A targeted neuropsychological examination of children with a history of sport-related concussion.

Experimental research suggests that sport-related concussion can lead to persistent alterations in children's neurophysiology and cognition. However, the search for neuropsychological tests with a similar ability to detect long-term deficits continues. PRIMARY OBJECTIVE: The current study assessed whether a target battery of neuropsychological measures of higher cognition and academic achievement would detect lingering deficits in children 2 years after injury. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURE: A total of 32 pre-adolescent children (16 concussion history, 16 control) completed a targeted battery of neuropsychological and academic tests. MAIN OUTCOMES AND RESULTS: Children with a history of concussion exhibited selective deficits during the Raven's Coloured Progressive Matrices, Comprehensive Trail-Making Test, and the mathematics sub-section of the WRAT-3. Deficit magnitude was significantly related to age at injury, but not time since injury. CONCLUSIONS: The current results suggest that neuropsychological measures of higher cognition and academic achievement may be sensitive to lingering deficits, and that children injured earlier in life may exhibit worse neuropsychological and academic performance.

Enhanced Learning through Multimodal Training: Evidence from a Comprehensive Cognitive, Physical Fitness, and Neuroscience Intervention.

The potential impact of brain training methods for enhancing human cognition in healthy and clinical populations has motivated increasing public interest and scientific scrutiny. At issue is the merits of intervention modalities, such as computer-based cognitive training, physical exercise training, and non-invasive brain stimulation, and whether such interventions synergistically enhance cognition. To investigate this issue, we conducted a comprehensive 4-month randomized controlled trial in which 318 healthy, young adults were enrolled in one of five interventions: (1) Computer-based cognitive training on six adaptive tests of executive function; (2) Cognitive and physical exercise training; (3) Cognitive training combined with non-invasive brain stimulation and physical exercise training; (4) Active control training in adaptive visual search and change detection tasks; and (5) Passive control. Our findings demonstrate that multimodal training significantly enhanced learning (relative to computer-based cognitive training alone) and provided an effective method to promote skill learning across multiple cognitive domains, spanning executive functions, working memory, and planning and problem solving. These results help to establish the beneficial effects of multimodal intervention and identify key areas for future research in the continued effort to improve human cognition.

Underlying sources of cognitive-anatomical variation in multi-modal neuroimaging and cognitive testing.

Healthy adults have robust individual differences in neuroanatomy and cognitive ability not captured by demographics or gross morphology (Luders, Narr, Thompson, & Toga, 2009). We used a hierarchical independent component analysis (hICA) to create novel characterizations of individual differences in our participants (N=190). These components fused data across multiple cognitive tests and neuroanatomical variables. The first level contained four independent, underlying sources of phenotypic variance that predominately modeled broad relationships within types of data (e.g., "white matter," or "subcortical gray matter"), but were not reflective of traditional individual difference measures such as sex, age, or intracranial volume. After accounting for the novel individual difference measures, a second level analysis identified two underlying sources of phenotypic variation. One of these made strong, joint contributions to both the anatomical structures associated with the core fronto-parietal "rich club" network (van den Heuvel & Sporns, 2011), and to cognitive factors. These findings suggest that a hierarchical, data-driven approach is able to identify underlying sources of individual difference that contribute to cognitive-anatomical variation in healthy young adults.

Cognitive and anatomical data in a healthy cohort of adults.

We present data from a sample of 190 healthy adults including assessments of 4 cognitive factor scores, 12 cognitive tests, and 115 MRI-assessed neuroanatomical variables (cortical thicknesses, cortical and sub-cortical volumes, fractional anisotropy, and radial diffusivity). These data were used in estimating underlying sources of individual variation via independent component analysis (Watson et al., In press) [25].

The Relationship between Total Water Intake and Cognitive Control among Prepubertal Children.

