scholarly journals Altered Functional Connectivity of the Nucleus Accumbens Network Between Deficit and Non-deficit Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Zhou ◽  
Chen Xue ◽  
Jiu Chen ◽  
Nousayhah Amdanee ◽  
Xiaowei Tang ◽  
...  

Deficit schizophrenia (DS), which is marked by stable negative symptoms, is regarded as a homogeneous subgroup of schizophrenia. While DS patients have structurally altered nucleus accumbens (NAcc) compared to non-deficit schizophrenia (NDS) patients and healthy individuals, the investigation of NAcc functional connectivity (FC) with negative symptoms and neurocognition could provide insights into the pathophysiology of schizophrenia. 58 DS, 93 NDS, and 113 healthy controls (HCs) underwent resting-state functional magnetic resonance (rsfMRI). The right and left NAcc were respectively used as seed points to construct the functional NAcc network in whole-brain FC analysis. ANCOVA compared the differences in NAcc network FC and partial correlation analysis explored the relationships between altered FC of NAcc, negative symptoms and neurocognition. Compared to HCs, both DS and NDS patients showed decreased FC between the left NAcc (LNAcc) and bilateral middle cingulate gyrus, and between the right NAcc (RNAcc) and right middle frontal gyrus (RMFG), as well as increased FC between bilateral NAcc and bilateral lingual gyrus. Moreover, the FC between the LNAcc and bilateral calcarine gyrus (CAL) was lower in the DS group compared to NDS patients. Correlation analysis indicated that FC value of LNAcc-CAL was negatively correlated to negative symptoms. Furthermore, aberrant FC values within the NAcc network were correlated with severity of clinical symptoms and neurocognitive impairments in DS and NDS patients. This study demonstrated abnormal patterns of FC in the NAcc network between DS and NDS. The presence of altered LNAcc-CAL FC might be involved in the pathogenesis of negative symptoms in schizophrenia.

2018 ◽  
Vol 45 (5) ◽  
pp. 1051-1059 ◽  
Author(s):  
Dinesh K Shukla ◽  
Joshua John Chiappelli ◽  
Hemalatha Sampath ◽  
Peter Kochunov ◽  
Stephanie M Hare ◽  
...  

AbstractNegative symptoms represent a distinct component of psychopathology in schizophrenia (SCZ) and are a stable construct over time. Although impaired frontostriatal connectivity has been frequently described in SCZ, its link with negative symptoms has not been carefully studied. We tested the hypothesis that frontostriatal connectivity at rest may be associated with the severity of negative symptoms in SCZ. Resting state functional connectivity (rsFC) data from 95 mostly medicated patients with SCZ and 139 healthy controls (HCs) were acquired. Negative symptoms were assessed using the Brief Negative Symptom Scale. The study analyzed voxel-wise rsFC between 9 frontal “seed regions” and the entire striatum, with the intention to reduce potential biases introduced by predefining any single frontal or striatal region. SCZ showed significantly reduced rsFC between the striatum and the right medial and lateral orbitofrontal cortex (OFC), lateral prefrontal cortex, and rostral anterior cingulate cortex compared with HCs. Further, rsFC between the striatum and the right medial OFC was significantly associated with negative symptom severity. The involved striatal regions were primarily at the ventral putamen. Our results support reduced frontostriatal functional connectivity in SCZ and implicate striatal connectivity with the right medial OFC in negative symptoms. This task-independent resting functional magnetic resonance imaging study showed that medial OFC–striatum functional connectivity is reduced in SCZ and associated with severity of negative symptoms. This finding supports a significant association between frontostriatal connectivity and negative symptoms and thus may provide a potential circuitry-level biomarker to study the neurobiological mechanisms of negative symptoms.


