Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review.

Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences. Emerging evidence suggests that vitamin B-12 may have an important role in other aspects of human health, including the composition and function of the gastrointestinal (gut) microbiome. Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required for over a dozen enzymes in bacteria, compared to only 2 in humans. However, the impact of vitamin B-12 on the gut microbiome has not been established. This systematic review was conducted to examine the evidence that links vitamin B-12 and the gut microbiome. A structured search strategy was used to identify in vitro, animal, and human studies that assessed vitamin B-12 status, dietary intake, or supplementation, and the gut microbiome using culture-independent techniques. A total of 22 studies (3 in vitro, 8 animal, 11 human observational studies) were included. Nineteen studies reported that vitamin B-12 intake, status, or supplementation was associated with gut microbiome outcomes, including beta-diversity, alpha-diversity, relative abundance of bacteria, functional capacity, or short-chain fatty acids (SCFA) production. Evidence suggests that vitamin B-12 may be associated with changes in bacterial abundance. While results from in vitro studies suggest that vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), findings from animal studies and observational human studies were heterogeneous. Based on evidence from in vitro and animal studies, microbiome outcomes may differ by cobalamin form and co-intervention. To date, few prospective observational studies and no randomized trials have been conducted to examine the effects of vitamin B-12 on the human gut microbiome. The impact of vitamin B-12 on the gut microbiome needs to be elucidated to inform screening and public health interventions.

Delayed cortical processing of auditory stimuli in children with autism spectrum disorder: A meta-analysis of electrophysiological studies.

Several researchers have hypothesised that individuals with Autism Spectrum Disorder (ASD) show encoding delays in their obligatory event-related potentials (ERPs)/ event-related fields (ERFs) for low-level auditory information compared to neurotypical (NT) samples. However, empirical research has yielded varied findings, such as low-level auditory processing in ASD samples being unimpaired, superior, or impaired compared to NT samples. Diverse outcomes have also been reported for studies investigating ASD-NT differences in functional lateralisation of delays. The lack of consistency across studies has prevented a comprehensive understanding of the overall effects in the autistic population. Therefore, this meta-analysis compared long-latency ERPs and ERFs produced by autistic and NT individuals to non-linguistic auditory stimuli to test, firstly, the robustness of auditory processing differences and, secondly, whether these differences are observed in one or both hemispheres. Nine articles meeting the inclusion criteria were included in the meta-analysis. Meta-analytic results indicated that autistic individuals demonstrate bilaterally delayed P1/ M50 peaks and lateralised delays in the right but not left hemisphere N1/ M100 peak. These results further inform our understanding of auditory processing and lateralisation across the autism spectrum.

Fast fronto-parietal cortical dynamics of conflict detection and context updating in a flanker task.

Recent research has found that the traditional target P3 consists of a family of P3-like positivities that can be functionally and topographically dissociated from one another. The current study examined target N2 and P3-like subcomponents indexing conflict detection and context updating at low- and high-order levels in the neural hierarchy during cognitive control. Electroencephalographic signals were recorded from 45 young adults while they completed a hybrid go/nogo flanker task, and Residue Iteration Decomposition (RIDE) was applied to functionally dissociate these peaks. Analyses showed a stimulus-locked frontal N2 revealing early detection and fast perceptual categorization of nogo, congruent and incongruent trials, resulting in frontal P3-like activity elicited by nogo trials in the latency-variable RIDE cluster, and by incongruent trials in the response-locked cluster. The congruent trials did not elicit frontal P3-like activity. These findings suggest that behavioral incongruency effects are related to intermediate and later stages of motor response re-programming.

The relationship between naturalistic sleep variation and error monitoring in young adults: An event-related potential (ERP) study.

