scholarly journals Oxytocin Enhances an Amygdala Circuit Associated With Negative Symptoms in Schizophrenia: A Single-Dose, Placebo-Controlled, Crossover, Randomized Control Trial

2019 ◽  
Vol 46 (3) ◽  
pp. 661-669
Author(s):  
Samantha V Abram ◽  
Lize De Coster ◽  
Brian J Roach ◽  
Bryon A Mueller ◽  
Theo G M van Erp ◽  
...  
Keyword(s):  
Single Dose ◽  
Functional Connectivity ◽  
Negative Symptoms ◽  
Angular Gyrus ◽  
Middle Temporal Gyrus ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Promising Treatment ◽  
Specific Association ◽  
Left Middle Temporal Gyrus

Abstract Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.

scholarly journals Intermittent theta burst stimulation for negative symptoms of schizophrenia—A double-blind, sham-controlled pilot study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rémy Bation ◽  
Charline Magnin ◽  
Emmanuel Poulet ◽  
Marine Mondino ◽  
Jérôme Brunelin
Keyword(s):  
Functional Connectivity ◽  
Negative Symptoms ◽  
Biological Effects ◽  
Occipital Cortex ◽  
Angular Gyrus ◽  
Treatment Resistant ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Left Dlpfc ◽  
Theta Burst

AbstractOptimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.

scholarly journals Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

2019 ◽  
Vol 237 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Grant McQueen ◽  
Aderlee Lay ◽  
John Lally ◽  
Anthony S. Gabay ◽  
Tracy Collier ◽  
...  
Keyword(s):  
Single Dose ◽  
Functional Connectivity ◽  
Resting State ◽  
Pharmacological Action ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Frontal Pole ◽  
Resting State Functional Connectivity ◽  
Placebo Condition ◽  
Double Blind

Abstract Rationale There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. Objectives The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). Methods In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. Results Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). Conclusions These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

scholarly journals Functional Connectivity and Networks Underlying Complex Tool-Use Movement in Assembly Workers: An fMRI Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Seira Taniguchi ◽  
Yuichiro Higashi ◽  
Hirotaka Kataoka ◽  
Hiroshi Nakajima ◽  
Tetsuya Shimokawa
Keyword(s):  
Functional Connectivity ◽  
Tool Use ◽  
Repeated Measures ◽  
Inferior Frontal Gyrus ◽  
Real Life ◽  
Analysis Of Covariance ◽  
Repeated Measure ◽  
Angular Gyrus ◽  
Middle Temporal Gyrus ◽  
Resting State Functional Connectivity

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW &gt; UTW) and condition (task &gt; resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate corrected p-value, p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms

2018 ◽  
Vol 48 (15) ◽  
pp. 2492-2499 ◽  
Author(s):  
J. Ferri ◽  
J. M. Ford ◽  
B. J. Roach ◽  
J. A. Turner ◽  
T. G. van Erp ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Negative Symptoms ◽  
Brain Connectivity ◽  
Statistical Significance ◽  
Superior Temporal Gyrus ◽  
Anterior Cingulate ◽  
Middle Temporal Gyrus ◽  
Resting State Functional Connectivity ◽  
Cortical Regions

AbstractBackgroundSchizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.MethodResting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.ResultsHC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.ConclusionsThalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

scholarly journals The Brain Resting-State Functional Connectivity Underlying Violence Proneness: Is It a Reliable Marker for Neurocriminology? A Systematic Review

2019 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Ángel Romero-Martínez ◽  
Macarena González ◽  
Marisol Lila ◽  
Enrique Gracia ◽  
Luis Martí-Bonmatí ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Effective Treatment ◽  
Resting State ◽  
Brain Structures ◽  
Prevention Programs ◽  
Angular Gyrus ◽  
Resting State Functional Connectivity ◽  
Treatment And Prevention ◽  
Reliable Marker ◽  
The Brain

Introduction: There is growing scientific interest in understanding the biological mechanisms affecting and/or underlying violent behaviors in order to develop effective treatment and prevention programs. In recent years, neuroscientific research has tried to demonstrate whether the intrinsic activity within the brain at rest in the absence of any external stimulation (resting-state functional connectivity; RSFC) could be employed as a reliable marker for several cognitive abilities and personality traits that are important in behavior regulation, particularly, proneness to violence. Aims: This review aims to highlight the association between the RSFC among specific brain structures and the predisposition to experiencing anger and/or responding to stressful and distressing situations with anger in several populations. Methods: The scientific literature was reviewed following the PRISMA quality criteria for reviews, using the following digital databases: PubMed, PsycINFO, Psicodoc, and Dialnet. Results: The identification of 181 abstracts and retrieval of 34 full texts led to the inclusion of 17 papers. The results described in our study offer a better understanding of the brain networks that might explain the tendency to experience anger. The majority of the studies highlighted that diminished RSFC between the prefrontal cortex and the amygdala might make people prone to reactive violence, but that it is also necessary to contemplate additional cortical (i.e. insula, gyrus [angular, supramarginal, temporal, fusiform, superior, and middle frontal], anterior and posterior cingulated cortex) and subcortical brain structures (i.e. hippocampus, cerebellum, ventral striatum, and nucleus centralis superior) in order to explain a phenomenon as complex as violence. Moreover, we also described the neural pathways that might underlie proactive violence and feelings of revenge, highlighting the RSFC between the OFC, ventral striatal, angular gyrus, mid-occipital cortex, and cerebellum. Conclusions. The results from this synthesis and critical analysis of RSFC findings in several populations offer guidelines for future research and for developing a more accurate model of proneness to violence, in order to create effective treatment and prevention programs.

