Jordan Grafman

Publications of Jordan Grafman

• A Voxel-Based Lesion Study On Facial Emotion Recognition After Penetrating Brain Injury.

  Authors: Olga Dal Monte, Frank Krueger, Jeffrey Solomon, Selene Schintu, Kristine M Knutson, Maren Strenziok, Matteo Pardini, Anne Leopold, Vanessa Raymont, Jordan Grafman

  Social cognitive and affective neuroscience. 04/2012;

  The ability to read emotions in other people's face is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulateThe ability to read emotions in other people's face is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VSLM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings adds empirical evidence indicating that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving a common bilateral fronto-temporo-limbic network, but also unique bilateral brain regions responsible for recognizing emotional valence.

• Screening for C9ORF72 repeat expansion in FTLD.

  Authors: Raffaele Ferrari, Kin Mok, Jorge H Moreno, Stephanie Cosentino, Jill Goldman, Pietro Pietrini, Richard Mayeux, Michael C Tierney, Dimitrios Kapogiannis, Gregory A Jicha, Jill R Murrell, Bernardino Ghetti, Eric M Wassermann, Jordan Grafman, John Hardy, Edward D Huey, Parastoo Momeni

  Neurobiology of aging. 03/2012;

  In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologicallyIn the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples.

• An integrative architecture for general intelligence and executive function revealed by lesion mapping.

  Authors: Aron K Barbey, Roberto Colom, Jeffrey Solomon, Frank Krueger, Chad Forbes, Jordan Grafman

  Brain : a journal of neurology. 03/2012;

  Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control, the broader functional networks that support high-levelAlthough cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control, the broader functional networks that support high-level cognition and give rise to general intelligence remain to be well characterized. Here, we investigated the neural substrates of the general factor of intelligence (g) and executive function in 182 patients with focal brain damage using voxel-based lesion-symptom mapping. The Wechsler Adult Intelligence Scale and Delis-Kaplan Executive Function System were used to derive measures of g and executive function, respectively. Impaired performance on these measures was associated with damage to a distributed network of left lateralized brain areas, including regions of frontal and parietal cortex and white matter association tracts, which bind these areas into a coordinated system. The observed findings support an integrative framework for understanding the architecture of general intelligence and executive function, supporting their reliance upon a shared fronto-parietal network for the integration and control of cognitive representations and making specific recommendations for the application of the Wechsler Adult Intelligence Scale and Delis-Kaplan Executive Function System to the study of high-level cognition in health and disease.

• BDNF Polymorphism-Dependent OFC and DLPFC Plasticity Differentially Moderates Implicit and Explicit Bias.

  Authors: Chad E Forbes, Joshua C Poore, Aron K Barbey, Frank Krueger, Jeffrey Solomon, Robert H Lipsky, Colin A Hodgkinson, David Goldman, Jordan Grafman

  Cerebral cortex (New York, N.Y. : 1991). 11/2011;

  This study examined the role of orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) plasticity in controlling implicit and explicit social biases. Normal controls and patients withThis study examined the role of orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) plasticity in controlling implicit and explicit social biases. Normal controls and patients with varied OFC and DLPFC lesion size and single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor (BDNF) gene, which promotes (methionine-valine [Met/Val] SNP) or stifles (valine-valine [Val/Val] SNP) plasticity in damaged PFC regions, completed measures of implicit and explicit social bias. Patients and controls demonstrated comparable levels of implicit bias, but patients with Met/Val SNPs exhibited less implicit bias when they had smaller OFC lesions compared with Val/Val patients with similar size lesions and those with large OFC lesions. Both patients and controls demonstrated patterns of explicit bias consistent with hypotheses. Patients with Met/Val SNPs exhibited less explicit bias when they had smaller DLPFC lesions sizes compared with Val/Val patients with similar size lesions and those with large DLPFC lesions. OFC lesion size and BDNF SNP type did not moderate explicit bias; DLPFC lesion size and BDNF SNP type did not moderate implicit bias (nor did other medial or lateral regions). Findings suggest that plasticity within specific PFC regions modulates the type and degree of social bias that individuals' exhibit.

• Damage to the left ventromedial prefrontal cortex impacts affective theory of mind.