Sleep deprivation studies have highlighted the importance of adequate sleep for optimal daytime functioning. However, there is limited research exploring whether variations in natural sleep patterns produce similar difficulties to those seen in sleep deprivation studies. The aim of the current study was to explore whether naturalistic reductions in sleep duration and/or sleep quality were associated with behavioural and electrophysiological measures of cognitive control. Sixty undergraduate students were asked to wear an actigraph for 7 consecutive nights before completing a hybrid Flanker-Go/NoGo task whilst continuous EEG data were recorded. Participants were assigned to high or low sleep quality and short or long sleep duration groups using the National Sleep Foundation guidelines. Results indicated that individuals who, on average, slept <7 h each night showed inefficiencies in error-monitoring, as reflected by a reduction in amplitude of the error-related negativity (ERN) in comparison to those with longer sleep duration. These findings suggest that natural variations in sleep quantity are associated with atypical error detection.

Development of inhibition and switching: A longitudinal study of the maturation of interference suppression and reversal processes during childhood.

Inhibition and switching are executive functions (EFs) that have different developmental trajectories across childhood. The development of specific processes unique to each EF may contribute to these trajectories. Interference suppression and reversal were examined in a large sample of children aged 7 and 9 years (n = 120) and followed-up after two-years to investigate developmental trajectories of inhibition and switching. The N2 and P3b components provided neural correlates of conflict monitoring and attentional processing of conflict involved in interference suppression and reversal. Interference suppression improved over time, however, switching performance did not significantly change between 7 and 11 years. Improvements in correct RT with age and time indicated increased efficiency of stimulus evaluation, response preparation and execution. N2 amplitude decreased with both age and time, indicating less reliance on conflict monitoring to signal cognitive control to manage stimulus and response conflict. P3b amplitude modulations indicated that different amounts of attention were allocated to updating mental representations of interference suppression and reversal task features. These data indicated different developmental trajectories of specific processes unique to inhibition and switching across the childhood period of 7-11 years, providing further empirical evidence that 7-11 years is a critical period for cognitive development.

Hemispheric asymmetries in rapid temporal processing at age 7 predict subsequent phonemic decoding 2 years later: A longitudinal event-related potential (ERP) study.

The asymmetric sampling in time hypothesis (AST) suggests that the left and right secondary auditory areas process auditory stimuli according to different sampling rates (Poeppel, 2003). We investigated whether asymmetries consistent with the AST are observable in children at age 7 and whether they become more pronounced at age 9. Data were collected from 50 children who attended a 2-day research program at age 7 and were followed up 2 years later. At both time points, children were presented with tone-pairs, each composed of two 50 ms, 1000 Hz, sinusoidal tones separated by inter-stimulus intervals (ISIs) of 25, 50, 100, or 200 ms. Stimuli were presented binaurally whilst the EEG was recorded. The Ta and Tb, which are components of the auditory event-related potential (ERP), were used as electrophysiological indices of auditory processing. There was no significant effect of age on Ta or Tb responses. Tb responses to the second tone of tone-pairs indicated a left-hemisphere preference for rapidly presented stimuli (50 ms ISI) and a right hemisphere preference for more slowly presented stimuli (100 and 200 ms ISI). The results provide evidence that auditory areas of the left hemisphere preferentially respond to fast temporal rates, and those of the right hemisphere preferentially respond to slow temporal rates in children at age 7 and 9. In 7-year-old children, leftward lateralisation of responses to rapidly presented tones predicted better phonemic decoding ability 2 years later, which suggests that hemispheric specialisation may be a precursor for subsequent phonemic decoding skills.

The error-related negativity (ERN) is an electrophysiological marker of motor impulsiveness on the Barratt Impulsiveness Scale (BIS-11) during adolescence.

OBJECTIVES: Previous studies have postulated that the error-related negativity (ERN) may reflect individual differences in impulsivity; however, none have used a longitudinal framework or evaluated impulsivity as a multidimensional construct. The current study evaluated whether ERN amplitude, measured in childhood and adolescence, is predictive of impulsiveness during adolescence. METHODS: Seventy-five children participated in this study, initially at ages 7-9 years and again at 12-18 years. The interval between testing sessions ranged from 5 to 9 years. The ERN was extracted in response to behavioural errors produced during a modified visual flanker task at both time points (i.e. childhood and adolescence). Participants also completed the Barratt Impulsiveness Scale - a measure that considers impulsiveness to comprise three core sub-traits - during adolescence. RESULTS: At adolescence, the ERN amplitude was significantly larger than during childhood. Additionally, ERN amplitude during adolescence significantly predicted motor impulsiveness at that time point, after controlling for age, gender, and the number of trials included in the ERN. In contrast, ERN amplitude during childhood did not uniquely predict impulsiveness during adolescence. CONCLUSIONS: These findings provide preliminary evidence that ERN amplitude is an electrophysiological marker of self-reported motor impulsiveness (i.e. acting without thinking) during adolescence.

