Developmental maturation of dynamic causal control signals in higher-order cognition: a neurocognitive network model.
ABSTRACT: Cognitive skills undergo protracted developmental changes resulting in proficiencies that are a hallmark of human cognition. One skill that develops over time is the ability to problem solve, which in turn relies on cognitive control and attention abilities. Here we use a novel multimodal neurocognitive network-based approach combining task-related fMRI, resting-state fMRI and diffusion tensor imaging (DTI) to investigate the maturation of control processes underlying problem solving skills in 7-9 year-old children. Our analysis focused on two key neurocognitive networks implicated in a wide range of cognitive tasks including control: the insula-cingulate salience network, anchored in anterior insula (AI), ventrolateral prefrontal cortex and anterior cingulate cortex, and the fronto-parietal central executive network, anchored in dorsolateral prefrontal cortex and posterior parietal cortex (PPC). We found that, by age 9, the AI node of the salience network is a major causal hub initiating control signals during problem solving. Critically, despite stronger AI activation, the strength of causal regulatory influences from AI to the PPC node of the central executive network was significantly weaker and contributed to lower levels of behavioral performance in children compared to adults. These results were validated using two different analytic methods for estimating causal interactions in fMRI data. In parallel, DTI-based tractography revealed weaker AI-PPC structural connectivity in children. Our findings point to a crucial role of AI connectivity, and its causal cross-network influences, in the maturation of dynamic top-down control signals underlying cognitive development. Overall, our study demonstrates how a unified neurocognitive network model when combined with multimodal imaging enhances our ability to generalize beyond individual task-activated foci and provides a common framework for elucidating key features of brain and cognitive development. The quantitative approach developed is likely to be useful in investigating neurodevelopmental disorders, in which control processes are impaired, such as autism and ADHD.
Project description:Cognitive control plays an important role in goal-directed behavior, but dynamic brain mechanisms underlying it are poorly understood. Here, using multisite fMRI data from over 100 participants, we investigate causal interactions in three cognitive control tasks within a core Frontal-Cingulate-Parietal network. We found significant causal influences from anterior insula (AI) to dorsal anterior cingulate cortex (dACC) in all three tasks. The AI exhibited greater net causal outflow than any other node in the network. Importantly, a similar pattern of causal interactions was uncovered by two different computational methods for causal analysis. Furthermore, the strength of causal interaction from AI to dACC was greater on high, compared with low, cognitive control trials and was significantly correlated with individual differences in cognitive control abilities. These results emphasize the importance of the AI in cognitive control and highlight its role as a causal hub in the Frontal-Cingulate-Parietal network. Our results further suggest that causal signaling between the AI and dACC plays a fundamental role in implementing cognitive control and are consistent with a two-stage cognitive control model in which the AI first detects events requiring greater access to cognitive control resources and then signals the dACC to execute load-specific cognitive control processes.
Project description:Cognitive control allows the coordination of cognitive processes to achieve goals. Control may be sustained in anticipation of goal-relevant cues (proactive control) or transient in response to the cues themselves (reactive control). Adolescents typically exhibit a more reactive pattern than adults in the absence of incentives. We investigated how reward modulates cognitive control engagement in a letter-array working memory (WM) task in 30 adolescents (12-17 years) and 20 adults (23-30 years) using a mixed block- and event-related functional magnetic resonance imaging design. After a Baseline run without rewards, participants performed a Reward run where 50% trials were monetarily rewarded. Accuracy and reaction time (RT) differences between Reward and Baseline runs indicated engagement of proactive control, which was associated with increased sustained activity in the bilateral anterior insula (AI), right dorsolateral prefrontal cortex (PFC) and right posterior parietal cortex (PPC). RT differences between Reward and No reward trials of the Reward run suggested additional reactive engagement of cognitive control, accompanied with transient activation in bilateral AI, lateral PFC, PPC, supplementary motor area, anterior cingulate cortex, putamen and caudate. Despite behavioural and neural differences during Baseline WM task performance, adolescents and adults showed similar modulations of proactive and reactive control by reward.
Project description:The frontal lobes are one of the most complex brain structures involved in both domain-general and specific functions. The goal of this work was to assess the anatomical and cognitive affectations from a unique case with massive bilateral frontal affectation. We report the case of GC, an eight-year old child with nearly complete affectation of bilateral frontal structures and spared temporal, parietal, occipital, and cerebellar regions. We performed behavioral, neuropsychological, and imaging (MRI, DTI, fMRI) evaluations. Neurological and neuropsychological examinations revealed a mixed pattern of affected (executive control/abstraction capacity) and considerably preserved (consciousness, language, memory, spatial orientation, and socio-emotional) functions. Both structural (DTI) and functional (fMRI) connectivity evidenced abnormal anterior connections of the amygdala and parietal networks. In addition, brain structural connectivity analysis revealed almost complete loss of frontal connections, with atypical temporo-posterior pathways. Similarly, functional connectivity showed an aberrant frontoparietal network and relative preservation of the posterior part of the default mode network and the visual network. We discuss this multilevel pattern of behavioral, structural, and functional connectivity results. With its unique pattern of compromised and preserved structures and functions, this exceptional case offers new constraints and challenges for neurocognitive theories.
Project description:Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes.
