Inhibition, Shifting and Updating: Inter and intra-domain commonalities and differences from an executive functions activation likelihood estimation meta-analysis.

Executive functions are higher-order mental processes that support goal-directed behavior. Among these processes, Inhibition, Updating, and Shifting have been considered core executive domains. In this meta-analysis, we comprehensively investigate the neural networks of these executive domains and we synthesize for the first time the neural convergences and divergences among the most frequently used executive paradigms within those domains. A systematic search yielded 1055 published neuroimaging studies (including 26,191 participants in total). Our study revealed that a fronto-parietal network was shared by the three main domains. Furthermore, we executed conjunction analyses among the paradigms of the same domain to extract the core distinctive components of the main executive domains. This approach showed that Inhibition and Shifting are characterized by a strongly lateralized neural activation in the right and left hemisphere, respectively. In addition, both networks overlapped with the Updating network but not with each other. Remarkably, our study detected heterogeneity among the paradigms from the same domain. More specifically, analysis of Inhibition tasks revealed differing activations for Response Inhibition compared to Interference Control paradigms, suggesting that Inhibition encompasses relatively heterogeneous sub-functions. Shifting analyses revealed a bilateral overlap of the Wisconsin Card Sorting Task with the Updating network, but this pattern was absent for Rule Switching and Dual Task paradigms. Moreover, our Updating meta-analyses revealed the neural signatures associated with the specific modules of the Working Memory model from Baddeley and Hitch. To our knowledge, this is the most comprehensive meta-analysis of executive functions to date. Its paradigm-driven analyses provide a unique contribution to a better understanding of the neural convergences and divergences among executive processes that are relevant for clinical applications, such as cognitive enhancement and neurorehabilitation interventions.

Sex differences in risk-based decision making in adolescents with conduct disorder.

Altered decision making processes and excessive risk-seeking behaviours are key features of conduct disorder (CD). Previous studies have provided compelling evidence of abnormally increased preference for risky options, higher sensitivity to rewards, as well as blunted responsiveness to aversive outcomes in adolescents with CD. However, most studies published to date have focused on males only; thus, it is not known whether females with CD show similar alterations in decision making. The current study investigated potential sex differences in decision making and risk-seeking behaviours in adolescents with CD. Forty-nine adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18 years, performed a computerised task assessing decision making under risk-the Risky Choice Task. Participants made a series of decisions between two gamble options that varied in terms of their expected values and probability of gains and losses. This enabled the participants' risk preferences to be determined. Taking the sample as a whole, adolescents with CD exhibited increased risk-seeking behaviours compared to healthy controls. However, we found a trend towards a sex-by-group interaction, suggesting that these effects may vary by sex. Follow-up analyses showed that males with CD made significantly more risky choices than their typically developing counterparts, while females with CD did not differ from typically developing females in their risk-seeking behaviours. Our results provide preliminary evidence that sex may moderate the relationship between CD and alterations in risk attitudes and reward processing, indicating that there may be sex differences in the developmental pathways and neuropsychological deficits that lead to CD.

Altered intrinsic organisation of brain networks implicated in attentional processes in adult attention-deficit/hyperactivity disorder: a resting-state study of attention, default mode and salience network connectivity.

Deficits in task-related attentional engagement in attention-deficit/hyperactivity disorder (ADHD) have been hypothesised to be due to altered interrelationships between attention, default mode and salience networks. We examined the intrinsic connectivity during rest within and between these networks. Six-minute resting-state scans were obtained. Using a network-based approach, connectivity within and between the dorsal and ventral attention, the default mode and the salience networks was compared between the ADHD and control group. The ADHD group displayed hyperconnectivity between the two attention networks and within the default mode and ventral attention network. The salience network was hypoconnected to the dorsal attention network. There were trends towards hyperconnectivity within the dorsal attention network and between the salience and ventral attention network in ADHD. Connectivity within and between other networks was unrelated to ADHD. Our findings highlight the altered connectivity within and between attention networks, and between them and the salience network in ADHD. One hypothesis to be tested in future studies is that individuals with ADHD are affected by an imbalance between ventral and dorsal attention systems with the former playing a dominant role during task engagement, making individuals with ADHD highly susceptible to distraction by salient task-irrelevant stimuli.

Anticipatory processes in brain state switching - evidence from a novel cued-switching task implicating default mode and salience networks.

