Dysregulation of working memory and default‐mode networks in schizophrenia using independent component analysis,an fBIRN and MCIC study

Deficits in working memory (WM) are a consistent neurocognitive marker for schizophrenia. Previous studies have suggested that WM is the product of coordinated activity in distributed functionally connected brain regions. Independent component analysis (ICA) is a data‐driven approach that can identify temporally coherent networks that underlie fMRI activity. We applied ICA to an fMRI dataset for 115 patients with chronic schizophrenia and 130 healthy controls by performing the Sternberg Item Recognition Paradigm. Here, we describe the first results using ICA to identify differences in the function of WM networks in schizophrenia compared to controls. ICA revealed six networks that showed significant differences between patients with schizophrenia and healthy controls. Four of these networks were negatively task‐correlated and showed deactivation across the posterior cingulate, precuneus, medial prefrontal cortex, anterior cingulate, inferior parietal lobules, and parahippocampus. These networks comprise brain regions known as the default‐mode network (DMN), a well‐characterized set of regions shown to be active during internal modes of cognition and implicated in schizophrenia. Two networks were positively task‐correlated, with one network engaging WM regions such as bilateral DLPFC and inferior parietal lobules while the other network engaged primarily the cerebellum. Our results suggest that DLPFC dysfunction in schizophrenia might be lateralized to the left and intrinsically tied to other regions such as the inferior parietal lobule and cingulate gyrus. Furthermore, we found that DMN dysfunction in schizophrenia exists across multiple subnetworks of the DMN and that these subnetworks are individually relevant to the pathophysiology of schizophrenia. In summary, this large multsite study identified multiple temporally coherent networks, which are aberrant in schizophrenia versus healthy controls and suggests that both task‐correlated and task‐anticorrelated networks may serve as potential biomarkers. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Temporally anticorrelated brain networks during working memory performance reveal aberrant prefrontal and hippocampal connectivity in patients with schizophrenia

Functional neuroimaging studies on cognitive dysfunction in schizophrenia have suggested regional brain activation changes in the dorsolateral prefrontal cortex and the medial temporal lobe. However, less is known about the functional coupling of these areas during cognitive performance. In this study, we used functional magnetic resonance imaging, a verbal working memory (WM) task and multivariate statistical techniques to investigate the functional coupling of temporally anticorrelated neural networks during cognitive processing in patients with schizophrenia (n = 16) compared to healthy controls (n = 16). Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included temporally anticorrelated networks which were most highly associated with the delay period of the task in both healthy controls and patients with schizophrenia. Functional network abnormalities in patients with schizophrenia were detected within a “task-positive” lateral frontoparietal network, where increased functional connectivity was found in bilateral dorsolateral prefrontal regions. In addition, aberrant functional coupling of the hippocampal cortex in patients with schizophrenia was detected within a “task-negative” medial frontotemporal network. In patients with schizophrenia, functional connectivity indices in the left dorsolateral prefrontal cortex and the right hippocampal cortex were positively correlated with accuracy during the WM task, while the connectivity strength in the right dorsolateral prefrontal cortex was negatively correlated with measures of symptom severity. These data suggest that within two temporally anticorrelated network states, patients with schizophrenia exhibit increased and persistent dorsolateral prefrontal and hippocampal connectivity during WM performance.     

fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence

Cocaine use is associated with poorer HIV clinical outcomes and may contribute to neurobiological impairments associated with impulsive decision making. This study examined the effect of cocaine dependence on brain activation during a delay discounting task involving choices between smaller immediate rewards and larger delayed ones. Participants were 39 HIV-positive adults on antiretroviral therapy who had current cocaine dependence (“active,” n = 15), past cocaine dependence (“recovered,” n = 13), or no lifetime substance dependence (“naïve,” n = 11). Based on responses on a traditional delay discounting task, three types of choices were individualized for presentation during functional magnetic resonance imaging: hard (similarly valued), easy (disparately valued), and no (single option). Active participants had significantly smaller increases in activation than naïve participants during hard versus easy choices bilaterally in the precentral gyrus and anterior cingulate cortex and in the right frontal pole (including dorsolateral, ventrolateral, and orbitofrontal cortex). During hard and easy choices relative to no choices, active participants had smaller increases in activation compared to naïve participants in frontoparietal cortical regions. These deficits in the executive network during delay discounting choices may contribute to impulsive decision making among HIV-positive cocaine users, with implications for risk behaviors associated with disease transmission and progression.     