BACKGROUND: Cognitive control (also known as executive function) encompasses mental processes that underlie goal-directed behavior, and it enables us to adjust our behavior according to changing environmental demands. Previous research among children has demonstrated that aerobic fitness and obesity have contrasting and selective effects on cognitive control. However, the relationship between water intake and childhood cognitive control remains inadequately studied. This study investigated the relationship between total water intake and cognitive control among prepubertal children (8-9-year olds). METHODS: Children between 8 and 9 years of age (n = 63) performed a modified flanker task to assess cognitive control related to inhibition (ability to resist distractions and maintain focus). Diet was measured using 3-day food records. Total water was defined as water consumed from drinking water, beverages, and food. RESULTS: A comparison of task performance across the median intake of total water revealed that children above the median exhibited shorter reaction times across multiple conditions of the flanker task, requiring variable amounts of cognitive control. Further, after adjustment of age, IQ, socioeconomic status, weight status, and aerobic fitness level, the proportion of intake comprised of water (%TW) was negatively correlated with reaction time interference, that is, the ability to maintain task performance when task conditions demanded greater inhibition. CONCLUSIONS: These results indicate an association between water intake and cognitive control using a task that modulates inhibition. Specifically, higher water intake correlated with greater ability to maintain task performance when inhibitory demands are increased. Future work is needed to determine the mechanism by which water influences cognitive control among children.

From cognitive motor preparation to visual processing: The benefits of childhood fitness to brain health.

The association between a fit body and a fit brain in children has led to a rise of behavioral and neuroscientific research. Yet, the relation of cardiorespiratory fitness on premotor neurocognitive preparation with early visual processing has received little attention. Here, 41 healthy, lower and higher fit preadolescent children were administered a modified version of the Eriksen flanker task while electroencephalography (EEG) and behavioral measures were recorded. Event-related potentials (ERPs) locked to the stimulus onset with an earlier than usual baseline (-900/-800 ms) allowed investigation of both the usual post-stimulus (i.e., the P1, N1 and P2) as well as the pre-stimulus ERP components, such as the Bereitschaftspotential (BP) and the prefrontal negativity (pN component). At the behavioral level, aerobic fitness was associated response accuracy, with higher fit children being more accurate than lower fit children. Fitness-related differences selectively emerged at prefrontal brain regions during response preparation, with larger pN amplitude for higher than lower fit children, and at early perceptual stages after stimulus onset, with larger P1 and N1 amplitudes in higher relative to lower fit children. Collectively, the results suggest that the benefits of being aerobically fit appear at the stage of cognitive preparation prior to stimulus presentation and the behavioral response during the performance of a task that challenges cognitive control. Further, it is likely that enhanced activity in prefrontal brain areas may improve cognitive control of visuo-motor tasks, allowing for stronger proactive inhibition and larger early allocation of selective attention resources on relevant external stimuli.

Aerobic fitness is associated with greater efficiency of the network underlying cognitive control in preadolescent children.

This study examined whether individual differences in aerobic fitness are associated with differences in activation of cognitive control brain networks in preadolescent children. As expected, children performed worse on a measure of cognitive control compared with a group of young adults. However, individual differences in aerobic fitness were associated with cognitive control performance among children. Lower-fit children had disproportionate performance cost in accuracy with increasing task difficulty, relative to higher-fit children. Brain activation was compared between performance-matched groups of lower- and higher-fit children. Fitness groups differed in brain activity for regions associated with response execution and inhibition, task set maintenance, and top-down regulation. Overall, differing activation patterns coupled with different patterns of brain-behavior correlations suggest an important role of aerobic fitness in modulating task strategy and the efficiency of neural networks that implement cognitive control in preadolescent children.

Preliminary assessment of safety and effectiveness in humans of ProBiora3, a probiotic mouthwash.

AIMS: To conduct a pilot human clinical trial to assess the safety and to test the ability of a probiotic mouthwash, ProBiora(3), to affect the levels of Streptococcus mutans and certain known periodontal pathogens in the mouth when administered twice daily over a period of 4 weeks. METHODS AND RESULTS: The mouthwash contained three specific strains of naturally occurring oral bacteria and was tested at two dose levels: 10(6) and 10(8) colony forming units each of Strep. oralis strain KJ3sm, Strep. uberis strain KJ2sm, and the spontaneous lactic acid-deficient variant of Strep. rattus, strain JH145. Substantial decreases in the levels of the marker bacteria were observed. No safety issues were noted with the twice daily application of this mouthwash. CONCLUSIONS: Despite the small number of subjects and the use of young, orally healthy adults, along with the inherent variability in the microbiological measurements, the probiotic mouthwash was able to substantially affect the levels of dental pathogens in saliva and periodontal pathogens in subgingival plaque. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this pilot human study suggest that the probiotic mouthwash product may be safe for daily use as an aid in maintaining both dental and periodontal health.

A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries.

