Default Mode Network Subregions Research Articles

Abnormal topological parameters in the default mode network in patients with impaired cognition undergoing maintenance hemodialysis.

ObjectiveThe role of the default mode network (DMN) in the cognitive impairment experienced by patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD) remains unknown. This study tested the hypothesis that the topological architecture of the DMN plays a key role in ESRD-related cognitive impairment.MethodsFor this study, 43 ERSD patients receiving MHD and 41 healthy control (HC) volunteers matched for gender, age and education underwent resting-state functional magnetic resonance imaging examinations. DMN architecture was depicted by 20 selected DMN subregions. Graph theory approaches were applied to investigate multiple topological parameters within the DMN in resting state at the global, local and edge levels.ResultsGlobally, the MHD group exhibited topological irregularities as indicated by reduced values for the clustering coeffcient (Cp), normalized Cp (γ), world-index (σ), and local effciency (Eloc) compared with the HC group. Locally, the MHD group showed greater nodal betweenness in the left retrosplenial cortex (RC) compared with the HC group. At the edge level, the MHD group exhibited disconnected resting-state functional connections (RSFCs) in the medial temporal lobe (MTL) subsystem including the ventral medial prefrontal cortex (VMPC)–left posterior inferior parietal lobule, VMPC–right parahippocampal cortex (PC), and right RC–left PC RSFCs. Additionally, the VMPC–right PC RSFC was positively correlated with the Digit Span Test score and Eloc, and the right RC–left PC RSFC was positively correlated with the Montreal Cognitive Assessment score and Eloc in the MHD group.ConclusionsESRD patients undergoing MHD showed local inefficiency, abnormal nodal centralities, and hypoconnectivity within the DMN, implying that the functional differentiation and local information transmission efficiency of the DMN are disturbed in ESRD. The disconnected RSFCs in the MTL subsystem likely facilitated topological reconfiguration in the DMN of ESRD patients, leading to impairments of multidomain neurocognition including memory and emotion regulation.

Local inefficiency of the default mode network in young men with narcissistic personality disorder

Neuroimaging studies have shown structural deficits in the default mode network (DMN) in patients with narcissistic personality disorder (NPD); however, the functional basis of the DMN in NPD remains unclear. This study aimed to explore the functional basis of the DMN in NPD from the perspective of the connectome. Nineteen young male patients with NPD (mean age, 18.47 ± 0.77 years; range, 18–20 years) and 19 young male healthy control (HC) participants (mean age, 19.05 ± 1.31 years; range, 18–22 years) were recruited for resting-state functional magnetic resonance imaging examinations. The DMN architecture was depicted by 20 DMN subregions. Graph theory approaches were applied to investigate the functional topology within the DMN in NPD, and Pearson correlations between network parameters and psychological scores were assessed. The NPD group demonstrated topological anomalies in the DMN indicated by a decrease in the clustering coefficient and local efficiency compared with the HC group. Additionally, the NPD group showed increased nodal clustering and efficiency in the right posterior cingulate cortex. In the NPD group, local efficiency within the DMN was found to be positively correlated with the Narcissistic Personality Inventory score and negatively correlated the Hiding the Self score. The NPD group showed abnormal topology within the DMN, indicating that the functional segregation of the DMN is disturbed in NPD. The destroyed topology of the DMN may represent a functional basis of the pathogenesis of NPD in young adult males and may be related to the increased vulnerability in NPD, including hiding the self.

Viewing personalized video clips recommended by TikTok activates default mode network and ventral tegmental area

Cutting-edge recommendation algorithms have been widely used by media platforms to suggest users with personalized content. While such user-specific recommendations may satisfy users’ needs to obtain intended information, some users may develop a problematic use pattern manifested by addiction-like undesired behaviors. Using a popular video sharing and recommending platform (TikTok) as an example, the present study first characterized use-related undesired behaviors with a questionnaire, then investigated how personally recommended videos modulated brain activity with an fMRI experiment. We found more undesired symptoms were related to lower self-control ability among young adults, and about 5.9% of TikTok users may have significant problematic use. The fMRI results showed higher brain activations in sub-components of the default mode network (DMN), ventral tegmental area, and discrete regions including lateral prefrontal, anterior thalamus, and cerebellum when viewing personalized videos in contrast to non-personalized ones. Psychophysiological interaction analyses revealed stronger coupling between activated DMN subregions and neural pathways underlying auditory and visual processing, as well as the frontoparietal network. This study highlights the functional heterogeneity of DMN in viewing personalized videos and may shed light on the neural underpinnings of how recommendation algorithms are able to keep the user's attention to suggested contents.

