High Sleep Disturbance and Longer Concussion Duration in Repeat Concussions.

Objectives: The relationship between repeated concussions and sleep disturbance is yet to be fully understood. The objective of this study was to examine the relationship between sleep disturbance, concussion duration, and repeated concussions by assessing postconcussive symptoms and cognition. Methods: Subjects (ages 13-33 years) underwent postconcussion cognitive function evaluation and reported postconcussion symptoms including severity of disturbed sleep (drowsiness, trouble falling asleep, sleeping more than usual, and sleeping less than usual), mood disturbance (sadness, irritability, nervousness, and emotional lability), and headache. Data on cognitive function and concussive symptoms were collected for 430 subjects after first concussion, 192 subjects after second concussion, and 118 subjects after three or more concussions. A subset of subjects (119) were monitored longitudinally to assess concussion duration. Analyses included group comparisons, regression, and correlation; data were adjusted for age and gender. Results: Sleep disturbance differed significantly by group (mean[SEM]: 1st concussion = 2.56[0.2]; 2nd concussion = 3.65[0.34]; 3+ concussions = 4.32[0.43]). Concussion history predicts concussion duration (R2 = 0.20, F[1,116] = 27.33, p < 0.001). Furthermore, trouble falling asleep (ß = 0.15) and sleeping less than usual (ß = 0.15) predicted concussion duration (R2 = 0.062, F[1,116] = 3.15, p = 0.047). Reported sleep disturbance after repeated concussions was higher in patients with higher headache (F[2,732] = 3.15, p = 0.043) and mood disturbance (F[2,733] = 3.35, p = 0.036) severity. In addition, after repeated concussions, the positive correlation between sleep disturbance and cognitive dysfunction strengthened. Conclusions: History of repeated concussion is associated with longer concussion duration and higher reported sleep disturbance. Furthermore, those with sleep disturbance after repeated concussion exhibit more severe headaches, mood disturbance, and cognitive dysfunction.Abbreviations: ImPACT: Immediate Postconcussion Assessment and Cognitive Assessment (ImPACT); this is a computer-based test that assesses an individual's cognitive function and cumulatively documents current concussion symptoms. PCSS: Post Concussion Symptom Scale; this scale assesses the severity of concussion symptoms. SPSS: Statistical Package for Social Sciences. This is a statistical software package.

The role of task-based neural activation research in understanding cognitive deficits in pediatric epilepsy.

Children with epilepsy can experience significant cognitive dysfunction that can lead to academic underachievement. Traditionally believed to be primarily due to the effects of factors such as the chronicity of epilepsy, medication effects, or the location of the primary epileptogenic lesion;, recent evidence has indicated that disruption of cognition-specific distributed neural networks may play a significant role as well. Specifically, over the last decade, researchers have begun to characterize the mechanisms underlying disrupted cognitive substrates by evaluating neural network abnormalities observed during specific cognitive tasks, using task-based functional magnetic resonance imaging (fMRI). This targeted review assesses the current literature investigating the relationship between neural network abnormalities and cognitive deficits in pediatric epilepsy. The findings indicate that there are indeed neural network abnormalities associated with deficits in executive function, language, processing speed, and memory. Overall, cognitive dysfunction in pediatric epilepsy is associated with a decrease in neural network activation/deactivation as well as increased recruitment of brain regions not typically related to the specific cognitive task under investigation. The research to date has focused primarily on children with focal epilepsy syndromes with small sample sizes and differing research protocols. More extensive research in children with a wider representation of epilepsy syndromes (including generalized epilepsy syndromes) is necessary to fully understand these relationships and begin to identify underlying cognitive phenotypes that may account for the variability observed across children with epilepsy. Furthermore, more uniformity in fMRI protocols and neuropsychological tasks would be ideal to advance this literature.

Irregular Sleep-Wake Rhythm Disorder.