Allelic variation in dopamine D2 receptor gene is associated with attentional impulsiveness on the Barratt Impulsiveness Scale (BIS-11).

OBJECTIVES: Previous studies have postulated that noradrenergic and/or dopaminergic gene variations are likely to underlie individual differences in impulsiveness, however, few have shown this. The current study examined the relationship between catecholamine gene variants and self-reported impulsivity, as measured by the Barratt Impulsiveness Scale (Version 11; BIS-11) Methods: Six hundred and seventy-seven non-clinical adults completed the Barratt Impulsiveness Scale (BIS-11). DNA was analysed for a set of 142 single-nucleotide polymorphisms (SNPs) across 20 autosomal catecholamine genes. Association was tested using an additive regression model with permutation testing used to control for the influence of multiple comparison. RESULTS: Analysis revealed an influence of rs4245146 of the dopamine D2 receptor (DRD2) gene on the BIS-11 attention first-order factor, such that self-reported attentional impulsiveness increased in an additive fashion with each copy of the T allele. CONCLUSIONS: These findings provide preliminary evidence that allelic variation in DRD2 may influence impulsiveness by increasing the propensity for attentional lapses.

Verbal Learning and Memory in Cannabis and Alcohol Users: An Event-Related Potential Investigation.

Aims: Long-term heavy use of cannabis and alcohol are known to be associated with memory impairments. In this study, we used event-related potentials to examine verbal learning and memory processing in a commonly used behavioral task. Method: We conducted two studies: first, a small pilot study of adolescent males, comprising 13 Drug-Naive Controls (DNC), 12 heavy drinkers (HD) and 8 cannabis users (CU). Second, a larger study of young adults, comprising 45 DNC (20 female), 39 HD (16 female), and 20 CU (9 female). In both studies, participants completed a modified verbal learning task (the Rey Auditory Verbal Learning Test, RAVLT) while brain electrical activity was recorded. ERPs were calculated for words which were subsequently remembered vs. those which were not remembered, and for presentations of learnt words, previously seen words, and new words in a subsequent recognition test. Pre-planned principal components analyses (PCA) were used to quantify the ERP components in these recall and recognition phases separately for each study. Results: Memory performance overall was slightly lower than published norms using the standardized RAVLT delivery, but was generally similar and showed the expected changes over trials. Few differences in performance were observed between groups; a notable exception was markedly poorer delayed recall in HD relative to DNC (Study 2). PCA identified components expected from prior research using other memory tasks. At encoding, there were no between-group differences in the usual P2 recall effect (larger for recalled than not-recalled words). However, alcohol-related differences were observed in a larger P540 (indexing recollection) in HD than DNC, and cannabis-related differences were observed in a smaller N340 (indexing familiarity) and a lack of previously seen > new words effect for P540 in Study 2. Conclusions: This study is the first examination of ERPs in the RAVLT in healthy control participants, as well as substance-using individuals, and represents an important advance in methodology. The results indicate alterations in recognition memory processing, which even if not manifesting in overt behavioral impairment, underline the potential for brain dysfunction with early exposure to alcohol and cannabis.

Assessing hemispheric specialization for processing arithmetic skills in adults: A functional transcranial doppler ultrasonography (fTCD) study.

