Age-related decline in positive emotional reactivity and emotion regulation in a population-derived cohort.

Human older age ushers in functional decline across the majority of cognitive domains. A notable exception seems to be affective processing, with older people reporting higher levels of emotional well-being. Here we evaluated age-related changes in emotional reactivity and regulation in a representative subsample (N = 104; age range: 23-88 years) of the population-derived Cambridge Centre for Ageing and Neuroscience cohort. Performance on a film-based emotion reactivity and regulation task in the magnetic resonance imaging scanner showed an age-related decline in positive reactivity, alongside a similar decline in the capacity to down-regulate negative affect. Decreased positivity with age was associated with reduced activation in the middle frontal gyrus. These findings, from the largest neuroimaging investigation to-date, provide no support for age-related increases in positive emotional reactivity.

Understanding mental health in the research environment: A Rapid Evidence Assessment.

This study aimed to establish what is known about the mental health of researchers based on the existing literature. There is limited published evidence on the prevalence of specific mental health conditions among researchers. The majority of the identified literature on prevalence relates to work-related stress among academic staff and postgraduate students in university settings. Survey data indicate that the majority of university staff find their job stressful. Levels of burnout appear higher among university staff than in general working populations and are comparable to "high-risk" groups such as healthcare workers. The proportions of both university staff and postgraduate students with a risk of having or developing a mental health problem, based on self-reported evidence, were generally higher than for other working populations. Large proportions (>40 per cent) of postgraduate students report symptoms of depression, emotion or stress-related problems, or high levels of stress. Factors including increased job autonomy, involvement in decision making and supportive management were linked to greater job satisfaction among academics, as was the amount of time spent on research. Opportunities for professional development were also associated with reduced stress. UK higher education (HE) and research staff report worse wellbeing, as compared to staff in other sectors, in most aspects of work that can affect workers' stress levels. The evidence around the effectiveness of interventions to support the mental health of researchers specifically is thin. Few interventions are described in the literature and even fewer of those have been evaluated.

Developmental differences in intra-individual variability in children with ADHD and ASD.

BACKGROUND: Intra-individual variability reflects temporal variation within an individual's performance on a cognitive task. Children with developmental disorders, such as ADHD and ASD show increased levels of intra-individual variability. In typical development, intra-individual variability decreases sharply between the ages 6 and 20. The tight link between intra-individual variability and age has led to the suggestion that it may be marker of neural development. As there is accumulating evidence that ADHD and ASD are characterised by atypical neurodevelopmental trajectories, we set out to explore developmental changes in intra-individual variability in subjects with ADHD and ASD. METHOD: We used propensity score matching to match a cross-sectional sample of children with ADHD, ASD and control subjects (N = 405, aged 6-19 years old) for age, IQ and gender. We used ex-Gaussian distribution parameters to characterise intra-individual variability on fast responses (sigma) and slow responses (tau). RESULT: Results showed that there was a similar decrease in mean response times with age across groups, and an interaction between age and group for measures of variability, where there was a much lower rate of change in the variability parameters (sigma and tau) for subjects with ASD compared with the other two groups. Subjects with ADHD had higher intra-individual variability, reflected by both sigma and tau, but the rate of decrease in variability with age was similar to that of the controls. CONCLUSION: These results suggest that subjects with ADHD, ASD and controls differ in the rate at which intra-individual variability decreases during development, and support the idea that intra-individual variability may be a marker of neural development, mimicking the neurodevelopmental changes in these disorders.

Capturing the dynamics of response variability in the brain in ADHD.

ADHD is characterized by increased intra-individual variability in response times during the performance of cognitive tasks. However, little is known about developmental changes in intra-individual variability, and how these changes relate to cognitive performance. Twenty subjects with ADHD aged 7-24 years and 20 age-matched, typically developing controls participated in an fMRI-scan while they performed a go-no-go task. We fit an ex-Gaussian distribution on the response distribution to objectively separate extremely slow responses, related to lapses of attention, from variability on fast responses. We assessed developmental changes in these intra-individual variability measures, and investigated their relation to no-go performance. Results show that the ex-Gaussian measures were better predictors of no-go performance than traditional measures of reaction time. Furthermore, we found between-group differences in the change in ex-Gaussian parameters with age, and their relation to task performance: subjects with ADHD showed age-related decreases in their variability on fast responses (sigma), but not in lapses of attention (tau), whereas control subjects showed a decrease in both measures of variability. For control subjects, but not subjects with ADHD, this age-related reduction in variability was predictive of task performance. This group difference was reflected in neural activation: for typically developing subjects, the age-related decrease in intra-individual variability on fast responses (sigma) predicted activity in the dorsal anterior cingulate gyrus (dACG), whereas for subjects with ADHD, activity in this region was related to improved no-go performance with age, but not to intra-individual variability. These data show that using more sophisticated measures of intra-individual variability allows the capturing of the dynamics of task performance and associated neural changes not permitted by more traditional measures.