This article focuses on irregular sleep-wake rhythm disorder (ISWRD) and its associations with several other comorbidities. Irregular sleep-wake rhythm disorder is a circadian disorder characterized by a lack of a clear sleep-wake pattern. The disorder has yet to be fully understood from pathophysiologic perspective. Treatments are available, but there is a need for development of novel interventions. The goal of this article is to focus on multiple aspects of ISWRD.

The Timing, Nature, and Range of Neurobehavioral Comorbidities in Juvenile Myoclonic Epilepsy.

BACKGROUND: Accumulating evidence suggests that considerable cognitive and psychiatric comorbidity is associated with juvenile myoclonic epilepsy, for which the etiology remains controversial. Our goal was to comprehensively characterize the status of multiple neurobehavioral comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy, before effects of chronic seizures and medications. METHODS: A total of 111 children aged eight to 18 years (41 new- or recent-onset juvenile myoclonic epilepsy and 70 first-degree cousin controls) underwent neuropsychological assessment (attention, executive, verbal, perceptual, speed), structured review of need for supportive academic services, parent reports of behavior and executive function (Child Behavior Checklist and Behavior Rating Inventory of Executive Function), and formal structured psychiatric interview and diagnosis (Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version). RESULTS: Children with juvenile myoclonic epilepsy performed worse than controls across all tested cognitive domains (F(1,105) = 3.85, P < 0.01), utilized more academic services (47% versus 19%, P = 0.002), had more parent-reported behavioral problems and dysexecutive function with lower competence (P < 0.001), and had a higher prevalence of current Axis I diagnoses (attention-deficit/hyperactivity disorder, depression, and anxiety; 54% versus 23%, P = 0.001). Academic and psychiatric problems occurred antecedent to epilepsy onset compared with comparable timeline in controls. CONCLUSION: Comprehensive assessment of cognitive, academic, behavioral, and psychiatric comorbidities in youth with new- or recent-onset juvenile myoclonic epilepsy reveals a pattern of significantly increased neurobehavioral comorbidities across a broad spectrum of areas. These early evident comorbidities are of clear clinical importance with worrisome implications for future cognitive, behavioral, and social function. It is important for health care providers to avoid delays in intervention by assessing potential comorbidities early in the course of the disorder to optimize their patients' social, academic and behavioral progress.

Default mode network deactivation in pediatric temporal lobe epilepsy: Relationship to a working memory task and executive function tests.

OBJECTIVES: Children with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. There is limited evidence of different functional network alterations associated with this clinical executive dysfunction. This study investigates working memory deficits in children with TLE by assessing deactivation of the default mode network (DMN) on functional Magnetic Resonance Imaging (fMRI) and the relationship of DMN deactivation with fMRI behavioral findings and neuropsychological test performance. EXPERIMENTAL DESIGN: fMRI was conducted on 15 children with TLE and 15 healthy controls (age: 8-16 years) while performing the N-back task in order to assess deactivation of the DMN. N-back accuracy, N-back reaction time, and neuropsychological tests of executive function (Delis-Kaplan Executive Function System [D-KEFS] Color-Word Interference and Card Sort tests) were also assessed. PRINCIPAL OBSERVATIONS: During the N-back task, children with TLE exhibited significantly less deactivation of the DMN, primarily in the precuneus/posterior cingulate cortex compared with controls. These alterations significantly correlated with N-back behavioral findings and D-KEFS results. CONCLUSIONS: Children with TLE exhibit executive dysfunction which correlates with DMN alterations. These findings suggest that the level of deactivation of specific functional networks may contribute to cognitive impairment in children with TLE. The findings also indicate that children with TLE have network alterations in extratemporal lobe brain regions.

Executive dysfunction is associated with an altered executive control network in pediatric temporal lobe epilepsy.

