Project description:The frontoparietal control network (FPCN) plays a central role in executive control. It has been predominantly viewed as a unitary domain general system. Here, we examined patterns of FPCN functional connectivity (FC) across multiple conditions of varying cognitive demands, to test for FPCN heterogeneity. We identified two distinct subsystems within the FPCN based on hierarchical clustering and machine learning classification analyses of within-FPCN FC patterns. These two FPCN subsystems exhibited distinct patterns of FC with the default network (DN) and the dorsal attention network (DAN). FPCNA exhibited stronger connectivity with the DN than the DAN, whereas FPCNB exhibited the opposite pattern. This twofold FPCN differentiation was observed across four independent datasets, across nine different conditions (rest and eight tasks), at the level of individual-participant data, as well as in meta-analytic coactivation patterns. Notably, the extent of FPCN differentiation varied across conditions, suggesting flexible adaptation to task demands. Finally, we used meta-analytic tools to identify several functional domains associated with the DN and DAN that differentially predict activation in the FPCN subsystems. These findings reveal a flexible and heterogeneous FPCN organization that may in part emerge from separable DN and DAN processing streams. We propose that FPCNA may be preferentially involved in the regulation of introspective processes, whereas FPCNB may be preferentially involved in the regulation of visuospatial perceptual attention.
Project description:Attention dysfunction is a common but often undiagnosed cognitive impairment in Parkinson's disease that significantly reduces quality of life. We sought to increase understanding of the mechanisms underlying attention dysfunction using functional neuroimaging. Functional MRI was acquired at two repeated sessions in the resting state and during the Attention Network Test, for 25 non-demented subjects with Parkinson's disease and 21 healthy controls. Behavioral and MRI contrasts were calculated for alerting, orienting, and executive control components of attention. Brain regions showing group differences in attention processing were used as seeds in a functional connectivity analysis of a separate resting state run. Parkinson's disease subjects showed more activation during increased executive challenge in four regions of the dorsal attention and frontoparietal networks, namely right frontal eye field, left and right intraparietal sulcus, and precuneus. In three regions we saw reduced resting state connectivity to the default mode network. Further, whereas higher task activation in the right intraparietal sulcus correlated with reduced resting state connectivity between right intraparietal sulcus and the precuneus in healthy controls, this relationship was absent in Parkinson's disease subjects. Our results suggest that a weakened interaction between the default mode and task positive networks might alter the way in which the executive response is processed in PD.
Project description:The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as underconnected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD.Resting-state functional magnetic resonance imaging and an anatomically informed approach were used to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate regression analyses were used to test whether altered patterns of connectivity are predictive of social impairment severity.Compared with TD children, children with ASD demonstrated hyperconnectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypoconnectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyperconnectivity was linked with severity of social impairments in ASD, whereas precuneus hypoconnectivity was unrelated to social deficits. Consistent with previous work in healthy adults, a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children was observed.This work links hyperconnectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity.
Project description:Focusing on sex differences is necessary to fully understand basic neurobiological processes such as the engagement of large-scale brain networks involved in attention. Prior work suggests that women show enhanced attention during tasks of reward/punishment relative to men. Yet, sex differences in the engagement of neural networks sub serving internal and external focus has been unexplored in regard to reward and punishment. Using data from a large sample (n = 190) of healthy participants from the Human Connectome Project, we investigated sex differences in default mode network (DMN), dorsal attention network (DAN), and frontal parietal network (FPN) activation during exposure to reward and punishment. To determine if sex differences are specific to valenced stimuli, we analyzed network activation during working memory. Results indicate that, relative to men, women have increased suppression of the DMN and greater activation of the DAN during exposure to reward and punishment. Given the relative roles of these networks in internal (DMN) and external (DAN) attention, this pattern of activation suggests that women have enhanced external attention to reward and punishment. In contrast, there were no sex differences in network activation during working memory, indicating that this sex difference is specific to the processing of reward and punishment. These findings suggest a neurobiological explanation for prior work showing women have greater sensitivity to reward/punishment and are more prone to psychiatric disorders characterized by enhanced attention to such stimuli. Furthermore, given the large sample from the Human Connectome Project, the current findings provide general implications for the study of sex as a biological variable in investigation of reward processes.
Project description:Attention-deficit/hyperactivity disorder (ADHD) is a major public health concern. It has been suggested that the brain's default network may provide a crucial avenue for understanding the neurobiology of attention deficit/hyperactivity disorder. Evaluations of the default network have increased over recent years with the applied technique of resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). These investigations have established that spontaneous activity in this network is highly correlated at rest in young adult populations. This coherence seems to be reduced in adults with ADHD. This is an intriguing finding, as coherence in spontaneous activity within the default network strengthens with age. Thus, the pathophysiology of ADHD might include delayed or disrupted maturation of the default network. If so, it is important to determine whether an altered developmental picture can be detected using rs-fcMRI in children with ADHD.This study used the typical developmental context provided previously by Fair et al. (2008) to examine coherence of brain activity within the default network using rs-fcMRI in children with (n = 23) and without attention deficit/hyperactivity disorder (n = 23).We found that functional connections previously shown as developmentally dynamic in the default network were atypical in children with attention deficit/hyperactivity disorder-consistent with perturbation or failure of the maturational processes.These findings are consistent with the hypothesis that atypical consolidation of this network over development plays a role in attention deficit/hyperactivity disorder.
