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People with multiple sclerosis (MS) exhibit pronounced changes in brain structure, activity, and connectivity. While considerable work has begun to elucidate how these neural changes contribute to behavior, the heterogeneity of symptoms and diagnoses makes interpretation of findings and application to clinical practice challenging. In particular, whether MS related changes

People with multiple sclerosis (MS) exhibit pronounced changes in brain structure, activity, and connectivity. While considerable work has begun to elucidate how these neural changes contribute to behavior, the heterogeneity of symptoms and diagnoses makes interpretation of findings and application to clinical practice challenging. In particular, whether MS related changes in brain activity or brain connectivity protect against or contribute to worsening motor symptoms is unclear. With the recent emergence of neuromodulatory techniques that can alter neural activity in specific brain regions, it is critical to establish whether localized brain activation patterns are contributing to (i.e. maladaptive) or protecting against (i.e. adaptive) progression of motor symptoms. In this manuscript, we consolidate recent findings regarding changes in supraspinal structure and activity in people with MS and how these changes may contribute to motor performance. Furthermore, we discuss a hypothesis suggesting that increased neural activity during movement may be either adaptive or maladaptive depending on where in the brain this increase is observed. Specifically, we outline preliminary evidence suggesting sensorimotor cortex activity in the ipsilateral cortices may be maladaptive in people with MS. We also discuss future work that could supply data to support or refute this hypothesis, thus improving our understanding of this important topic.

ContributorsPeterson, Daniel (Author) / Fling, Brett W. (Author) / College of Health Solutions (Contributor)
Created2017-09-28
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Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children

Recent studies suggest a role for the microbiota in autism spectrum disorders (ASD), potentially arising from their role in modulating the immune system and gastrointestinal (GI) function or from gut–brain interactions dependent or independent from the immune system. GI problems such as chronic constipation and/or diarrhea are common in children with ASD, and significantly worsen their behavior and their quality of life. Here we first summarize previously published data supporting that GI dysfunction is common in individuals with ASD and the role of the microbiota in ASD. Second, by comparing with other publically available microbiome datasets, we provide some evidence that the shifted microbiota can be a result of westernization and that this shift could also be framing an altered immune system. Third, we explore the possibility that gut–brain interactions could also be a direct result of microbially produced metabolites.

ContributorsKrajmalnik-Brown, Rosa (Author) / Lozupone, Catherine (Author) / Kang, Dae Wook (Author) / Adams, James (Author) / Biodesign Institute (Contributor)
Created2015-03-12
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Description

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

ContributorsFrye, Richard E. (Author) / Slattery, John (Author) / MacFabe, Derrick F. (Author) / Allen-Vercoe, Emma (Author) / Parker, William (Author) / Rodakis, John (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Bolte, Ellen (Author) / Kahler, Stephen (Author) / Jennings, Jana (Author) / James, Jill (Author) / Cerniglia, Carl E. (Author) / Midtvedt, Tore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-07
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Description

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children

Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

Results: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phage deep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).

Conclusions: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.

ContributorsKang, Dae Wook (Author) / Adams, James (Author) / Gregory, Ann C. (Author) / Borody, Thomas (Author) / Chittick, Lauren (Author) / Fasano, Alessio (Author) / Khoruts, Alexander (Author) / Geis, Elizabeth (Author) / Maldonado Ortiz, Juan (Author) / McDonough-Means, Sharon (Author) / Pollard, Elena (Author) / Roux, Simon (Author) / Sadowsky, Michael J. (Author) / Schwarzberg Lipson, Karen (Author) / Sullivan, Matthew B. (Author) / Caporaso, J. Gregory (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2017-01-23
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Description

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment,

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment, data collection, and data analytic protocols for the SPARC (Social impact of Physical Activity and nutRition in College) study, a longitudinal examination of the mechanisms by which friends and friendship networks influence nutrition and physical activity behaviors and weight gain in the transition to college life.

Methods: The SPARC study aims to follow 1450 university freshmen from a large university over an academic year, collecting data on multiple aspects of friends and friendship networks. Integrating multiple types of data related to student lives, ecological momentary assessments (EMAs) are administered via a cell phone application, devilSPARC. EMAs collected in four 1-week periods (a total of 4 EMA waves) are integrated with linked data from web-based surveys and anthropometric measurements conducted at four times points (for a total of eight data collection periods including EMAs, separated by ~1 month). University databases will provide student card data, allowing integration of both time-dated data on food purchasing, use of physical activity venues, and geographical information system (GIS) locations of these activities relative to other students in their social networks.