BACKGROUND: A major model of the cerebral circuits that underpin arithmetic calculation is the triple-code model of numerical processing. This model proposes that the lateralization of mathematical operations is organized across three circuits: a left-hemispheric dominant verbal code; a bilateral magnitude representation of numbers and a bilateral Arabic number code. NEW METHOD: This study simultaneously measured the blood flow of both middle cerebral arteries using functional transcranial Doppler ultrasonography to assess hemispheric specialization during the performance of both language and arithmetic tasks. The propositions of the triple-code model were assessed in a non-clinical adult group by measuring cerebral blood flow during the performance of multiplication and subtraction problems. Participants were 17 adults aged between 18-27 years. We obtained laterality indices for each type of mathematical operation and compared these in participants with left-hemispheric language dominance. It was hypothesized that blood flow would lateralize to the left hemisphere during the performance of multiplication operations, but would not lateralize during the performance of subtraction operations. RESULTS: Hemispheric blood flow was significantly left lateralized during the multiplication task, but was not lateralized during the subtraction task. COMPARISON WITH EXISTING METHOD(S): Compared to high spatial resolution neuroimaging techniques previously used to measure cerebral lateralization, functional transcranial Doppler ultrasonography is a cost-effective measure that provides a superior temporal representation of arithmetic cognition. CONCLUSIONS: These results provide support for the triple-code model of arithmetic processing and offer complementary evidence that multiplication operations are processed differently in the adult brain compared to subtraction operations.

Error monitoring and empathy: Explorations within a neurophysiological context.

Past literature has proposed that empathy consists of two components: cognitive and affective empathy. Error monitoring mechanisms indexed by the error-related negativity (ERN) have been associated with empathy. Studies have found that a larger ERN is associated with higher levels of empathy. We aimed to expand upon previous work by investigating how error monitoring relates to the independent theoretical domains of cognitive and affective empathy. Study 1 (N = 24) explored the relationship between error monitoring mechanisms and subcomponents of empathy using the Questionnaire of Cognitive and Affective Empathy and found no relationship. Study 2 (N = 38) explored the relationship between the error monitoring mechanisms and overall empathy. Contrary to past findings, there was no evidence to support a relationship between error monitoring mechanisms and scores on empathy measures. A subsequent meta-analysis (Study 3, N = 125) summarizing the relationship across previously published studies together with the two studies reported in the current paper indicated that overall there was no significant association between ERN and empathy and that there was significant heterogeneity across studies. Future investigations exploring the potential variables that may moderate these relationships are discussed.

N2 and P3 modulation during partial inhibition in a modified go/nogo task.

The neural response following the partial inhibition of responses can provide insight into the processes underlying response inhibition. We examined the N2 and P3 on trials where participants correctly responded to go stimuli, successfully inhibited their response to nogo stimuli, and nogo trials where they initiated but did not complete their response (partial inhibitions) in an adult sample (N=24, M(age)=21.17, SD(age)=3.52). An enhanced and delayed N2 was observed on partially inhibited compared to successfully inhibited nogo trials. Further analysis showed that this modulation was error-related. An enhanced central P3 was observed following successful inhibitions compared to correct go trials, but not following partial inhibitions. The results suggest that the central P3 enhancement is specific to the complete and successful inhibition of responses. Therefore, the absence of a central P3 on partial inhibitions could reflect insufficient inhibition or a monitored failure in inhibiting the response. Although, our findings provide support for the role of P3 in response inhibition, it raises questions about the processes involved in the subsequent inhibition or correction of the erroneous response. Further research examining the neural response following both partial and unsuccessful inhibitions could provide insight regarding these processes.

Global shape processing: A behavioral and electrophysiological analysis of both contour and texture processing.

The number of corners on the boundary of a closed contour is thought to be particularly critical for shape detection and discrimination. The aim of the current study was to examine the relative contribution of the number of corners and the angle between corners to shape discrimination in complex visual scenes as well as to determine the time course and neural substrates of global shape processing based on the presence or absence of these specific features. In Experiment 1, event-related potentials were recorded while participants discriminated between two radial frequency (RF) patterns with the same maximum local curvature defining corners but varying arrangements of those corners. The results showed that the angle separating corners was more critical than the overall number of corners for discrimination performance. An enhanced negativity (posterior N220) over the occipital lobe was elicited following the presentation of an RF with three modulation cycles (RF3) but not following a circle, suggesting that the posterior N220 is sensitive to variation in curvature on a contour. In Experiment 2, we confirm the primary effect of the presence of corners on the amplitude of the posterior N220 component and extend the stimuli to include shapes defined by texture. Source localization on the N170 and N220 components was conducted in Experiment 2, and a source in cortical area V4 was identified. These findings suggest that corners contain vital information for the discrimination of shapes. Additionally, this study shows that the perceptual characteristics and neuroanatomical substrates can be detected using electrophysiological measures.