The default mode network (DMN) is the core brain system supporting internally oriented cognition. The ability to attenuate the DMN when switching to externally oriented processing is a prerequisite for effective performance and adaptive self-regulation. Right anterior insula (rAI), a core hub of the salience network (SN), has been proposed to control the switching from DMN to task-relevant brain networks. Little is currently known about the extent of anticipatory processes subserved by DMN and SN during switching. We investigated anticipatory DMN and SN modulation using a novel cued-switching task of between-state (rest-to-task/task-to-rest) and within-state (task-to-task) transitions. Twenty healthy adults performed the task implemented in an event-related functional magnetic resonance imaging (fMRI) design. Increases in activity were observed in the DMN regions in response to cues signalling upcoming rest. DMN attenuation was observed for rest-to-task switch cues. Obversely, DMN was up-regulated by task-to-rest cues. The strongest rAI response was observed to rest-to-task switch cues. Task-to-task switch cues elicited smaller rAI activation, whereas no significant rAI activation occurred for task-to-rest switches. Our data provide the first evidence that DMN modulation occurs rapidly and can be elicited by short duration cues signalling rest- and task-related state switches. The role of rAI appears to be limited to certain switch types - those implicating transition from a resting state and to tasks involving active cognitive engagement.

Bridging cognition and action: executive functioning mediates the relationship between white matter fiber density and complex motor abilities in older adults.

Aging may be associated with motor decline that is attributed to deteriorating white matter microstructure of the corpus callosum (CC), among other brain-related factors. Similar to motor functioning, executive functioning (EF) typically declines during aging, with age-associated changes in EF likewise being linked to altered white matter connectivity in the CC. Given that both motor and executive functions rely on white matter connectivity via the CC, and that bimanual control is thought to rely on EF, the question arises whether EF can at least party account for the proposed link between CC-connectivity and motor control in older adults. To address this, diffusion magnetic resonance imaging data were obtained from 84 older adults. A fiber-specific approach was used to obtain fiber density (FD), fiber cross-section (FC), and a combination of both metrics in eight transcallosal white matter tracts. Motor control was assessed using a bimanual coordination task. EF was determined by a domain-general latent EF-factor extracted from multiple EF tasks, based on a comprehensive test battery. FD of transcallosal prefrontal fibers was associated with cognitive and motor performance. EF partly accounted for the relationship between FD of prefrontal transcallosal pathways and motor control. Our results underscore the multidimensional interrelations between callosal white matter connectivity (especially in prefrontal brain regions), EF across multiple domains, and motor control in the older population. They also highlight the importance of considering EF when investigating brain-motor behavior associations in older adults.

Cognition and action: a latent variable approach to study contributions of executive functions to motor control in older adults.

Aging is associated with profound alterations in motor control that may be exacerbated by age-related executive functioning decline. Executive functions span multiple facets including inhibition (suppressing unwanted response tendencies), shifting (switching between cognitive operations), and updating (managing working memory content). However, comprehensive studies regarding the contributions of single facets of executive functioning to movement control in older adults are still lacking. A battery of nine neuropsychological tasks was administered to n = 92 older adults in order to derive latent factors for inhibition, shifting, and updating by structural equation modeling. A bimanual task was used to assess complex motor control. A sample of n = 26 young adults served as a control group to verify age-related performance differences. In older adults, structural equation models revealed that performance on the most challenging condition of the complex motor task was best predicted by the updating factor and by general executive functioning performance. These data suggest a central role for working memory updating in complex motor performance and contribute to our understanding of how individual differences in executive functioning relate to movement control in older adults.

Altered proactive control in adults with ADHD: Evidence from event-related potentials during cued task switching.

Cognitive control has two distinct modes - proactive and reactive (Braver, T. S. (2012). The variable nature of cognitive control: a dual mechanisms framework. Trends in Cognitive Sciences, 16(2), 105-112). ADHD has been associated with cognitive control impairments. However, studies have mainly focused on reactive control and not proactive control. Here we investigated neural correlates of proactive and reactive cognitive control in a group of adults with ADHD versus healthy controls by employing a cued switching task while cue informativeness was manipulated and EEG recorded. On the performance level, only a trend to generally slower responding was found in the ADHD group. Cue-locked analyses revealed an attenuated informative-positivity - a differential component appearing when contrasting informative with non-informative alerting cues - and potentially altered lateralisation of the switch-positivity - evident in the contrast between switch and repeat trials for informative cues - in ADHD. No difference in target-locked activity was found. Our results indicate altered proactive rather than reactive control in adults with ADHD, evidenced by less use of cued advance information and abnormal preparatory processes for upcoming tasks.

Sex Differences in the Relationship Between Conduct Disorder and Cortical Structure in Adolescents.

OBJECTIVE: Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure. METHOD: As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status-matched controls (14-18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume. RESULTS: CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset. CONCLUSION: We found both similarities and differences between males and females in CD-cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments.

Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.