Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder.

It has been suggested that aberrant excitation/inhibition (E/I) balance and dysfunctional structure and function of relevant brain networks may underlie the symptoms of autism spectrum disorder (ASD). However, the nomological network linking these constructs to quantifiable measures and mechanistically relating these constructs to behavioral symptoms of ASD is lacking. Herein we describe a within-subject, controlled, proof-of-mechanism study investigating the pathophysiology of auditory/language processing in adolescents with ASD. We utilize neurophysiological and neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) metrics of language network structure and function. Additionally, we apply a single, individually targeted session of continuous theta burst stimulation (cTBS) as an experimental probe of the impact of perturbation of the system on these neurophysiological and neuroimaging outcomes. MRS, fMRI, and MEG measures are evaluated at baseline and immediately prior to and following cTBS over the posterior superior temporal cortex (pSTC), a region involved in auditory and language processing deficits in ASD. Also, behavioral measures of ASD and language processing and DWI measures of auditory/language network structures are obtained at baseline to characterize the relationship between the neuroimaging and neurophysiological measures and baseline symptom presentation. We hypothesize that local gamma-aminobutyric acid (GABA) and glutamate concentrations (measured with MRS), and structural and functional activity and network connectivity (measured with DWI and fMRI), will significantly predict MEG indices of auditory/language processing and behavioral deficits in ASD. Furthermore, a single session of cTBS over left pSTC is hypothesized to lead to significant, acute changes in local glutamate and GABA concentration, functional activity and network connectivity, and MEG indices of auditory/language processing. We have completed the pilot phase of the study (n=20 Healthy Volunteer adults) and have begun enrollment for the main phase with adolescents with ASD (n=86; age 14-17). If successful, this study will establish a nomological network linking local E/I balance measures to functional and structural connectivity within relevant brain networks, ultimately connecting them to ASD symptoms. Furthermore, this study will inform future therapeutic trials using cTBS to treat the symptoms of ASD.

Diffusion tensor imaging findings and neuropsychological performance in adults with TBI across the spectrum of severity in the chronic-phase.

PRIMARY OBJECTIVE: To examine associations between neuroimaging indicators of cerebral tract integrity and neurocognitive functioning in traumatic brain injury (TBI). RESEARCH DESIGN: Between-Groups design with two TBI groups and controls. METHOD AND PROCEDURES: Forty-four participants with TBI and 27 matched controls completed diffusion tensor imaging and neuropsychological measures of processing speed, attention, memory, and executive function. Multivariate analyses were conducted to examine group differences in white matter integrity (fractional anisotropy) for 11 regions of interest and cognitive performance among adult males with chronic phase, mild, moderate, or severe TBI. Correlational analyses investigated associations between white matter integrity, brain injury severity, and cognitive status. MAIN OUTCOMES AND RESULTS: Participants with moderate or severe TBI exhibited reduced white matter integrity in 8 of 11 ROIs and worse performance on most cognitive measures, relative to control participants. Persons with mild TBI did not differ from controls on white matter integrity values and differed on one measure of processing speed. Significant correlations were found between injury severity ratings and 10 ROIs, most notably between ROIs and measures of processing speed or memory. CONCLUSIONS: These findings provide nuanced information regarding white matter connectivity as it relates to neurocognitive abilities across the TBI severity spectrum.

Complexity analysis of resting state magnetoencephalography activity in traumatic brain injury patients.

Diagnosis of mild traumatic brain injuries (TBIs) has been difficult because of the absence of obvious focal brain lesions, using conventional computed tomography (CT) or magnetic resonance imaging (MRI) scans, in a large percentage of TBIs. One useful measure that can characterize potential tissue and neural network damage objectively is Lempel-Ziv complexity (LZC) applied to magnetoencephalography (MEG) signals. LZC is a model-independent estimator of system complexity that estimates the number of different patterns in a sequence. We hypothesized that because of the potential network damage, TBIs would show a reduced level of complexity in regions that are impaired. We included 18 healthy controls and 18 military veterans with TBI in the study. Resting state MEG data were acquired, and the LZCs were analyzed across the whole brain. Our results indicated reduced complexity in multiple brain areas in TBI patients relative to the healthy controls. In addition, we detected several neuropsychological measures associated with motor responses, visual perception, and memory, correlated with LZC, which likely explains some of the cognitive deficits in TBI patients.