  Authors: Anne Leopold, Frank Krueger, Olga Dal Monte, Matteo Pardini, Sarah J Pulaski, Jeffrey Solomon, Jordan Grafman

  Social cognitive and affective neuroscience. 10/2011;

  Studies investigating theory of mind (ToM) abilities (i.e. ability to understand and predict others' mental states) have revealed that affective and cognitive functions play a significant role andStudies investigating theory of mind (ToM) abilities (i.e. ability to understand and predict others' mental states) have revealed that affective and cognitive functions play a significant role and that each of those functions are associated with distinct neural networks. Cognitive facets of ToM have implicated the medial prefrontal cortex, temporo-parietal junction and the anterior paracingulate cortex, whereas affective facets have implicated the ventromedial prefrontal cortex (vmPFC). Although the vmPFC has repeatedly shown to be critical for affective functions, knowledge regarding the exact role of the left and right vmPFC in affective ToM is still obscure. Here, we compared performances of 30 patients with left, right and bilateral vmPFC lesions to two comparison groups (one without and one with brain injuries) on the Faux Pas Recognition task measuring the facets of ToM. We also investigated whether any deficits may be associated with other emotional measures, namely emotional empathy and emotional intelligence. Our results extend earlier findings by showing that the vmPFC is associated with abilities in affective ToM. More importantly, our results revealed that the left, and not the right vmPFC as indicated previously, is involved in affective ToM and that this deficit is associated with emotional intelligence.

• FUS and TDP43 genetic variability in FTD and CBS.

  Authors: Edward D Huey, Raffaele Ferrari, Jorge H Moreno, Christopher Jensen, Christopher M Morris, Felix Potocnik, Rajesh N Kalaria, Michael Tierney, Eric M Wassermann, John Hardy, Jordan Grafman, Parastoo Momeni

  Neurobiology of aging. 09/2011;

  This study aimed to evaluate genetic variability in the FUS and TDP-43 genes, known to be mainly associated with amyotrophic lateral sclerosis (ALS), in patients with the diagnoses of frontotemporalThis study aimed to evaluate genetic variability in the FUS and TDP-43 genes, known to be mainly associated with amyotrophic lateral sclerosis (ALS), in patients with the diagnoses of frontotemporal lobar degeneration (FTLD) and corticobasal syndrome (CBS). We screened the DNA of 228 patients for all the exons and flanking introns of FUS and TDP-43 genes. We identified 2 novel heterozygous missense mutations in FUS: P106L (g.22508384C>T) in a patient with behavioral variant frontotemporal dementia (bvFTD) and Q179H in several members of a family with behavioral variant FTD. We also identified the N267S mutation in TDP-43 in a CBS patient, previously only reported in 1 ALS family and 1 FTD patient. Additionally, we identified 2 previously reported heterozygous insertion and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180-4185 delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185-4186 insGAGGTG) in a patient with diagnosis of CBS. Not least, we have found a series of variants in FUS also in neurologically normal controls. In summary, we report that genetic variability in FUS and TDP-43 encompasses a wide range of phenotypes (including ALS, FTD, and CBS) and that there is substantial genetic variability in FUS gene in neurologically normal controls.

• Areas of left perisylvian cortex mediate auditory-verbal short-term memory.

  Authors: Michael Koenigs, Daniel J Acheson, Aron K Barbey, Jeffrey Solomon, Bradley R Postle, Jordan Grafman

  Neuropsychologia. 09/2011; 49(13):3612-9.

  A contentious issue in memory research is whether verbal short-term memory (STM) depends on a neural system specifically dedicated to the temporary maintenance of information, or instead relies onA contentious issue in memory research is whether verbal short-term memory (STM) depends on a neural system specifically dedicated to the temporary maintenance of information, or instead relies on the same brain areas subserving the comprehension and production of language. In this study, we examined a large sample of adults with acquired brain lesions to identify the critical neural substrates underlying verbal STM and the relationship between verbal STM and language processing abilities. We found that patients with damage to selective regions of left perisylvian cortex - specifically the inferior frontal and posterior temporal sectors - were impaired on auditory-verbal STM performance (digit span), as well as on tests requiring the production and/or comprehension of language. These results support the conclusion that verbal STM and language processing are mediated by the same areas of left perisylvian cortex.

• Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

  Authors: Katya Rascovsky, John R Hodges, David Knopman, Mario F Mendez, Joel H Kramer, John Neuhaus, John C van Swieten, Harro Seelaar, Elise G P Dopper, Chiadi U Onyike [......] Vincent Deramecourt, Florence Lebert, Yolande Pijnenburg, Tiffany W Chow, Facundo Manes, Jordan Grafman, Stefano F Cappa, Morris Freedman, Murray Grossman, Bruce L Miller

  Brain : a journal of neurology. 08/2011; 134(Pt 9):2456-77.

  Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validationBased on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

• Regional brain atrophy and impaired decision making on the balloon analog risk task in behavioral variant frontotemporal dementia.

  Authors: Maren Strenziok, Sarah Pulaski, Frank Krueger, Giovanna Zamboni, Deborah Clawson, Jordan Grafman

  Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology. 06/2011; 24(2):59-67.