Discussion: Findings are intended to guide the development of more effective interventions to enhance behaviors among college students that protect against weight gain during college.

ContributorsBruening, Meg (Author) / Ohri-Vachaspati, Punam (Author) / Brewis, Alexandra (Author) / Laska, Melissa (Author) / Todd, Michael (Author) / Hruschka, Daniel (Author) / Schaefer, David (Author) / Whisner, Corrie (Author) / Dunton, Genevieve (Author) / College of Health Solutions (Contributor)
Created2016-08-30
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Description

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

ContributorsKang, Dae Wook (Author) / Park, Jin (Author) / Ilhan, Zehra (Author) / Wallstrom, Garrick (Author) / LaBaer, Joshua (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2013-06-03
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Description

Background: The number of days of pedometer or accelerometer data needed to reliably assess physical activity (PA) is important for research that examines the relationship with health. While this important research has been completed in young to middle-aged adults, data is lacking in older adults. Further, data determining the number of

Background: The number of days of pedometer or accelerometer data needed to reliably assess physical activity (PA) is important for research that examines the relationship with health. While this important research has been completed in young to middle-aged adults, data is lacking in older adults. Further, data determining the number of days of self-reports PA data is also void. The purpose of this study was to examine the number of days needed to predict habitual PA and sedentary behaviour across pedometer, accelerometer, and physical activity log (PA log) data in older adults.

Methods: Participants (52 older men and women; age = 69.3 ± 7.4 years, range= 55-86 years) wore a Yamax Digiwalker SW-200 pedometer and an ActiGraph 7164 accelerometer while completing a PA log for 21 consecutive days. Mean differences each instrument and intensity between days of the week were examined using separate repeated measures analysis of variance for with pairwise comparisons. Spearman-Brown Prophecy Formulae based on Intraclass Correlations of .80, .85, .90 and .95 were used to predict the number of days of accelerometer or pedometer wear or PA log daily records needed to represent total PA, light PA, moderate-to-vigorous PA, and sedentary behaviour.

Results: Results of this study showed that three days of accelerometer data, four days of pedometer data, or four days of completing PA logs are needed to accurately predict PA levels in older adults. When examining time spent in specific intensities of PA, fewer days of data are needed for accurate prediction of time spent in that activity for ActiGraph but more for the PA log. To accurately predict average daily time spent in sedentary behaviour, five days of ActiGraph data are needed.

Conclusions: The number days of objective (pedometer and ActiGraph) and subjective (PA log) data needed to accurately estimate daily PA in older adults was relatively consistent. Despite no statistical differences between days for total PA by the pedometer and ActiGraph, the magnitude of differences between days suggests that day of the week cannot be completely ignored in the design and analysis of PA studies that involve < 7-day monitoring protocols for these instruments. More days of accelerometer data were needed to determine typical sedentary behaviour than PA level in this population of older adults.

ContributorsHart, Teresa (Author) / Swartz, Ann M. (Author) / Cashin, Susan E. (Author) / Strath, Scott J. (Author) / College of Health Solutions (Contributor)
Created2011-06-16
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Description

Background: Five accelerometer-derived methods of identifying nonwear and wear time were compared with a self-report criterion in adults ≥ 56 years of age.

Methods: Two hundred participants who reported wearing an Actical™ activity monitor for four to seven consecutive days and provided complete daily log sheet data (i.e., the criterion) were included. Four variables were

Background: Five accelerometer-derived methods of identifying nonwear and wear time were compared with a self-report criterion in adults ≥ 56 years of age.

Methods: Two hundred participants who reported wearing an Actical™ activity monitor for four to seven consecutive days and provided complete daily log sheet data (i.e., the criterion) were included. Four variables were obtained from log sheets: 1) dates the device was worn; 2) time(s) the participant put the device on each day; 3) time(s) the participant removed the device each day; and 4) duration of self-reported nonwear each day. Estimates of wear and nonwear time using 60, 90, 120, 150 and 180 minutes of consecutive zeroes were compared to estimates derived from log sheets.

