Toward precision brain health: accurate prediction of a cognitive index trajectory using neuroimaging metrics.

The goal of precision brain health is to accurately predict individuals' longitudinal patterns of brain change. We trained a machine learning model to predict changes in a cognitive index of brain health from neurophysiologic metrics. A total of 48 participants (ages 21-65) completed a sensorimotor task during 2 functional magnetic resonance imaging sessions 6 mo apart. Hemodynamic response functions (HRFs) were parameterized using traditional (amplitude, dispersion, latency) and novel (curvature, canonicality) metrics, serving as inputs to a neural network model that predicted gain on indices of brain health (cognitive factor scores) for each participant. The optimal neural network model successfully predicted substantial gain on the cognitive index of brain health with 90% accuracy (determined by 5-fold cross-validation) from 3 HRF parameters: amplitude change, dispersion change, and similarity to a canonical HRF shape at baseline. For individuals with canonical baseline HRFs, substantial gain in the index is overwhelmingly predicted by decreases in HRF amplitude. For individuals with non-canonical baseline HRFs, substantial gain in the index is predicted by congruent changes in both HRF amplitude and dispersion. Our results illustrate that neuroimaging measures can track cognitive indices in healthy states, and that machine learning approaches using novel metrics take important steps toward precision brain health.

Novel Oppositional Defiant Disorder or Conduct Disorder 24 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI). METHODS: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury. RESULTS: Of the children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified who were recruited in this study, 165 were included in this sample; 95 of these children returned for the 24-month assessment. Multiple imputation was used to address attrition. The prevalence of novel oppositional defiant disorder or conduct disorder was 23.7 out of 165 (14%). In univariable analyses, novel oppositional defiant disorder or conduct disorder was significantly associated with psychosocial adversity (p=0.049) and frontal white matter lesions (p=0.016) and was marginally but not significantly associated with SES. In the final multipredictor model, frontal white matter lesions were significantly associated with novel oppositional defiant disorder or conduct disorder (p=0.021), and psychosocial adversity score was marginally but not significantly associated with the outcome. The odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel depressive disorder was significantly higher for girls than boys (p=0.025), and the odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel attention-deficit hyperactivity disorder (ADHD) was significantly higher for boys than girls (p=0.006). CONCLUSION: Approximately 14% of children with TBI developed oppositional defiant disorder or conduct disorder. The risk for novel oppositional defiant disorder or conduct disorder can be understood from a biopsychosocial perspective. Sex differences were evident for comorbid novel depressive disorder and comorbid novel ADHD.

Novel Psychiatric Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the factors predictive of novel psychiatric disorders in the interval 0-6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years consecutively hospitalized for mild to severe TBI at five hospitals were recruited. Participants were evaluated at baseline (soon after injury) for pre-injury characteristics including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, family function, family psychiatric history, and adaptive function. In addition to the psychosocial variables, injury severity and lesion location detected with acquisition of a research MRI were measured to develop a biopsychosocial predictive model for development of novel psychiatric disorders. Psychiatric outcome, including occurrence of a novel psychiatric disorder, was assessed 6 months after the injury. RESULTS: The recruited sample numbered 177 children, and 141 children (80%) returned for the six-month assessment. Of the 141 children, 58 (41%) developed a novel psychiatric disorder. In univariable analyses, novel psychiatric disorder was significantly associated with lower SES, higher psychosocial adversity, and lesions in frontal lobe locations, such as frontal white matter, superior frontal gyrus, inferior frontal gyrus, and orbital gyrus. Multivariable analyses found that novel psychiatric disorder was independently and significantly associated with frontal-lobe white matter, superior frontal gyrus, and orbital gyrus lesions. CONCLUSION: The results demonstrate that occurrence of novel psychiatric disorders following pediatric TBI requiring hospitalization is common and has identifiable psychosocial and specific biological predictors. However, only the lesion predictors were independently related to this adverse psychiatric outcome.

