Contributions of posttraumatic stress disorder (PTSD) and mild TBI (mTBI) history to suicidality in the INTRuST consortium.

OBJECTIVE: Mild TBI (mTBI) and posttraumatic stress disorder (PTSD) are independent risk factors for suicidal behaviour (SB). Further, co-occurring mTBI and PTSD increase one's risk for negative health and psychiatric outcomes. However, little research has examined the role of comorbid mTBI and PTSD on suicide risk. METHODS: The present study utilized data from the Injury and TRaUmatic STress (INTRuST) Consortium to examine the prevalence of suicidal ideation (SI) and behaviours among four groups: 1) comorbid mTBI+PTSD, 2) PTSD only, 3) mTBI only, and 4) healthy controls. RESULTS: Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI+PTSD was 40%, 25%, and 19%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with PTSD only was 29%, 11%, and 11%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI only was 14%, 1%, and 2%, respectively. Group comparisons showed that individuals with mTBI alone experienced elevated rates of lifetime SI compared to healthy controls. History of mTBI did not add significantly to risk for suicidal ideation and behaviour beyond what is accounted for by PTSD. CONCLUSION: Findings suggest that PTSD seems to be driving risk for suicidal behaviour.

CVLT-II Forced Choice Recognition Trial as an Embedded Validity Indicator: A Systematic Review of the Evidence.

OBJECTIVES: The Forced Choice Recognition (FCR) trial of the California Verbal Learning Test, 2nd edition, was designed as an embedded performance validity test (PVT). To our knowledge, this is the first systematic review of classification accuracy against reference PVTs. METHODS: Results from peer-reviewed studies with FCR data published since 2002 encompassing a variety of clinical, research, and forensic samples were summarized, including 37 studies with FCR failure rates (N=7575) and 17 with concordance rates with established PVTs (N=4432). RESULTS: All healthy controls scored >14 on FCR. On average, 16.9% of the entire sample scored ≤14, while 25.9% failed reference PVTs. Presence or absence of external incentives to appear impaired (as identified by researchers) resulted in different failure rates (13.6% vs. 3.5%), as did failing or passing reference PVTs (49.0% vs. 6.4%). FCR ≤14 produced an overall classification accuracy of 72%, demonstrating higher specificity (.93) than sensitivity (.50) to invalid performance. Failure rates increased with the severity of cognitive impairment. CONCLUSIONS: In the absence of serious neurocognitive disorder, FCR ≤14 is highly specific, but only moderately sensitive to invalid responding. Passing FCR does not rule out a non-credible presentation, but failing FCR rules it in with high accuracy. The heterogeneity in sample characteristics and reference PVTs, as well as the quality of the criterion measure across studies, is a major limitation of this review and the basic methodology of PVT research in general. (JINS, 2016, 22, 851-858).

Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder.

Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.

Ice Hockey Summit II: zero tolerance for head hits and fighting.

OBJECTIVE: To present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building on the Ice Hockey Summit I action plan (2011) to reduce SRC. METHODS: The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards; and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. RESULTS: The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. CONCLUSIONS: The highest priority action items identified from the Summit includes the following: (1) eliminate head hits from all levels of ice hockey, (2) change body-checking policies, and (3) eliminate fighting in all amateur and professional hockey.

Ice Hockey Summit II: zero tolerance for head hits and fighting.

This study aimed to present currently known basic science and on-ice influences of sport-related concussion (SRC) in hockey, building upon the Ice Hockey Summit I action plan (2011) to reduce SRC. The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure for the science and discussion held during Summit II (Mayo Clinic, Rochester, MN, October 2013). Summit II focused on (1) Basic Science of Concussions in Ice Hockey: Taking Science Forward, (2) Acute and Chronic Concussion Care: Making a Difference, (3) Preventing Concussions via Behavior, Rules, Education, and Measuring Effectiveness, (4) Updates in Equipment: Their Relationship to Industry Standards, and (5) Policies and Plans at State, National, and Federal Levels To Reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were voted on subsequently for purposes of prioritization. The following proceedings include the knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators. The Summit II evidence-based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion. The highest-priority action items identified from the Summit include the following: (1) eliminate head hits from all levels of ice hockey, (2) change body checking policies, and (3) eliminate fighting in all amateur and professional hockey.

