Functional reorganization of intra‐ and internetwork connectivity in major depressive disorder after electroconvulsive therapy

Electroconvulsive therapy (ECT) is an effective and rapid treatment for major depressive disorder (MDD). However, the neurobiological underpinnings of ECT are still largely unknown. Recent studies have identified dysregulated brain networks in MDD. Therefore, we hypothesized that ECT may improve MDD symptoms through reorganizing these networks. To test this hypothesis, we used resting‐state functional connectivity to investigate changes to the intra‐ and internetwork architecture of five reproducible resting‐state networks: the default mode network (DMN), dorsal attention network (DAN), executive control network (CON), salience network (SAL), and sensory‐motor network. Twenty‐three MDD patients were assessed before and after ECT, along with 25 sex‐, age‐, and education‐matched healthy controls. At the network level, enhanced intranetwork connectivities were found in the CON in MDD patients after ECT. Furthermore, enhanced internetwork connectivities between the DMN and SAL, and between the CON and DMN, DAN, and SAL were also identified. At the nodal level, the posterior cingulate cortex had increased connections with the left posterior cerebellum, right posterior intraparietal sulcus (rpIPS), and right anterior prefrontal cortex. The rpIPS had increased connections with the medial PFC (mPFC) and left anterior cingulate cortex. The left lateral parietal had increased connections with the dorsal mPFC (dmPFC), left anterior prefrontal cortex, and right anterior cingulate cortex. The dmPFC had increased connection with the left anterolateral prefrontal cortex. Our findings indicate that enhanced interactions in intra‐ and internetworks may contribute to the ECT response in MDD patients. These findings provide novel and important insights into the neurobiological mechanisms underlying ECT.     

Overlapping and segregated resting‐state functional connectivity in patients with major depressive disorder with and without childhood neglect

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting‐state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole‐brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph‐theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal‐limbic‐thalamic‐cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole‐brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154–1166, 2014. © 2013 Wiley Periodicals, Inc.     

Local gyrification index in patients with major depressive disorder and its association with tryptophan hydroxylase‐2 (TPH2) polymorphism

The tryptophan hydroxylase‐2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD. One hundred and thirteen patients with MDD and eighty‐six healthy controls underwent T1‐weighted structural magnetic resonance imaging and genotyping for TPH2 rs4570625. The local gyrification index of 22 cortical regions in the prefrontal cortex and anterior cingulate cortex was analyzed using the FreeSurfer. The patients with MDD showed significant hypergyria in the right rostral anterior cingulate cortex (P = 0.001), medial orbitofrontal cortex (P = 0.003), and frontal pole (P = 0.001). There was a significant genotype‐by‐diagnosis interaction for the local gyrification index in the right rostral anterior cingulate cortex (P = 0.003). Their study revealed significant hypergyria of the anterior cingulate cortex and prefrontal cortex and an interactive effect between the diagnosis of MDD and the genotype in the anterior cingulate cortex. This might be associated with the dysfunction of neural circuits mediating emotion processing, which could contribute to pathophysiology of MDD. Hum Brain Mapp 38:1299–1310, 2017. © 2016 Wiley Periodicals, Inc.     

Alterations in amplitude of low frequency fluctuation in treatment‐naïve major depressive disorder measured with resting‐state fMRI

There are limited resting‐state functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD). Of these studies, functional connectivity analyses are mostly used. However, a new method based on the magnitude of low frequency fluctuation (LFF) during resting‐state fMRI may provide important insight into MDD. In this study, we examined the amplitude of LFF (ALFF) within the whole brain during resting‐state fMRI in 30 treatment‐naïve MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD subjects showed increased ALFF in the frontal cortex (including the bilateral ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex, ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior frontal cortex), basal ganglia (including the right putamen and left caudate nucleus), left insular cortex, right anterior entorhinal cortex and left inferior parietal cortex, together with decreased ALFF in the bilateral occipital cortex, cerebellum hemisphere, and right superior temporal cortex. These findings may relate to characteristics of MDD, such as excessive self‐referential processing and deficits in cognitive control of emotional processing, which may contribute to the persistent and recurrent nature of the disorder. Hum Brain Mapp 35:4979–4988, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

A data‐driven approach to mapping cortical and subcortical intrinsic functional connectivity along the longitudinal hippocampal axis

