Predictors of Responsivity to Interdisciplinary Pain Management.

Objective: This study investigated for whom interdisciplinary pain management (IPM) is most effective. Identification of predictors of treatment responsivity would facilitate development of patient-treatment matching algorithms to optimize outcomes. Design: Repeated measures prospective study of consecutive admissions to a two-week IPM program. Setting: Brisbane Pain Rehabilitation Service in Brisbane, Australia. Subjects: A total of 163 adults referred for chronic pain management. Methods: Self-report questionnaires and measures of physical performance were obtained at program entry and completion. Group-level analyses were performed using standard parametric statistics. Individual-level change was assessed using recommended criteria. Multivariate analysis of variance and logistic regression were used to examine outcomes and predictors of response. Results: Significant improvements were observed across psychological, social, and physical outcome domains. Up to 50% of participants had clinically meaningful improvements, while less than 10% deteriorated. Higher baseline depression, anxiety, stress, and pain catastrophizing scores predicted better group-level outcomes (Ps < 0.05). Participants with higher baseline depression scores were most likely to show significant individual-level improvement on at least one outcome (Ps < 0.05). Participants with nociceptive pain were more than four times more likely than those with neuropathic pain to show clinically meaningful improvement on multiple outcomes, while those participants who were older were more likely to be multidomain responders. Conclusions: Physical, psychological, and social outcomes all improved in a significant proportion of participants following the IPM. High baseline depression was a clinically reliable predictor of individual-level improvement. Individuals with nociceptive pain and those who were older, respectively, showed the largest response across multiple outcomes and domains.

Athletes' age, sex, and years of education moderate the acute neuropsychological impact of sports-related concussion: a meta-analysis.

The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1-10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = -0.54, -1.10, and -1.14, respectively). During this interval, females (d = -0.87), adolescent athletes competing in high school competitions (d = -0.60), and those with 10 years of education (d = -1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = -0.42), adults (d = -0.25), athletes competing at other levels of competition (d = -0.43 to -0.41), or those with 16 years of education (d = -0.15), respectively. However, these sub-groups' differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed.

Do injury characteristics predict the severity of acute neuropsychological deficits following sports-related concussion? A meta-analysis.

The utility of injury characteristics for predicting the severity of post-concussion outcomes remains equivocal. The purpose of this meta-analysis was to quantify the predictive relationship between these variables to inform classification of acute injury severity. Thirty-one empirical samples of concussed athletes, for which rates of loss of consciousness and/or amnesia were reported, were included in a meta-analysis evaluating acute outcomes following sports-related concussion. Outcome measures of interest were neuropsychological tests first administered 1-10 days post-injury. Loss of consciousness and anterograde amnesia significantly predicted more severe neuropsychological deficits within 10 days of concussion in studies using pre-injury baseline, but not control group, comparisons. Retrograde amnesia significantly predicted acute neuropsychological dysfunction (d = -1.03) irrespective of comparison group. Although small sample sizes require conservative interpretation and future replication, the evidence suggests that retrograde amnesia, rather than loss of consciousness, may be used to classify the acute severity of concussion.

Return-to-driving expectations following mild traumatic brain injury.

AIM: Although individuals recovering from mild traumatic brain injury (MTBI) could pose a risk to road safety, little is known about their intentions regarding return-to-driving. Reported are the expectations of a sample of emergency department patients with MTBI regarding their recovery and return-to-driving. METHOD: Eighty-one patients with MTBI were recruited from an emergency department. Participants completed an 11-item questionnaire measuring expectations regarding recovery from injury; five of the items addressed return-to-driving. RESULTS: Only 48% of the sample intended to reduce their driving following their injury. However, those that did intend to reduce their driving nominated a mean duration of 16.59 days (SD = 31.68) of reduced exposure. A logistic regression found that previous head injury experience and an interaction between pain and previous head injury experience predicted intentions to reduce driving. Similarly, a multiple regression revealed that pain level contributed significantly to the variance in time estimates of return-to-driving. CONCLUSION: The finding that half the individuals recovering from MTBI do not intend to moderate their driving exposure post-injury is cause for concern, as another study has shown that driving performance is compromised in this group immediately after injury.