Selective changes in white matter integrity in MCI and older adults with cognitive complaints.

BACKGROUND: White matter changes measured using diffusion tensor imaging have been reported in Alzheimer's disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. METHODS: In a cross-sectional analysis, older adults with mild cognitive impairment (n=28), older adults with cognitive complaints but without psychometric impairment (n=29) and healthy controls (n=35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. RESULTS: The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. CONCLUSIONS: These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimer's disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Rationale: Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. Methods: In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. Results: At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. Conclusion: In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments.

Pilot characterization of head kinematics in grassroots dirt track racing.

OBJECTIVE: The objective of this study was to utilize an instrumented mouthpiece sensor to characterize head kinematics experienced by grassroots dirt track race car drivers. METHODS: Four dirt track race car drivers (ages 16-19) were instrumented with custom mouthpiece sensors capable of accurately measuring head motion during racing. Sensors were deployed before races and recorded tri-axial linear acceleration and rotational velocity for approximately 10 min at 200 Hz. Film review was performed to identify data associated with racing laps. For each lap, moving average kinematics were computed and subtracted from the head motion signals to obtain 'adjusted' head motion accounting for lower frequency variance due to periodic motion around the track. From adjusted data, linear and angular head perturbations (i.e., deviations from moving average) were extracted using a custom algorithm. RESULTS: Data was collected during 400 driver-races. A total of 2438 laps were segmented from mouthpiece recordings. The median (95th percentile) peak linear acceleration, rotational velocity, and rotational acceleration of all laps were 5.33 (8.28) g, 2.89 (4.60) rad/s, and 179 (310) rad/s2, respectively. Angular perturbations occurred most frequently about the anterior-posterior axis (median lap frequency = 6.39 Hz); whereas linear perturbations occurred most frequently in the inferior-superior direction (7.96 Hz). Nine crash events were recorded by the mouthpiece sensors. The median (95th percentile) peak head kinematics of these events were 13.4 (36.6) g, 9.67 (21.9) rad/s, and 630 (1330) rad/s2. CONCLUSIONS: Mouthpiece sensors can be used to measure head kinematics during active racing. Laps, head perturbations, and crashes may be useful units of observation to describe typical head kinematic exposure experienced by drivers while racing. Subsequent research is needed to understand the associations between repetitive racing exposure and neurological function. Higher magnitude events (i.e., crashes) are not uncommon and may result in concussion or more severe injury. Results represent novel characterizations of head kinematic exposure experienced in a dirt track racing environment. This information may inform evidence-based strategies (e.g., vehicle/seat design) to improve driver safety.

Inferential-reasoning impairment in schizophrenia-spectrum disorders.

The performance of 15 participants with schizophrenia-spectrum disorders (SCZ) on an inferential-reasoning task was compared with that of 15 healthy-control participants (HC). The SCZ group showed poorer inferential reasoning than HCs, independent of their negative or positive symptoms. These findings are consistent with previous research showing deficits of reasoning in schizophrenia, and indicate that this deficit is independent of severity of delusions.

Dopaminergic challenge with bromocriptine one month after mild traumatic brain injury: altered working memory and BOLD response.

Catecholamines, particularly dopamine, modulate working memory (WM). Altered sensitivity to dopamine might play a role in WM changes observed after traumatic brain injury (TBI). Thirty-one healthy controls (HC) and 26 individuals with mild TBI (MTBI) 1 month after injury were challenged with bromocriptine versus placebo before administration of a verbal WM functional MRI task. Bromocriptine was associated with improved WM performance in the HC but not the MTBI group. On bromocriptine, the MTBI group showed increased activation outside of a task-specific region of interest. Findings are consistent with the hypothesis that individuals with MTBI have altered responsivity to dopamine.

Automated subject-specific, hexahedral mesh generation via image registration.