Hemispheric asymmetries in auditory temporal integration: a study of event-related potentials.

According to the asymmetric sampling in time hypothesis, the left auditory cortex processes stimuli using a short temporal integration window (~25-50 ms), whereas the right auditory cortex processes stimuli using a long temporal integration window (~200 ms). We examined N1 and T-complex responses to the second tone of tone-pairs presented with inter-stimulus intervals (ISIs) of 50 and 200 ms. Twenty-seven undergraduate students were presented with stimuli binaurally whilst the EEG was recorded. N1 and Ta responses were symmetric between hemispheres, with responses elicited by the second tone of the 50 ms ISI tone-pairs. Tb responses to the second tones were significantly attenuated over the right hemisphere when compared to the left hemisphere for the 50 ms ISI tone-pairs, but returned to similar amplitudes in the 200 ms condition. Our results suggest that temporal integration windows of the left and right primary auditory areas are symmetric whereas those of the left and right secondary auditory areas are asymmetric. These findings are consistent with the asymmetric sampling in time hypothesis and provide justification for further investigation of the involvement of temporal integration in higher order auditory processes.

Impaired practice effects following mild traumatic brain injury: an event-related potential investigation.

BACKGROUND: The negative effects of mild traumatic brain injury (mTBI) on attention are well established. Effects of practice on neuropsychological test performance have also been long recognized and more recently linked to electrophysiological indices of information processing. OBJECTIVE: The current study examined the behavioural and electrophysiological impact of mTBI on consistent practice of a neuropsychological test of attention. RESEARCH DESIGN: Prospective cohort study. METHODS: Adult participants with a history of mild TBI (n = 10; time since injury > 2 months, mean = 15.2 months) and healthy matched controls (n = 10) completed the Paced Auditory Serial Addition Task (PASAT) at four separate sessions. Event-related potentials (ERPs) were simultaneously recorded. RESULTS: Accuracy of PASAT performance in both groups improved significantly with practice. In healthy controls behavioural improvements were associated with significant attenuation of a frontally distributed ERP component marker of executive attention. These executive attention demands did not appear to ease with consistent practice in the mTBI group, who also endorsed more concussion-related symptoms. CONCLUSIONS: These preliminary results suggest sustained mental effort is required to achieve 'normal' performance levels following mTBI and support the use of practice-related, ERP indices of recovery from mTBI as a sensitive correlate of persistent post-concussion symptoms.

Predictive validity of the N2 and P3 ERP components to executive functioning in children: a latent-variable analysis.

Executive functions (EFs) are commonly theorized to be related yet separable constructs in adults, and specific EFs, such as prepotent response inhibition and working memory, are thought to have clear and distinct neural underpinnings. However, recent evidence suggests that EFs are unitary in children up to about 9 years of age. The aim of the current study was to test the hypothesis that peaks of the event-related potential (ERP) of specific EFs are related to behavioral performance, despite EFs being psychometrically indistinguishable in children. Specifically, N2 difference waveform (associated with cognitive control and response inhibition) and P3b peak (associated with updating of working memory) latent variables were created and entered into confirmatory factor analysis and structural equation models with a unitary executive functioning factor. Children aged 7-9 years (N = 215) completed eight measures of inhibition, working memory, and shifting. A modified flanker task was also completed during which EEG data were recorded. The N2 difference waveform and P3b mean amplitude factors both significantly correlated with (and were predictors of) the executive functioning factor, but the P3b latency factor did not. These results provide evidence of the electrophysiological indices of EFs being observable before the associated behavioral constructs are distinguishable from each other. From this, it is possible that ERPs could be used as a sensitive measure of development in the context of evaluation for neuropsychological interventions.

