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.

No data, no problem, no action: parenting programs in low-income countries. Making the social-emotional outcomes more visible.

BACKGROUND: Parenting programs are delivered in many low income countries in an effort to address the effects of insufficient cognitive stimulation, major social-emotional risk factors related to inadequate caregiver sensitivity and responsiveness, maternal depression, violence and biological risk factors. However, the outcomes of these programs are often untested because of methodological limitations in the existing evaluation tools available for cross-cultural research, and especially those related to social-emotional development and functioning. METHOD: This study takes an approach that involves organizing data from focus groups collected following caregiver participation in a parenting program, Learning Through Play (LTP) delivered in 11 low income countries. The LTP program has as its aim to increase parent knowledge and influence parental practice regarding the essential components of early development of children aged birth to 6 years. The purpose of systematically organizing focus group data was to illustrate a means by which program developers worldwide can discuss outcomes of program participation, particularly in social-emotional domains that have been overlooked in past studies on parenting programs. RESULTS AND CONCLUSION: The findings from this study suggest that qualitative outcome data can be organized to make the social-emotional outcomes of participation in parenting programs more visible.

A Phase-Locked Loop Epilepsy Network Emulator.

Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control.

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.

Prevention and control of rabies in an age of global travel: a review of travel- and trade-associated rabies events--United States, 1986-2012.

Rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. A notable example of this success is the elimination of canine rabies virus variant from the United States and many other countries. However, increased international travel and trade can pose risks for rapid, long-distance movements of ill or infected persons or animals. Such travel and trade can result in human exposures to rabies virus during travel or transit and could contribute to the re-introduction of canine rabies variant or transmission of other viral variants among animal host populations. We present a review of travel- and trade-associated rabies events that highlight international public health obligations and collaborative opportunities for rabies prevention and control in an age of global travel. Rabies is a fatal disease that warrants proactive coordination among international public health and travel industry partners (such as travel agents, tour companies and airlines) to protect human lives and to prevent the movement of viral variants among host populations.

Empathy in hippocampal amnesia.

Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy.

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.

Control of an outbreak due to an adamantane-resistant strain of influenza A (H3N2) in a chronic care facility.

BACKGROUND: Chronic care facility residents are at risk of severe influenza infection and death. Adamantanes have been used by chronic care facilities for influenza A prophylaxis; however, genotypic resistance has altered prophylaxis recommendations. An outbreak of influenza A (H3N2) in a chronic care facility housing neurologically impaired children and young adults and subsequent control measures are described. PATIENTS AND METHODS: Resident charts were retrospectively reviewed. Isolates were characterized by strain identification and pyrosequencing. RESULTS: Although 95 (97%) of 98 residents had been immunized against influenza at the start of the influenza season, 16 (84%) of 19 case patients were identified on the first floor. However, following implementation of enhanced infection control practices and adamantane prophylaxis, only 10 (13%) of 79 case patients were identified on the second floor. Subsequent pyrosequencing studies revealed a serine to asparagine mutation at position 31 of the M2 protein. CONCLUSIONS: Enhanced infection control precautions and adamantane prophylaxis were used to control spread of influenza in a chronic care facility. This outbreak demonstrates the importance of timely and consistent implementation of infection control measures in controlling influenza outbreaks in long term care facilities and raises questions about a possible role for adamantanes in preventing transmission of adamantane-resistant influenza A viruses.

Practice-related effects demonstrate complementary roles of anterior cingulate and prefrontal cortices in attentional control.

The purpose of this study was to test the hypothesis that the dorsolateral prefrontal cortex (DLFPC), not the anterior cingulate cortex (ACC), plays the predominant role in implementing top-down attentional control. To do so, we used fMRI to examine practice-related changes in neural activity during a variant of the Stroop task. The results indicated that the DLPFC's activity decreased gradually as the need for control was reduced (as indexed by behavioral measures), while the ACC's activity dropped off rapidly. Such a pattern is consistent with the DLPFC taking a leading role in implementing top-down attentional control and the ACC being involved in other aspects of attentional control, such as response-related processes. In addition, with practice, there was a reduction in activity within cortical systems handling the processing of task-irrelevant information capable of interfering with task performance. This finding suggests that with practice the brain is capable of identifying and strategically inhibiting such processing.

Attentional selection and the processing of task-irrelevant information: insights from fMRI examinations of the Stroop task.

