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1.  Septal nuclei enlargement in human temporal lobe epilepsy without mesial temporal sclerosis 
Neurology  2013;80(5):487-491.
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.
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.
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.
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.
PMCID: PMC3590047  PMID: 23303846
2.  Methodologic Issues in Neuropsychological Testing 
Journal of Athletic Training  2001;36(3):297-302.
To familiarize athletic trainers with methodologic issues regarding the development and implementation of neuropsychological tests used in programs for monitoring sport-related cerebral concussion.
Data Sources:
Knowledge base and MEDLINE and PsychLit searches from 1980–2000 using the terms sports, athletes, concussion, and brain.
Data Synthesis:
Neuropsychological testing is a proven method for evaluating symptoms of concussion that results from a variety of different causes. These tests have been shown to be effective in evaluating symptoms of subtle cognitive dysfunction in a number of patient groups. Applying these tests in an athletic population has required some procedural modifications, including the use of brief test batteries, collection of preseason baseline data, and evaluation of subtle postconcussive changes in test scores over time. New methods are now being used for improved evaluation of the reliability and validity of neuropsychological tests in athletes. Proper scientific analysis of the psychometric properties of neuropsychological tests and the ultimate value of their use in the sport setting will require years of detailed study on large numbers of athletes with and without symptoms of concussion.
Athletic trainers and related personnel need to be aware of the training and methodologic issues associated with neuropsychological testing. Knowledge of the scientific properties of these tests, their advantages, and current limitations will ultimately enhance the athletic trainer's ability to use information from neuropsychological testing in an effective manner.
PMCID: PMC155421  PMID: 12937499
concussion; head injury; assessment; psychometrics
3.  Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety 
Psychiatry research  2011;194(3):296-303.
Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discrimant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes.
PMCID: PMC3544472  PMID: 21803551
Subcortical Volumes; Cortical Thickness; Fear; Morphometry; Magnetic Resonance Imaging
4.  Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy 
Epilepsy & behavior : E&B  2011;23(1):64-67.
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 TLE patients 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.
PMCID: PMC3259282  PMID: 22099527
5.  Volume of the Human Septal Forebrain Region Is a Predictor of Source Memory Accuracy 
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 highlight the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases.
PMCID: PMC3339258  PMID: 22152217
Septal nuclei; Basal forebrain; Episodic memory CVLT; MRI; Morphometry; Parahippocampal gyrus
6.  Psychometric and Measurement Properties of Concussion Assessment Tools in Youth Sports 
Journal of Athletic Training  2006;41(4):399-408.
Context: Establishing psychometric and measurement properties of concussion assessments is important before these assessments are used by clinicians. To date, data have been limited regarding these issues with respect to neurocognitive and postural stability testing, especially in a younger athletic population.
Objective: To determine the test-retest reliability and reliable change indices of concussion assessments in athletes participating in youth sports. A secondary objective was to determine the relationship between the Standardized Assessment of Concussion (SAC) and neuropsychological assessments in young athletes.
Design: We used a repeated-measures design to evaluate the test-retest reliability of the concussion assessments in young athletes. Correlations were calculated to determine the relationship between the measures. All subjects underwent 2 test sessions 60 days apart.
Setting: Sports medicine laboratory and school or home environment.
Patients or Other Participants: Fifty healthy young athletes between the ages of 9 and 14 years.
Main Outcome Measure(s): Scores from the SAC, Balance Error Scoring System, Buschke Selective Reminding Test, Trail Making Test B, and Coding and Symbol Search subsets of the Wechsler Intelligence Scale for Children were used in the analysis.
Results: Our test-retest indices for each of the 6 scores were poor to good, ranging from r = .46 to .83. Good reliability was found for the Coding and Symbol Search tests. The reliable change scores provided a way of determining a meaningful change in score for each assessment. We found a weak relationship ( r < .36) between the SAC and each of the neuropsychological assessments; however, stronger relationships ( r > .70) were found between certain neuropsychological measures.
Conclusions: We found moderate test-retest reliability on the cognitive tests that assessed attention, concentration, and visual processing and the Balance Error Scoring System. Our results demonstrated only a weak relationship between performance on the SAC and the selected neuropsychological tests, so it is likely that these tests assess somewhat different areas of cognitive function. Our correlational findings provide more evidence for using the SAC along with a more complex neuropsychological assessment battery in the evaluation of concussion in young athletes.
