Faculty Bibliography

BACKGROUND AND PURPOSE: Recent neuroimaging studies suggest that abnormalities in brain function after concussion exist beyond the point of observed clinical recovery. This study investigated the relationship between an index of brain dysfunction (traumatic brain injury [TBI] Index), concussion severity, and outcome. METHODS: EEG was collected from forehead locations in 65 male athletes with concussion within 24 hours of concussion, with follow-up at 8 and 45 days postinjury. Neurocognitive and symptom assessments were also performed and used to classify subjects in mild or moderate concussion categories. Time to return to play was recorded. RESULTS: The TBI Index was higher in the moderate than mild concussion group at injury, day 8, and day 45. The moderate group had increased symptoms and decreased cognitive performance only at the time of injury. At the time of injury, only the TBI Index was significantly associated with the length of time to return to play. CONCLUSIONS: Recovery of brain function after sport-related concussion may extend well beyond the time course of clinical recovery and be related to clinical severity. An index of brain dysfunction may be an objective indicator of injury, recovery, and readiness to return to play. The relatively small sample indicates the need for further study on the time course of physiological recovery.

OBJECTIVE: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic. METHOD: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors. RESULTS: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. CONCLUSION: Septal nuclei are enlarged in patients with TLE without MTS. Further investigation of septal nuclei and antiepileptic septo-hippocampal neurocircuitry could be relevant to development of new therapeutic interventions such as septal stimulation for refractory TLE.

Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury.

The degree to which psychological factors are believed to influence the experience of pain has evolved significantly through history. Over the past 100 years, the trend has shifted from a focus on the study of sensory aspects of pain perception to one where psychological factors play a prominent role. Pain is now viewed as a complex subjective experience consisting of sensory, affective, and cognitive components. Psychological presentations of pain are commonly reduced to a differential among Pain Disorder, Somatization Disorder, and Malingering. Limitations in the use of the current DSM-IV-TR diagnostic classifications for pain will lead to changes in the upcoming DSM-V. Psychological testing is becoming increasingly recognized as a valuable evidence-based method for making diagnoses of psychological factors influencing pain presentations. There is a shift from the use of brief measures of pain intensity to multidimensional scales including assessment of affect and perceived functional disability. There is also increased attention to the use of validity scales for assessing symptom exaggeration and other types of response bias. Neuropsychologists, with specialized knowledge and background in evidence based assessment methods, are particularly well equipped to provide valuable input regarding psychological presentations of pain in forensic contexts and in consultation to multidisciplinary treatment teams.

The current study examined whether mood-congruent biases in emotion processing extend to epilepsy patients with depressive symptoms and the potentially moderating effects of age of seizure onset on these biases. In addition, we examined associations between depression (Beck Depression Inventory - 2nd Edition; BDI-II) and quality of life (Quality of Life in Epilepsy - 10-item questionnaire; QOLIE-10). Data from 101 epilepsy patients were analyzed, including 61 females and 40 males. Measures included the Comprehensive Affect Testing System - Abbreviated (CATS-A), from which indices of mood-congruent bias were derived. A significant interaction between BDI-II raw scores and age of seizure onset was found for mood-congruent bias scores in the facial affect modality (beta=-0.24, p<.03). Beck Depression Inventory - 2nd Edition raw scores were significantly and positively correlated with quality of life (QOLIE-10; r=.69, p<.01). Results of the current study show that epilepsy patients with an early age of seizure onset may be most at risk for mood-congruent biases when experiencing depressive symptoms and that such symptoms have real-world implications for quality of life for persons living with epilepsy.

Purpose: Despite the reported diagnostic value of the intracarotid amobarbital procedure (IAP) or "Wada test" for determining hemispheric lateralization and memory functioning, it has never undergone formal reliability testing because a prospective test-retest study design is neither feasible nor ethical. However, some patients require repeat testing for clinical purposes, a circumstance that allows for exploration of issues related to reliability. The current investigation sought to: (1) evaluate the frequency of and reasons for repeated IAPs and (2) describe the test-retest reliability of repeated IAPs in a large tertiary epilepsy center. Methods: A 10-year review (2001-2011) of the New York University Langone Medical Center Comprehensive Epilepsy Center patient registry revealed 630 IAPs. Review of medical records identified 20 individuals who underwent two or more IAPs on separate days. Because IAPs repeated due to technical problems should be considered separate from IAPs repeated for other reasons because these IAPs likely included a change in the procedure (e.g., lower medication dose) in an attempt to ameliorate the complication, patients were grouped accordingly. Six patients underwent repeated IAPs due to technical complication and 14 patients underwent a repeated IAP due to other reasons (e.g., unexpected memory outcome, reconsideration of surgery years after a previous surgical work-up in which no surgery was performed, and/or consideration of a second surgery). Given that data obtained from injections ipsilateral to a seizure focus are sometimes considered in a manner clinically different from data obtained from injections contralateral to the seizure focus, memory outcome was classified relative to the side of identified seizure focus. The degree to which language and memory data were consistent across repeated IAPs was examined. Key Findings: Language functioning was consistently lateralized across IAPs in all but one case. Among the six patients who experienced technical problems in the first IAP, three were fully participatory in the second procedure such that valid data were obtained. For the other three, the technical problem recurred with no change in outcome across procedures. Among the 14 patients with repeated IAPs due to other reasons, 79% of the available ipsilateral and 73% of the contralateral pass/fail outcomes were consistent across procedures. No difference between ipsilateral or contralateral injections was observed for the likelihood of a change in results (p = 0.57). Significance: Our data identified overall high reliability for both the ipsilateral and contralateral sides with repeated IAP testing. Results indicated that although patients for whom a correctable technical problem was identified during the IAP may benefit from a repeat study, there is little benefit to repeating the IAP in patients with discordant or unexpected results (i.e., results are not likely to change). These data support the overall reliability of both the language and memory data obtained from the IAP.

Depression in patients with temporal lobe epilepsy (TLE) is highly prevalent and carries significant morbidity and mortality. Its neural basis is poorly understood. We used quantitative, surface-based MRI analysis to correlate brain morphometry with severity of depressive symptoms in 38 patients with TLE and 45 controls. Increasing severity of depressive symptoms was associated with orbitofrontal cortex (OFC) thinning in controls, but with OFC thickening in TLE patients. These results demonstrate distinct neuroanatomical substrates for depression with and without TLE, and suggest a unique role for OFC, a limbic region for emotional processing strongly interconnected with medial temporal structures, in TLE-related depressive symptoms

Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and recall the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases. (JINS, 2012, 18, 157-161)