Novel Oppositional Defiant Disorder 12 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators examined the factors predictive of novel oppositional defiant disorder in the 6-12 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years old who experienced a TBI were recruited from consecutive admissions to five hospitals. Participants were evaluated soon after injury (baseline) for preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, and injury severity, to develop a biopsychosocial predictive model for development of novel oppositional defiant disorder. MRI analyses were conducted to examine potential brain lesions. Psychiatric outcome, including that of novel oppositional defiant disorder, was assessed 12 months after injury. RESULTS: Although 177 children were recruited for the study, 120 children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 12-month assessment. Of these 120 children, seven (5.8%) exhibited novel oppositional defiant disorder, and none developed conduct disorder or DBD NOS in the 6-12 months postinjury. Novel oppositional defiant disorder was significantly associated with lower socioeconomic status, higher psychosocial adversity, and lower preinjury adaptive functioning. CONCLUSIONS: These results demonstrate that novel oppositional defiant disorder following TBI selectively and negatively affects an identifiable group of children. Both proximal (preinjury adaptive function) and distal (socioeconomic status and psychosocial adversity) psychosocial variables significantly increase risk for this outcome.

Novel Oppositional Defiant Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: The investigators aimed to assess predictive factors of novel oppositional defiant disorder (ODD) among children and adolescents in the first 6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years who experienced a TBI were recruited from consecutive admissions to five hospitals. Testing of a biopsychosocial model that may elucidate the development of novel ODD included assessment soon after injury (baseline) of preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, injury severity, and postinjury processing speed (which may be a proxy for brain injury). MRI analyses were also conducted to examine potential brain lesions. Psychiatric outcome, including that of novel ODD, was assessed 6 months after the injury. RESULTS: A total of 177 children and adolescents were recruited for the study, and 134 who were without preinjury ODD, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 6-month assessment. Of those who returned 6 months postinjury, 11 (8.2%) developed novel ODD, and none developed novel conduct disorder or DBD NOS. Novel ODD was significantly associated with socioeconomic status, preinjury family functioning, psychosocial adversity, and processing speed. CONCLUSIONS: These findings show that an important minority of children with TBI developed ODD. Psychosocial and injury-related variables, including socioeconomic status, lower family function, psychosocial adversity, and processing speed, significantly increase risk for this outcome.

Neural correlates of reduced depressive symptoms following cognitive training for chronic traumatic brain injury.

Depression is the most frequent comorbid psychiatric condition among individuals with traumatic brain injury (TBI). Yet, little is known about changes in the brain associated with reduced depressive symptoms following rehabilitation for TBI. We identified whether cognitive training alleviates comorbid depressive symptoms in chronic TBI (>6 months post-injury) as a secondary effect. Further, we elucidated neural correlates of alleviated depressive symptoms following cognitive training. A total of seventy-nine individuals with chronic TBI (53 depressed and 26 non-depressed individuals, measured using the Beck Depressive Inventory [BDI]), underwent either strategy- or information-based cognitive training in a small group for 8 weeks. We measured psychological functioning scores, cortical thickness, and resting-state functional connectivity (rsFC) for these individuals before training, immediately post-training, and 3 months post-training. After confirming that changes in BDI scores were independent of training group affiliation, we identified that the depressive-symptoms group showed reductions in BDI scores over time relative to the non-depressed TBI controls (p < .01). Within the depressive-symptoms group, reduced BDI scores was associated with improvements in scores for post-traumatic stress disorder, TBI symptom awareness, and functional status (p < .00625), increases in cortical thickness in four regions within the right prefrontal cortex (pvertex  < .01, pcluster <.05), and decreases in rsFC with each of these four prefrontal regions (pvertex  < .01, pcluster  < .0125). Overall, these findings suggest that cognitive training can reduce depressive symptoms in TBI even when the training does not directly target psychiatric symptoms. Importantly, cortical thickness and brain connectivity may offer promising neuroimaging markers of training-induced improvement in mental health status in TBI.

Enhancing latent cognitive capacity in mild cognitive impairment with gist reasoning training: a pilot study.