Assessment of drivers' ability to anticipate traffic hazards after traumatic brain injury.

OBJECTIVES: The aim of this study was to examine the effect of traumatic brain injury (TBI) on drivers' ability to anticipate traffic hazards. Slower anticipation of hazards has been associated with higher crash rates, but this driving skill has never been assessed after TBI. METHODS: The anticipatory ability of 31 drivers with TBI and 24 age-matched uninjured controls was assessed with a validated drivers' Hazard Perception Test. The Hazard Perception Test displayed videos of genuine traffic scenes filmed from the driver's perspective, and participants had to respond as soon as they anticipated a traffic hazard in a scene. The primary dependent measure was mean response latency. RESULTS: Participants with TBI were significantly slower to anticipate traffic hazards than controls (p<0.001). Within the TBI group, while hazard perception response times were significantly related to duration of post-traumatic amnesia (Spearman ρ=0.63; p<0.001), they were not significantly related to Glasgow Coma Scale scores (r=-0.19; p=0.33). Also, participants with a complicated mild TBI were significantly faster in anticipating traffic conflicts than participants with moderate to severe TBI (p=0.04). CONCLUSIONS: Individuals with TBI were slower to anticipate traffic hazards than age-matched uninjured controls. This finding signifies the need for hazard perception testing and training as part of driving rehabilitation after TBI.

Driving after concussion: the acute effect of mild traumatic brain injury on drivers' hazard perception.

OBJECTIVE: No research has examined whether individuals recovering from a recent mild traumatic brain injury (MTBI) are safe to drive, despite cognitive impairment being a common consequence soon after MTBI. This study examined the acute effect of MTBI on drivers' hazard perception, which is defined as drivers' ability to search the road ahead to rapidly identify potentially dangerous traffic situations. Poorer hazard perception has been associated with higher crash rates in a number of studies. METHOD: Forty-two patients with MTBI and 43 patients with minor orthopedic injuries were recruited from the emergency department of a large metropolitan hospital within 24 hours of injury. Participants completed a computerized hazard perception test, in which they watched videos of genuine traffic scenes filmed from the driver's point of view. They were required to use the computer mouse to click on potential traffic hazards as early as possible. RESULTS: Participants with MTBI were significantly slower to respond to traffic hazards than participants with minor orthopedic injuries (p = .03, d = .48). CONCLUSIONS: This study provides the first indication that within the acute stage postinjury, MTBI is associated with impairment in a crash-related component of driving. This suggests that patients with MTBI should be advised to refrain from driving for at least the first 24 hours' postinjury.

Improved sensitivity of the rapid screen of mild traumatic brain injury.

This study aimed to investigate the acute effects of mild traumatic brain injury (mTBI) in an emergency department sample. A total of 246 (186 male, 60 female) cases of mTBI and 102 (65 male and 37 female) cases of orthopedic injuries were tested within 24 hours of injury. Mild TBI patients performed more poorly on all subtests of the Rapid Screen of Concussion (RSC) and completed fewer symbols on Digit Symbol than did orthopedic controls. RSC scores predicted group membership better than chance, and Digit Symbol scores contributed significantly to predicting group membership over and above the contribution of the RSC, resulting in 70.4% sensitivity and 74% specificity for the extended protocol. The results of this study indicate that learning and memory, orientation, and speed of information processing are impaired immediately following mTBI. Furthermore, a brief battery of tests that include word recall, orientation, and the Digit Symbol Substitution Test could assess the severity of dysfunction following mTBI, and assist in clinical decision making regarding discharge, return to routine activities, and management of the effects of injury.

Emergency department assessment of mild traumatic brain injury and the prediction of postconcussive symptoms: a 3-month prospective study.