The hippocampus (HPC) is functionally heterogeneous along the longitudinal anterior–posterior axis. In rodent models, gene expression maps define at least three discrete longitudinal subregions, which also differ in function, and in anatomical connectivity with the rest of the brain. In humans, equivalent HPC subregions are less well defined, resulting in a lack of consensus in neuroimaging approaches that limits translational study. This study determined whether a data‐driven analysis, namely independent component analysis (ICA), could reproducibly define human HPC subregions, and map their respective intrinsic functional connectivity (iFC) with the rest of the brain. Specifically, we performed ICA of resting‐state fMRI activity spatially restricted within the HPC, to determine the configuration and reproducibility of functional HPC components. Using dual regression, we then performed multivariate analysis of iFC between resulting HPC components and the whole brain, including detailed connectivity with the hypothalamus, a functionally important connection not yet characterized in human. We found hippocampal ICA resulted in highly reproducible longitudinally discrete components, with greater functional heterogeneity in the anterior HPC, consistent with animal models. Anterior hippocampal components shared iFC with the amygdala, nucleus accumbens, medial prefrontal cortex, posterior cingulate cortex, midline thalamus, and periventricular hypothalamus, whereas posterior hippocampal components shared iFC with the anterior cingulate cortex, retrosplenial cortex, and mammillary bodies. We show that spatially masked hippocampal ICA with dual regression reproducibly identifies functional subregions in the human HPC, and maps their respective brain intrinsic connectivity. Hum Brain Mapp 37:462–476, 2016. © 2015 Wiley Periodicals, Inc.     

Altered superficial amygdala–cortical functional link in resting state after 36 hours of total sleep deprivation

The superficial amygdala (SFA) is important in human emotion/affective processing via its strong connection with other limbic and cerebral cortex for receptive and expressive emotion processing. Few studies have investigated the functional connectivity changes of the SFA under extreme conditions, such as prolonged sleep loss, although the SFA showed a distinct functional connectivity pattern throughout the brain. In this study, resting‐state functional magnetic resonance imaging (rs‐fMRI) was employed to investigate the changes of SFA–cortical functional connectivity after 36 hr of total sleep deprivation (TSD). Fourteen healthy male volunteers aged 25.9 ± 2.3 years (range 18–28 years) enrolled in this within‐subject crossover study. We found that the right SFA showed increased functional connectivity with the right medial prefrontal cortex (mPFC) and decreased functional connectivity with the right dorsal posterior cingulate cortex (dPCC) in the resting brain after TSD compared with that during rested wakefulness. For the left SFA, decreased connectivity with the right dorsal anterior cingulate cortex (dACC) and right dPCC was found. Further regression analysis indicated that the functional link between mPFC and SFA significantly correlated with the Profile of Mood State scores. Our results suggest that the amygdala cannot be treated as a single unit in human neuroimaging studies and that TSD may alter the functional connectivity pattern of the SFA, which in turn disrupts emotional regulation. © 2015 Wiley Periodicals, Inc.     

Functional connectivity mapping of regions associated with self‐ and other‐processing

Neuroscience literature increasingly suggests a conceptual self composed of interacting neural regions, rather than independent local activations, yet such claims have yet to be investigated. We, thus, combined task‐dependent meta‐analytic connectivity modeling (MACM) with task‐independent resting‐state (RS) connectivity analysis to delineate the neural network of the self, across both states. Given psychological evidence implicating the self's interdependence on social information, we also delineated the neural network underlying conceptual other‐processing. To elucidate the relation between the self‐/other‐networks and their function, we mined the MACM metadata to generate a cognitive–behavioral profile for an empirically identified region specific to conceptual self, the pregenual anterior cingulate (pACC), and conceptual other, posterior cingulate/precuneus (PCC/PC). Mining of 7,200 published, task‐dependent, neuroimaging studies, using healthy human subjects, yielded 193 studies activating the self‐related seed and were conjoined with RS connectivity analysis to delineate a differentiated self‐network composed of the pACC (seed) and anterior insula, relative to other functional connectivity. Additionally, 106 studies activating the other‐related seed were conjoined with RS connectivity analysis to delineate a differentiated other‐network of PCC/PC (seed) and angular gyrus/temporoparietal junction, relative to self‐functional connectivity. The self‐network seed related to emotional conflict resolution and motivational processing, whereas the other‐network seed related to socially oriented processing and contextual information integration. Notably, our findings revealed shared RS connectivity between ensuing self‐/other‐networks within the ventromedial prefrontal cortex and medial orbitofrontal cortex, suggesting self‐updating via integration of self‐relevant social information. We, therefore, present initial neurobiological evidence corroborating the increasing claims of an intricate self‐network, the architecture of which may promote social value processing. Hum Brain Mapp 36:1304–1324, 2015. © 2014 Wiley Periodicals, Inc.     