Generating subject-specific, all-hexahedral meshes for finite element analysis continues to be of significant interest in biomechanical research communities. To date, most automated methods "morph" an existing atlas mesh to match with a subject anatomy, which usually result in degradation in mesh quality because of mesh distortion. We present an automated meshing technique that produces satisfactory mesh quality and accuracy without mesh repair. An atlas mesh is first developed using a script. A subject-specific mesh is generated with the same script after transforming the geometry into the atlas space following rigid image registration, and is transformed back into the subject space. By meshing the brain in 11 subjects, we demonstrate that the technique's performance is satisfactory in terms of both mesh quality (99.5% of elements had a scaled Jacobian >0.6 while <0.01% were between 0 and 0.2) and accuracy (average distance between mesh boundary and geometrical surface was 0.07 mm while <1% greater than 0.5mm). The combined computational cost for image registration and meshing was <4 min. Our results suggest that the technique is effective for generating subject-specific, all-hexahedral meshes and that it may be useful for meshing a variety of anatomical structures across different biomechanical research fields.

Stability of Subjective Executive Functioning in Older Adults with aMCI and Subjective Cognitive Decline.

OBJECTIVE: Subjective memory concerns are characteristic of individuals with amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), though subjective changes in executive functions have also been reported. In a cohort study, we examined the temporal stability of subjective report of executive functioning in a high education (mean = 16.8 years) sample of cognitively normal (CN) older adults and those with aMCI or SCD. METHOD: Participants (CN, n = 22; aMCI, n = 21; SCD, n = 24) and their informants completed the BRIEF-A and neuropsychological tests at two time points separated by approximately 1 year. RESULTS: Analyses focused on those with diagnostic stability (95.7%). Participants with aMCI and SCD, and their informants, endorsed worse executive functions relative to CN at both time points. No group by time interaction was observed for subjective or objective measures of executive function. CONCLUSIONS: Diagnostically stable CN older adults, and those with prodromal dementia conditions, report stable executive functioning at 1-year follow-up.

Differential Effects of Pergolide and Bromocriptine on Working Memory Performance and Brain Activation after Mild Traumatic Brain Injury.

Dopamine D1 and D2 receptors differ with respect to patterns of regional brain distribution and behavioral effects. Pre-clinical work suggests that D1 agonists enhance working memory, but the absence of selective D1 agonists has constrained using this approach in humans. This study examines working memory performance in mild traumatic brain injury (mTBI) patients when given pergolide, a mixed D1/D2 agonist, compared with bromocriptine, a selective D2 agonist. Fifteen individuals were studied 1 month after mTBI and compared with 17 healthy controls. At separate visits, participants were administered 1.25 mg bromocriptine or 0.05 mg pergolide prior to functional magnetic resonance imaging (MRI) using a working memory task (visual-verbal n-back). Results indicated a significant group-by-drug interaction for mean performance across n-back task conditions, where the mTBI group showed better performance on pergolide relative to bromocriptine, whereas controls showed the opposite pattern. There was also a significant effect of diagnosis, where mTBI patients performed worse than controls, particularly while on bromocriptine, as shown in our prior work. Functional MRI activation during the most challenging task condition (3-back > 0-back contrast) showed a significant group-by-drug interaction, with the mTBI group showing increased activation relative to controls in working memory circuitry while on pergolide, including in the left inferior frontal gyrus. Across participants there was a positive correlation between change in activation in this region and change in performance between drug conditions. Results suggest that activation of the D1 receptor may improve working memory performance after mTBI. This has implications for the development of pharmacological strategies to treat cognitive deficits after mTBI.

Nonclinical obsessive-compulsive symptoms and executive functions in schizophrenia.

The impact of nonclinical obsessive-compulsive symptoms (OCS) on neuropsychological functioning in schizophrenia has received little investigation. The authors evaluated whether severity and subtype of OCS are associated with executive functioning in schizophrenia. Twenty-nine patients with schizophrenia and 32 healthy comparison subjects completed questionnaire and performance-based measures of executive functioning. Overall OCS severity in patients was associated with poorer monitoring and cognitive flexibility. Obsessing, hoarding, and checking were related to poorer executive functioning in daily life. Performance-based scores showed few correlations with OCS. Findings indicate that severity of nonclinical OCS subtypes contributes to the heterogeneity of executive functions in schizophrenia.

Genetic pathway-based hierarchical clustering analysis of older adults with cognitive complaints and amnestic mild cognitive impairment using clinical and neuroimaging phenotypes.