  The goal of this study was 2-fold, first, to compare decision making in behavioral variant frontotemporal dementia (bvFTD) patients and healthy adults using the Balloon Analog Risk Task (BART), and,The goal of this study was 2-fold, first, to compare decision making in behavioral variant frontotemporal dementia (bvFTD) patients and healthy adults using the Balloon Analog Risk Task (BART), and, second, to identify the regions of gray matter atrophy associated with bvFTD patients' BART performance. Stimulus-reinforcement learning is required to evaluate the results of previously chosen actions to improve future decisions. Although there is a well established literature suggesting altered decision making in FTD patients and data from lesion studies suggest orbitofrontal cortex (OFC) involvement in decision making, there is very little research looking at the brain correlates of decision making in FTD populations specifically. Twenty-seven bvFTD patients and 19 age-matched and education-matched normal controls completed the BART. Voxel-based morphometry analysis was performed on the magnetic resonance imaging scans of a subset of patients. Compared with healthy controls, the bvFTD patients did not learn and pumped less to inflate a balloon to receive a reward, indicating altered stimulus-reinforcement learning. The voxel-based morphometry analysis indicated that bvFTD patients' impaired BART performance was related to atrophy in the right lateral OFC. The right lateral OFC is crucial for stimulus-reinforcement learning required for the adjustment of behavior under changing reward contingencies.

• Reward processing abnormalities in Parkinson's disease.

  Authors: Dimitrios Kapogiannis, Eric Mooshagian, Paul Campion, Jordan Grafman, Trelawny J Zimmermann, Kelsey C Ladt, Eric M Wassermann

  Movement disorders : official journal of the Movement Disorder Society. 04/2011; 26(8):1451-7.

  The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receiveThe primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid-A-mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk-taking behavior in patients on agonist treatment.

• Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration.

  Authors: Alice S Chen-Plotkin, Maria Martinez-Lage, Patrick M A Sleiman, William Hu, Robert Greene, Elisabeth McCarty Wood, Shaoxu Bing, Murray Grossman, Gerard D Schellenberg, Kimmo J Hatanpaa [......] Christine Van Broeckhoven, Thomas D Bird, Nigel J Cairns, Allison Goate, Matthew P Frosch, Peter F Riederer, Nenad Bogdanovic, Virginia M Y Lee, John Q Trojanowski, Vivianna M Van Deerlin

  Archives of neurology. 04/2011; 68(4):488-97.

  To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobarTo assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobar degeneration (FTLD). A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases of FTLD with TAR DNA-binding protein of 43-kDa (TDP-43)-positive inclusions (FTLD-TDP). We identified 97 individuals with FTLD-TDP with pathogenic GRN mutations (GRN+ FTLD-TDP), assessed their genetic and clinical characteristics, and compared them with 453 patients with FTLD-TDP in which GRN mutations were excluded (GRN- FTLD-TDP). No patients were known to be related. Neuropathologic characteristics were confirmed as FTLD-TDP in 79 of the 97 GRN+ FTLD-TDP cases and all of the GRN- FTLD-TDP cases. Age at onset of FTLD was younger in patients with GRN+ FTLD-TDP vs GRN- FTLD-TDP (median, 58.0 vs 61.0 years; P < .001), as was age at death (median, 65.5 vs 69.0 years; P < .001). Concomitant motor neuron disease was much less common in GRN+ FTLD-TDP vs GRN- FTLD-TDP (5.4% vs 26.3%; P < .001). Fifty different GRN mutations were observed, including 2 novel mutations: c.139delG (p.D47TfsX7) and c.378C>A (p.C126X). The 2 most common GRN mutations were c.1477C>T (p.R493X, found in 18 patients, representing 18.6% of GRN cases) and c.26C>A (p.A9D, found in 6 patients, representing 6.2% of cases). Patients with the c.1477C>T mutation shared a haplotype on chromosome 17; clinically, they resembled patients with other GRN mutations. Patients with the c.26C>A mutation appeared to have a younger age at onset of FTLD and at death and more parkinsonian features than those with other GRN mutations. GRN+ FTLD-TDP differs in key features from GRN- FTLD-TDP.

• Orbitofrontal contributions to human working memory.

  Authors: Aron K Barbey, Michael Koenigs, Jordan Grafman

  Cerebral cortex (New York, N.Y. : 1991). 04/2011; 21(4):789-95.

  Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in human memory, the necessity of the orbitofrontal cortex for key competenciesAlthough cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in human memory, the necessity of the orbitofrontal cortex for key competencies of working memory remains largely unexplored. We therefore studied human brain lesion patients to determine whether the orbitofrontal cortex is necessary for working memory function, administering subtests of the Wechsler memory scale, the Wechsler adult intelligence scale, and the n-back task to 3 participant groups: orbitofrontal lesions (n = 24), prefrontal lesions not involving orbitofrontal cortex (n = 40), and no brain lesions (n = 54). Orbitofrontal damage was reliably associated with deficits on neuropsychological tests involving the coordination of working memory maintenance, manipulation, and monitoring processes (n-back task) but not on pure tests of working memory maintenance (digit/spatial span forward) or manipulation (digit/spatial span backward and letter-number sequencing). Our findings elucidate a central component of the neural architecture of working memory, providing key neuropsychological evidence for the necessity of the orbitofrontal cortex in executive control functions underlying the joint maintenance, manipulation, and monitoring of information in working memory.

• Implicit attitudes in prosopagnosia.

  Authors: Kristine M Knutson, Karen A DeTucci, Jordan Grafman

  Neuropsychologia. 03/2011; 49(7):1851-62.

  We studied a male with acquired prosopagnosia using a battery of Implicit Association Tests (IATs) to investigate whether observing faces varying by social category would activate the patient'sWe studied a male with acquired prosopagnosia using a battery of Implicit Association Tests (IATs) to investigate whether observing faces varying by social category would activate the patient's implicit social biases. We also asked him to categorize faces explicitly by race, gender, and political party. The patient, G.B., was marginally slower to categorize black compared to white faces. He showed congruency effects in the race and celebrity IATs, but not in the gender or political IATs. These results indicate that G.B. possesses an implicit social sensitivity to certain facial stimuli despite an inability to overtly recognize familiar faces. The results demonstrate that social biases can be retrieved based on facial stimuli via pathways bypassing the fusiform gyri. Thus the IAT effect can be added to the list of covert recognition effects found in prosopagnosia.

• A need for improved training interventions for the remediation of impairments in social functioning following brain injury.

  Authors: David M Driscoll, Olga Dal Monte, Jordan Grafman

  Journal of neurotrauma. 02/2011; 28(2):319-26.

  Social functioning deficits are a prominent feature of many neurological and psychiatric conditions, and may include disruption in the acquisition or application of basic or complex social skills.Social functioning deficits are a prominent feature of many neurological and psychiatric conditions, and may include disruption in the acquisition or application of basic or complex social skills. Such disturbances are often resistant to treatment, and individuals with such conditions are often faced with lifelong difficulties in maintaining personal relationships, employment, and independent living. In recent years, a number of psychosocial treatments have been developed to address this growing problem. In this article, we review studies investigating the use of psychosocial training interventions in individuals with acquired brain injuries, which frequently require intervention for impairments in cognitive and social functioning. We then discuss limitations of these studies and highlight specific areas in which such treatments might be improved in the future.

• Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia.

  Authors: Jorge Moll, Roland Zahn, Ricardo de Oliveira-Souza, Ivanei E Bramati, Frank Krueger, Bernardo Tura, Alyson L Cavanagh, Jordan Grafman

  NeuroImage. 01/2011; 54(2):1735-42.

  Poets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care aboutPoets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care about others and to be concerned about our mistakes. Functional imaging studies have implicated frontopolar, ventromedial frontal and basal forebrain regions in the experience of prosocial sentiments. Patients with lesions of the frontopolar and ventromedial frontal areas were observed to behave inappropriately and less prosocially, which could be attributed to a generalized emotional blunting. Direct experimental evidence for brain regions distinctively associated with moral sentiment impairments is lacking, however. We investigated this issue in patients with the behavioral variant of frontotemporal dementia, a disorder in which early and selective impairments of social conduct are consistently observed. Using a novel moral sentiment task, we show that the degree of impairment of prosocial sentiments is associated with the degree of damage to frontopolar cortex and septal area, as assessed with 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an established measure of neurodegenerative damage. This effect was dissociable from impairment of other-critical feelings (anger and disgust), which was in turn associated with dorsomedial prefrontal and amygdala dysfunction. Our findings suggest a critical role of the frontopolar cortex and septal region in enabling prosocial sentiments, a fundamental component of moral conscience.

• "Studying injured minds" - the Vietnam head injury study and 40 years of brain injury research.

  Authors: Vanessa Raymont, Andres M Salazar, Frank Krueger, Jordan Grafman

  Frontiers in neurology. 01/2011; 2:15.

