Effects of Methylphenidate on Somatic Symptoms and Brain Functional Connectivity in Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study

NREM sleep stages specifically alter dynamical integration of large-scale brain networks.

FIGURE 1. Changes in cortical thickness provide one measure of brain maturation. A large longitudinal study found that for most areas of cortex, children with attention deficit hyperactivity disorder (ADHD) reach peak cortical thickness several years later than typically developing children, supporting presence of developmental delay. The rate of cortical thinning also differed between the group who continued to meet diagnostic criteria into adulthood (persistent ADHD) and those who did not (remitted ADHD). Areas of cortex in which the rate of thinning correlated with adult symptom level (green, more symptoms associated with more thinning) are approximated on medial and lateral simplified representations of cortex. An earlier study also identified multiple areas in which cortex was thinner in adults with persistent ADHD compared with controls (orange). In addition, this study noted some areas of thicker cortex in remitted ADHD when compared with persistent ADHD (blue).

Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy

The default mode network (DMN) could be divided into subsystems, the functional connectivity of which are different across the Alzheimer's disease (AD) spectrum. However, the functional connectivity patterns within the subsystems are unknown in presymptomatic autosomal dominant AD (ADAD). To investigate functional connectivity patterns within the subsystems of the DMN in presymptomatic subjects carrying PSEN1, PSEN2, or APP gene mutations. Twenty-six presymptomatic mutation carriers (PMC) and twenty-nine cognitively normal non-carriers as normal controls (NC) from the same families underwent resting state functional MRI and structural MRI. Seed-based analyses were done to obtain functional connectivity of posterior and anterior DMN. For the regions that showed significant connectivity difference between PMC and NC, volumes were extracted and compared between the two groups. Connectivity measures were then correlated with cognitive tests scores. The posterior DMN showed connectivity decrease in the PMC group as compared with the NC group, which was primarily the connectivity of left precuneus with right precuneus and superior frontal gyrus; the anterior DMN showed significant connectivity decrease in the PMC group, which was the connectivity of medial frontal gyrus with middle frontal gyrus. In the brain regions showing connectivity changes in the PMC group, there was no group difference in volume. A positive correlation was observed between the precuneus connectivity value and Mini-Mental State Examination total score. Functional connectivity within both posterior and anterior DMN were disrupted in the presymptomatic stage of ADAD. Connectivity disruption within the posterior DMN may be useful for early identification of general cognitive decline and a potential imaging biomarker for early diagnosis.

BackgroundDespite impulse control and emotion regulation being altered in borderline personality disorder (BPD), the specific mechanism of these clinical features remains unclear. This study investigated the functional connectivity (FC) abnormalities within- and between- default mode network (DMN), salience network (SN), and central executive network (CEN) in BPD, and examined the association between aberrant FC and clinical features. We aimed to explore whether the abnormal large-scale networks underlie the pathophysiology of impulsivity and emotion dysregulation in BPD.MethodsForty-one young, drug-naïve patients with BPD (24.98 ± 3.12 years, 20 males) and 42 healthy controls (HCs; 24.74 ± 1.29 years, 17 males) were included in resting-state functional magnetic resonance imaging analyses. Independent component analysis was performed to extract subnetworks of the DMN, CEN, and SN. Additionally, partial correlation was performed to explore the association between brain imaging variables and clinical features in BPD.ResultsCompared with HCs, BPD showed significant decreased intra-network FC of right medial prefrontal cortex in the anterior DMN and of right angular gyrus in the right CEN. Intra-network FC of right angular gyrus in the anterior DMN was significantly negatively correlated with attention impulsivity in BPD. The patients also showed decreased inter-network FC between the posterior DMN and left CEN, which was significantly negatively correlated with emotion dysregulation.ConclusionThese findings suggest that impaired intra-network FC may underlie the neurophysiological mechanism of impulsivity, and abnormal inter-network FC may elucidate the neurophysiological mechanism of emotion dysregulation in BPD.

Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network (SN) and default mode network (DMN) begets positive and negative symptoms of schizophrenia, yet prior studies have predominately reported links between disrupted SN/DMN functional communication and positive symptoms. It remains unclear whether disrupted SN/DMN functional communication explains (1) solely positive symptoms or (2) both positive and negative symptoms of schizophrenia. To address this question, we incorporate time-lag-shifted functional network connectivity (FNC) analyses that explored coherence of the resting-state functional magnetic resonance imaging signal of 3 networks (anterior DMN, posterior DMN, and SN) with fixed time lags introduced between network time series (1 TR = 2 s; 2 TR = 4 s). Multivariate linear regression analysis revealed that severity of disordered thought and attentional deficits were negatively associated with 2 TR-shifted FNC between anterior DMN and posterior DMN. Meanwhile, severity of flat affect and bizarre behavior were positively associated with 1 TR-shifted FNC between anterior DMN and SN. These results provide support favoring the hypothesis that lagged SN/DMN functional communication is associated with both positive and negative symptoms of schizophrenia.

SPECIALTY GRAND CHALLENGE article Front. Psychiatry, 23 March 2012Sec. Child and Adolescent Psychiatry Volume 3 - 2012 | https://doi.org/10.3389/fpsyt.2012.00027

Anterior and posterior default mode network functional connectivity and segregation in aging

An evolutionary gap in primate default mode network organization

Decline in self-awareness is a prevalent symptom in Alzheimer’s disease (AD). Current data suggest that an early breakdown in the brain’s default mode network (DMN) is closely associated with the main symptomatic features in AD patients. In parallel, the integrity of the DMN has been shown to be heavily implicated in retained self-awareness abilities in healthy individuals and AD patients. However, the global contribution to awareness skills of other large-scale networks is still poorly understood. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were acquired and pre-processed from 53 early-stage AD individuals. A group-level independent component analysis was run to isolate and reconstruct four intrinsic connectivity large-scale brain functional networks, namely left and right central executive fronto-parietal networks (FPN), salience network, and anterior and posterior DMN. Hypothesis-driven seed-based connectivity analyses were run to clarify the region-specific underpinnings of multi-domain anosognosia. Multiple regression models were run on large-scale network- and seed-based connectivity maps, including scores of memory, non-memory and total anosognosia obtained via the Measurement of Anosognosia Questionnaire. Memory anosognosia scores were associated with selective lower fronto-temporal connectivity and higher parieto-temporal connectivity. Non-memory anosognosia scores were associated with higher connectivity between the anterior DMN and the cerebellum, between the left medial prefrontal seeds and the contralateral prefrontal cortex, and between the left hippocampal seed and the left insula; lower connectivity was observed between the right prefrontal cortex and the right lingual seed. Lastly, total anosognosia scores were associated with large-scale network alterations, namely reduced left-FPN expression in the left posterior cingulate, reduced right-FPN expression in the left inferior lingual gyrus and adjacent inferior occipital cortex, and increased right-FPN expression in the right anterior cingulate. Seed-based analyses yielded significant connectivity differences only in the connectivity pattern associated with the left hippocampal seed by displaying lower intercommunication with the right prefrontal cortex, but higher connectivity with the left caudate nucleus. These findings support the hypothesis that alterations in functional connectivity of frontal lobe regions involved in executive-related mechanisms represent the neural correlates of domain-specific anosognosia in early AD. Up-regulated connectivity with subcortical structures appears to contribute to changes in the network dynamics interplay and fosters the appearance of anosognosia.

Default mode network functional connectivity after multiple concussions in children and adolescents

Somatic Symptoms During Adolescence: Does Parenting Style Play a Role?