Project description:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by degeneration of upper motor neurons (UMN) arising from the motor cortex in the brain and lower motor neurons (LMN) in the brainstem and spinal cord. Cerebral changes create differences in brain activity captured by functional magnetic resonance imaging (fMRI), including the spontaneous and simultaneous activity occurring between regions known as the resting state networks (RSNs). Progressive neurodegeneration as observed in ALS may lead to a disruption of RSNs which could provide insights into the disease process. Previous studies have reported conflicting findings of increased, decreased, or unaltered RSN functional connectivity in ALS and do not report the contribution of UMN changes to RSN connectivity. We aimed to bridge this gap by exploring two networks, the default mode network (DMN) and the sensorimotor network (SMN), in 21 ALS patients and 40 age-matched healthy volunteers. An UMN score dichotomized patients into UMN+ and UMN- groups. Subjects underwent resting state fMRI scan on a high field MRI operating at 4.7 tesla. The DMN and SMN changes between subject groups were compared. Correlations between connectivity and clinical measures such as the ALS Functional Rating Scale-Revised (ALSFRS-R), disease progression rate, symptom duration, UMN score and finger tapping were assessed. Significant group differences in resting state networks between patients and controls were absent, as was the dependence on degree of UMN burden. However, DMN connectivity was increased in patients with greater disability and faster progression rate, and SMN connectivity was reduced in those with greater motor impairment. These patterns of association are in line with literature supporting loss of inhibitory interneurons.
Project description:Recent developments in network neuroscience suggest reconsidering what we thought we knew about the default mode network (DMN). Although this network has always been seen as unitary and associated with the resting state, a new deconstructive line of research is pointing out that the DMN could be divided into multiple subsystems supporting different functions. By now, it is well known that the DMN is not only deactivated by tasks, but also involved in affective, mnestic, and social paradigms, among others. Nonetheless, it is starting to become clear that the array of activities in which it is involved, might also be extended to more extrinsic functions. The present meta-analytic study is meant to push this boundary a bit further. The BrainMap database was searched for all experimental paradigms activating the DMN, and their activation likelihood estimation maps were then computed. An additional map of task-induced deactivations was also created. A multidimensional scaling indicated that such maps could be arranged along an anatomo-psychological gradient, which goes from midline core activations, associated with the most internal functions, to that of lateral cortices, involved in more external tasks. Further multivariate investigations suggested that such extrinsic mode is especially related to reward, semantic, and emotional functions. However, an important finding was that the various activation maps were often different from the canonical representation of the resting-state DMN, sometimes overlapping with it only in some peripheral nodes, and including external regions such as the insula. Altogether, our findings suggest that the intrinsic-extrinsic opposition may be better understood in the form of a continuous scale, rather than a dichotomy.
Project description:T follicular helper cells (TFH) are heterogenic population of CD4+ T cells, expressing CXCR5+ and PD-1+ on their surface. Their role is linked to supporting formation of germinal centres (GC) and these cells are thought to express high levels of PD-1 marker. Two models of immunisation were used to investigate the role of PD-1 low TFH. In Salmonella enterica infection high frequency of T follicular helper cells expressing low levels of PD-1 surface molecule are observed within first week of infection but GC do not appear until much a later stage (week 7-8). Sheep red blood cell immunisation (SRBC) gives rise to both TFH and GC B cells within first week of response and these TFH express low to high level of PD-1 molecule. Microarray analysis was applied in order to investigate the relationship between and characteristics of different TFH populations in order to elucidate their role in GC support, developmental stage and contributions to memory T cell pool.
Project description:Recent reports demonstrate the anti-correlated behaviors between the default (DF) and the dorsal attention (DA) networks. We aimed to investigate the roles of the frontal parietal control (FPC) network in regulating the two anti-correlated networks through three experimental conditions, including resting, continuous self-paced/attended sequential finger tapping (FT), and natural movie watching (MW), respectively. The two goal-directed tasks were chosen to engage either one of the two competing networks-FT for DA whereas MW for default. We hypothesized that FPC will selectively augment/suppress either network depending on how the task targets the specific network; FPC will positively correlate with the target network, but negatively correlate with the network anti-correlated with the target network. We further hypothesized that significant causal links from FPC to both DA and DF are present during all three experimental conditions, supporting the initiative regulating role of FPC over the two opposing systems. Consistent with our hypotheses, FPC exhibited a significantly higher positive correlation with DA (P = 0.0095) whereas significantly more negative correlation with default (P = 0.0025) during FT when compared to resting. Completely opposite to that observed during FT, the FPC was significantly anti-correlated with DA (P = 2.1e-6) whereas positively correlated with default (P = 0.0035) during MW. Furthermore, extensive causal links from FPC to both DA and DF were observed across all three experimental states. Together, our results strongly support the notion that the FPC regulates the anti-correlated default and DA networks.
Project description:The human brain is organized into large-scale networks identifiable using resting-state functional connectivity (RSFC). These functional networks correspond with broad cognitive domains; for example, the Default-mode network (DMN) is engaged during internally oriented cognition. However, functional networks may contain hierarchical substructures corresponding with more specific cognitive functions. Here, we used individual-specific precision RSFC to test whether network substructures could be identified in 10 healthy human brains. Across all subjects and networks, individualized network subdivisions were more valid-more internally homogeneous and better matching spatial patterns of task activation-than canonical networks. These measures of validity were maximized at a hierarchical scale that contained ∼83 subnetworks across the brain. At this scale, nine DMN subnetworks exhibited topographical similarity across subjects, suggesting that this approach identifies homologous neurobiological circuits across individuals. Some DMN subnetworks matched known features of brain organization corresponding with cognitive functions. Other subnetworks represented separate streams by which DMN couples with other canonical large-scale networks, including language and control networks. Together, this work provides a detailed organizational framework for studying the DMN in individual humans.