Faculty Bibliography

Previous research has shown that emotional information aids conflict resolution in working memory (Levens & Phelps, 2008). Using a Recency-probes working memory (WM) paradigm, Levens and Phelps found that positive and negative emotional stimuli reduced the amount of interference created when information that was once relevant conflicted with currently relevant information, suggesting that emotional information facilitates interference resolution in WM. To determine what regions of the prefrontal cortex (PFC) and temporal lobes are critical to the influence of emotional stimuli on interference resolution, we conducted a Recency-probes emotion paradigm with right and left unilateral frontal and temporal lobe lesion patients. The frontal lobe lesion patient group comprised individuals with unilateral ventral and dorsal PFC lesions. The temporal lobe lesion patient group comprised individuals with lesions of the amygdala and surrounding structures. Results indicate that when the left amygdala is damaged, emotional facilitation of interference resolution is absent (equal emotional and neutral interference levels), when the right orbital frontal cortex (OFC) is damaged, in contrast, emotional interference resolution is impaired (emotional interference levels are higher than neutral levels are). Based on these unique patterns we propose specific contributions for these regions in the emotional facilitation of interference resolution in WM

Periodic transmeningeal administration of muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug. Rats were chronically implanted with an epidural cup and adjacent epidural EEG electrodes over the right parietal cortex. After recovery 1.0mM muscimol was delivered into the implanted cortical area through the cup while the animal behaved freely, once per day for 4 consecutive days in each week, with each delivery followed within 3min by the delivery of a seizure-inducing concentration of acetylcholine (Ach) into the same area. The study lasted for 3 weeks. In each week, one day was used to test the epileptogenicity of the examined cortical site by replacing muscimol with saline prior to Ach delivery. The duration of Ach-induced EEG seizures was measured in each experimental session to assess the antiepileptic efficacy of muscimol, while the rat's behavior was also monitored. The daily epidural muscimol pretreatments prevented Ach-induced EEG and behavioral seizures in all rats. This antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of muscimol into the neocortex over three weeks do not induce tolerance to the localized antiepileptic effects of this drug

OBJECT: Many children with epilepsy and tuberous sclerosis complex (TSC) have multiple tubers on MR imaging and poorly localized/lateralized video electroencephalography (EEG) findings. Given the long-term risks associated with frequent seizures and multiple antiepileptic drugs, along with improved success in identifying focal epileptogenic zones in patients with multifocal lesions, the authors used bilateral intracranial EEG to lateralize the epileptogenic zone in patients with nonlateralizable noninvasive preoperative evaluations. METHODS: A retrospective analysis from January 1, 1998, to June 30, 2008, identified 62 children with TSC who were presented at a surgical conference. Of the 52 patients undergoing diagnostic or therapeutic procedures during the study period, 20 underwent bilateral intracranial EEG. The presurgical testing results, intracranial EEG findings, surgical interventions, and outcomes were reviewed. RESULTS: Fourteen of 20 patients had intracranial EEG findings consistent with a resectable epileptogenic zone. One patient is awaiting further resection. Five patients had findings consistent with a nonresectable epileptogenic zone, and 1 of these patients underwent a callosotomy. Seven patients had Engel Class I outcomes, 1 was Class II, 3 were Class III, and 3 were Class IV (mean follow-up 25 months). CONCLUSIONS: Bilateral intracranial EEG can identify potential resectable seizure foci in nonlateralizable epilepsy in TSC. Although 6 of 20 patients did not undergo resection (1 patient is pending future resection), significant improvements in seizures (Engel Class I or II) were noted in 8 patients. In the authors' experience, this invasive monitoring provided a safe method for identifying the ictal onset zone

Blurring of the cortical gray and white matter border on MRI is associated with normal aging, pathological aging, and the presence of focal cortical dysplasia. However, it remains unclear whether normal variations in signal intensity contrast at the gray and white matter junction reflect the functional integrity of subjacent tissue. This study explores the relationship between verbal abilities and gray and white matter contrast (GWC) in healthy human adults. Participants were scanned at 3 T MRI and administered standardized measures of verbal expression and verbal working memory. GWC was estimated by calculating the non-normalized T1 image intensity contrast above and below the cortical gray/white matter interface. Spherical averaging and whole-brain correlational analyses were performed. Sulcal regions exhibited higher contrast compared to gyral regions. We found a strongly lateralized and regionally specific profile with reduced verbal expression abilities associated with blurring in left hemisphere inferior frontal cortex and temporal pole. Reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomical substrates of cognition in healthy and diseased populations

OBJECTIVE: This study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms. METHODS: Adults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control. RESULTS: Of the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055). CONCLUSION: Although study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood

Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling. AED-delivery systems comprise drug releasing polymers and neuroprosthetic devices that can deliver AEDs into the brain via intraparenchymal, ventricular, or transmeningeal routes. One such device is the subdural Hybrid Neuroprosthesis (HNP), designed to deliver AEDs, such as muscimol, into the subdural/subarachnoid space overlaying neocortical epileptogenic zones, with electrophysiological feedback from the treated tissue. The idea of intracranial pharmacotherapy and HNP treatment for epilepsy originated from multiple sources, including the advent of implanted medical devices, safety data for intracranial electrodes and catheters, evidence for the seizure-controlling efficacy of intracerebral AEDs, and further understanding of the pathophysiology of focal epilepsy. Successful introduction of intracranial pharmacotherapy into clinical practice depends on how the intertwined scientific, engineering, clinical, neurosurgical and regulatory challenges will be met to produce an effective and commercially viable device.

A 51-year-old right-handed man developed hypersexuality after a second right temporal lobectomy to treat epilepsy. His hypersexuality started with increased marital intercourse and masturbation but he later downloaded child pornography. Hyperphagia and distractibility, other features of the Kluver-Bucy syndrome, also developed. Resection of the amygdala and/or temporal lobe neocortical areas that inhibit other limbic areas may contribute to the pathogenesis of hypersexuality. Neurological factors mitigate the criminal responsibility for hypersexual activity in patients with Kluver-Bucy syndrome. Most previously reported patients were never charged with a crime despite uninvited physical contact in some instances. Our patient was convicted and imprisoned

Using separate generalized mixed-effects models, we assessed seizure recall and prediction, as well as contributing diagnostic variables, in 83 adult patients with epilepsy undergoing video/EEG monitoring. The model revealed that when participants predicted a seizure, probability equaled 0.320 (95% CI: 0.149-0.558), a significant (P<0.05) increase over negative predictions (0.151, 95% CI: 0.71-0.228]). With no seizure, the rate of remembering was approximately 0.130 (95% CI: 0.73-0.219), increasing significantly to 0.628 (95% CI: 0.439 to 0.784) when a seizure occurred (P<0.001). Of the variables analyzed, only inpatient seizure rate influenced predictability (P<0.001) or recollection (P<0.001). These models reveal that patients were highly aware of their seizures, and in many cases, were able to make accurate predictions, for which seizure rate may be an important factor