

Objective: In this study, we aimed to uncover distinct antecedents of autobiographic memory dysfunction in patients with epilepsy with early (childhood/adolescence) vs late (adulthood) disease onset. Methods: One hundred sixty-six adults participated: 92 patients with focal epilepsy, whose cognitive and psychiatric functioning were compared to that of 74 healthy controls. Predictors of autobiographic memory deficit were contrasted between patients with early-onset (n = 47) vs late-onset (n = 45) epilepsy. Results: Overall, people with epilepsy performed significantly worse on measures of both semantic and episodic autobiographic memory and showed markedly high rates of depressive symptoms and disorders (p < 0.001). Reduced autobiographic memory in patients with early-onset epilepsy was associated with young age at onset, more frequent seizures, and reduced working memory. In contrast, the difficulty that patients with late-onset epilepsy had in recalling autobiographic information was linked to depression and the presence of an MRI-identified lesion. Conclusions: This study reveals that memory deficits in people with focal epilepsy have differing antecedents depending on the timing of the disease onset. While neurobiological factors strongly underpin reduced autobiographic function in patients with early-onset epilepsy, psychological maladjustment gives rise to the impairments seen in patients with late-onset epilepsy. More broadly, these findings support the practice of subtyping patients according to distinct clinical characteristics to find individualized predictors of cognitive dysfunction.

Behavioral profiles in frontal lobe epilepsy: Autobiographic memory versus mood impairment

Autobiographic memory encompasses the encoding and retrieval of episodes, people, and places encountered in everyday life. It can be impaired in both epilepsy and frontal lobe damage. Here, we performed an initial investigation of how autobiographic memory is impacted by chronic frontal lobe epilepsy (FLE) together with its underlying pathology.

The Contribution of Cognitive Networks to Depression in Epilepsy

This review poses the question: Does disruption to cognitive brain networks in epilepsy contribute to the problem of comorbid depression? Initial evidence suggests that the network disease that gives rise to seizures has a predilection for the same cognition-related networks that regulate mood, with comorbidity reflective of more extensive disease. Framing both epilepsy and its psychiatric comorbidities in terms of dysfunction in overlapping (cognitive) networks raises the possibility that depression can be a primary feature of the disease in some cases and facilitates an epilepsy classification system where behavioral features of the disorder are embedded in a neurobiological mechanism.

The dynamics of functional connectivity in neocortical focal epilepsy

Focal epilepsy is characterised by paroxysmal events, reflecting changes in underlying local brain networks. To capture brain network activity at the maximal temporal resolution of the acquired functional magnetic resonance imaging (fMRI) data, we have previously developed a novel analysis framework called Dynamic Regional Phase Synchrony (DRePS). DRePS measures instantaneous mean phase coherence within neighbourhoods of brain voxels. We use it here to examine how the dynamics of the functional connections of regional brain networks are altered in neocortical focal epilepsy. Using task-free fMRI data from 21 subjects with focal epilepsy and 21 healthy controls, we calculated the power spectral density of DRePS, which is a measure of signal variability in local connectivity estimates. Whole-brain averaged power spectral density of DRePS, or signal variability of local connectivity, was significantly higher in epilepsy subjects compared to healthy controls. Maximal increase in DRePS spectral power was seen in bilateral inferior frontal cortices, ipsilateral mid-cingulate gyrus, superior temporal gyrus, caudate head, and contralateral cerebellum. Our results provide further evidence of common brain abnormalities across people with focal epilepsy. We postulate that dynamic changes in specific cortical brain areas may help maintain brain function in the presence of pathological epileptiform network activity in neocortical focal epilepsy.