Maturation of cognitive control: delineating response inhibition and interference suppression.

Cognitive control is integral to the ability to attend to a relevant task whilst suppressing distracting information or inhibiting prepotent responses. The current study examined the development of these two subprocesses by examining electrophysiological indices elicited during each process. Thirteen 18 year-old adults and thirteen children aged 8-11 years (mean=9.77 years) completed a hybrid Go/Nogo flanker task while continuous EEG data were recorded. The N2 topography for both response inhibition and interference suppression changed with increasing age. The neural activation associated with response inhibition became increasingly frontally distributed with age, and showed decreases of both amplitude and peak latency from childhood to adulthood, possibly due to reduced cognitive demands and myelination respectively occurring during this period. Interestingly, a significant N2 effect was apparent in adults, but not observed in children during trials requiring interference suppression. This could be due to more diffuse activation in children, which would require smaller levels of activation over a larger region of the brain than is reported in adults. Overall, these results provide evidence of distinct maturational processes occurring throughout late childhood and adolescence, highlighting the separability of response inhibition and interference suppression.

Performance monitoring among non-patients with obsessive-compulsive symptoms: ERP evidence of aberrant feedback monitoring.

Electrophysiological studies have shown that obsessive-compulsive disorder (OCD) is associated with hyperactive performance monitoring, as indexed by the error-related negativity (ERN). The aim of the present study was to determine whether feedback monitoring is enhanced in addition to error monitoring among young adults with obsessive-compulsive symptomatology during performance of a learning task. The ERN was equivalent in amplitude for low and high OC groups. The feedback-related negativity (FRN) was more negative following presentation of incorrect feedback relative to correct feedback for the low OC group. For the high OC group, the FRN was equivalent in amplitude for correct and incorrect feedback. Young adults with high levels of obsessive-compulsive symptoms demonstrate aberrant feedback monitoring characterised by a lack of differentiation to the valence of feedback. This pattern of results may be indicative of a cognitive bias in outcome prediction associated with obsessive-compulsive symptomatology.

Dissociable components of cognitive control: an event-related potential (ERP) study of response inhibition and interference suppression.

BACKGROUND: Cognitive control refers to the ability to selectively attend and respond to task-relevant events while resisting interference from distracting stimuli or prepotent automatic responses. The current study aimed to determine whether interference suppression and response inhibition are separable component processes of cognitive control. METHODOLOGY/PRINCIPAL FINDINGS: Fourteen young adults completed a hybrid Go/Nogo flanker task and continuous EEG data were recorded concurrently. The incongruous flanker condition (that required interference suppression) elicited a more centrally distributed topography with a later N2 peak than the Nogo condition (that required response inhibition). CONCLUSIONS/SIGNIFICANCE: These results provide evidence for the dissociability of interference suppression and response inhibition, indicating that taxonomy of inhibition is warranted with the integration of research evidence from neuroscience.

Maturation of rapid auditory temporal processing and subsequent nonword repetition performance in children.

According to the rapid auditory processing theory, the ability to parse incoming auditory information underpins learning of oral and written language. There is wide variation in this low-level perceptual ability, which appears to follow a protracted developmental course. We studied the development of rapid auditory processing using event-related potentials (ERPs) elicited by tone pairs presented at varying inter-stimulus intervals (25, 50, 100, 200, and 400 ms) in a sample of children (N = 103) aged 7-9 years initially and again at 9-11 years. We also assessed their ability to repeat nonsense words at both time-points. The amount of difference between the ERP to single tones and paired tones (as assessed by the intra-class correlation coefficient, ICC) provided a measure of the brain's capacity to discriminate auditory information delivered at different presentation rates. Results showed that older children showed greater neural discrimination to tone pairs than younger children at rapid presentation rates, although these differences were reduced at slower presentation rates. The ICC at time 1 significantly predicted nonword repetition scores two years later, providing support for the view that rapid auditory temporal processing ability affects oral language development in typically developing children.