In this chapter, we discuss our research that reveals how attentional mechanisms can modulate activity of posterior brain regions responsible for processing the unattended attribute of a stimulus. To do so, we utilized fMRI to reveal patterns of regional brain activity for variants of the Stroop task that differ in the nature of the task-irrelevant stimulus attribute. In all variants, individuals had to identify the ink color in which an item was presented. To vary attentional demands, we manipulated whether or not the task-irrelevant information contained conflicting color information. The variants differed in whether the conflicting color information was contained in a word naming a color (e.g. the word 'red' in blue ink), a word naming an object highly associated with a specific color (e.g. the word 'frog' in red ink), or a line drawing of an object highly associated with a specific color (e.g. a drawing of a frog in red ink). When the unattended stimulus attribute contained color information that conflicted with an item's ink color, increased activity was observed in the posterior brain region that processes the aspect of the task-irrelevant attribute related to color. Increased activity was observed in the left precuneus and left superior parietal cortex when the conflicting information arose from a color word; in the middle temporal gyrus and insular cortex when the word named an object highly associated with a specific color, and included extensive regions of early portions of the ventral visual processing stream when a line drawing was highly associated with a specific color. These areas have been implicated in word processing, semantic processing, and visual processing, respectively. Our results suggest that attentional selection can occur by: (1) increasing the gain on all posterior regions responsible for processing information related to the task demands, regardless of whether that information is contained in the task-relevant or task-irrelevant dimension; (2) limiting the processing of task-irrelevant information in order to reduce interference; and (3) modulating the processing of representations varying from those of a low-level perceptual nature up through those of a higher-order semantic nature.

The relative involvement of anterior cingulate and prefrontal cortex in attentional control depends on nature of conflict.

While numerous studies have implicated both anterior cingulate and prefrontal cortex in attentional control, the nature of their involvement remains a source of debate. Here we determine the extent to which their relative involvement in attentional control depends upon the levels of processing at which the conflict occurs (e.g., response, non-response). Using a combination of blocked and rapid presentation event-related functional magnetic resonance imaging techniques, we compared neural activity during incongruent Stroop trial types that produce conflict at different levels of processing. Our data suggest that the involvement of anterior cingulate and right prefrontal cortex in attentional control is primarily limited to situations of response conflict, while the involvement of left prefrontal cortex extends to the occurrence of conflict at non-response levels.

Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks.

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

General and task-specific frontal lobe recruitment in older adults during executive processes: a fMRI investigation of task-switching.

Performance deteriorates when subjects must shift between two different tasks relative to performing either task separately. This switching cost is thought to result from executive processes that are not inherent to the component operations of either task when performed alone. Medial and dorsolateral frontal cortices are theorized to subserve these executive processes. Here we show that larger areas of activation were seen in dorsolateral and medial frontal cortex in both younger and older adults during switching than repeating conditions, confirming the role of these frontal brain regions in executive processes. Younger subjects activated these medial and dorsolateral frontal cortices only when switching between tasks; in contrast, older subjects recruited similar frontal regions while performing the tasks in isolation as well as alternating between them. Older adults recruit medial and dorsolateral frontal areas, and the processes computed by these areas, even when no such demands are intrinsic to the current task conditions. This neural recruitment may be useful in offsetting the declines in cognitive function associated with ageing.

WAIS-III and WMS-III profiles of mildly to severely brain-injured patients.

Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III; The Psychological Corporation, 1997) scores of patients with mild traumatic brain injury (MTBI, n = 23) to moderate-severe traumatic brain injury (M-S TBI, n = 22) were compared to those of 45 matched normal control patients. WAIS-III results revealed that IQ and index scores of MTBI patients did not significantly differ from those of controls, whereas M-S TBI patients received significantly lower mean scores on all measures. All M-S TBI patients' WMS-III index scores also revealed significantly lower scores in comparison to those of control participants, with the exception of Delayed Auditory Recognition. MTBI patients showed significantly lower mean index scores compared to normal controls on measures of immediate and delayed auditory memory, immediate memory, visual delayed memory, and general memory. Eta-squared analyses revealed that WMS-III visual indexes and WAIS-III processing speed showed particularly large effect sizes. These results suggest that symptomatic MTBI patients obtain some low WMS-III test scores comparable to those of more severely injured patients.