OBJECTIVES: Children with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. However, there is limited evidence of neural network alterations associated with this clinical executive dysfunction. The objective of this study was to characterize working memory deficits in children with TLE via activation of the executive control network on functional magnetic resonance imaging (fMRI) and determine the relationships to fMRI behavioral findings and traditional neuropsychological tests. EXPERIMENTAL DESIGN: Functional magnetic resonance imaging was conducted on 17 children with TLE and 18 healthy control participants (age 8-16 years) while they performed the N-back task in order to assess activation of the executive control network. N-back accuracy, N-back reaction time, and traditional neuropsychological tests (Delis-Kaplan Executive Function System [D-KEFS] color-word interference and card-sort test) were also assessed. PRINCIPAL OBSERVATIONS: Children with TLE exhibited executive dysfunction on D-KEFS testing, reduced N-back accuracy, and increased N-back reaction time compared with healthy controls; D-KEFS and N-back behavioral findings were significantly correlated. Children with TLE also exhibited significant reduction in activation of the frontal lobe within the executive control network compared to healthy controls. These alterations were significantly correlated with N-back behavioral findings and D-KEFS testing. CONCLUSIONS: Children with TLE exhibit executive dysfunction, which correlates with executive control network alterations. This lends validity to the theory that the executive control network contributes to working memory function. The findings also indicate that children with TLE have network alterations in nontemporal brain regions.

Postconcussive Symptoms After Single and Repeated Concussions in 10- to 20-Year-Olds: A Cross-Sectional Study.

The objective was to characterize cognitive deficits and postconcussive symptoms in a pediatric population with no concussion, a single concussion, and ≥2 concussions, using a cross-sectional design. Cognitive function and postconcussive symptoms were assessed in participants (age 10-20) with no concussion (n = 1118), single concussion (n = 368), and repeated (≥2) concussions (n = 252). Analyses were adjusted for age and gender. Individuals with ≥2 concussions exhibited more total postconcussive symptoms; more loss of consciousness, amnesia and confusion; more headaches; and poorer cognitive function compared to no concussion and single concussion. Postconcussive symptoms may play a modulatory role in cognitive dysfunction after repeated concussions as those with loss of consciousness, amnesia, confusion, or headaches exhibited worse verbal memory, visual memory, visual-motor processing, and poorer impulse control compared to those without these symptoms. This analysis demonstrates that repeated concussions is associated with poorer cognitive function and postconcussive symptoms compared to a single concussion.

Gender differences in sleep symptoms after repeat concussions.

OBJECTIVES: There are notable gender differences in concussion as well as sleep. Sleep disturbance is a major symptom of post-concussive syndrome. The interplay between sleep disturbance, concussion, and gender has yet to be examined. The objective of this study was to determine whether sleep disturbance plays a role in the known gender differences associated with concussion. METHODS: Males and females (ages 10-35 years) completed a pre-concussion and post-concussion evaluation. Levels of sleep disturbance were assessed at baseline (N = 1284), after first concussion (N = 432) and after repeated concussions (one or more concussions, N = 296). Sleep disturbance levels were also compared among males and females with headaches, mood changes, and cognitive dysfunction. Analyses included group comparisons and correlations of post-concussive symptoms and cognitive dysfunction, respectively. Data was adjusted for age. RESULTS: Compared to males, females reported higher levels of sleep disturbance after a single concussion; however, levels of sleep disturbance equalized after repeated concussions. Females with higher levels of sleep disturbance had more headaches and more mood changes requiring medical treatment, compared to males. In addition, sleep disturbance was more strongly correlated with cognitive dysfunction in females compared to males. CONCLUSION: Gender differences in concussion recovery after repeat concussions may be primarily due to a difference in sleep disturbance between the genders. This difference in sleep appears to moderate the levels of other post-concussive symptoms. This indicates that sleep disturbance should be closely monitored and treated in females after a concussion. Further studies are required to determine the underlying reasons for these gender differences.

Gender Differences in Concussion and Postinjury Cognitive Findings in an Older and Younger Pediatric Population.