AIMS: To study the ability of daily applications of Streptococcus rattus strain JH145 to affect the numbers of an implanted Streptococcus mutans strain in a rat model. METHODS AND RESULTS: A spontaneous L(+)-lactate dehydrogenase (LDH)-deficient mutant of Streptococcus rattus, JH146, was isolated by screening on selective medium and compared with a previously isolated spontaneous LDH deficient strain, JH145. Both strains were shown to have single base pair deletion mutations in the structural gene (ldh) for LDH, and reversion frequencies were approximately the same. Animals treated once daily with >or=10(6) CFU (colony forming units) of JH145 showed a statistically significant decrease in the proportion of implanted S. mutans to total cultivable bacteria in oral swab samples. The rate of decrease in S. mutans levels was dose-dependent. No adverse effects were observed by in-life observation of treated animals, and histopathological, haematological and blood chemistry analyses were unremarkable. CONCLUSIONS: The results presented indicate that daily application of JH145, a naturally occurring LDH-deficient variant of S. rattus, can compete with S. mutans for its habitat on the tooth surface. SIGNIFICANCE AND IMPACT OF THE STUDY: S. rattus JH145 has potential as a probiotic for use in the prevention of dental caries.

The effect of acute treadmill walking on cognitive control and academic achievement in preadolescent children.

The effect of an acute bout of moderate treadmill walking on behavioral and neuroelectric indexes of the cognitive control of attention and applied aspects of cognition involved in school-based academic performance were assessed. A within-subjects design included 20 preadolescent participants (age=9.5+/-0.5 years; eight female) to assess exercise-induced changes in performance during a modified flanker task and the Wide Range Achievement Test 3. The resting session consisted of cognitive testing followed by a cardiorespiratory fitness assessment to determine aerobic fitness. The exercise session consisted of 20 min of walking on a motor-driven treadmill at 60% of estimated maximum heart rate followed by cognitive testing once heart rate returned to within 10% of pre-exercise levels. Results indicated an improvement in response accuracy, larger P3 amplitude, and better performance on the academic achievement test following aerobic exercise relative to the resting session. Collectively, these findings indicate that single, acute bouts of moderately-intense aerobic exercise (i.e. walking) may improve the cognitive control of attention in preadolescent children, and further support the use of moderate acute exercise as a contributing factor for increasing attention and academic performance. These data suggest that single bouts of exercise affect specific underlying processes that support cognitive health and may be necessary for effective functioning across the lifespan.

Fitness and action monitoring: evidence for improved cognitive flexibility in young adults.

To improve behavior, one must detect errors and initiate subsequent corrective adaptations. This action monitoring process has been widely studied, but little is known about how one may improve this aspect of cognition. To examine the relationship between cardiorespiratory fitness and action monitoring, we recorded the error-related negativity (ERN), an event-related brain potential believed to index action monitoring, as well as post-error behavioral indices of action monitoring from healthy young adults (18-25 years) who varied in cardiorespiratory fitness. These measures were collected during the execution of flanker tasks emphasizing response accuracy or speed to better assess the specificity of any potential relationships between fitness and action monitoring. Higher fitness was associated with greater post-error accuracy and ERN amplitude during task conditions emphasizing accuracy, as well as greater modulation of these indices across task instruction conditions. These findings suggest that higher fitness is associated with increased cognitive flexibility, evidenced through greater change in action monitoring indices as a function of task parameters. Thus, fitness may benefit action monitoring by selectively increasing cognitive control under conditions where error detection and performance adjustments are more salient.

Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials.

AIMS: To construct a genetically modified strain of Streptococcus mutans for dental caries prevention. The strain has significantly reduced cariogenicity owing to a deletion of the entire open reading frame for lactate dehydrogenase, and has excellent colonization potential through the production of a natural antibiotic called mutacin 1140. For use in human clinical trials, additional mutations were introduced to enable rapid elimination of the strain in case of adverse side effects and to increase genetic stability. METHODS: Deletion mutations were introduced into the dal gene for d-alanine biosynthesis and the comE gene for genetic transformation. The resulting strain, A2JM, was tested for dependence on exogenous d-alanine and its ability to be eradicated from colonized rats. The strain was also tested for its ability to exchange DNA with another strain of S. mutans in in vitro and in vivo models. CONCLUSIONS: A2JM was completely dependent on exogenous d-alanine, but could colonize the oral cavity of rats in low numbers in the absence of dietary d-alanine. Results indicated that A2JM can scavenge d-alanine from other plaque bacteria. Lowering of the total oral bacterial load through daily application of chlorhexidine enabled virtually complete eradication of A2JM. The introduction of the comE gene did not significantly decrease the transformability of A2JM in in vitro or in vivo models. The addition of a deletion in the comE gene does, nonetheless, provide additional safety as it has a very low reversion frequency. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the safety and efficacy profiles established in vitro and in animal models, A2JM appears suitable for safe use in human clinical trials.