Age‐related changes in amygdala–frontal connectivity during emotional face processing from childhood into young adulthood

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age‐related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7–25 years. We found age‐related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age‐related change (shifting from positive to negative correlation) in amygdala–anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom‐up amygdala excitatory signaling to ACC/mPFC in children and later development of top‐down inhibitory control of ACC/mPFC over amygdala in adults. Age‐related changes in amygdala–ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala–ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat‐specific processing. Hum Brain Mapp 37:1684–1695, 2016. © 2016 Wiley Periodicals, Inc .     

Resting-state connectivity in the default mode network and insula during experimental low back pain简

Functional magnetic resonance imaging studies have shown that the insular cortex has a significant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the default mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy subjects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the importance of the interaction between these regions in pain processing.     

Partially impaired functional connectivity states between right anterior insula and default mode network in autism spectrum disorder

Time‐invariant resting‐state functional connectivity studies have illuminated the crucial role of the right anterior insula (rAI) in prominent social impairments of autism spectrum disorder (ASD). However, a recent dynamic connectivity study demonstrated that rather than being stationary, functional connectivity patterns of the rAI vary significantly across time. The present study aimed to explore the differences in functional connectivity in dynamic states of the rAI between individuals with ASD and typically developing controls (TD). Resting‐state functional magnetic resonance imaging data obtained from a publicly available database were analyzed in 209 individuals with ASD and 298 demographically matched controls. A k‐means clustering algorithm was utilized to obtain five dynamic states of functional connectivity of the rAI. The temporal properties, frequency properties, and meta‐analytic decoding were first identified in TD group to obtain the characteristics of each rAI dynamic state. Multivariate analysis of variance was then performed to compare the functional connectivity patterns of the rAI between ASD and TD groups in obtained states. Significantly impaired connectivity was observed in ASD in the ventral medial prefrontal cortex and posterior cingulate cortex, which are two critical hubs of the default mode network (DMN). States in which ASD showed decreased connectivity between the rAI and these regions were those more relevant to socio‐cognitive processing. From a dynamic perspective, these findings demonstrate partially impaired resting‐state functional connectivity patterns between the rAI and DMN across states in ASD, and provide novel insights into the neural mechanisms underlying social impairments in individuals with ASD.     

Directed functional connections underlying spontaneous brain activity

Neuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole‐brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG‐based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.     

Altered inter‐ and intrahemispheric functional connectivity dynamics in autistic children

Emerging evidence has associated autism spectrum disorder (ASD) with static functional connectivity abnormalities between multiple brain regions. However, the temporal dynamics of intra‐ and interhemispheric functional connectivity patterns remain unknown in ASD. Resting‐state functional magnetic resonance imaging data were analyzed for 105 ASD and 102 demographically matched typically developing control (TC) children (age range: 7–12 years) available from the Autism Brain Imaging Data Exchange database. Whole‐brain functional connectivity was decomposed into ipsilateral and contralateral functional connectivity, and sliding‐window analysis was utilized to capture the intra‐ and interhemispheric dynamic functional connectivity density (dFCD) patterns. The temporal variability of the functional connectivity dynamics was further quantified using the standard deviation (SD) of intra‐ and interhemispheric dFCD across time. Finally, a support vector regression model was constructed to assess the relationship between abnormal dFCD variance and autism symptom severity. Both intra‐ and interhemispheric comparisons showed increased dFCD variability in the anterior cingulate cortex/medial prefrontal cortex and decreased variability in the fusiform gyrus/inferior temporal gyrus in autistic children compared with TC children. Autistic children additionally showed lower intrahemispheric dFCD variability in sensorimotor regions including the precentral/postcentral gyrus. Moreover, aberrant temporal variability of the contralateral dFCD predicted the severity of social communication impairments in autistic children. These findings demonstrate altered temporal dynamics of the intra‐ and interhemispheric functional connectivity in brain regions incorporating social brain network of ASD, and highlight the potential role of abnormal interhemispheric communication dynamics in neural substrates underlying impaired social processing in ASD.     

Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

Although in theory sham repetitive transcranial magnetic stimulation (rTMS) has no inherent therapeutic value, nonetheless, such placebo stimulations may have relevant therapeutic effects in clinically depressed patients. On the other hand, antidepressant responses to sham rTMS are quite heterogeneous across individuals and its neural underpinnings have not been explored yet. The current brain imaging study aims to detect baseline neural fingerprints resulting in clinically beneficial placebo rTMS treatment responses. We collected resting‐state functional magnetic resonance imaging data prior to a registered randomized clinical trial of accelerated placebo stimulation protocol in patients documented with treatment‐resistant depression ( http://clinicaltrials.gov/show/NCT01832805 ). In addition to global brain connectivity and rostral anterior cingulate cortex (rACC) seed‐based functional connectivity (FC), elastic‐net regression and cross‐validation procedures were used to identify baseline intrinsic brain connectivity biomarkers for sham‐rTMS responses. Placebo responses to accelerated sham rTMS were correlated with baseline global brain connectivity in the rACC/ventral medial prefrontal cortex (vmPFC). Concerning the rACC seed‐based FC analysis, the placebo response was associated positively with the precuneus/posterior cingulate (PCun/PCC) cortex and negatively with the middle frontal gyrus. Our findings provide first brain imaging evidence for placebo responses to sham stimulation being predictable from rACC rsFC profiles, especially in brain areas implicated in (re)appraisal and self‐focus processes.     

Developmental changes in within- and between-network connectivity between late childhood and adulthood

A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain–behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.     

Functional organization of the fusiform gyrus revealed with connectivity profiles

Within the object recognition‐related ventral visual stream, the human fusiform gyrus (FG), which topographically connects the striate cortex to the inferior temporal lobe, plays a pivotal role in high‐level visual/cognitive functions. However, though there are many previous investigations of distinct functional modules within the FG, the functional organization of the whole FG in its full functional heterogeneity has not yet been established. In the current study, a replicable functional organization of the FG based on distinct anatomical connectivity patterns was identified. The FG was parcellated into medial (FGm), lateral (FGl), and anterior (FGa) regions using diffusion tensor imaging. We validated the reasonability of such an organizational scheme from the perspective of resting‐state whole brain functional connectivity patterns and the involvement of functional subnetworks. We found corroborating support for these three distinct modules, and suggest that the FGm serves as a transition region that combines multiple stimuli, the FGl is responsible for categorical recognition, and the FGa is involved in semantic understanding. These findings support two organizational functional transitions of the ventral temporal gyrus, a posterior/anterior direction of visual/semantic processing, and a media/lateral direction of high‐level visual processing. Our results may facilitate a more detailed study of the human FG in the future. Hum Brain Mapp 37:3003–3016, 2016. © 2016 Wiley Periodicals, Inc .     

Altered Brain Long-Range Functional Interactions Underlying the Link Between Aberrant Self-experience and Self-other Relationship in First-Episode Schizophrenia

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain.Key words: psychosis, posterior insula, ventral premotor cortex, posterior cingulate cortex, functional magnetic resonance imaging, connectivity     

Breakdown of the affective‐cognitive network in functional dystonia

Previous studies suggested that brain regions subtending affective‐cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective‐cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS‐fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD‐age‐matched [yHC]; 29 old MobFD‐age‐matched [oHC]). FC of brain regions of interest, known to be involved in affective‐cognitive processes, and independent component analysis of RS‐fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective‐cognitive seeds of interest and the fronto‐subcortical and limbic circuits; enhanced FC between the right affective‐cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective‐cognitive seeds of interest and the sensorimotor and high‐order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective‐cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.     

Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

The cingulum and cingulate U‐fibers in children and adolescents with autism spectrum disorders

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U‐fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra‐cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U‐fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U‐fibers, an atypical age‐related decline in right posterior cingulate U‐fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U‐fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U‐fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.     

Altered frontostriatal coupling in pre‐manifest Huntington’s disease: effects of increasing cognitive load

Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre‐symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre‐HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre‐HD individuals. Methods: Sixteen healthy controls and sixteen pre‐HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load‐dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre‐HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre‐HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre‐HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre‐HD individuals are modulated by cognitive demand.