Hierarchical clustering is frequently used for grouping results in expression or haplotype analyses. These methods can elucidate patterns between measures that can then be applied to discerning their validity in discriminating between experimental conditions. Here a hierarchical clustering method is used to analyze the results of an imaging genetics study using multiple brain morphology and cognitive testing endpoints for older adults with amnestic mild cognitive impairment (MCI) or cognitive complaints (CC) compared to healthy controls (HC). The single nucleotide polymorphisms (SNPs) are a subset of those included on a larger array that are found in a reported Alzheimer's disease (AD) and neurodegeneration pathway. The results indicate that genetic models within the endpoints cluster together, while there are 4 distinct sets of SNPs that differentiate between the endpoints, with most significant results associated with morphology endpoints rather than cognitive testing of patients' reported symptoms. The genes found in at least one cluster are ABCB1, APBA1, BACE1, BACE2, BCL2, BCL2L1, CASP7, CHAT, CST3, DRD3, DRD5, IL6, LRP1, NAT1, and PSEN2. The greater associations with morphology endpoints suggests that changes in brain structure can be influenced by an individual's genetic background in the absence of dementia and in some cases (Cognitive Complaints group) even without those effects necessarily being detectable on commonly used clinical tests of cognition. The results are consistent with polygenic influences on early neurodegenerative changes and demonstrate the effectiveness of hierarchical clustering in identifying genetic associations among multiple related phenotypic endpoints.

Comparison of season-long diffusivity measures in a cohort of non-concussed contact and non-contact athletes.

INTRODUCTION: Concern surrounding short- and long-term consequences of participation in contact sports has become a significant public health topic. Previous literature utilizing diffusion tensor imaging in sports-related concussion has exhibited notable variety of analysis methods and analyzed regions of interest, and largely focuses on acute effects of concussion. The current study aimed to compare diffusivity metrics across a single season within athlete cohorts with no history of concussion. METHODS: A prospective cohort of 75 contact and 79 non-contact division I athletes were compared across diffusion tensor imaging metrics (i.e. TRACULA); examinations were also performed assessing the relationship between neuroimaging metrics, head impact exposure metrics (in-helmet accelerometer), and neurocognitive variables. Assessment occurred at pre-and post-season time points. RESULTS: Seasonal changes in fractional anisotropy and mean diffusivity values did not differ between athlete cohorts, nor did they differ within cohort groups, across pre- and post-season scans. Specific to contact athletes, positive associations were found between uncinate fasciculus mean diffusivity values and season linear acceleration (p =.018), season rotational acceleration (p =.017), and season hit severity (p =.021). CONCLUSIONS: Results suggest an influence of impact frequency, type, and severity on white matter integrity in select brain regions in contact athletes. Current findings expand our knowledge of anatomical changes over the course of a single season, and underscore the importance of considering methodology when interpreting findings in this population, as differing image analysis techniques may lead to different conclusions regarding significant effects.

Lack of relationship between psychological denial and unawareness of illness in schizophrenia-spectrum disorders.

Numerous theories have been proposed to explain the unawareness of illness that is commonly seen in schizophrenia-spectrum disorders, including the theory that unawareness is the result of a psychological denial mechanism used to mitigate the emotional consequences of having a psychiatric illness. The present study was an attempt to determine whether increased denial (in the form of self-deception) is associated with impaired awareness, consistent with the denial theory. Participants included 40 patients with schizophrenia-spectrum disorders and 25 healthy comparison participants. Patients' levels of awareness and symptom attribution were assessed through interview, and all participants completed self-report questionnaires measuring mood symptoms as well as their use of self-deception. Awareness of negative symptoms was associated with increased depression. However, self-deception was not significantly correlated with awareness measures. When patients were divided on the basis of their awareness and attribution scores, no group differences emerged regarding use of self-deception. The patient group and the healthy comparison group did not differ in their use of self-deception. The current results do not support the psychological denial theory of unawareness of illness in schizophrenia-spectrum disorders.

Associations between neuropsychiatric and health status outcomes in individuals with probable mTBI.