Acute loading and aging effects on myostatin pathway biomarkers in human skeletal muscle after three sequential bouts of resistance exercise.

To determine the influence of age and resistance exercise on myostatin pathway-related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1-T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway-related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism.

IGF-1 splice variant and IGF-1 peptide expression patterns in young and old human skeletal muscle prior to and following sequential exercise bouts.

Genes and proteins involved in insulin-like growth factor (IGF)-1 signaling are thought to be differentially expressed in older versus younger mammalian skeletal muscle following acute exercise. The purpose of this study was to examine how multiple bouts of conventional resistance training meant to elicit hypertrophy affect the mRNA expression of IGF-1EA and IGF-1EC (MGF) as well as the expression of total IGF-1 peptides in human skeletal muscle. Ten younger (18-25 years) and 10 older (60-75 years) males completed three sequential workouts (M, W, F) consisting of nine sets of lower body exercises with ten repetitions per set at an intensity of 80% of one repetition maximum. Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). RT-PCR was performed to assess baseline and changes in MGF and IGF-IEA mRNA. Samples were also assayed for total muscle IGF-1 peptides using ELISA-based methods. There were no baseline differences in MGF or IGF-1EA mRNA expression and IGF-1 peptides between age groups. Interestingly, MGF expression increased at T2-T4 in the older group relative to baseline values (p < 0.05), albeit muscle IGF-1EA mRNA and IGF-1 peptides remained stably expressed throughout the intervention in both age groups. Repeated conventional exercise bouts resulted in a summative increase in MGF mRNA expression only in older individuals which is contrary to previous research examining this gene at different post-exercise time points, albeit the physiological consequences of these findings remain unknown.

International society of sports nutrition position stand: caffeine and performance.

Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (>/= 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance.

International Society of Sports Nutrition position stand: nutrient timing.

Position Statement: The position of the Society regarding nutrient timing and the intake of carbohydrates, proteins, and fats in reference to healthy, exercising individuals is summarized by the following eight points: 1.) Maximal endogenous glycogen stores are best promoted by following a high-glycemic, high-carbohydrate (CHO) diet (600 - 1000 grams CHO or ~8 - 10 g CHO/kg/d), and ingestion of free amino acids and protein (PRO) alone or in combination with CHO before resistance exercise can maximally stimulate protein synthesis. 2.) During exercise, CHO should be consumed at a rate of 30 - 60 grams of CHO/hour in a 6 - 8% CHO solution (8 - 16 fluid ounces) every 10 - 15 minutes. Adding PRO to create a CHO:PRO ratio of 3 - 4:1 may increase endurance performance and maximally promotes glycogen re-synthesis during acute and subsequent bouts of endurance exercise. 3.) Ingesting CHO alone or in combination with PRO during resistance exercise increases muscle glycogen, offsets muscle damage, and facilitates greater training adaptations after either acute or prolonged periods of supplementation with resistance training. 4.) Post-exercise (within 30 minutes) consumption of CHO at high dosages (8 - 10 g CHO/kg/day) have been shown to stimulate muscle glycogen re-synthesis, while adding PRO (0.2 g - 0.5 g PRO/kg/day) to CHO at a ratio of 3 - 4:1 (CHO: PRO) may further enhance glycogen re-synthesis. 5.) Post-exercise ingestion (immediately to 3 h post) of amino acids, primarily essential amino acids, has been shown to stimulate robust increases in muscle protein synthesis, while the addition of CHO may stimulate even greater levels of protein synthesis. Additionally, pre-exercise consumption of a CHO + PRO supplement may result in peak levels of protein synthesis. 6.) During consistent, prolonged resistance training, post-exercise consumption of varying doses of CHO + PRO supplements in varying dosages have been shown to stimulate improvements in strength and body composition when compared to control or placebo conditions. 7.) The addition of creatine (Cr) (0.1 g Cr/kg/day) to a CHO + PRO supplement may facilitate even greater adaptations to resistance training. 8.) Nutrient timing incorporates the use of methodical planning and eating of whole foods, nutrients extracted from food, and other sources. The timing of the energy intake and the ratio of certain ingested macronutrients are likely the attributes which allow for enhanced recovery and tissue repair following high-volume exercise, augmented muscle protein synthesis, and improved mood states when compared with unplanned or traditional strategies of nutrient intake.