Prefrontal regions play a predominant role in imposing an attentional 'set': evidence from fMRI.

fMRI was used to determine whether prefrontal regions play a predominant role in imposing an attentional 'set' that drives selection of task-relevant information. While monitoring for an atypical item, individuals viewed Stroop stimuli that were either colored words or colored objects. Attentional demands were varied, being greater when the stimuli contained two distinct and incongruent sources of information about the task-relevant attribute (e.g., when attending to color, seeing the word 'blue' in red ink) as compared to only one source (e.g., seeing the word 'late' in red ink). Prefrontal but not anterior cingulate regions exhibited greater activation on incongruent than neutral trials, suggesting that prefrontal cortex has a major role in imposing an attentional 'set'. In addition, we found that prefrontal activation is most likely to occur when that attentional set is difficult to impose.

The interface between ADHD and language impairment: an examination of language, achievement, and cognitive processing.

Language impairments are commonly observed among children referred for psychiatric services. The most frequent psychiatric diagnosis of children with language impairment (LI) is Attention Deficit Hyperactivity Disorder (ADHD). It is not clear whether there are differences between children with ADHD and comorbid LI and children with other psychiatric disorders who are also comorbid for LI. In the present study the language, achievement, and cognitive processing characteristics of 166 psychiatrically referred 7-14-year-old children were examined using a 2 x 2 (ADHD, LI) design to examine four groups: children with ADHD + LI, children with ADHD who have normally developing language, children with psychiatric diagnoses other than ADHD with a language impairment (OPD + LI) or without a LI (OPD). Results indicated that children with LI were at the most disadvantage regardless of the nature of the psychiatric diagnosis. Contrary to prediction, working memory measures, used to tap the core cognitive deficit of ADHD in executive functions, were more closely associated with LI than with ADHD. It was concluded that caution must be exercised in attributing to children with ADHD what might be a reflection of problems for children with language impairment generally. As most therapies are verbally based it is notable that language competence is rarely evaluated systematically before such therapies are undertaken.

fMri studies of Stroop tasks reveal unique roles of anterior and posterior brain systems in attentional selection.

The brain's attentional system identifies and selects information that is task-relevant while ignoring information that is task-irrelevant. In two experiments using functional magnetic resonance imaging, we examined the effects of varying task-relevant information compared to task-irrelevant information. In the first experiment, we compared patterns of activation as attentional demands were increased for two Stroop tasks that differed in the task-relevant information, but not the task-irrelevant information: a color-word task and a spatial-word task. Distinct subdivisions of dorsolateral prefrontal cortex and the precuneus became activated for each task, indicating differential sensitivity of these regions to task-relevant information (e.g., spatial information vs. color). In the second experiment, we compared patterns of activation with increased attentional demands for two Stroop tasks that differed in task-irrelevant information, but not task-relevant information: a color-word task and color-object task. Little differentiation in activation for dorsolateral prefrontal and precuneus regions was observed, indicating a relative insensitivity of these regions to task-irrelevant information. However, we observed a differentiation in the pattern of activity for posterior regions. There were unique areas of activation in parietal regions for the color-word task and in occipitotemporal regions for the color-object task. No increase in activation was observed in regions responsible for processing the perceptual attribute of color. The results of this second experiment indicate that attentional selection in tasks such as the Stroop task, which contain multiple potential sources of relevant information (e.g., the word vs. its ink color), acts more by modulating the processing of task-irrelevant information than by modulating processing of task-relevant information.

Amnesia is a deficit in relational memory.

Eye movements were monitored to assess memory for scenes indirectly (implicitly). Two eye movement-based memory phenomena were observed: (a) the repetition effect, a decrease in sampling of previously viewed scenes compared with new scenes, reflecting memory for those scenes, and (b) the relational manipulation effect, an increase in viewing of the regions where manipulations of relations among scene elements had occurred. In normal control subjects, the relational manipulation effect was expressed only in the absence of explicit awareness of the scene manipulations. Thus, memory representations of scenes contain information about relations among elements of the scenes, at least some of which is not accessible to verbal report. But amnesic patients with severe memory impairment failed to show the relational manipulation effect. Their failure to show any demonstrable memory for relations among the constituent elements of scenes suggests that amnesia involves a fundamental deficit in relational (declarative) memory processing.