Aberrant functional connectivity of neural circuits associated with thought-action fusion in patients with obsessive-compulsive disorder.

Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

The Effects of Music Intervention on Pallidum-DMN Circuit of Schizophrenia.

Music intervention has been applied to improve symptoms of schizophrenic subjects as a complementary treatment in medicine. Although the psychiatric symptoms, especially for motivation and emotion, could be increased in schizophrenia, the underlying neural mechanisms remain poorly understood. We employed a longitudinal study to measure the alteration of striatum functional networks in schizophrenic subjects undergoing Mozart music listening using resting-state functional magnetic resonance imaging (fMRI). Forty-five schizophrenic inpatients were recruited and randomly assigned to two groups. Under the standard care with antipsychotic medication, one group received music intervention for 1 month and the other group is set as control. Both schizophrenic groups were compared to healthy subjects. Resting-state fMRI was acquired from schizophrenic subjects at baseline and after one-month music intervention and from healthy subjects at baseline. Striatum network was assessed through seed-based static and dynamic functional connectivity (FC) analyses. After music intervention, increased static FC was observed between pallidum and ventral hippocampus in schizophrenic subjects. Increased dynamic FCs were also found between pallidus and subregions of default mode network (DMN), including cerebellum crus and posterior cingulate cortex. Moreover, static pallidus-hippocampus FC increment was positively correlated with the improvement of negative symptoms in schizophrenic subjects. Together, these findings provided evidence that music intervention might have an effect on the FC of the striatum-DMN circuit and might be related to the remission of symptoms of schizophrenia.

Changes in the topological organization of the default mode network in autism spectrum disorder.

Neuroimaging studies have demonstrated that autism spectrum disorder (ASD) is accompanied by abnormal functional and structural features in specific brain regions of the default mode network (DMN). However, little is known about the alterations of the topological organization and the functional connectivity (FC) of the DMN in ASD patients. Thirty-seven ASD patients and 38 healthy control (HC) participants underwent a resting-state functional magnetic resonance imaging scan. Twenty DMN subregions were specifically selected to construct the DMN architecture. We applied graph theory approaches to the topological configuration and compare the FC patterns of the DMN. We then examined the relationships between the neuroimaging measures of the DMN and clinical characteristics in patients with ASD. The current study revealed that both the ASD and HC participants showed a small-world regimen in the DMN; however there were no significant differences in global network measures. Compared with the HC group, the ASD group exhibited significantly decreased nodal centralities in the bilateral anterior medial prefrontal cortex and increased nodal centralities in the right lateral temporal cortex and the right retrosplenial cortex. Patients with ASD displayed significantly reduced and increased FC within the DMN. Our findings demonstrated that ASD patients showed a pattern of disrupted FC metrics and nodal network metrics in the DMN, which could be a potential biomarker for objective ASD diagnoses and for the level of autism spectrum traits. HIGHLIGHTS: We used graph theoretical approaches and functional connectivity (FC) to investigate the topological configuration and FC patterns of the DMN in ASD. The current study revealed that both ASD and HC participants exhibited small-world regimes in the DMN, however there were no significant differences in global network measures. The ASD group showed abnormal nodal centralities in the bilateral aMPFC, the right LTC and the Rsp of the DMN, and ASD was characterized by altered FC patterns, including decreased and increased FC within the DMN.

Psychosis risk is associated with decreased resting-state functional connectivity between the striatum and the default mode network.

Psychosis is linked to aberrant salience or to viewing neutral stimuli as self-relevant, suggesting a possible impairment in self-relevance processing. Psychosis is also associated with increased dopamine in the dorsal striatum, especially the anterior caudate (Kegeles et al., 2010). Critically, the anterior caudate is especially connected to (a) the cortical default mode network (DMN), centrally involved in self-relevance processing, and (b) to a lesser extent, the cortical frontoparietal network (FPN; Choi, Yeo, & Buckner, 2012). However, no previous study has directly examined striatal-cortical DMN connectivity in psychosis risk. In Study 1, we examined resting-state functional connectivity in psychosis risk (n = 18) and control (n = 19) groups between (a) striatal DMN and FPN subregions and (b) cortical DMN and FPN. The psychosis risk group exhibited decreased connectivity between the striatal subregions and the cortical DMN. In contrast, the psychosis risk group exhibited intact connectivity between the striatal subregions and the cortical FPN. Additionally, recent distress was also associated with decreased striatal-cortical DMN connectivity. In Study 2, to determine whether the decreased striatal-cortical DMN connectivity was specific to psychosis risk or was related to recent distress more generally, we examined the relationship between connectivity and distress in individuals diagnosed with nonpsychotic emotional distress disorders (N = 25). In contrast to Study 1, here we found that distress was associated with evidence of increased striatal-cortical DMN connectivity. Overall, the present results suggest that decreased striatal-cortical DMN connectivity is associated with psychosis risk and could contribute to aberrant salience.