Author(s):  
Michael Maes ◽  
Buranee Kanchanatawan ◽  
Sunee Sirivichayakul ◽  
Andre F. Carvalho

Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative specific epitopes (OSEs), which are a first line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls.Deficit schizophrenia was characterized by significantly increased IgA responses to Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii and Klebsiella pneumoniae as compared with non-deficit schizophrenia. The presence of deficit schizophrenia was highly predicted by increased IgA responses to Pseudomonas putida and IgM responses to all 5 Gram-negative bacteria and lowered natural IgM to MDA and azelaic acid with a bootstrap area under the ROC curve of 0.960 (2000 random curves). A large proportion of the variance (41.5%) in the PANSS negative score was explained by the regression on IgA responses to K. pneumoniae and IgM responses to the 5 enterobacteria coupled with lowered IgM antibodies to azelaic acid. There were significant associations between IgA levels to Gram-negative bacteria and Mini Mental State Examination, Boston naming test, Verbal Fluency and Word List Memory test scores.These findings provide further evidence that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by an increased impact of Gram-negative commensal bacteria coupled with a deficit in natural IgM, pointing to aberrations in B1 cells. It is concluded that increased bacterial translocation and deficits in the compensatory immune-regulatory system (CIRS) may drive negative symptoms and neurocognitive impairments, which are hallmarks of deficit schizophrenia.


1991 ◽  
Vol 158 (2) ◽  
pp. 158-164 ◽  
Author(s):  
A. H. Young ◽  
D. H. R. Blackwood ◽  
H. Roxborough ◽  
J. K. McQueen ◽  
M. J. Martin ◽  
...  

Thirty-one patients with schizophrenia and 33 normal control subjects underwent MRI. The BPRS was used to rate clinical symptoms and the NART to estimate premorbid IQ. All were right handed. The temporal lobe was significantly smaller on the left than the right in both the control and schizophrenic groups. The amygdala was smaller on the left than the right in controls but not in schizophrenics. The parahippocampal gyrus was smaller on the left side in the schizophrenic group but not in controls. In the schizophrenic group, ventricular enlargement and cerebral atrophy were significantly related to severity of symptoms. Patients with marked negative symptoms had a bilateral reduction in the size of the head of caudate and the two measures were significantly correlated. Patients with marked positive symptoms had larger VBRs and again the clinical and morphometric changes were significantly correlated. There were no morphometric differences between patients with short duration (two years or less) and chronic symptoms.


2018 ◽  
Vol 49 (07) ◽  
pp. 1156-1165 ◽  
Author(s):  
Tingting Xu ◽  
Qing Zhao ◽  
Pei Wang ◽  
Qing Fan ◽  
Jue Chen ◽  
...  

AbstractBackgroundThe role of the cerebellum in obsessive-compulsive disorder (OCD) has drawn increasing attention. However, the functional connectivity between the cerebellum and the cerebral cortex has not been investigated in OCD, nor has the relationship between such functional connectivity and clinical symptoms.MethodsA total of 27 patients with OCD and 21 healthy controls (HCs) matched on age, sex and education underwent magnetic resonance imaging (MRI). Seed-based connectivity analyses were performed to examine differences in cerebellar-cerebral connectivity in patients with OCD compared with HCs. Associations between functional connectivity and clinical features in OCD were analyzed.ResultsCompared with HCs, OCD patients showed significantly decreased cerebellar-cerebral functional connectivity in executive control and emotion processing networks. Within the OCD group, decreased functional connectivity in an executive network spanning the right cerebellar Crus I and the inferior parietal lobule was positively correlated with symptom severity, and decreased connectivity in an emotion processing network spanning the left cerebellar lobule VI and the lingual gyrus was negatively correlated with illness duration.ConclusionsAltered functional connectivity between the cerebellum and cerebral networks involved in cognitive-affective processing in patients with OCD provides further evidence for the involvement of the cerebellum in the pathophysiology of OCD, and is consistent with impairment in executive control and emotion regulation in this condition.


2016 ◽  
Vol 22 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Chiao-Yun Chen ◽  
Ju-Yu Yen ◽  
Peng-Wei Wang ◽  
Gin-Chung Liu ◽  
Cheng-Fang Yen ◽  
...  