  The study of those who have sustained traumatic brain injuries (TBI) during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology,The study of those who have sustained traumatic brain injuries (TBI) during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology, and neuroimaging. The Vietnam Head Injury Study (VHIS) is a prospective, long-term follow-up study of a cohort of 1,221 Vietnam veterans with mostly penetrating brain injuries, which has stretched over more than 40 years. The scope of this study, both in terms of the types of injury and fields of examination, has been extremely broad. It has been instrumental in extending the field of TBI research and in exposing pressing medical and social issues that affect those who suffer such injuries. This review summarizes the history of conflict-related TBI research and the VHIS to date, as well as the vast range of important findings the VHIS has established.

• The role of the Met66 brain-derived neurotrophic factor allele in the recovery of executive functioning after combat-related traumatic brain injury.

  Authors: Frank Krueger, Matteo Pardini, Edward D Huey, Vanessa Raymont, Jeffrey Solomon, Robert H Lipsky, Colin A Hodgkinson, David Goldman, Jordan Grafman

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 01/2011; 31(2):598-606.

  Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes withBrain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the recovery of executive functioning after TBI. We genotyped a sample of male Vietnam combat veterans consisting of a frontal lobe lesion group with focal penetrating head injuries and a non-head-injured control group for the Val66Met BDNF polymorphism. The Delis-Kaplan Executive Function System as a standardized psychometric battery was administrated to examine key domains of executive functions. The results revealed that the Met allele but not the hypothesized Val allele promotes recovery of executive functioning. Overall, the Met66 carriers in the lesion group performed as well as the Met66 carriers in the control group. The Met66 allele accounted for 6.2% of variance for executive functioning independently of other significant predictors including preinjury intelligence, left hemisphere volume loss, and dorsolateral PFC volume loss. The findings point to different mechanisms of the Val66Met BDNF gene in complex phenotypes under normal and pathological conditions. A better understanding of these mechanisms could be instrumental in the development and application of effective therapeutic strategies to facilitate recovery from TBI.

• BDNF polymorphism predicts general intelligence after penetrating traumatic brain injury.

  Authors: Elham Rostami, Frank Krueger, Serguei Zoubak, Olga Dal Monte, Vanessa Raymont, Matteo Pardini, Colin A Hodgkinson, David Goldman, Mårten Risling, Jordan Grafman

  PloS one. 01/2011; 6(11):e27389.

  Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an importantNeuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10-15 years post-injury, and Phase III (30-35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery.

• Left dorsomedial frontal brain damage is associated with insomnia.

  Authors: Michael Koenigs, Jessica Holliday, Jeffrey Solomon, Jordan Grafman

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 11/2010; 30(47):16041-3.

  Insomnia is a common sleep disorder, yet its pathophysiological basis remains poorly understood. Studying a group of 192 patients with focal brain lesions, we show a significant association betweenInsomnia is a common sleep disorder, yet its pathophysiological basis remains poorly understood. Studying a group of 192 patients with focal brain lesions, we show a significant association between insomnia and left dorsomedial prefrontal damage. Our findings are the first to demonstrate a link between insomnia and a discrete locus of brain damage, providing novel insight into the neurobiological mechanisms of sleep maintenance.

• Fronto-parietal regulation of media violence exposure in adolescents: a multi-method study.

  Authors: Maren Strenziok, Frank Krueger, Gopikrishna Deshpande, Rhoshel K Lenroot, Elke van der Meer, Jordan Grafman

  Social cognitive and affective neuroscience. 10/2010; 6(5):537-47.

  Adolescents spend a significant part of their leisure time watching TV programs and movies that portray violence. It is unknown, however, how the extent of violent media use and the severity ofAdolescents spend a significant part of their leisure time watching TV programs and movies that portray violence. It is unknown, however, how the extent of violent media use and the severity of aggression displayed affect adolescents' brain function. We investigated skin conductance responses, brain activation and functional brain connectivity to media violence in healthy adolescents. In an event-related functional magnetic resonance imaging experiment, subjects repeatedly viewed normed videos that displayed different degrees of aggressive behavior. We found a downward linear adaptation in skin conductance responses with increasing aggression and desensitization towards more aggressive videos. Our results further revealed adaptation in a fronto-parietal network including the left lateral orbitofrontal cortex (lOFC), right precuneus and bilateral inferior parietal lobules, again showing downward linear adaptations and desensitization towards more aggressive videos. Granger causality mapping analyses revealed attenuation in the left lOFC, indicating that activation during viewing aggressive media is driven by input from parietal regions that decreased over time, for more aggressive videos. We conclude that aggressive media activates an emotion-attention network that has the capability to blunt emotional responses through reduced attention with repeated viewing of aggressive media contents, which may restrict the linking of the consequences of aggression with an emotional response, and therefore potentially promotes aggressive attitudes and behavior.