Results: Compared with the log sheet, mean daily wear time varied from -84, -43, -24, -14 and -8 min/day for the 60-min, 90-min, 120-min, 150-min and 180-min algorithms, respectively. Daily log sheets indicated 8.5 nonwear bouts per week with 120-min, 150-min and 180-min algorithms estimating 8.2-8.9 nonwear bouts per week. The 60-min and 90-min methods substantially overestimated number of nonwear bouts per week and underestimated time spent in sedentary behavior. Sensitivity (number of compliant days correctly identified as compliant) improved with increasing minutes of consecutive zero counts and stabilized at the 120-min algorithm. The proportion of wear time being sedentary and absolute and proportion of time spent in physical activity of varying intensities were nearly identical for each method.

Conclusions: Utilization of at least 120 minutes of consecutive zero counts will provide dependable population-based estimates of wear and nonwear time, and time spent being sedentary and active in older adults wearing the Actical™ activity monitor.

ContributorsHutto, Brent (Author) / Howard, Virginia J. (Author) / Blair, Steven N. (Author) / Colabianchi, Natalie (Author) / Vena, John E. (Author) / Rhodes, David (Author) / Hooker, Stephen (Author) / College of Health Solutions (Contributor)
Created2013-10-25
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In spite of well-documented health benefits of vegetarian diets, less is known regarding the effects of these diets on athletic performance. In this cross-sectional study, we compared elite vegetarian and omnivore adult endurance athletes for maximal oxygen uptake (VO2 max) and strength. Twenty-seven vegetarian (VEG) and 43 omnivore (OMN) athletes

In spite of well-documented health benefits of vegetarian diets, less is known regarding the effects of these diets on athletic performance. In this cross-sectional study, we compared elite vegetarian and omnivore adult endurance athletes for maximal oxygen uptake (VO2 max) and strength. Twenty-seven vegetarian (VEG) and 43 omnivore (OMN) athletes were evaluated using VO2 max testing on the treadmill, and strength assessment using a dynamometer to determine peak torque for leg extensions. Dietary data were assessed using detailed seven-day food logs. Although total protein intake was lower among vegetarians in comparison to omnivores, protein intake as a function of body mass did not differ by group (1.2 ± 0.3 and 1.4 ± 0.5 g/kg body mass for VEG and OMN respectively, p = 0.220). VO2 max differed for females by diet group (53.0 ± 6.9 and 47.1 ± 8.6 mL/kg/min for VEG and OMN respectively, p < 0.05) but not for males (62.6 ± 15.4 and 55.7 ± 8.4 mL/kg/min respectively). Peak torque did not differ significantly between diet groups. Results from this study indicate that vegetarian endurance athletes’ cardiorespiratory fitness was greater than that for their omnivorous counterparts, but that peak torque did not differ between diet groups. These data suggest that vegetarian diets do not compromise performance outcomes and may facilitate aerobic capacity in athletes.

ContributorsLynch, Heidi (Author) / Wharton, Christopher (Author) / Johnston, Carol (Author) / College of Health Solutions (Contributor)
Created2016-11-15
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This manuscript explores the role of embodied views of language comprehension and production in bilingualism and specific language impairment. Reconceptualizing popular models of bilingual language processing, the embodied theory is first extended to this area. Issues such as semantic grounding in a second language and potential differences between early and

This manuscript explores the role of embodied views of language comprehension and production in bilingualism and specific language impairment. Reconceptualizing popular models of bilingual language processing, the embodied theory is first extended to this area. Issues such as semantic grounding in a second language and potential differences between early and late acquisition of a second language are discussed. Predictions are made about how this theory informs novel ways of thinking about teaching a second language. Secondly, the comorbidity of speech, language, and motor impairments and how embodiment theory informs the discussion of the etiology of these impairments is examined. A hypothesis is presented suggesting that what is often referred to as specific language impairment may not be so specific due to widespread subclinical motor deficits in this population. Predictions are made about how weaknesses and instabilities in speech motor control, even at a subclinical level, may disrupt the neural network that connects acoustic input, articulatory motor plans, and semantics. Finally, I make predictions about how this information informs clinical practice for professionals such as speech language pathologists and occupational and physical therapists. These new hypotheses are placed within the larger framework of the body of work pertaining to semantic grounding, action-based language acquisition, and action-perception links that underlie language learning and conceptual grounding.

ContributorsAdams, Ashley (Author) / College of Health Solutions (Contributor)
Created2016-08-17