OBJECTIVE: To investigate the utility of a brief emergency department (ED) bedside screen for the prediction of postconcussive symptoms at 3 months following mild traumatic brain injury (MTBI). PARTICIPANTS: One hundred patients with MTBI (78% men; mean age = 33.6 years); 2 control groups (each n = 100), a "minor nonhead injury" group (77% men; mean age = 32.2 years) and an "uninjured ED visitor" group (78% men; mean age = 33.6 years). MAIN MEASURES: Brief measures of neuropsychological functioning, acute pain, and postural stability were collected in the ED; telephone follow-up at 3 months using the Rivermead Post-Concussion Symptoms Questionnaire was undertaken. RESULTS: Neuropsychological deficits, acute pain, and postural instability in the ED were significantly associated with postconcussive symptoms at 3-month follow-up. A regression formula using 3 easily obtainable measures obtained during acute stage of injury-immediate and delayed memory for 5 words and a visual analog scale score of acute headache-provided 80% sensitivity and 76% specificity for the prediction of clinically significant symptoms at 3 months postinjury. CONCLUSION: A small combination of variables assessable in the ED may predict MTBI patients likely to experience persistent postconcussive symptoms.

Genetic influences on handedness: data from 25,732 Australian and Dutch twin families.

Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

Genetic covariation among facets of openness to experience and general cognitive ability.

Genetic and environmental sources of covariation among cognitive measures of verbal IQ, performance IQ (PIQ), academic achievement, 2-choice reaction time (CRT), inspection time (IT) and the 6 Openness facets of the NEO Personality Inventory-Revised (NEO PI-R) were examined. The number of twin and twin-sibling pairs ranged from 432 (182 MZ, 350 DZ/sibling) to 1023 (273 MZ, 750 DZ/sibling) for cognitive measures, and between 432 (90 MZ, 342 DZ/sibling) - 437 (91 MZ, 346 DZ/sibling) for Openness facets. Structural equation modeling best supported a model with a 3-factor additive genetic structure. A genetic general factor subsumed the 5 cognitive measures and 5 of the 6 Openness facets (Actions did not load significantly). A second additive genetic factor incorporated the 6 Openness facets, and a third additive genetic factor incorporated the 5 cognitive measures. Specific additive and dominance genetic effects were also evident, as were shared common and shared unique environmental influences, and specific unique environmental effects. The Openness facets of Ideas and Values evidenced the strongest phenotypic correlations with cognitive indices, particularly verbal measures. The genetic correlations among Openness facets and cognitive measures ranged from -.06 to .79. Results were interpreted as suggesting that Openness is related to general cognitive ability (g) through a genetic mechanism and that gengenders a minor but discernable disposition towards Openness for the majority of facets.

QTLs identified for P3 amplitude in a non-clinical sample: importance of neurodevelopmental and neurotransmitter genes.

BACKGROUND: The P3(00) event-related potential is an index of processing capacity (P3 amplitude) and stimulus evaluation (P3 latency) as well as a phenotypic marker of various forms of psychopathology where P3 abnormalities have been reported. METHODS: A genome-wide linkage scan of 400-761 autosomal markers, at an average spacing of 5-10 centimorgans (cM), was completed in 647 twins/siblings (306 families mostly comprising dizygotic twins), mean age 16.3, range 15.4-20.1 years, for whom P3 amplitude and latency data were available. RESULTS: Significant linkage for P3 amplitude was observed on chromosome 7q for the central recording site (logarithm-of-odds [LOD] = 3.88, p = .00002) and in the same region for both frontal (LOD = 2.19, p = .0015) and parietal (LOD = 1.67, p = .0053) sites, with multivariate analysis also identifying linkage in this region (LOD = 2.14, p = .0017). Suggestive linkage was also identified on 6p (LOD(max) = 2.49) and 12q (LOD(max) = 2.24), with other promising regions identified on 9q (LOD(max) = 2.14) and 10p (LOD(max) = 2.18). Less striking were the results for P3 latency; LOD > 1.5 were found on chromosomes 1q, 9q, 10q, 12q, and 19p. CONCLUSIONS: This is a first step in the identification of genes for normal variation in the P3. Loci identified here for P3 amplitude suggest the possible importance of neurodevelopmental genes in addition to those influencing neurotransmitters, fitting with the evidence that P3 amplitude is sensitive to diverse types of brain abnormalities.

Memory systems involved in professional skills: a case of dense amnesia due to herpes simplex viral encephalitis.