BACKGROUND: Studies have documented gender differences associated with concussion. The purpose of this study was to determine if these gender differences are also noted within a pediatric population. METHODS: This prospective study analyzed 1971 patients who had completed preconcussion and postconcussion neuropsychological testing within the Washington, DC, area. RESULTS: Our results showed that children and adolescents with concussion exhibit gender differences with respect to risk factors, recovery, and symptomatology. Females are more likely to present with a concussion (P < 0.001), experience more discomfort from a concussion (P < 0.001), and seek treatment for postconcussive headaches (P < 0.001). On the other hand, males are more likely to sustain a concussion from a contact sport (P < 0.001) and experience loss of consciousness, confusion, and amnesia with a concussion more frequently than females (P < 0.001). Postconcussive cognitive function also differs by gender. Both males and females exhibit a decline in cognitive testing compared with baseline (P < 0.001); however, visual memory (P = 0.02) is more affected in females than in males. These findings remain unchanged among pediatric patients aged ≥14 years; however, no gender differences were noted in individuals aged ≤13 years. CONCLUSION: It is important for health care providers, schools, athletic trainers, and coaches to be aware of these gender differences associated with concussion in order to provide adequate surveillance and appropriate monitoring and support during the recovery period.

The efficacy of three different mask styles on a PAP titration night.

BACKGROUND: This study compared the efficacy of three different masks, nasal pillows, nasal masks and full face (oronasal) masks, during a single night of titration with continuous positive airway pressure (CPAP). METHODS: Fifty five subjects that included men (n=33) and women (n=22) were randomly assigned to one of three masks and underwent a routine titration with incremental CPAP applied through the different masks. RESULTS: CPAP applied through the nasal pillows and nasal mask was equally effective in treating mild, moderate, and severe sleep apnea. However, CPAP applied through the oronasal mask required a significantly higher pressure compared to nasal masks to treat moderately severe (2.8 cm of H(2)O ± 2.1 SD) and severe (6.0 cm of H(2)O ± 3.2 SD) obstructive sleep apnea. CONCLUSION: CPAP applied with either nasal mask was effective in treating mild, moderate, and severe sleep apnea. The oronasal mask required significantly higher pressures in subjects with moderate to severe disease. Therefore, when changing from a nasal to an oronasal mask, a repeat titration is required to ensure effective treatment of sleep apnea, especially in patients with moderate to severe disease.

Independent and additive contributions of postvictory testosterone and social experience to the development of the winner effect.

The processes through which salient social experiences influence future behavior are not well understood. Winning fights, for example, can increase the odds of future victory, yet little is known about the internal mechanisms that underlie such winner effects. Here, we use the territorial California mouse (Peromyscus californicus) to investigate how the effects of postvictory testosterone (T) release and winning experience individually mediate positive changes in future winning ability and antagonistic behavior. Male mice were castrated and implanted with T capsules to maintain basal levels of this hormone. We found that males form a robust winner effect if they win three separate territorial disputes and experience a single T surge roughly 45 min after each encounter. Meanwhile, males exhibit only an intermediate winner effect if they either 1) acquire three previous wins but do not experience a change in postvictory T or 2) acquire no previous wins but experience three separate T pulses. The results indicate that the effect of postvictory T must be coupled with that of winning experience to trigger the maximum positive shift in winning ability, which highlights the importance of social context in the development of the winner effect. At the same time, however, postvictory T and winning experience are each capable of increasing future winning ability independently, and this finding suggests that these two factors drive plasticity in antagonistic behavior via distinct mechanistic channels. More broadly, our data offer insight into the possible ways in which various species might be able to adjust their behavioral repertoire in response to social interactions through mechanisms that are unlinked from the effects of gonadal steroid action.

The nature and extent of cerebellar atrophy in chronic temporal lobe epilepsy.