Does hypofrontality expand to global brain area in progression of schizophrenia?: A cross-sectional study between first-episode and chronic schizophrenia

Although to date there have been no conclusive pathophysiological findings in support of the degenerative theory of the etiology of schizophrenia, the results of neuroimaging studies have suggested that progressive changes in the brain do occur during the clinical course of schizophrenia. However, there has been no report on alterations in regional cerebral blood flow (rCBF) under resting condition, which was compared between the first-episode and the chronic patients of schizophrenia and healthy controls. Therefore, in this study, we applied three-dimensional stereotactic surface projection analysis of resting SPECT (3D-SSP SPECT) in patients with first-episode (n = 18) and chronic schizophrenia (n = 23) and age-/sex-matched healthy controls (n = 40). The rCBFs in the middle/inferior/medial frontal gyrus and the anterior cingulate gyrus were significantly decreased in both patient groups, relative to the respective controls (Z > 3.0, P < 0.001, uncorrected). The chronic group showed significant hypoperfused region in the left inferior parietal lobule and middle/inferior temporal gyrus. Furthermore, within-cases comparison between the first-episode and chronic schizophrenia, revealed that the significant hypoperfused regions in the chronic group, compared to the first-episode group, were not only the lateral and medial prefrontal cortex, but also the inferior parietal cortex, posterior part of the temporal lobe, and the cuneus. The present study suggested that the reduction in rCBF occurs in the posterior brain area in addition to the frontal lobe across all clinical stages of schizophrenia.     

Cognitive and default‐mode resting state networks: Do male and female brains “rest” differently?

Variability in human behavior related to sex is supported by neuroimaging studies showing differences in brain activation patterns during cognitive task performance. An emerging field is examining the human connectome, including networks of brain regions that are not only temporally‐correlated during different task conditions, but also networks that show highly correlated spontaneous activity during a task‐free state. Both task‐related and task‐free network activity has been associated with individual task performance and behavior under certain conditions. Therefore, our aim was to determine whether sex differences exist during a task‐free resting state for two networks associated with cognitive task performance (executive control network (ECN), salience network (SN)) and the default mode network (DMN). Forty‐nine healthy subjects (26 females, 23 males) underwent a 5‐min task‐free fMRI scan in a 3T MRI. An independent components analysis (ICA) was performed to identify the best‐fit IC for each network based on specific spatial nodes defined in previous studies. To determine the consistency of these networks across subjects we performed self‐organizing group‐level ICA analyses. There were no significant differences between sexes in the functional connectivity of the brain areas within the ECN, SN, or the DMN. These important findings highlight the robustness of intrinsic connectivity of these resting state networks and their similarity between sexes. Furthermore, our findings suggest that resting state fMRI studies do not need to be controlled for sex. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Antipsychotic dose and diminished neural modulation: a multi-site fMRI study

Background

The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.

Methods

Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.

Results

Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t₇₇ = 2.01, P = 0.048).

Conclusion

The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.     

Functional brain network abnormalities during verbal working memory performance in adolescents and young adults with dyslexia

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional neuroanatomy underlying cognitive dysfunction in dyslexia. In this study, functional magnetic resonance imaging and multivariate analytic techniques were used to investigate patterns of functional connectivity during a verbal WM task in individuals with dyslexia (n = 12) and control subjects (n = 13). Dyslexics were not significantly slower than controls; however, they were less accurate with increasing WM demand. Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included functional networks which were positively correlated with the delay period of the activation task in both healthy controls and dyslexics. Connectivity abnormalities in dyslexics were detected within both networks of interest: within a “phonological” left-lateralized prefrontal network, increased functional connectivity was found in left prefrontal and inferior parietal regions. Within an “executive” bilateral frontoparietal network, dyslexics showed a decreased connectivity pattern comprising bilateral dorsolateral prefrontal and posterior parietal regions, while increased connectivity was found in the left angular gyrus, the left hippocampal cortex and the right thalamus. The functional connectivity strength in the latter regions was associated with WM task accuracy and with the numbers of errors during a spelling test. These data suggest functional connectivity abnormalities in two spatiotemporally dissociable brain networks underlying WM dysfunction in individuals with dyslexia.     

Functional resting-state networks are differentially affected in schizophrenia

Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia.     

Nicotinic modulation of salience network connectivity and centrality in schizophrenia

Although functional abnormalities of the salience network are associated with schizophrenia, the acute effects of nicotine on its function and network dynamics during the resting state in patients are poorly understood. In this study, the effects of a 7 mg nicotine patch (vs. placebo) on salience network connectivity were examined in 17 patients with schizophrenia and 19 healthy subjects. We hypothesized abnormal connectivity between the salience network and other major networks (e.g. executive network) in patients under placebo administration and amelioration of this difference after nicotine. We also examined effects of nicotine on betweenness centrality (a measure of the influence of a region on information transfer throughout the brain) and local efficiency (a measure of local information transfer) of the network. A hybrid independent component analysis (ICA)/seed-based connectivity approach was implemented in which the salience network was extracted by ICA and cortical network peaks (anterior cingulate cortex (ACC), left and right insula) were used as seeds for whole-brain seed-to-voxel connectivity analysis. Significant drug X diagnosis interactions were observed between the ACC seed and superior parietal lobule and ventrolateral prefrontal cortex. A significant interaction effect was also observed between the left insula seed and middle cingulate cortex. During placebo conditions, abnormal connectivity predicted negative symptom severity and lower global functioning in patients. A significant drug X diagnosis interaction was also observed for betweenness centrality of the ACC. These results suggest that nicotine may target abnormalities in functional connectivity between salience and executive network areas in schizophrenia as well as affect the ability of the salience network to act as an integrator of global signaling in the disorder.     