Cardiorespiratory fitness and acute aerobic exercise effects on neuroelectric and behavioral measures of action monitoring.

Cardiorespiratory fitness and acute aerobic exercise effects on cognitive function were assessed for 28 higher- and lower-fit adults during a flanker task by comparing behavioral and neuroelectric indices of action monitoring. The error-related negativity, error positivity, and N2 components, as well as behavioral measures of response speed, accuracy, and post-error slowing were measured following a 30-minute acute bout of treadmill exercise or following 30-minutes of rest. A graded maximal exercise test was used to measure cardiorespiratory fitness by assessing maximal oxygen uptake. Results indicated that higher-fit adults exhibited reduced error-related negativity amplitude, increased error positivity amplitude, and increased post-error response slowing compared with lower-fit adults. However, acute exercise was not related to any of the dependent measures. These findings suggest that cardiorespiratory fitness, but not acute aerobic exercise, may be beneficial to behavioral and neuroelectric indices of action monitoring following errors of commission by increasing top-down attentional control.

Food deprivation and emotional reactions to food cues: implications for eating disorders.

Two studies examined emotional responding to food cues. In experiment 1, normal college students were assigned to 0-, 6- or 24-h of food deprivation prior to presentations of standard emotional and food-related pictures. Food deprivation had no impact on responses elicited by standard emotional pictures. However, subjective and psychophysiological reactions to food pictures were affected significantly by deprivation. Importantly, food-deprived subjects viewing food pictures showed an enhanced startle reflex and increased heart rate. Experiment 2 replicated the food deprivation effects from experiment 1, and examined participants reporting either a habitual pattern of restrained (anorexia-like) or binge (bulimia-like) eating. Food-deprived and binge eater groups showed startle potentiation to food cues, and rated these stimuli as more pleasant, relative to restrained eaters and control subjects. The results are interpreted from the perspective that startle modulation reflects activation of defensive or appetitive motivation. Implications of the data for understanding eating disorders are considered.

Motor and nonmotor event-related potentials during a complex processing task.

Identification of the necessary stimulus properties to elicit the stimulus preceding negativity (SPN) has been the impetus for numerous research studies. The current study was conducted to explore the possibility that the SPN is an index of cognitive resource allocation. An auditory warning stimulus (S1) indicated whether an easy or difficult discrimination would occur at S2. The SPN was collected before a nonmotor discrimination task (S2) that consisted of identifying the higher of two bars. To eliminate the influence of motor processing prior to S2, a button press on the side of the higher bar was held until perception of a response cue (S3). Additionally, P3, contingent negative variation (CNV), and behavioral measures were collected to assist in assessing the SPN. Results indicated that although the SPN exhibited increased negativity, no differences were observed based on task difficulty. However, task difficulty did affect P3 data for both the warning tone and the discrimination task, an effect not observed for the CNV. Overall, the data did not support that hypothesis that the SPN provides an index of cognitive demand.

An electrocortical comparison of executed and rejected shots in skilled marksmen.

Electroencephalographic (EEG) activity during the preshot period was investigated in seven skilled marksmen. Specifically, alpha and beta spectral power were obtained for the 4-s period prior to the execution or rejection of shots. Rejected shots were defined as those that resulted in the marksman's self-initiated decision to withdraw their rifle from the target rather than execute the shot. EEG activity during the preparatory period was contrasted between the executed and rejected shots to better understand the involved attentional processes associated with the preshot state. Results for rejected compared with executed shots revealed a progressive increase in alpha and beta power for rejected compared with executed shots, which increased across the preparatory period. Furthermore, increased spectral power was found in the left compared with the right hemisphere for both executed and rejected shots, and in the different regions of the scalp. Therefore, the decision to reject a shot seems to be characterized by inappropriate allocation of the neural resources associated with task execution.