Modulation by task-difficulty in the default mode network varies with the complexity of perpetual information during decision making

Modulation by task-difficulty in the default mode network varies with the complexity of perpetual information during decision making

Topological Reorganization of the Default Mode Network in Severe Male Obstructive Sleep Apnea

Impaired spontaneous regional activity and altered topology of the brain network have been observed in obstructive sleep apnea (OSA). However, the mechanisms of disrupted functional connectivity (FC) and topological reorganization of the default mode network (DMN) in patients with OSA remain largely unknown. We explored whether the FC is altered within the DMN and examined topological changes occur in the DMN in patients with OSA using a graph theory analysis of resting-state functional magnetic resonance imaging data and evaluated the relationship between neuroimaging measures and clinical variables. Resting-state data were obtained from 46 male patients with untreated severe OSA and 46 male good sleepers (GSs). We specifically selected 20 DMN subregions to construct the DMN architecture. The disrupted FC and topological properties of the DMN in patients with OSA were characterized using graph theory. The OSA group showed significantly decreased FC of the anterior–posterior DMN and within the posterior DMN, and also showed increased FC within the DMN. The DMN exhibited small-world topology in both OSA and GS groups. Compared to GSs, patients with OSA showed a decreased clustering coefficient (Cp) and local efficiency, and decreased nodal centralities in the left posterior cingulate cortex and dorsal medial prefrontal cortex, and increased nodal centralities in the ventral medial prefrontal cortex and the right parahippocampal cortex. Finally, the abnormal DMN FC was significantly related to Cp, path length, global efficiency, and Montreal cognitive assessment score. OSA showed disrupted FC within the DMN, which may have contributed to the observed topological reorganization. These findings may provide further evidence of cognitive deficits in patients with OSA.

Correspondent Functional Topography of the Human Left Inferior Parietal Lobule at Rest and Under Task Revealed Using Resting-State fMRI and Coactivation Based Parcellation.

The human left inferior parietal lobule (LIPL) plays a pivotal role in many cognitive functions and is an important node in the default mode network (DMN). Although many previous studies have proposed different parcellation schemes for the LIPL, the detailed functional organization of the LIPL and the exact correspondence between the DMN and LIPL subregions remain unclear. Mounting evidence indicates that spontaneous fluctuations in the brain are strongly associated with cognitive performance at the behavioral level. However, whether a consistent functional topographic organization of the LIPL during rest and under task can be revealed remains unknown. Here, they used resting-state functional connectivity (RSFC) and task-related coactivation patterns separately to parcellate the LIPL and identified seven subregions. Four subregions were located in the supramarginal gyrus (SMG) and three subregions were located in the angular gyrus (AG). The subregion-specific networks and functional characterization revealed that the four anterior subregions were found to be primarily involved in sensorimotor processing, movement imagination and inhibitory control, audition perception and speech processing, and social cognition, whereas the three posterior subregions were mainly involved in episodic memory, semantic processing, and spatial cognition. The results revealed a detailed functional organization of the LIPL and suggested that the LIPL is a functionally heterogeneous area. In addition, the present study demonstrated that the functional architecture of the LIPL during rest corresponds with that found in task processing. Hum Brain Mapp 38:1659-1675, 2017. © 2017 Wiley Periodicals, Inc.

Diurnal Variations in Neural Activity of Healthy Human Brain Decoded with Resting-State Blood Oxygen Level Dependent fMRI.

It remains an ongoing investigation about how the neural activity alters with the diurnal rhythms in human brain. Resting-state functional magnetic resonance imaging (RS-fMRI) reflects spontaneous activities and/or the endogenous neurophysiological process of the human brain. In the present study, we applied the ReHo (regional homogeneity) and ALFF (amplitude of low frequency fluctuation) based on RS-fMRI to explore the regional differences in the spontaneous cerebral activities throughout the entire brain between the morning and evening sessions within a 24-h time cycle. Wide spread brain areas were found to exhibit diurnal variations, which may be attributed to the internal molecular systems regulated by clock genes, and the environmental factors including light-dark cycle, daily activities and homeostatic sleep drive. Notably, the diurnal variation of default mode network (DMN) suggests that there is an adaptation or compensation response within the subregions of DMN, implying a balance or a decoupling of regulation between these regions.