OBJECTIVE: Cognitive training offers a promising way to mitigate cognitive deterioration in individuals with mild cognitive impairment (MCI). This randomized control pilot trial examined the effects of Gist Reasoning Training on cognition as compared with a training involving New Learning in a well-characterized MCI group. METHODS: Fifty participants with amnestic MCI were randomly assigned to the experimental Gist Training group or an active control New Learning group. Both groups received 8 h of training over a 4-week period. We compared pre-training with post-training changes in cognitive functions between the two training groups. RESULTS: The Gist Training group showed higher performance in executive function (strategic control and concept abstraction) and memory span compared with the New Learning group. Conversely, the New Learning group showed gains in memory for details. CONCLUSION: These findings suggest that cognitive training in general yields benefits, and more specifically, training programs that target top-down cognitive functions such as gist reasoning may have a broad impact on improving cognition in MCI. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Disrupted Intrinsic Connectivity among Default, Dorsal Attention, and Frontoparietal Control Networks in Individuals with Chronic Traumatic Brain Injury.

OBJECTIVES: Individuals with chronic traumatic brain injury (TBI) often show detrimental deficits in higher order cognitive functions requiring coordination of multiple brain networks. Although assessing TBI-related deficits in higher order cognition in the context of network dysfunction is promising, few studies have systematically investigated altered interactions among multiple networks in chronic TBI. METHOD: We characterized disrupted resting-state functional connectivity of the default mode network (DMN), dorsal attention network (DAN), and frontoparietal control network (FPCN) whose interactions are required for internally and externally focused goal-directed cognition in chronic TBI. Specifically, we compared the network interactions of 40 chronic TBI individuals (8 years post-injury on average) with those of 17 healthy individuals matched for gender, age, and years of education. RESULTS: The network-based statistic (NBS) on DMN-DAN-FPCN connectivity of these groups revealed statistically significant (p NBS2.58) reductions in within-DMN, within-FPCN, DMN-DAN, and DMN-FPCN connectivity of the TBI group over healthy controls. Importantly, such disruptions occurred prominently in between-network connectivity. Subsequent analyses further exhibited the disrupted connectivity patterns of the chronic TBI group occurring preferentially in long-range and inter-hemispheric connectivity of DMN-DAN-FPCN. Most importantly, graph-theoretic analysis demonstrated relative reductions in global, local and cost efficiency (p<.05) as a consequence of the network disruption patterns in the TBI group. CONCLUSION: Our findings suggest that assessing multiple networks-of-interest simultaneously will allow us to better understand deficits in goal-directed cognition and other higher order cognitive phenomena in chronic TBI. Future research will be needed to better understand the behavioral consequences related to these network disruptions.

Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors.

Complex mental activity induces improvements in cognition, brain function, and structure in animals and young adults. It is not clear to what extent the aging brain is capable of such plasticity. This study expands previous evidence of generalized cognitive gains after mental training in healthy seniors. Using 3 MRI-based measurements, that is, arterial spin labeling MRI, functional connectivity, and diffusion tensor imaging, we examined brain changes across 3 time points pre, mid, and post training (12 weeks) in a randomized sample (n = 37) who received cognitive training versus a control group. We found significant training-related brain state changes at rest; specifically, 1) increases in global and regional cerebral blood flow (CBF), particularly in the default mode network and the central executive network, 2) greater connectivity in these same networks, and 3) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy. Improvements in cognition were identified along with significant CBF correlates of the cognitive gains. We propose that cognitive training enhances resting-state neural activity and connectivity, increasing the blood supply to these regions via neurovascular coupling. These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors.

Reasoning training in veteran and civilian traumatic brain injury with persistent mild impairment.

