Faculty Bibliography

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.

BACKGROUND:Reading disability (RD) and attention deficit/hyperactivity disorder (ADHD) are comorbid and genetically correlated, especially the inattentive dimension of ADHD (ADHD-I). However, previous research indicates that RD and ADHD enter into opposite gene by environment (G × E) interactions. METHODS:This study used behavioral genetic methods to replicate these opposite G × E interactions in a sample of same-sex monozygotic and dizygotic twin pairs from the Colorado Learning Disabilities Research Center (CLDRC; DeFries et al., 1997) and to test a genetic hypothesis for why these opposite interactions occur. RESULTS:We replicated opposite G × E interactions for RD (bioecological) and ADHD-I (diathesis-stress) with parental education in the same sample of participants. The genetic hypothesis for this opposite pattern of interactions is that only genes specific to each disorder enter into these opposite interactions, not the shared genes underlying their comorbidity. To test this hypothesis, we used single models with an exploratory three-way interaction, in which the G × E interactions for each disorder were moderated by comorbidity. Neither three-way interaction was significant. The heritability of RD did not vary as a function of parental education and ADHD-I. Similarly, the heritability of ADHD-I did not vary as a function of parental education and RD. CONCLUSIONS:We documented opposite G × E interactions in RD and ADHD-I in the same overall twin sample, but the explanation for this apparent paradox remains unclear. Examining specific genes and more specific environmental factors may help resolve the paradox.

The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia--two single-deficit models, two multiple-deficit models, and one hybrid model--in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individual's level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.

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)

Over the past 20 years, clinical neuropsychologists have been at the forefront of both scientific and clinical initiatives aimed at developing evidence-based approaches to the evaluation and management of sport-related concussion (SRC). These efforts have directly impacted current policy on strategies for injury assessment and return-to-play by athletes after concussion. Many states are considering legislation requiring (a) education of athletes, parents, coaches, and school/organization officials on the recognition, evaluation, and management of SRCs; (b) removal from play of any youth athlete that is suspected of having sustained a concussion; and (c) not allowing the student to return to participation until the student is evaluated and cleared for return to participation in writing by an appropriate healthcare professional. It is the official position of the American Academy of Clinical Neuropsychology (AACN), American Board of Professional Neuropsychology (ABN), Division 40 (Neuropsychology) of the American Psychological Association (APA), and the National Academy of Neuropsychology (NAN) that neuropsychologists should be included among the licensed healthcare professionals authorized to evaluate, clinically manage, and provide return to play clearance for athletes who sustain a SRC.

PRIMARY OBJECTIVE: To follow recovery from concussion in a sample of athletes using an electroencephalographic (EEG) index of quantitative brain activity developed previously on an independent Emergency Department (ED) sample of head-injured subjects with traumatic brain injury. METHODS AND PROCEDURES: EEG recordings from five frontal electrode sites were obtained on 59 injured athletes and 31 controls at the time of injury and at 8 and 45 days afterward. All subjects also completed standardized clinical assessment of post-concussion symptoms, postural stability and cognitive functioning at injury and 8 and 45 days post-injury. RESULTS: Abnormalities in clinical assessment measures were observed in injured subjects only at time of injury. Statistical analysis of brain electrical activity measures with the ED-based algorithm revealed significant differences between injured athletes vs controls at the time of injury and at day 8. Measures from the two groups did not differ on day 45. CONCLUSIONS: This study demonstrated that an algorithm of brain electrical activity developed on an independent sample of ED subjects with head injury is sensitive to the effects of sport-related concussion. Using this algorithm, abnormal features of brain electrical activity were detected in athletes with concussion at the time of injury and persisted beyond the point of recovery on clinical measures

Despite decades of cognitive, neuropsychological and neuroimaging studies, it is unclear if letters are identified before word-form encoding during reading, or if letters and their combinations are encoded simultaneously and interactively. Here using functional magnetic resonance imaging, we show that a 'letter-form' area (responding more to consonant strings than false fonts) can be distinguished from an immediately anterior 'visual word-form area' in ventral occipito-temporal cortex (responding more to words than consonant strings). Letter-selective magnetoencephalographic responses begin in the letter-form area approximately 60 ms earlier than word-selective responses in the word-form area. Local field potentials confirm the latency and location of letter-selective responses. This area shows increased high-gamma power for approximately 400 ms, and strong phase-locking with more anterior areas supporting lexico-semantic processing. These findings suggest that during reading, visual stimuli are first encoded as letters before their combinations are encoded as words. Activity then rapidly spreads anteriorly, and the entire network is engaged in sustained integrative processing.