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Sequential then interactive processing of letters and words in the left fusiform gyrus
Thesen, Thomas; McDonald, Carrie R; Carlson, Chad; Doyle, Werner; Cash, Syd; Sherfey, Jason; Felsovalyi, Olga; Girard, Holly; Barr, William; Devinsky, Orrin; Kuzniecky, Ruben; Halgren, Eric
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.
PMCID:4407686
PMID: 23250414
ISSN: 2041-1723
CID: 204072
The intracarotid amobarbital procedure: When is it worth repeating?
Whitman, Lindsay A; Morrison, Chris E; Becske, Tibor; Barr, William B; Carlson, Chad
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.
PMID: 22309160
ISSN: 0013-9580
CID: 163568
Role of neuropsychologists in the evaluation and management of sport-related concussion: an inter-organization position statement
Echemendia, Ruben J; Iverson, Grant L; McCrea, Michael; Broshek, Donna K; Gioia, Gerard A; Sautter, Scott W; Macciocchi, Stephen N; Barr, William B
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.
PMID: 22180540
ISSN: 0887-6177
CID: 157665
Measuring brain electrical activity to track recovery from sport-related concussion
Barr, William B; Prichep, Leslie S; Chabot, Robert; Powell, Matthew R; McCrea, Michael
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
PMID: 22107157
ISSN: 1362-301x
CID: 149954
Volume of the human septal forebrain region is a predictor of source memory accuracy
Butler, Tracy; Blackmon, Karen; Zaborszky, Laszlo; Wang, Xiuyuan; Dubois, Jonathan; Carlson, Chad; Barr, William B; French, Jacqueline; Devinsky, Orrin; Kuzniecky, Ruben; Halgren, Eric; Thesen, Thomas
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)
PMCID:3339258
PMID: 22152217
ISSN: 1469-7661
CID: 147692
Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy
Butler T; Blackmon K; McDonald CR; Carlson C; Barr WB; Devinsky O; Kuzniecky R; Dubois J; French J; Halgren E; Thesen T
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
PMCID:3259282
PMID: 22099527
ISSN: 1525-5069
CID: 141935
Role of neuropsychologists in the evaluation and management of sport-related concussion: an inter-organization position statement
Echemendia, Ruben J; Iverson, Grant L; McCrea, Michael; Broshek, Donna K; Gioia, Gerard A; Sautter, Scott W; Macciocchi, Stephen N; Barr, William B
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. 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 sport-related concussions; (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 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 health care professionals authorized to evaluate, clinically manage, and provide return to play clearance for athletes who sustain a sport-related concussion.
PMID: 22171535
ISSN: 1385-4046
CID: 753462
Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety
Blackmon K; Barr WB; Carlson C; Devinsky O; Dubois J; Pogash D; Quinn BT; Kuzniecky R; Halgren E; Thesen T
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 discriminant 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:3544472
PMID: 21803551
ISSN: 0165-1781
CID: 139495
Medically refractory epilepsy in autism
Sansa, Gemma; Carlson, Chad; Doyle, Werner; Weiner, Howard L; Bluvstein, Judith; Barr, William; Devinsky, Orrin
Purpose: Epilepsy and electroencephalographic abnormalities are frequent in idiopathic autism, but there is little information regarding treatment-resistant epilepsy (TRE) in this group. We sought to define the clinical and electrophysiologic characteristics and treatment outcomes in these patients. Methods: We retrospectively reviewed clinical and laboratory data of patients with idiopathic autism evaluated at NYU Epilepsy Center during a 20-year period. Key Findings: One hundred twenty-seven patients had idiopathic autism and at least one epileptic seizure; 33.9% had TRE and 27.5% were seizure free. The remaining 38.6% of patients had infrequent seizures or insufficient data to categorize. Patients with TRE had a significantly earlier onset of seizures than seizure-free patients, and a trend for more developmental regression and motor and language delays. Three patients had surgical resection (two had limited improvement and one had no improvement) and one had an anterior callosotomy (no improvement). Vagus nerve stimulator (VNS) implantation provided limited improvement (2 patients) and no improvement (7). Significance: This study found that TRE is common in idiopathic autism and more common with early age of seizure onset. Relatively few patients underwent surgical resection due to multifocal partial epilepsy, comorbid generalized epilepsy, or limited impact of ongoing partial seizures given other problems related to autism. Our small sample suggests that surgical and VNS outcomes in this group are less favorable than in other TRE populations
PMID: 21671922
ISSN: 1528-1167
CID: 134461
Long-term association between seizure outcome and depression after resective epilepsy surgery
Hamid, H; Liu, H; Cong, X; Devinsky, O; Berg, A T; Vickrey, B G; Sperling, M R; Shinnar, S; Langfitt, J T; Walczak, T S; Barr, W B; Dziura, J; Bazil, C W; Spencer, S S
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
PMCID:3235357
PMID: 22094480
ISSN: 1526-632x
CID: 149924