Traumatic brain injury (TBI) is a chronic health condition. The prevalence of TBI, combined with limited advances in protocols to mitigate persistent TBI-related impairments in higher order cognition, present a significant challenge. In this randomised study (n = 60), we compared the benefits of Strategic Memory Advanced Reasoning Training (SMART, n = 31), a strategy-based programme shown to improve cognitive control, versus an active learning programme called Brain Health Workshop (BHW, n = 29) in individuals with TBI with persistent mild functional deficits. Outcomes were measured on cognitive, psychological health, functional, and imaging measures. Repeated measures analyses of immediate post-training and 3-month post-training demonstrated gains on the cognitive control domain of gist reasoning (ability to abstract big ideas/goals from complex information/tasks) in the SMART group as compared to BHW. Gains following the SMART programme were also evident on improved executive function, memory, and daily function as well as reduced symptoms associated with depression and stress. The SMART group showed an increase in bilateral precuneus cerebral blood flow (CBF). Improvements in gist reasoning in the SMART group were also associated with an increase in CBF in the left inferior frontal region, the left insula and the bilateral anterior cingulate cortex. These results add to prior findings that the SMART programme provides an efficient set of strategies that have the potential to improve cognitive control performance and associated executive functions and daily function, to enhance psychological health, and facilitate positive neural plasticity in adults with persistent mild impairment after TBI.

Personality Change Due to Traumatic Brain Injury in Children and Adolescents: Neurocognitive Correlates.

Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

Psychiatric disorders in children and adolescents 24 months after mild traumatic brain injury.

This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5-14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning.

Dissipation and heating in solar wind turbulence: from the macro to the micro and back again.

The past decade has seen a flurry of research activity focused on discerning the physics of kinetic scale turbulence in high-speed astrophysical plasma flows. By 'kinetic' we mean spatial scales on the order of or, in particular, smaller than the ion inertial length or the ion gyro-radius--the spatial scales at which the ion and electron bulk velocities decouple and considerable change can be seen in the ion distribution functions. The motivation behind most of these studies is to find the ultimate fate of the energy cascade of plasma turbulence, and thereby the channels by which the energy in the system is dissipated. This brief Introduction motivates the case for a themed issue on this topic and introduces the topic of turbulent dissipation and heating in the solar wind. The theme issue covers the full breadth of studies: from theory and models, massive simulations of these models and observational studies from the highly rich and vast amount of data collected from scores of heliospheric space missions since the dawn of the space age. A synopsis of the theme issue is provided, where a brief description of all the contributions is discussed and how they fit together to provide an over-arching picture on the highly topical subject of dissipation and heating in turbulent collisionless plasmas in general and in the solar wind in particular.

Neuropsychological performance of youth with secondary attention-deficit/hyperactivity disorder 6- and 12-months after traumatic brain injury.

The present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6-16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions.

Inhibitory control gains from higher-order cognitive strategy training.

The present study examined the transfer of higher-order cognitive strategy training to inhibitory control. Middle school students enrolled in a comprehension- and reasoning-focused cognitive strategy training program and passive controls participated. The training program taught students a set of steps for inferring essential gist or themes from materials. Both before and after training or a comparable duration in the case of the passive controls, participants completed a semantically cued Go/No-Go task that was designed to assess the effects of depth of semantic processing on response inhibition and components of event-related potentials (ERP) related to response inhibition. Depth of semantic processing was manipulated by varying the level of semantic categorization required for response selection and inhibition. The SMART-trained group showed inhibitory control gains and changes in fronto-central P3 ERP amplitudes on inhibition trials; whereas, the control group did not. The results provide evidence of the transfer of higher-order cognitive strategy training to inhibitory control and modulation of ERPs associated with semantically cued inhibitory control. The findings are discussed in terms of implications for cognitive strategy training, models of cognitive abilities, and education.

Multimodal Predictive Modeling: Scalable Imaging Informed Approaches to Predict Future Brain Health.