Mild traumatic brain injury (mTBI) is a common occurrence, and may impact distal outcomes in a subgroup of individuals. Improved characterization of health outcomes and identification of factors associated with poor outcomes is needed to better understand the impact of mTBI, particularly in those with co-occurring posttraumatic stress disorder (PTSD). Participants in a data repository of the Injury and Traumatic Stress (INTRuST) Clinical Consortium (n = 625) completed functional disability [FD] and health-related quality of life [HRQOL] questionnaires, and a subset completed a neuropsychological assessment. FD and HRQOL were compared among participants with probable mTBI (mTBI), probable mTBI with PTSD (mTBI/PTSD), and health comparison participants (HC). Associations between symptoms, neuropsychological performance, and health outcomes were examined in those with probable mTBI with and without PTSD (n = 316). Individuals in the mTBI/PTSD group endorsed poorer health outcomes than those in the mTBI group, who endorsed poorer outcomes than those in the HC group. Individuals in either mTBI group performed worse than those in the HC on verbal learning and memory and psychomotor speed. Health outcomes were correlated with mental health and postconcussive symptoms, as well as neuropsychological variables. mTBI may adversely impact self-reported health, with the greatest effect observed in individuals with co-occurring mTBI/PTSD.

Apathy and the processing of novelty in schizophrenia.

Apathy is a common negative symptom in schizophrenia that has been associated with poor medication compliance and treatment outcome. Recent studies in neurological patients have observed an association between apathy and reduced attention to novel stimuli. We evaluated whether patients with schizophrenia demonstrate a similar relationship. Participants included 20 patients with schizophrenia and 20 healthy comparison subjects matched for age, sex, handedness, and parental education. A self-paced visual novelty task was presented which assessed the duration that participants looked at frequent standard stimuli, infrequent target stimuli, and novel stimuli. Attention to novelty was defined as the duration of viewing novel relative to standard stimuli. Apathy was assessed with the Marin Apathy Evaluation Scale. Results revealed significantly greater self- and informant-reported apathy, slower reaction time to target stimuli, and longer viewing times to the stimuli, but not reduced attention to the novel stimuli, in the patient group. Although greater self-report of apathy was associated with longer viewing times for all stimuli in the patient group, this was accounted for by depressed mood. The present findings indicate that schizophrenia is associated with slowed information processing, but do not support the hypothesis that apathy in schizophrenia is associated with abnormal processing of novelty.

Single nucleotide polymorphisms in ANKK1 and the dopamine D2 receptor gene affect cognitive outcome shortly after traumatic brain injury: a replication and extension study.

OBJECTIVE: The two objectives of this study were (1) to replicate the previous finding that a single nucleotide polymorphism (SNP) in the ANKK1 gene (SNP rs1800497 formerly known as the DRD2 TAQ1 A allele) is associated with measures of learning and response latency after traumatic brain injury (TBI) and (2) to further characterize the genetic basis of the effect by testing the strength of association and degree of linkage disequilibrium between the cognitive outcome measures and a selected ensemble of 31 polymorphisms from three adjacent genes in the region of rs1800497. METHOD: A cohort of 54 patients with TBI and 21 comparison subjects were genotyped for the DRD2 TAQ1 A polymorphism (rs1800497). Ninety-three patients with TBI and 48 comparison subjects (the current cohort and an earlier independent cohort) were also genotyped for 31 additional neighbouring polymorphisms in NCAM, ANKK1 and DRD2. TBI patients were studied 1 month after injury. All subjects completed memory and attention tests, including the California Verbal Learning Test (CVLT) recognition task and the Gordon Continuous Performance Test (CPT). RESULTS: As in a previous study the T allele of TAQ1 A (rs1800497) was associated with poorer performance on the CVLT recognition trial in both TBI and control subjects. There was also a significant diagnosis-by-allele interaction on CPT measures of response latency, largely driven by slower performance in the TBI participants with the T allele. Analysis of 31 additional neighbouring polymorphisms from NCAM, ANKK1 and DRD2 in the TBI patients showed four haploblocks. A haploblock of three SNPs in ANKK1 (rs11604671, rs4938016 and rs1800497 (TAQ1A)) showed the greatest association with cognitive outcome measures. CONCLUSIONS: The results confirm a previously published association between the TAQ1 A (rs1800497) T allele and cognitive outcome measures 1 month after TBI and suggest that a haploblock of polymorphisms in ANKK1, rather than the adjacent DRD2 gene, has the highest association with these measures after TBI.