Numerous resting-state functional magnetic resonance imaging studies have revealed that major depressive disorder (MDD) is associated with abnormal functional connectivity (FC) within and between large-scale functional networks such as the default mode network (DMN), cognitive control network (CCN) and affective network (AN). Compared with healthy controls, individuals with MDD usually show (i) increased FC within the anterior DMN and decreased FC within the posterior DMN, (ii) decreased FC within the CCN and (iii) increased FC within limbic system and decreased FC in the reward system in the AN. Depression related interactive changes between networks have also been reported: (i) decreased FC between DMN and CCN, (ii) increased FC between DMN and AN, and (iii) decreased FC between CCN and AN. These findings on network interaction may represent impaired resource allocation and information integration in MDD. Major weakness in the present rfMRI studies of depression resides in small sample and lack of multidimensional features. Meanwhile, as several brain disorders may show commonly disrupted functional architectures, depression-related specific alterations are typically lacking. We suggest that future studies may advance by combining multidimensional big data and individualized characterization, as well as examining shared and distinct functional network mechanisms of MDD in the spectrum of psychiatric disorders.

Despite its high heritability, few risk genes have been identified for attention-deficit/hyperactivity disorder (ADHD). Brain-based phenotypes could aid gene discovery. There is a myriad of structural and functional connections that support cognition. Disruption of such connectivity is a key pathophysiologic mechanism for ADHD, and identifying heritable phenotypes within these connections could provide candidates for genomic studies. To identify the structural and functional connections that are heritable and pertinent to ADHD. Members of extended multigenerational families enriched for ADHD were evaluated. Structural connectivity was defined by diffusion tensor imaging (DTI) of white matter tract microstructure and functional connectivity through resting-state functional magnetic resonance imaging (rsfMRI). Heritability and association with ADHD symptoms were estimated in 24 extended multigenerational families enriched for ADHD (305 members with clinical phenotyping, 213 with DTI, and 193 with rsfMRI data). Findings were confirmed in 52 nuclear families (132 members with clinical phenotypes, 119 with DTI, and 84 with rsfMRI). The study and data analysis were conducted from April 1, 2010, to September 1, 2016. In the 52 nuclear families, 86 individuals (65.2%) were male and the mean (SD) age at imaging was 20.9 (15.0) years; in the 24 multigenerational extended families, 145 individuals (47.5%) were male and mean age at imaging was 30.4 (19.7) years. Microstructural properties of white matter tracts connecting ipsilateral cortical regions and the corpus callosum were significantly heritable, ranging from total additive genetic heritability (h2) = 0.69 (SE, 0.13; P = .0000002) for radial diffusivity of the right superior longitudinal fasciculus to h2 = 0.46 (SE, 0.15; P = .0009) for fractional anisotropy of the right inferior fronto-occipital fasciculus. Association with ADHD symptoms was found in several tracts, most strongly for the right superior longitudinal fasciculus (t = -3.05; P = .003). Heritable patterns of functional connectivity were detected within the default mode (h2 = 0.36; SE, 0.16; cluster level significance, P < .002), cognitive control (h2 = 0.32; SE, 0.15; P < .002), and ventral attention networks (h2 = 0.36; SE, 0.16; P < .002). In all cases, subregions within each network showed heritable functional connectivity with the rest of that network. More symptoms of hyperactivity/impulsivity (t = -2.63; P = .008) and inattention (t = -2.34; P = .02) were associated with decreased functional connectivity within the default mode network. Some cross-modal correlations were purely phenotypic, such as that between axial diffusivity of the right superior longitudinal fasciculus and heritable aspects of the default mode network (phenotypic correlation, ρp = -0.12; P = .03). A genetic cross-modal correlation was seen between the ventral attention network and radial diffusivity of the right inferior fronto-occipital fasciculus (genetic correlation, ρg = -0.45, P = .02). Analysis of data on multigenerational extended and nuclear families identified the features of structural and functional connectivity that are both significantly heritable and associated with ADHD. In addition, shared genetic factors account for some phenotypic correlations between functional and structural connections. Such work helps to prioritize the facets of the brain's connectivity for future genomic studies.

The imbalanced anterior and posterior default mode network in the primary insomnia