Working memory dysfunction in obsessive-compulsive disorder: A neuropsychological and functional MRI study

Previous neuropsychological studies indicate that OCD subtypes such as checking rituals might be associated with a working memory deficit. On the other hand, functional neuroimaging studies found functional abnormalities of the frontal cortex and subcortical structures in OCD. Combined with functional imaging method, we applied neuropsychological batteries to demonstrate a working memory deficit in OCD by comparison with normal controls. In addition, working memory and brain activation were further examined with symptom-based analysis. Forty patients with OCD and 25 normal controls were examined using neuropsychological tests including the WAIS-R, WCST, WMS-R, and R-OCFT and functional MRI (fMRI) during the N-back task including 0- and 2-back task. On fMRI, the brain regions activated during the performance and the differences in the activation between patients and controls were identified. Additional analyses of severity and subtypes were conducted by using Y-BOCS severity score, symptom-checklist and Leckman’s four-factor model, respectively. On the neuropsychological tests, the OCD patients had significantly lower scores on the delayed recall section of the WMS-R and the immediate recall section of the R-OCFT compared to the controls. On fMRI, the patients showed greater activation in the right dorsolateral prefrontal cortex (DLPFC), left superior temporal gyrus (STG), left insula, and cuneus during two-back task compared to the controls. Right orbitofrontal cortex activity showed a significant positive correlation with Y-BOCS scores in OCD. Furthermore, patients with obsessions/checking rituals (n = 10) showed severer memory deficits and decreased activity in the postcentral gyrus than patients with cleanliness/washing rituals (n = 14). In conclusion, we found neuropsychological dysfunction and brain abnormalities in OCD. Furthermore, our results suggested that symptom severity and symptom subtype such as obsessions/checking might affect neuropsychological dysfunction and related brain activities.     

Independent component analysis of resting state activity in pediatric obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty‐three pediatric OCD patients and 23 healthy volunteers (age range 9–17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp 35:5306–5315, 2014. © 2014 Wiley Periodicals, Inc.     

Aberrant "default mode" functional connectivity in schizophrenia

OBJECTIVE: The "default mode" has been defined as a baseline condition of brain function and is of interest because its component brain regions are believed to be abnormal in schizophrenia. It was hypothesized that the default mode network would show abnormal activation and connectivity in patients with schizophrenia. METHOD: Patients with schizophrenia (N=21) and healthy comparison subjects (N=22) performed an auditory oddball task during functional magnetic resonance imaging (fMRI). Independent component analysis was used to identify the default mode component. Differences in the spatial and temporal aspects of the default mode network were examined in patients versus comparison subjects. RESULTS: Healthy comparison subjects and patients had significant spatial differences in the default mode network, most notably in the frontal, anterior cingulate, and parahippocampal gyri. In addition, activity in patients in the medial frontal, temporal, and cingulate gyri correlated with severity of positive symptoms. The patients also showed significantly higher frequency fluctuations in the temporal evolution of the default mode. CONCLUSIONS: Schizophrenia is associated with altered temporal frequency and spatial location of the default mode network. The authors hypothesized that this network may be under- or overmodulated by key regions, including the anterior and posterior cingulate cortex. In addition, the altered temporal fluctuations in patients may result from a change in the connectivity of these regions with other brain networks.     

The role of trauma-related distractors on neural systems for working memory and emotion processing in posttraumatic stress disorder

The relevance of emotional stimuli to threat and survival confers a privileged role in their processing. In PTSD, the ability of trauma-related information to divert attention is especially pronounced. Information unrelated to the trauma may also be highly distracting when it shares perceptual features with trauma material. Our goal was to study how trauma-related environmental cues modulate working memory networks in PTSD. We examined neural activity in participants performing a visual working memory task while distracted by task-irrelevant trauma and non-trauma material. Recent post-9/11 veterans were divided into a PTSD group (n = 22) and a trauma-exposed control group (n = 20) based on the Davidson trauma scale. Using fMRI, we measured hemodynamic change in response to emotional (trauma-related) and neutral distraction presented during the active maintenance period of a delayed-response working memory task. The goal was to examine differences in functional networks associated with working memory (dorsolateral prefrontal cortex and lateral parietal cortex) and emotion processing (amygdala, ventrolateral prefrontal cortex, and fusiform gyrus). The PTSD group showed markedly different neural activity compared to the trauma-exposed control group in response to task-irrelevant visual distractors. Enhanced activity in ventral emotion processing regions was associated with trauma distractors in the PTSD group, whereas activity in brain regions associated with working memory and attention regions was disrupted by distractor stimuli independent of trauma content. Neural evidence for the impact of distraction on working memory is consistent with PTSD symptoms of hypervigilance and general distractibility during goal-directed cognitive processing.     