Project description:Juvenile myoclonic epilepsy (JME) is characterized by myoclonic jerks of the upper limbs, often triggered by cognitive stressors. Here we aim to reconcile this particular seizure phenotype with the known frontal lobe type neuropsychological profile, photosensitivity, hyperexcitable motor cortex, and recent advanced imaging studies that identified abnormal functional connectivity of the motor cortex and supplementary motor area (SMA).We acquired fMRI and diffusion tensor imaging (DTI) in a cohort of 29 patients with JME and 28 healthy control subjects. We used fMRI to determine functional connectivity and DTI-based region parcellation and voxel-wise comparison of probabilistic tractography data to assess the structural connectivity profiles of the mesial frontal lobe.Patients with JME showed alterations of mesial frontal connectivity with increased structural connectivity between the prefrontal cognitive cortex and motor cortex. We found a positive correlation between DTI and fMRI-based measures of structural and functional connectivity: the greater the structural connectivity between these 2 regions, the greater the observed functional connectivity of corresponding areas. Furthermore, connectivity was reduced between prefrontal and frontopolar regions and increased between the occipital cortex and the SMA.The observed alterations in microstructural connectivity of the mesial frontal region may represent the anatomic basis for cognitive triggering of motor seizures in JME. Changes in the mesial frontal connectivity profile provide an explanatory framework for several other clinical observations in JME and may be the link between seizure semiology, neurophysiology, neuropsychology, and imaging findings in JME.
Project description:BACKGROUND:Attentional disruptions are common in PTSD, but findings across neuropsychological and neuroimaging studies have been variable. Few PTSD studies have investigated abnormalities in attention networks using a multi-modal imaging approach and attentional tasks that include emotionally-salient images. This study combined a behavioral task that included these images (emotional Stroop) with functional and structural neuroimaging (fMRI and diffusion tensor imaging; DTI) methods to comprehensively investigate attentional control abnormalities in a highly-traumatized civilian sample. METHODS:48 traumatized women with and without PTSD received clinical assessments, fMRI and DTI. During fMRI, the Affective Stroop (AS), an attentional control task that includes emotionally-salient distractor images (trauma-relevant, positive, neutral) and variable task demands, was administered. RESULTS:In response to more difficult AS trials, participants with PTSD demonstrated lower activation in the dorsal and rostral anterior cingulate cortex and greater activation in the insula. This group also showed comparatively poorer performance on positive AS distractor trials, even after adjusting for trauma exposure. Performance on these trials inversely correlated with structural integrity of the cingulum bundle and uncinate fasciculus. CONCLUSIONS:Even after adjusting for trauma exposure, participants with PTSD showed worse performance on an attentional control task in the context of emotional stimuli. They also showed relatively lower cognitive control network activation and greater salience network activation. Fronto-parietal and fronto-limbic white matter connectivity corresponded with AS performance. Our findings indicate that attentional control impairments in PTSD are most evident in the context of emotional cues, and are related to decrements in function and structure of cognitive control and salience networks.
Project description:The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects.
Project description:BACKGROUND AND PURPOSE:Diffusion and fMRI has been providing insights to brain development in addition to anatomic imaging. This study aimed to evaluate the microstructure of white matter tracts underlying the default mode network in premature infants by using resting-state functional MR imaging in conjunction with diffusion tensor imaging-based tractography. MATERIALS AND METHODS:A cohort of 44 preterm infants underwent structural T1-weighted imaging, resting-state fMRI, and DTI at 3T, including 21 infants with brain injuries and 23 infants with normal-appearing structural imaging as controls. Neurodevelopment was evaluated with the Bayley Scales of Infant Development at 12 months' adjusted age. Probabilistic independent component analysis was applied to resting-state fMRI data to explore resting-state networks. The localized clusters of the default mode network were used as seeding for probabilistic tractography. The DTI metrics (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) of the reconstructed primary tracts within the default mode network-cingula were measured. RESULTS:Results revealed decreased fractional anisotropy (0.20 ± 0.03) and elevated radial diffusivity values (1.24 ± 0.16) of the cingula in the preterm infants with brain injuries compared with controls (fractional anisotropy, 0.25 ± 0.03; P < .001; radial diffusivity, 1.06 ± 0.16; P = .001). The Bayley Scales of Infant Development cognitive scores were significantly associated with cingulate fractional anisotropy (P = .004) and radial diffusivity (P = .021); this association suggests that the microstructural properties of interconnecting axonal pathways within the default mode network are of critical importance in the early neurocognitive development of infants. CONCLUSIONS:This study of combined resting-state fMRI and DTI at rest suggests that such studies may allow the investigation of key functional brain circuits in premature infants, which could function not only as diagnostic tools but also as biomarkers for long-term neurodevelopmental outcomes.
Project description:Huntington's disease (HD) is a genetically caused neurodegenerative disorder characterized by heterogeneous motor, psychiatric, and cognitive symptoms. Although motor symptoms may be the most prominent presentation, cognitive symptoms such as memory deficits and executive dysfunction typically co-occur. We used functional magnetic resonance imaging (fMRI) and task fMRI-based dynamic causal modeling (DCM) to evaluate HD-related changes in the neural network underlying working memory (WM). Sixty-four pre-symptomatic HD mutation carriers (preHD), 20 patients with early manifest HD symptoms (earlyHD), and 83 healthy control subjects performed an <i>n</i>-back fMRI task with two levels of WM load. Effective connectivity was assessed in five predefined regions of interest, comprising bilateral inferior parietal cortex, left anterior cingulate cortex, and bilateral dorsolateral prefrontal cortex. HD mutation carriers performed less accurately and more slowly at high WM load compared with the control group. While between-group comparisons of brain activation did not reveal differential recruitment of the cortical WM network in mutation carriers, comparisons of brain connectivity as identified with DCM revealed a number of group differences across the whole WM network. Most strikingly, we observed decreasing connectivity from several regions toward right dorsolateral prefrontal cortex (rDLPFC) in preHD and even more so in earlyHD. The deterioration in rDLPFC connectivity complements results from previous studies and might mirror beginning cortical neural decline at premanifest and early manifest stages of HD. We were able to characterize effective connectivity in a WM network of HD mutation carriers yielding further insight into patterns of cognitive decline and accompanying neural deterioration.