scholarly journals Aberrant Frontostriatal Connectivity in Negative Symptoms of Schizophrenia

2018 ◽  
Vol 45 (5) ◽  
pp. 1051-1059 ◽  
Author(s):  
Dinesh K Shukla ◽  
Joshua John Chiappelli ◽  
Hemalatha Sampath ◽  
Peter Kochunov ◽  
Stephanie M Hare ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Negative Symptom ◽  
Negative Symptoms ◽  
Imaging Study ◽  
Anterior Cingulate ◽  
Functional Magnetic Resonance ◽  
Resting State Functional Connectivity ◽  
Symptom Scale ◽  
Distinct Component ◽  
The Right

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.

scholarly journals Differential resting state connectivity responses to glycemic state in type 1 diabetes

2019 ◽  
Author(s):  
Lisa Parikh ◽  
Dongju Seo ◽  
Cheryl Lacadie ◽  
Renata Belfort-DeAguiar ◽  
Derek Groskreutz ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Functional Connectivity ◽  
Resting State ◽  
Medical Center ◽  
Academic Medical Center ◽  
Angular Gyrus ◽  
Resting State Functional Connectivity ◽  
The Impact ◽  
Resting State Connectivity

Abstract Context Individuals with type 1 diabetes (T1DM) have alterations in brain activity which have been postulated to contribute to the adverse neurocognitive consequences of T1DM; however, the impact of T1DM and hypoglycemic unawareness on the brain’s resting state activity remains unclear. Objective To determine whether individuals with T1DM and hypoglycemia unawareness (T1DM-Unaware) had changes in the brain resting state functional connectivity compared to healthy controls (HC) and those with T1DM and hypoglycemia awareness (T1DM-Aware). Design Observational study Setting Academic medical center Participants 27 individuals with T1DM and 12 healthy control volunteers participated in the study. Intervention All participants underwent BOLD resting state fMRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60mg/dl) clamp. Outcome Changes in resting state functional connectivity Results Using two separate methods of functional connectivity analysis, we identified distinct differences in the resting state brain responses to mild hypoglycemia amongst HC, T1DM-Aware and T1DM-Unaware participants, particularly in the angular gyrus, an integral component of the default mode network (DMN). Furthermore, changes in angular gyrus connectivity also correlated with greater symptoms of hypoglycemia (r = 0.461, P = 0.003) as well as higher scores of perceived stress (r = 0.531, P = 0.016). Conclusion These findings provide evidence that individuals with T1DM have changes in the brain’s resting state connectivity patterns, which may be further associated with differences in awareness to hypoglycemia. These changes in connectivity may be associated with alterations in functional outcomes amongst individuals with T1DM.

scholarly journals Abnormal functional connectivity density in patients with dysthyroid optic neuropathy

2020 ◽  
Author(s):  
Yunhai Tu ◽  
Pingping Huang ◽  
Chuanwan Mao ◽  
Xiaozheng Liu ◽  
Jianlu Gao
Keyword(s):  
Visual Field ◽  
Functional Connectivity ◽  
Optic Neuropathy ◽  
Middle Temporal Gyrus ◽  
Functional Connectivity Density ◽  
Dysthyroid Optic Neuropathy ◽  
Middle Temporal ◽  
The Right ◽  
Left Middle Temporal Gyrus ◽  
Left Middle

[Objective] Functional connectivity density (FCD) mapping was used to investigate abnormalities and factors related to brain functional connectivity (F.C.) in cortical regions of patients with dysthyroid optic neuropathy (DON) and to analyze the pathogenesis of DON further. [Methods] Patients diagnosed with thyroid-associated ophthalmopathy (TAO) in the Eye Hospital were enrolled. All patients underwent comprehensive eye examinations and best-corrected visual acuity, visual field(V.F.) test. MRI data collection and analysis were completed in the 2nd Affiliated Hospital of Wenzhou Medical University. The patients were divided into two groups: the DON group, with an average visual field, mean deviation (M.D.) of both eyes < -5 dB, and the non-DON group (nDON group), with an average visual field M.D. of both eyes ≥ -2 dB. [Results] A total of 30 TAO patients (14 men, 16 women) with complete data who met the experimental requirements were enrolled. The average age was 48.79 (40~ 57) years. There were 16 patients in the DON group and 14 patients in the nDON group. No significant differences in age, gender, education level, and the maximum horizontal diameter of either medial rectus muscle were found between the two groups. The difference of brain FCD between the two groups showed significant abnormal connectivity in the right orbital gyri of the frontal lobe (Frontal_Inf_Orb_R) and the left precuneus in the DON group compared with the nDON group. As demonstrated by decreased FCD values in the right inferior frontal gyrus/orbital part, the relevant brain regions were the left middle temporal gyrus, left precuneus, left middle frontal gyrus, right postcentral gyrus, and brain gyri (excluding the supramarginal gyrus and angular gyrus) below the left parietal bone. The FCD associated with the left precuneus was increased, and the relevant brain areas were the left middle temporal gyrus, right cuneus, superior occipital gyrus, and right fusiform gyrus. A significant correlation was identified between the MD. of the binocular visual field and brain FCD. [Conclusion] The abnormal FCD in the cortex of DON patients suggests that a central nervous system mechanism may be related to the pathogenesis of the DON.

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