Common and unique neural networks for proactive and reactive response inhibition revealed by independent component analysis of functional MRI data.

Response inhibition involves proactive and reactive modes. Proactive inhibition is goal-directed, triggered by warning cues, and serves to restrain actions. Reactive inhibition is stimulus-driven, triggered by salient stop-signals, and used to stop actions completely. Functional MRI studies have identified brain regions that activate during proactive and reactive inhibition. It remains unclear how these brain regions operate in functional networks, and whether proactive and reactive inhibition depend on common networks, unique networks, or a combination. To address this we analyzed a large fMRI dataset (N=65) of a stop-signal task designed to measure proactive and reactive inhibition, using independent component analysis (ICA). We found 1) three frontal networks that were associated with both proactive and reactive inhibition, 2) one network in the superior parietal lobe, which also included dorsal premotor cortex and left putamen, that was specifically associated with proactive inhibition, and 3) two right-lateralized frontal and fronto-parietal networks, including the right inferior frontal gyrus and temporoparietal junction as well as a bilateral fronto-temporal network that were uniquely associated with reactive inhibition. Overlap between networks was observed in dorsolateral prefrontal and parietal cortices. Taken together, we offer a new perspective on the neural underpinnings of inhibitory control, by showing that proactive inhibition and reactive inhibition are supported by a group of common and unique networks that appear to integrate and interact in frontoparietal areas.

Deficits in cognitive control, timing and reward sensitivity appear to be dissociable in ADHD.

Recent neurobiological models of ADHD suggest that deficits in different neurobiological pathways may independently lead to symptoms of this disorder. At least three independent pathways may be involved: a dorsal frontostriatal pathway involved in cognitive control, a ventral frontostriatal pathway involved in reward processing and a frontocerebellar pathway related to temporal processing. Importantly, we and others have suggested that disruptions in these three pathways should lead to separable deficits at the cognitive level. Furthermore, if these truly represent separate biological pathways to ADHD, these cognitive deficits should segregate between individuals with ADHD. The present study tests these hypotheses in a sample of children, adolescents and young adults with ADHD and controls. 149 Subjects participated in a short computerized battery assessing cognitive control, timing and reward sensitivity. We used Principal Component Analysis to find independent components underlying the variance in the data. The segregation of deficits between individuals was tested using Loglinear Analysis. We found four components, three of which were predicted by the model: Cognitive control, reward sensitivity and timing. Furthermore, 80% of subjects with ADHD that had a deficit were deficient on only one component. Loglinear Analysis statistically confirmed the independent segregation of deficits between individuals. We therefore conclude that cognitive control, timing and reward sensitivity were separable at a cognitive level and that deficits on these components segregated between individuals with ADHD. These results support a neurobiological framework of separate biological pathways to ADHD with separable cognitive deficits.

Differential brain development with low and high IQ in attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development.In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is associated more with a delay of cortical development.

Imaging gene and environmental effects on cerebellum in Attention-Deficit/Hyperactivity Disorder and typical development.

This study investigates the effects of XKR4, a recently identified candidate gene for Attention-Deficit/Hyperactivity Disorder (ADHD), birth weight, and their interaction on brain volume in ADHD. XKR4 is expressed in cerebellum and low birth weight has been associated both with changes in cerebellum and with ADHD, probably due to its relation with prenatal adversity. Anatomical MRI scans were acquired in 58 children with ADHD and 64 typically developing controls and processed to obtain volumes of cerebrum, cerebellum and gray and white matter in each structure. DNA was collected from saliva. Analyses including data on birth weight were conducted in a subset of 37 children with ADHD and 51 controls where these data were retrospectively collected using questionnaires. There was an interaction between genotype and birth weight for cerebellum gray matter volume (p = .020). The combination of homozygosity for the G-allele (the allele previously found to be overtransmitted in ADHD) and higher birth weight was associated with smaller volume. Furthermore, birth weight was positively associated with cerebellar white matter volume in controls, but not ADHD (interaction: p = .021). The interaction of genotype with birth weight affecting cerebellum gray matter is consistent with models that emphasize increased influence of genetic risk-factors in an otherwise favorable prenatal environment. The absence of an association between birth weight and cerebellum white matter volume in ADHD suggests that other genetic or environmental effects may be at play, unrelated to XKR4. These results underscore the importance of considering environmental effects in imaging genetics studies.