JL, a 25-year-old physiotherapist, became densely amnesic following herpes simplex viral encephalitis (HSVE), causing bilateral damage to medial and ventral areas of her frontal and temporal lobes and their associated circuitry. Three years post-onset, her WAIS-R full scale IQ (Verbal 74, Performance 102) showed an estimated loss of +/- 50 points. She displayed severe global amnesia and markedly impaired social cognition. However, her immediate memory, perceptual priming, and cognitive problem-solving abilities were relatively spared. Her retention of professional skills was assessed using simulated physiotherapy scenarios. JL was able to demonstrate some procedural skills spontaneously, but was unable to apply them precisely and flexibly to individual patient needs. She showed no memory of theoretical or propositional physiotherapy knowledge, and could neither plan treatment nor reason clinically. Her performance was well below that of four other physiotherapists who had also not practised for 4 years. Thus, despite the relative sparing of her implicit memory, JL's performance lacked the co-ordinated operation of declarative and implicit long-term memory and the links to working memory that are necessary for the flexible performance of complex professional procedures.

The contribution of pre-existing depression to the acute cognitive sequelae of mild traumatic brain injury.

PRIMARY OBJECTIVE: To determine the effect of pre-existing depression on the cognitive sequelae of mild traumatic brain injury (mTBI) within 24 hours of injury. RESEARCH DESIGN: A 2 x 2 between-subjects design was used to examine the effect of depression and injury type on neuropsychological test performance. The independent variables were the injury type (mTBI or control) and the presence of depression (depressed or not depressed). METHODS AND PROCEDURES: Participants who had sustained mTBI (30 with depression, 30 without depression) within the previous 24 hours and control participants (19 with depression, 30 without depression) were assessed on the Digit Symbol Substitution Test (DSS), Hopkins Verbal Learning Test (HVLT) and the Speed of Comprehension Test. RESULTS: Participants with mTBI performed worse than controls on the tests, particularly HVLT delayed recall and DSS total correct. Participants with depression did not perform worse than participants without depression. However, there was a significant univariate interaction for HVLT recognition, participants who had sustained mTBI and were classified in the depressed group exhibited worse recognition compared to mTBI participants without depression. CONCLUSIONS: The results indicate that depression may interact with mTBI to impair word recognition during the acute phase after a head injury.

Common and specific genetic influences on EEG power bands delta, theta, alpha, and beta.

It is difficult to study the genetic basis of psychological function/dysfunction due to its etiological complexity. Instead, we studied a biological marker, EEG power, which is associated with various psychological phenotypes and is closer to gene function. Previous studies have consistently demonstrated high heritability of EEG band power, but less is known about how common or specific genes influence each power band. For 519 adolescent twin pairs, spectral powers were calculated for delta, theta, alpha, and beta bands at bilateral occipital and frontal sites. All four bands were entered into a multivariate genetic model, with occipital and frontal sites modelled separately. Variance was decomposed into additive (A) and dominant (D) genetic factors, and common (C) and unique (E) environmental factors. Band heritabilities were higher at occipital (0.75-0.86) than frontal sites (0.46-0.80). Both common and specific genetic factors influenced the bands, with common genetic and specific genetic factors having more influence in the occipital and frontal regions, respectively. Non-additive genetic effects on beta power and a common environment effect on delta, theta, and alpha powers were observed in the frontal region.

The rapid screen of concussion: an evaluation of the non-word repetition test for use in mTBI research.

PRIMARY OBJECTIVES: (1) To investigate the Nonword Repetition test (NWR) as an index of sub-vocal rehearsal deficits after mild traumatic brain injury (mTBI); (2) to assess the reliability, validity and sensitivity of the NWR; and (3) to compare the NWR to more sensitive tests of verbal memory. RESEARCH DESIGN: An independent groups design. METHODS AND PROCEDURES: Study 1 administered the NWR to 46 mTBI and 61 uninjured controls with the Rapid Screen of Concussion (RSC). Study 2 compared mTBI, orthopaedic and uninjured participants on the NWR and the Hopkins Verbal Learning Test (HVLT-R). MAIN OUTCOMES AND RESULTS: The NWR did not improve the diagnostic accuracy of the RSC. However, it is reliable and indexes sub-vocal rehearsal speed. These findings provide evidence that although the current form of the NWR lacks sensitivity to the impact of mTBI, the development of a more sensitive test of sub-vocal rehearsal deficits following mTBI is warranted.