Background: Predicting future brain health is a complex endeavor that often requires integrating diverse data sources. The neural patterns and interactions identified through neuroimaging serve as the fundamental basis and early indicators that precede the manifestation of observable behaviors or psychological states. New Method: In this work, we introduce a multimodal predictive modeling approach that leverages an imaging-informed methodology to gain insights into future behavioral outcomes. We employed three methodologies for evaluation: an assessment-only approach using support vector regression (SVR), a neuroimaging-only approach using random forest (RF), and an image-assisted method integrating the static functional network connectivity (sFNC) matrix from resting-state functional magnetic resonance imaging (rs-fMRI) alongside assessments. The image-assisted approach utilized a partially conditional variational autoencoder (PCVAE) to predict brain health constructs in future visits from the behavioral data alone. Results: Our performance evaluation indicates that the image-assisted method excels in handling conditional information to predict brain health constructs in subsequent visits and their longitudinal changes. These results suggest that during the training stage, the PCVAE model effectively captures relevant information from neuroimaging data, thereby potentially improving accuracy in making future predictions using only assessment data. Comparison with Existing Methods: The proposed image-assisted method outperforms traditional assessment-only and neuroimaging-only approaches by effectively integrating neuroimaging data with assessment factors. Conclusion: This study underscores the potential of neuroimaging-informed predictive modeling to advance our comprehension of the complex relationships between cognitive performance and neural connectivity.

Greater physical fitness ( VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ ) in healthy older adults associated with increased integrity of the locus coeruleus-noradrenergic system.

AIM: Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo 2 max $$ {\mathrm{Vo}}_{2_{\mathrm{max}}} $$ - a measure of oxygen uptake and physical fitness (PF). METHODS: We hypothesized that greater Vo 2 max $$ {\mathrm{Vo}}_{2_{\mathrm{max}}} $$ would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel-Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine). RESULTS: As hypothesized, greater Vo 2 max $$ {\mathrm{Vo}}_{2_{\mathrm{max}}} $$ related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators. CONCLUSION: This newly established link between Vo 2 max $$ {\mathrm{Vo}}_{2_{\mathrm{max}}} $$ and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC-NA system resilience to neurodegeneration via Vo 2 max $$ {\mathrm{Vo}}_{2_{\mathrm{max}}} $$ enhancement.

ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells.

We demonstrate that a Rho kinase inhibitor (Y-27632), in combination with fibroblast feeder cells, induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro, without transduction of exogenous viral or cellular genes. Primary prostate and mammary cells, for example, are reprogrammed toward a basaloid, stem-like phenotype and form well-organized prostaspheres and mammospheres in Matrigel. However, in contrast to the selection of rare stem-like cells, the described growth conditions can generate 2 × 10(6) cells in 5 to 6 days from needle biopsies, and can generate cultures from cryopreserved tissue and from fewer than four viable cells. Continued cell proliferation is dependent on both feeder cells and Y-27632, and the conditionally reprogrammed cells (CRCs) retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors. For example, CRCs established from human prostate adenocarcinoma displayed instability of chromosome 13, proliferated abnormally in Matrigel, and formed tumors in mice with severe combined immunodeficiency. The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host.

Effects of moderate to severe traumatic brain injury on anticipating consequences of actions in adolescents: a preliminary study.

For this pilot study, we compared performance of 15 adolescents with moderate-severe traumatic brain injury (TBI) to that of 13 typically developing (TD) adolescents in predicting social actions and consequences for avatars in a virtual microworld environment faced with dilemmas involving legal or moral infractions. Performance was analyzed in relation to cortical thickness in brain regions implicated in social cognition. Groups did not differ in number of actions predicted nor in reasons cited for predictions when presented only the conflict situation. After viewing the entire scenario, including the choice made by the avatar, TD and TBI adolescents provided similar numbers of short-term consequences. However, TD adolescents provided significantly more long-term consequences (p = .010). Additionally, for the Overall qualitative score, TD adolescents' responses were more likely to reflect the long-term impact of the decision made (p = .053). Groups differed in relation of the Overall measure to thickness of right medial prefrontal cortex/frontal pole and precuneus, with stronger relations for the TD group (p < .01). For long-term consequences, the relations to the posterior cingulate, superior medial frontal, and precentral regions, and to a lesser extent, the middle temporal region, were stronger for the TBI group (p < .01).