Default mode network activity in schizophrenia studied at resting state using probabilistic ICA

Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.     

Reduced functional connectivity within and between ‘social’ resting state networks in autism spectrum conditions

Individuals with Autism Spectrum Conditions (ASC) have difficulties in social interaction and communication, which is reflected in hypoactivation of brain regions engaged in social processing, such as medial prefrontal cortex (mPFC), amygdala and insula. Resting state studies in ASC have identified reduced connectivity of the default mode network (DMN), which includes mPFC, suggesting that other resting state networks incorporating ‘social’ brain regions may also be abnormal. Using Seed-based Connectivity and Group Independent Component Analysis (ICA) approaches, we looked at resting functional connectivity in ASC between specific ‘social’ brain regions, as well as within and between whole networks incorporating these regions. We found reduced functional connectivity within the DMN in individuals with ASC, using both ICA and seed-based approaches. Two further networks identified by ICA, the salience network, incorporating the insula and a medial temporal lobe network, incorporating the amygdala, showed reduced inter-network connectivity. This was underlined by reduced seed-based connectivity between the insula and amygdala. The results demonstrate significantly reduced functional connectivity within and between resting state networks incorporating ‘social’ brain regions. This reduced connectivity may result in difficulties in communication and integration of information across these networks, which could contribute to the impaired processing of social signals in ASC.     

Resting state brain network function in major depression – Depression symptomatology,antidepressant treatment effects,future research

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.     

Hypo-activation in the executive core of the sustained attention network in adolescent offspring of schizophrenia patients mediated by premorbid functional deficits

Adolescent offspring of schizophrenia patients (SCZ-Off) are vulnerable to psychiatric disorders. Assessing relationships between clinical and biological measures (such as functional magnetic resonance imaging, fMRI) may elucidate pathways of vulnerability in this group. Here we assessed the relationship between clinically assessed premorbid function, and cortico-striatal activity during sustained attention in controls (HC: with no family history of psychosis) and SCZ-Off. Subjects (n = 39) were assessed using the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. Based on the Global Assessment of Functioning (GAF) score, SCZ-Off were cleaved into "high" or “low” clinically functioning sub-groups (SCZ-Off_HF, SCZ-Off_LF respectively). During fMRI, subjects participated in a modified continuous performance task (CPT-IP). fMRI was conducted on a Bruker MedSpec 4 T system (345 EPI scans; TR = 2 s; 24 slices; 3.8 × 3.8 × 4 mm). Results show SCZ-Off_LF evinced less activation than both HC and SCZ-Off_HF in the executive core of the brain's attentional system (anterior cingulate, dorsal prefrontal cortex and caudate), but not visuo-spatial regions such as primary visual or superior parietal cortex. Differences were independent of behavioral performance, and reduction in activity was related to GAF score in a dose-dependent manner. Assessing the relationship between clinical measures and brain activity in domains such as attention provides a window into mechanisms of vulnerability in the developing adolescent brain.     

Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum

The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior.     

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

ObjectiveThe functional connectivity of the brain in chronic pancreatitis (CP) remains unknown. This study aimed to investigate functional connectivity in CP patients using resting state functional magnetic resonance imaging (fMRI) and explore the associations to clinical parameters and altered cerebral metabolites.MethodsSeed-based and ROI-to-ROI analyses were performed to assess connectivity within and between the default mode network (DMN) and salience network (SN). Additionally, functional connectivity in these networks were investigated in relation to clinical parameters (CP etiology, pain, medication, etc.) and cerebral glutamate/creatine level in the anterior cingulate cortex.ResultsThirty CP patients and 23 healthy controls were analyzed. CP patients showed hyper-connectivity in DMN and SN as compared to healthy controls. Furthermore, CP patients had reduced anti-correlated functional connectivity between DMN and SN (all P ≤ 0.009). The altered DMN connectivity correlated to glutamate/creatine level (r = 0.503, P = 0.020) in patients with pain, but not to the clinical parameters.ConclusionsCP patients had altered functional connectivity within and between brain networks. Altered DMN functional connectivity had an association to cerebral metabolic changes.SignificanceAltered functional connectivity in CP share similarities with other chronic pain conditions, and support our understanding of altered brain circuitry associated with the CP disease.     

Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study

Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.