Functional connectivity between cognitive control regions is sensitive to familial risk for ADHD.

Familial risk for attention-deficit hyperactivity disorder (ADHD) has been associated with changes in brain activity related to cognitive control. However, it is not clear whether changes in activation are the primary deficit or whether they are related to impaired communication between regions involved in this ability. We investigated whether (1) functional connectivity between regions involved in cognitive control was affected by familial risk and (2) changes were specific to these regions. Correlational seed analyses were used to investigate temporal covariance between cognitive control and motor regions in two independent samples of typically developing controls, subjects with ADHD and their unaffected siblings. In both samples, correlation coefficients between cognitive control regions were greater for typically developing controls than for subjects with ADHD, with intermediate values for unaffected siblings. Within the motor network, unaffected siblings showed correlations similar to typically developing children. There were no differences in activity between the brain regions involved. These data show that functional connectivity between cognitive control regions is sensitive to familial risk for ADHD. Results suggest that changes in connectivity associated with cognitive control may be suitable as an intermediate phenotype for future studies.

Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has long been conceptualized as a neurobiological disorder of the prefrontal cortex and its connections. Circuits with the prefrontal cortex relevant to ADHD include dorsal frontostriatal, orbitofronto-striatal, and fronto-cerebellar circuits. Dorsal frontostriatal circuitry has been linked to cognitive control, whereas orbitofronto-striatal loops have been related to reward processing. Fronto-cerebellar circuits have been implicated in timing. Neurobiological dysfunction in any of these circuits could lead to symptoms of ADHD, as behavioral control could be disturbed by: 1) deficits in the prefrontal cortex itself; or 2) problems in the circuits relaying information to the prefrontal cortex, leading to reduced signaling for control. This article suggests a model for differentiating between interlinked reciprocal circuits with the prefrontal cortex in ADHD. If such a differentiation can be achieved, it might permit a neurobiological subtyping of ADHD, perhaps by defining "dorsal fronto-striatal," "orbitofronto-striatal," or "fronto-cerebellar" subtypes of ADHD. This could be useful as a template for investigating the neurobiology of ADHD and, ultimately, clinically.

Basic impairments in regulating the speed-accuracy tradeoff predict symptoms of attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by poor optimization of behavior in the face of changing demands. Theoretical accounts of ADHD have often focused on higher-order cognitive processes and typically assume that basic processes are unaffected. It is an open question whether this is indeed the case. METHOD: We explored basic cognitive processing in 25 subjects with ADHD and 30 typically developing children and adolescents with a perceptual decision-making paradigm. We investigated whether individuals with ADHD were able to balance the speed and accuracy of decisions. RESULTS: We found impairments in the optimization of the speed-accuracy tradeoff. Furthermore, these impairments were directly related to the hyperactive and impulsive symptoms that characterize the ADHD-phenotype. CONCLUSIONS: These data suggest that impairments in basic cognitive processing are central to the disorder. This calls into question conceptualizations of ADHD as a "higher-order" deficit, as such simple decision processes are at the core of almost every paradigm used in ADHD research.

The effects of time-on-task and concurrent cognitive load on normal visuospatial bias.

Research suggests that the severity of left spatial neglect can be modulated by changes in general alertness. Analogous effects in healthy volunteers now suggest that this may reflect an amplified form of a normal pattern. Recent neuropsychological studies also suggest that concurrent cognitive load may exacerbate rightward bias. In this study, for the first time, the authors examined the effect of both factors on spatial bias in healthy volunteers. Participants performed a task in which as many letters as possible needed to be reported from a briefly presented visual array under three conditions (alone, with a syllable-discrimination secondary task and with a pitch-discrimination secondary task). The results confirmed a significant rightward shift associated with time-on-task across all conditions--the first demonstration of such an effect within a fixation controlled, brief presentation task. While the secondary tasks influenced overall visual performance, there was no discernable effect on bias.