Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Bornali Kundu, Andrea A. Brock, Dario J. Englot, Christopher R. Butson and John D. Rolston
Victoria L. Morgan, Baxter P. Rogers, Adam W. Anderson, Bennett A. Landman and Dario J. Englot
The objectives of this study were to identify functional and structural network properties that are associated with early versus long-term seizure outcomes after mesial temporal lobe epilepsy (mTLE) surgery and to determine how these compare to current clinically used methods for seizure outcome prediction.
In this case-control study, 26 presurgical mTLE patients and 44 healthy controls were enrolled to undergo 3-T MRI for functional and structural connectivity mapping across an 8-region network of mTLE seizure propagation, including the hippocampus (left and right), insula (left and right), thalamus (left and right), one midline precuneus, and one midline mid-cingulate. Seizure outcome was assessed annually for up to 3 years. Network properties and current outcome prediction methods related to early and long-term seizure outcome were investigated.
A network model was previously identified across 8 patients with seizure-free mTLE. Results confirmed that whole-network propagation connectivity patterns inconsistent with the mTLE model predict early surgical failure. In those patients with networks consistent with the mTLE network, specific bilateral within-network hippocampal to precuneus impairment (rather than unilateral impairment ipsilateral to the seizure focus) was associated with mild seizure recurrence. No currently used clinical variables offered the same ability to predict long-term outcome.
It is known that there are important clinical differences between early surgical failure that lead to frequent disabling seizures and late recurrence of less frequent mild seizures. This study demonstrated that divergent network connectivity variability, whole-network versus within-network properties, were uniquely associated with these disparate outcomes.
Victoria L. Morgan, Baxter P. Rogers, Hernán F. J. González, Sarah E. Goodale and Dario J. Englot
Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery.
Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters.
The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery.
The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.