PMCID: PMC1752194  PMID: 17273465
neuropsychological testing; brain injury; athletic injuries; reliability
7.  Is Neuropsychological Testing Useful in the Management of Sport-Related Concussion? 
Journal of Athletic Training  2005;40(3):139-152.
Objective: Neuropsychological (NP) testing has been used for several years as a way of detecting the effects of sport-related concussion in order to aid in return-to-play determinations. In addition to standard pencil-and-paper tests, computerized NP tests are being commercially marketed for this purpose to professional, collegiate, high school, and elementary school programs. However, a number of important questions regarding the clinical validity and utility of these tests remain unanswered, and these questions present serious challenges to the applicability of NP testing for the management of sport-related concussion. Our purpose is to outline the criteria that should be met in order to establish the utility of NP instruments as a tool in the management of sport-related concussion and to review the degree to which existing tests have met these criteria.
Data Sources: A comprehensive literature review of MEDLINE and PsychLit from 1990 to 2004, including all prospective, controlled studies of NP testing in sport-related concussion.
Data Synthesis: The effects of concussion on NP test performance are so subtle even during the acute phase of injury (1–3 days postinjury) that they often fail to reach statistical significance in group studies. Thus, this method may lack utility in individual decision making because of a lack of sensitivity. In addition, most of these tests fail to meet other psychometric criteria (eg, adequate reliability) necessary for this purpose. Finally, it is unclear that NP testing can detect impairment in players once concussion-related symptoms (eg, headache) have resolved. Because no current guideline for the management of sport-related concussion allows a symptomatic player to return to sport, the incremental utility of NP testing remains questionable.
Conclusions/Recommendations: Despite the theoretic rationale for the use of NP testing in the management of sport-related concussion, no NP tests have met the necessary criteria to support a clinical application at this time. Additional research is necessary to establish the utility of these tests before they can be considered part of a routine standard of care, and concussion recovery should be monitored via the standard clinical examination and subjective symptom checklists until NP testing or other methods are proven effective for this purpose.
PMCID: PMC1250250  PMID: 16284633
neurocognitive function; traumatic brain injury; athletic injury
8.  Individual Differences in Verbal Abilities Associated with Regional Blurring of the Left Gray and White Matter Boundary 
The Journal of Neuroscience  2011;31(43):15257-15263.
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.
PMCID: PMC3865435  PMID: 22031871
9.  Phonetically Irregular Word Pronunciation and Cortical Thickness in the Adult Brain 
NeuroImage  2010;51(4):1453-1458.
Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to–phonemic conversion.
PMCID: PMC2873116  PMID: 20302944
Cortical Thickness; Dyslexia; Reading; Exception Words
10.  Concussion Symptom Inventory: An Empirically Derived Scale for Monitoring Resolution of Symptoms Following Sport-Related Concussion 
Self-report post-concussion symptom scales have been a key method for monitoring recovery from sport-related concussion, to assist in medical management, and return-to-play decision-making. To date, however, item selection and scaling metrics for these instruments have been based solely upon clinical judgment, and no one scale has been identified as the “gold standard”. We analyzed a large set of data from existing scales obtained from three separate case–control studies in order to derive a sensitive and efficient scale for this application by eliminating items that were found to be insensitive to concussion. Baseline data from symptom checklists including a total of 27 symptom variables were collected from a total of 16,350 high school and college athletes. Follow-up data were obtained from 641 athletes who subsequently incurred a concussion. Symptom checklists were administered at baseline (preseason), immediately post-concussion, post-game, and at 1, 3, and 5 days post-injury. Effect-size analyses resulted in the retention of only 12 of the 27 variables. Receiver-operating characteristic analyses were used to confirm that the reduction in items did not reduce sensitivity or specificity. The newly derived Concussion Symptom Inventory is presented and recommended as a research and clinical tool for monitoring recovery from sport-related concussion.
PMCID: PMC2800775  PMID: 19549721
Brain injury; Post-concussion; Scale

Results 1-11 (11)