Aims: A possible addiction mechanism has been represented by altered functional connectivity (FC) in the resting state. The aim of this study was to evaluate the FCs of the insula and nucleus accumbens among subjects with Internet gaming disorder (IGD). Methods: We recruited 30 males with IGD and 30 controls and evaluated their FC using functional magnetic imaging scanning under resting, a state with relaxation, closed eyes, with inducement to think of nothing systematically, become motionless, and instructed not to fall asleep. Results: Subjects with IGD had a lower FC with the left insula over the left dorsolateral prefrontal cortex (DLPFC) and orbital frontal lobe and a higher FC with the insula with the contralateral insula than controls. The inter-hemispheric insula connectivity positively correlated with impulsivity. Further, they had lower FC with the left nucleus accumbens over the left DLPFC and with the right nucleus accumbens over the left DLPFC, and insula and a higher FC with that over the right precuneus. Conclusion: The elevated inter-hemispheric insula FC is found to be associated with impulsivity and might explain why it is involved in IGD. The attenuated frontostriatal suggests that the emotion-driven gaming urge through nucleus accumbens could not be well regulated by the frontal lobe of subjects with IGD.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yunhui Chen ◽  
Yangpan Ou ◽  
Dan Lv ◽  
Jidong Ma ◽  
Chuang Zhan ◽  
...  

Background. Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods. The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results. Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion. The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.


2019 ◽  
Author(s):  
Julia M. Sheffield ◽  
Baxter P. Rogers ◽  
Jennifer Urbano Blackford ◽  
Stephan Heckers ◽  
Neil D. Woodward

AbstractThe insula is structurally abnormal in schizophrenia, demonstrating robust reductions in gray matter volume, cortical thickness, and altered gyrification during prodromal, early and chronic stages of the illness. Despite compelling structural alterations, less is known about its functional connectivity, limited by studies considering the insula as a whole or only within the context of resting-state networks. There is evidence, however, from healthy subjects that the insula is comprised of sub-regions with distinct functional profiles, with dorsal anterior insula (dAI) involved in cognitive processing, ventral anterior insula (vAI) involved in affective processing, and posterior insula (PI) involved in somatosensory processing. The current study builds on this prior work and characterizes insula resting-state functional connectivity sub-region profiles in a large cohort of schizophrenia (N=191) and healthy (N=196) participants and hypothesizes specific associations between insula sub-region connectivity abnormalities and clinical characteristics related to their functional profiles. Functional dysconnectivity of the insula in schizophrenia is broadly characterized by reduced connectivity within insula sub-networks and hyper-connectivity with regions not normally connected with that sub-region, reflected in significantly greater similarity of dAI and PI connectivity profiles and significantly lower similarity of dAI and vAI connectivity profiles (p<.05). In schizophrenia, hypo-connectivity of dAI correlates with cognitive function (r=.18, p=.014), whereas hyper-connectivity between vAI and superior temporal sulcus correlates with negative symptoms (r=.27, p<.001). These findings reveal altered insula connectivity in all three sub-regions and converges with recent evidence of reduced differentiation of insula connectivity in schizophrenia, implicating functional dysconnectivity of the insula in cognitive and clinical symptoms.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S189-S190
Author(s):  
Fabien Carruzzo ◽  
Matthias Kirschner ◽  
Stefan Kaiser

Abstract Background Recent studies have pointed at the ventral striatum as one of the main candidates underlying motivational dysfunctions in schizophrenia. Patients with negative symptoms show decreased BOLD activity in the ventral striatum and this activity strongly correlates with apathy scores during reward anticipation. While in patients with schizophrenia blunted ventral striatal activation during reward anticipation has been widely reported, little is known about abnormal striatal functional connectivity during reward anticipation. In this study, we performed generalized whole-brain psychophysiological interaction (gPPI) analyses using the right and left ventral striatum as seeds in schizophrenia patients with apathy and reduced ventral striatal activation from two published fMRI studies (Kirschner et al., 2016; Stepien et al., 2018). Methods Forty-four healthy controls (18 females, mean age = 31.1) and 40 patients with schizophrenia (10 females, mean age = 32.5) performed a variant of the Monetary Incentive Delay task within an fMRI design. Negative symptoms were assessed with the Brief Negative Symptoms Scale (BNSS). GPPI analyses were done using the PPPI toolbox on SPM 8. To examine potential difference in striatal functional connectivity, we performed two sample t-tests between patients with schizophrenia and healthy controls using the contrast [High Reward Anticipation – No Reward Anticipation]. Results Patients with schizophrenia showed increased functional connectivity between the right ventral striatum and the anterior cingulate cortex, posterior cingulate cortex, cerebellum, motor cortex, parietal cortex, temporo-parietal junction and thalamus compared to controls (cluster-level FDR p&lt;0.05). No higher connectivity was found in controls compared to patients. For the regions with increased functional connectivity, we performed correlations between the patients’ gPPI signal and apathy. We found significant correlations between apathy and functional connectivity between the right ventral striatum and the right posterior cingulate cortex (r=0.40, p&lt;.05) and right parietal cortex (r=0.39, p&lt;.05). Discussion Our preliminary results indicate that physiological changes in the ventral striatum lead to dysfunctional connectivity with a cortex-wide network, affecting both cortico-striatal-thalamic-cortical and cortico-striatal-thalamic-cerebellar pathways. In addition, we show that some of these changes are related to apathy levels. This work provides novel insights in cortico-striatal network dysfunction during reward processing in patients with schizophrenia.