Emergency department assessment of mild traumatic brain injury and prediction of post-concussion symptoms at one month post injury.

Mild traumatic brain injury (mTBI) is a common injury and a significant proportion of those affected report chronic symptoms. This study investigated prediction of post-concussion symptoms using an Emergency Department (ED) assessment that examined neuropsychological and balance deficits and pain severity of 29 concussed individuals. Thirty participants with minor orthopedic injuries and 30 ED visitors were recruited as control subjects. Concussed and orthopedically injured participants were followed up by telephone at one month to assess symptom severity. In the ED, concussed subjects performed worse on some neuropsychological tests and had impaired balance compared to controls. They also reported significantly more post-concussive symptoms at follow-up. Neurocognitive impairment, pain and balance deficits were all significantly correlated with severity of post-concussion symptoms. The findings suggest that a combination of variables assessable in the ED may be useful in predicting which individuals will suffer persistent post-concussion problems.

Handedness in twins: joint analysis of data from 35 samples.

Simultaneous analysis of handedness data from 35 samples of twins (with a combined sample size of 21,127 twin pairs) found a small but significant additive genetic effect accounting for 25.47% of the variance (95% confidence interval [CI] 15.69-29.51%). No common environmental influences were detected (C = 0.00; 95% CI 0.00-7.67%), with the majority of the variance, 74.53%, explained by factors unique to the individual (95% CI 70.49-78.67%). No significant heterogeneity was observed within studies that used similar methods to assess handedness, or across studies that used different methods. At an individual level the majority of studies had insufficient power to reject a purely unique environmental model due to insufficient power to detect familial aggregation. This lack of power is seldom mentioned within studies, and has contributed to the misconception that twin studies of handedness are not informative.

A linkage study of academic skills defined by the Queensland core skills test.

This study used genome-wide linkage analysis to detect Quantitative Trait Loci (QTLs) implicated in variation in general academic achievement as measured by the Queensland Core Skills Test (QCST) (Queensland Studies Authority, 2004). Data from 210 families were analysed. While no empirically derived significant or suggestive peaks for general academic achievement were indicated a peak on chromosome 2 was observed in a region where Posthuma et al. (2005) reported significant linkage for Performance IQ (PIQ) and suggestive linkage for Full Scale IQ (FSIQ), and Luciano et al. (this issue) observed significant linkage for PIQ and word reading. A peak on chromosome 18 was also observed approximately 20 cM removed from a region recently implicated in reading achievement. In addition, on chromosomes 2 and 18 peaks for a number of specific academic skills, two of which were suggestive, coincided with the general academic achievement peaks. The findings suggest that variation in general academic achievement is influenced by genes on chromosome 2 which have broad influence on a variety of cognitive abilities.

Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample.

To further clarify the mode of genetic transmission on individual alpha frequency (IAF) and alpha power, the extent to which individual differences in these alpha indices are influenced by genetic factors were examined in a large sample of adolescent twins (237 MZ, 282 DZ pairs; aged 16). EEG was measured at rest (eyes closed) from the right occipital site, and a second EEG recording for 50 twin pairs obtained approximately 3 months after the initial collection, enabled an estimation of measurement error. Analyses confirmed a strong genetic influence on both IAF (h(2)=0.81) and alpha power (h(2)=0.82), and there was little support for non-additive genetic (dominance) variance. A small but significant negative correlation (-0.18) was found between IAF and alpha power, but genetic influences on IAF and alpha power were largely independent. All non-genetic variance was due to unreliability, with no significant variance attributed to unique environmental factors. Relationships between the alpha and IQ indices were also explored but were generally either non-significant or very low. The findings confirm the high heritability for both IAF and alpha power, they further suggest that the mode of genetic transmission is due to additive genetic factors, that genetic influences on the underlying neural mechanisms of alpha frequency and power are largely specific, and that individual differences in alpha activity are influenced little by developmental plasticity and individual experiences.