Spontaneous default network activity reflects behavioral variability independent of mind-wandering

The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report.

The effects of apolipoprotein ε 4 on aging brain in cognitively normal Chinese elderly: a surface-based morphometry study.

Default mode network (DMN) has been reported to be susceptible to APOE ε 4 genotype. However, the APOE ε 4-related brain changes in young carriers are different from the ones in elderly carriers. The current study aimed to evaluate the cortical morphometry of DMN subregions in cognitively normal elderly with APOE ε 4. 11 cognitively normal senior APOE ε 4 carriers and 27 matched healthy controls (HC) participated the neuropsychological tests, genotyping, and magnetic resonance imaging (MRI) scanning. Voxel-based morphometry (VBM) analysis was used to assess the global volumetric changes. Surface-based morphometry (SBM) analysis was performed to measure regional gray matter volume (GMV) and gray matter thickness (GMT). Advancing age was associated with decreased GMV of DMN subregions. Compared to HC, APOE ε 4 carriers presented cortical atrophy in right cingulate gyrus (R_CG) (GMV: APOE carriers: 8475.23 ± 1940.73 mm3, HC: 9727.34 ± 1311.57 mm3, t = 2.314, p = 0.026, corrected) and left insular (GMT: APOE ε 4 carriers: 3.83 ± 0.37 mm, HC: 4.05 ± 0.25 mm, t = 2.197, p = 0.033, corrected). Our results highlight the difference between different cortical measures and suggest that the cortical reduction of CG and insular maybe a potential neuroimaging marker for APOE 4 ε senior carriers, even in the context of relatively intact cognition.

Abnormal resting-state functional connectivity within the default mode network subregions in male patients with obstructive sleep apnea.

Background and objectiveAbnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA.MethodsForty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA.ResultsCompared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033).ConclusionOSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients.

Topological Reorganization of the Default Mode Network in Irritable Bowel Syndrome.

The aim of this study was to investigate the topological reorganization of the brain default mode network (DMN) in patients with irritable bowel syndrome (IBS) using resting-state functional magnetic resonance imaging (rs-fMRI). With approval by our ethics committee, rs-fMRI was prospectively performed in 31 IBS patients (25 male, 27 ± 8years) and 32 healthy controls (25 male, 29 ± 9years). The DMN was determined by unbiased seed-based functional connectivity (FC) analysis and then parcellated into several subregions. FC across all pairs of DMN subregions was computed to construct the DMN architecture, for which topological properties were characterized by graph theoretical approaches. Pearson correlation was performed between abnormal DMN inter-regional FC and network measures and clinical indices in IBS patients. Compared to healthy controls, IBS patients showed decreased DMN inter-regional FC between the anterior cingulate cortex and precuneus, the medial orbital of the superior frontal gyrus (ORBsupmed) and precuneus, and the middle temporal gyrus and precuneus. IBS patients also showed decreased DMN global efficiency (E glob). Inclusion of anxiety and depression as covariates abolished FC between ORBsupmed and precuneus and some E glob differences. The average DMN FC was positively correlated with average E glob (r = 0.47, P = 0.008) and negatively correlated with symptom severity score (r = -0.37, P = 0.04) in IBS patients. In conclusion, IBS patients showed topological reorganization of the DMN to a non-optimized regularity configuration, which may partly be ascribed to high levels of anxiety and depression.

Functional connectivity of paired default mode network subregions in primary insomnia.

ObjectiveThe aim of this study is to explore the resting-state functional connectivity (FC) differences between the paired default mode network (DMN) subregions in patients with primary insomnia (PIs).MethodsForty-two PIs and forty-two age- and sex-matched good sleepers (GSs) were recruited. All subjects underwent the resting-state functional magnetic resonance imaging scans. The seed-based region-to-region FC method was used to evaluate the abnormal connectivity within the DMN subregions between the PIs and the GSs. Pearson correlation analysis was used to investigate the relationships between the abnormal FC strength within the paired DMN subregions and the clinical features in PIs.ResultsCompared with the GSs, the PIs showed higher Pittsburgh Sleep Quality Index score, Hamilton Anxiety Rating Scale score, Hamilton Depression Rating Scale score, Self-Rating Depression Scale score, Self Rating Anxiety Scale score, Self-Rating Scale of Sleep score, and Profile of Mood States score (P<0.001). Compared with the GSs, the PIs showed significant decreased region-to-region FC between the medial prefrontal cortex and the right medial temporal lobe (t=−2.275, P=0.026), and between the left medial temporal lobe and the left inferior parietal cortices (t=−3.32, P=0.001). The abnormal FC strengths between the DMN subregions did not correlate with the clinical features.ConclusionPIs showed disrupted FC within the DMN subregions.