2021 ◽  
Vol 11 (1) ◽  
pp. 61
Author(s):  
Giulia M. Giordano ◽  
Pasquale Pezzella ◽  
Mario Quarantelli ◽  
Paola Bucci ◽  
Anna Prinster ◽  
...  

Deficit schizophrenia is a subtype of schizophrenia presenting primary and enduring negative symptoms (NS). Although one of the most updated hypotheses indicates a relationship between NS and impaired motivation, only a few studies have investigated abnormalities of motivational circuits in subjects with deficit schizophrenia (DS). Our aim was to investigate structural connectivity within motivational circuits in DS. We analyzed diffusion tensor imaging (DTI) data from 46 subjects with schizophrenia (SCZ) and 35 healthy controls (HCs). SCZ were classified as DS (n = 9) and non-deficit (NDS) (n = 37) using the Schedule for Deficit Syndrome. The connectivity index (CI) and the Fractional Anisotropy (FA) of the connections between selected brain areas involved in motivational circuits were examined. DS, as compared with NDS and HCs, showed increased CI between the right amygdala and dorsal anterior insular cortex and increased FA of the pathway connecting the left nucleus accumbens with the posterior insular cortex. Our results support previous evidence of distinct neurobiological alterations underlying different clinical subtypes of schizophrenia. DS, as compared with NDS and HCs, may present an altered pruning process (consistent with the hyperconnectivity) in cerebral regions involved in updating the stimulus value to guide goal-directed behavior.


2005 ◽  
Vol 8 (1) ◽  
pp. 49 ◽  
Author(s):  
Mersa M. Baryalei ◽  
Theodorus Tirilomis ◽  
Wolfgang Buhre ◽  
Stephan Kazmaier ◽  
Friedrich A. Schoendube ◽  
...  

Background: Myocardial bridging of the left anterior descending (LAD) artery may result in clinical symptoms. Surgery with cardiopulmonary bypass (CPB) is a therapeutic option with considerable risk. We hypothesized that off-pump supraarterial myotomy could be an effective treatment modality. Methods: Between October 1998 and May 2000, 13 patients were referred for surgery. All were symptomatic despite medical therapy. Anteroseptal ischemia had been proven by thallium scintigraphy in all 13 patients, exercise testing was positive in 11. All patients were operated on with an off-pump approach after median sternotomy. Results: Mean patient age was 61 8 years (range, 43-71 years). Coronary artery disease mandating additional bypasses was present in 3 patients. The bypasses were done off pump in 2 patients. Conversion to on-pump surgery was necessary in 3 of 13 patients (23%) because of hemodynamic compromise (1 patient), opening of the right ventricle (1 patient), and injury to the LAD (1 patient). Supraarterial myotomy was performed in all patients. One patient who underwent surgery with CPB developed postoperative anteroseptal myocardial infarction. Postoperative exercise testing was performed in all patients and did not reveal any persistent ischemia. Mortality was 0%. All patients were free from symptoms and had not undergone repeat interventions after an average of 51 7 months of follow-up. Conclusions: Off-pump supraarterial myotomy effectively relieves coronary obstruction but has a certain periprocedural risk as evidenced by 1 myocardial infarction, 1 right ventricular injury, and 1 LAD injury. Long-term freedom from symptoms and from reintervention favor further investigation of this surgical therapy.


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