PURPOSE: Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. METHODS: Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). KEY FINDINGS: There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p's > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. SIGNIFICANCE: Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

Testosterone release and social context: when it occurs and why.

The functions of rapid increases in testosterone seem paradoxical because they can occur in response to different social contexts, such as male-male aggressive encounters and male-female sexual encounters. This suggests that context may impact the functional consequences of changes in testosterone, whether transient or long term. Many studies, including those with California mice (Peromyscus californicus), have addressed these issues using manipulations and species comparisons, but many areas remain to be investigated. We report a study here that suggests transient increases in testosterone after social competition influence future competitive behavior, but social experience alone may also be critical in determining future behavior. In other rodents, a comparable testosterone surge occurs in response to sexual stimulation, but the function is not entirely understood. In addition to competitive and sexual behavior, testosterone impacts other systems instrumental to social behaviors, including paternal behavior and degree of monogamy. Thus, mechanisms regulated by testosterone, such as the vasopressin and aromatase systems, may also be influenced by rapid surges of testosterone in aggressive or sexual contexts. We discuss how the functions of testosterone may overlap in some contexts.

Weak winner effect in a less aggressive mammal: correlations with corticosterone but not testosterone.

We investigated the existence of the "winner effect" (winning an aggressive encounter following previous victories) and an associated rise in testosterone (T) in the white-footed mouse (Peromyscus leucopus) which generally display low levels of aggression and territoriality. We compared the effect of previously winning three, two, one, or zero resident-intruder encounters on the likelihood of winning a subsequent aggressive encounter. Although 50% of males were removed during training because of peaceful encounters, the winner effect was weak and not significant. We hypothesize that territoriality/aggression may be associated with the strength of the winner effect and discuss whether the slight winner effect exhibited by P. leucopus may become significant when population densities increase and males become more territorial. There was also no associated change in T with winning; however, corticosterone (Cort) changed with experience as winners had low Cort levels compared to losers and controls. Furthermore, low Cort levels in winners were associated with quicker attack latencies. These results contrast with findings of a significant winner effect and increase in T in males of the highly territorial and aggressive California mouse (Peromyscus californicus) using an identical methodology. California mice also attacked their opponents at more caudal regions of the body compared to white-footed mice that attacked their opponents at more rostral regions of the body, possibly related to different levels/types of aggression expressed by the two species.

Winning fights elevates testosterone levels in California mice and enhances future ability to win fights.

The 'winner effect' has been studied in a variety of species, but only rarely in mammals. We compared effects of winning three, two, one, or zero resident-intruder encounters on the likelihood of winning a subsequent aggressive encounter in the California mouse (Peromyscus californicus). During the training phase, we ensured that resident males won all encounters by staging contests with mildly sedated, smaller intruders. During the test phase, the resident male encountered an unfamiliar, more evenly matched intruder that had experience winning an encounter and was larger than the resident. Testosterone (T) plasma levels significantly increased after the final test when they had experienced two prior winning encounters, and the probability of winning a future encounter increased significantly after three prior wins independent of intrinsic fighting ability. We hypothesize a 'winner-challenge' effect in which increased T levels serve to reinforce the winner effect in male California mice.

Quantitative measurement of cortical surface features in localization-related temporal lobe epilepsy.

Differences in cortical surface features between healthy controls (n = 48) and patients with temporal lobe epilepsy (n = 46), ages 14-59, were characterized by means of advanced quantitative MRI processing techniques. Cortical surface features of interest included gyral and sulcal curvature, cortical depth, and total cortical surface area. Epilepsy patients and controls differed on measures of gyrification; the abnormalities generalized despite the focal nature of the primary epileptic process. Changes in cortical surface features were associated with increasing chronological age in both groups. Abnormalities in gyrification were associated with cognitive performance and with other morphometric measurements (e.g., surface cerebral spinal fluid). These findings are related to the literature regarding morphometric changes associated with temporal lobe epilepsy and normal aging.