The posteromedial region of the default mode network shows attenuated task-induced deactivation in psychopathic prisoners.

Psychopathy is a personality disorder with symptoms that include lack of empathy or remorse, antisocial behavior, and excessive self-focus. Previous neuroimaging studies have linked psychopathy to dysfunction in the default mode network (DMN), a brain network that deactivates during externally focused tasks and is more engaged during self-referential processing. Specifically, the DMN has been found to remain relatively active in individuals with psychopathic tendencies during externally focused tasks, suggesting a failure to properly deactivate. However, the exact extent and nature of task-induced DMN dysfunction is poorly understood, including (a) the degree to which specific DMN subregions are affected in criminal psychopaths, and (b) how activity in these subregions relates to affective/interpersonal and antisocial/lifestyle traits of psychopathy. We performed a group independent component analysis to assess DMN activation during a Go/NoGo task in a group of 22 high-psychopathy and 22 low-psychopathy prisoners. The identified group-level DMN was parcellated into 6 subregions, and group differences in task-induced activity were examined. In general, DMN subregions failed to deactivate beneath baseline in the high-psychopathy group. A group comparison with the low-psychopathy group localized this attenuated task-induced deactivation to the posteromedial cortical (mPC) region of the DMN. Moreover, multiple regression analyses revealed that activity in the mPC was associated with affective/interpersonal traits of psychopathy. These findings suggest that attenuated deactivation of the mPC subregion of the DMN is intrinsic to psychopathy, and is a pattern that may be more associated with affective psychopathic traits, including lack of concern for others.

Altered inter-subregion connectivity of the default mode network in relapsing remitting multiple sclerosis: a functional and structural connectivity study.

Background and PurposeLittle is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients.MethodsTwenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the inter-subregion structural-functional connectivity (SC-FC) within the DMN and its correlations with clinical markers.ResultsCompared with healthy subjects, the RRMS patients showed the following: 1) significantly decreased SC and increased FC in the pair-wise subregions; 2) two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/PCUN-bilateral mTL connections; 3) SC alterations [log(N track) of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4) decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track) of PCC/PCUN-left mTL connections) was positively correlated with brain atrophy.ConclusionsIn the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the disruption of this long-distance “inter-subregion” connectivity (white matter) may significantly impact the integrity of the network's function.

Diagnostic Classification Based on Functional Connectivity in Chronic Pain: Model Optimization in Fibromyalgia and Rheumatoid Arthritis

The combination of functional magnetic resonance imaging (fMRI) of the brain with multivariate pattern analysis (MVPA) has been proposed as a possible diagnostic tool. Goal of this investigation was to identify potential functional connectivity (FC) differences in the salience network (SN) and default mode network (DMN) between fibromyalgia syndrome (FMS), rheumatoid arthritis (RA), and controls (HC) and to evaluate the diagnostic applicability of derived pattern classification approaches. The resting period during an fMRI examination was retrospectively analyzed in women with FMS (n = 17), RA (n = 16), and HC (n = 17). FC was calculated for SN and DMN subregions. Classification accuracies of discriminative MVPA models were evaluated with cross-validation: (1) inferential test of a single method, (2) explorative model optimization. No inferentially tested model was able to classify subjects with statistically significant accuracy. However, the diagnostic ability for the differential diagnostic problem exhibited a trend to significance (accuracy: 69.7%, P = .086). Optimized models in the explorative analysis reached accuracies up to 73.5% (FMS vs. HC), 78.8% (RA vs. HC), and 78.8% (FMS vs. RA) whereas other models performed at or below chance level. Comparable support vector machine approaches performed above average for all three problems. Observed accuracies are not sufficient to reliably differentiate between FMS and RA for diagnostic purposes. However, some indirect evidence in support of the feasibility of this approach is provided. This exploratory analysis constitutes a fundamental model optimization effort to be based on in further investigations.

Disentangling linear and nonlinear brain responses to evoked deep tissue pain

Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region’s functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.