Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

AbstractThe anterior cingulate area (ACA) is an integral part of the prefrontal cortex in mice and has been implicated in several cognitive functions. Previous anatomical and functional imaging studies demonstrated that the ACA is highly interconnected with numerous brain regions acting as a hub region in functional networks. However, the importance of the ACA in regulating functional network activity and connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal activity. In this study, we used an inhibitory kappa-opioid receptor DREADDs (KORD) to temporally inhibit neuronal firing in the right ACA of mice and assessed functional network activity and connectivity using non-invasive functional MRI. We demonstrated that KORD-induced inhibition of the right ACA induced blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions throughout of hemispheres. Furthermore, these modulations in neuronal activity were associated with decreased intra- and interhemispheric functional connectivity. These results demonstrate that the combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool for unraveling the underlying mechanisms of network function and dysfunction.

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Aberrant Resting-State Functional Connectivity of the Dorsal Attention Network in Tinnitus

Neural Plasticity ◽

10.1155/2021/2804533 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Haimeng Hu ◽

Yining Lyu ◽

Shihong Li ◽

Zheng Yuan ◽

Chuntao Ye ◽

...

Keyword(s):

Functional Connectivity ◽

Brain Regions ◽

Anterior Cingulate ◽

Healthy Controls ◽

Resting State Functional Connectivity ◽

Attention Network ◽

Superior Frontal Gyrus ◽

Functional Connections ◽

Dorsal Attention Network ◽

The Right

Previous functional magnetic resonance imaging (fMRI) analyses have shown that the dorsal attention network (DAN) is involved in the pathophysiological changes of tinnitus, but few relevant studies have been conducted, and the conclusions to date are not uniform. The purpose of this research was to test whether there is a change in intrinsic functional connectivity (FC) patterns between the DAN and other brain regions in tinnitus patients. Thirty-one patients with persistent tinnitus and thirty-three healthy controls were enrolled in this study. A group independent component analysis (ICA), degree centrality (DC) analysis, and seed-based FC analysis were conducted. In the group ICA, the tinnitus patients showed increased connectivity in the left superior parietal gyrus in the DAN compared to the healthy controls. Compared with the healthy controls, the tinnitus patients showed increased DC in the left inferior parietal gyrus and decreased DC in the left precuneus within the DAN. The clusters within the DAN with significant differences in the ICA or DC analysis between the tinnitus patients and the healthy controls were selected as regions of interest (ROIs) for seeds. The tinnitus patients exhibited significantly increased FC from the left superior parietal gyrus to several brain regions, including the left inferior parietal gyrus, the left superior marginal gyrus, and the right superior frontal gyrus, and decreased FC to the right anterior cingulate cortex. The tinnitus patients exhibited decreased FC from the left precuneus to the left inferior occipital gyrus, left calcarine cortex, and left superior frontal gyrus compared with the healthy controls. The findings of this study show that compared with healthy controls, tinnitus patients have altered functional connections not only within the DAN but also between the DAN and other brain regions. These results suggest that it may be possible to improve the disturbance and influence of tinnitus by regulating the DAN.

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Systemic Inflammation Impairs Mood Function by Disrupting the Resting-State Functional Network in a Rat Animal Model Induced by Lipopolysaccharide Challenge

Mediators of Inflammation ◽

10.1155/2019/6212934 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Xia Zhu ◽

Mu-Huo Ji ◽

Shu-Ming Li ◽

Bin Li ◽

Li Mei ◽

...

Keyword(s):

Animal Model ◽

Functional Connectivity ◽

Systemic Inflammation ◽

Resting State ◽

Forced Swim Test ◽

Retrosplenial Cortex ◽

Anterior Cingulate ◽

Functional Network ◽

Control Group ◽

The Right

Background. Systemic inflammation impairs cognitive performance, yet the brain networks mediating this process remain to be elucidated. The purpose of the current study was to use resting-state functional magnetic resonance imaging (fMRI) to explore changes in the functional connectivity in a lipopolysaccharide- (LPS-) induced systemic inflammation animal model. Materials and Methods. We used the regional homogeneity (ReHo) method to examine abnormal brain regions between the control and LPS groups and then considered them as seeds of functional connectivity analysis. Results. Compared with the control group, our study showed that (1) LPS impaired mood function, as reflected by a depression-like behavior in the forced swim test; (2) LPS induced significantly increased ReHo values in the anterior cingulate cortex (ACC) and caudate putamen (CPu); (3) the ACC seed showed increased functional connectivity with the retrosplenial cortex, superior colliculus, and inferior colliculus; and (4) the right CPu seed showed increased functional connectivity with the left CPu. Linear regression analysis showed a LPS-induced depression-like behavior which was associated with increased ReHo values in the ACC and right CPu. Moreover, the LPS-induced depression-like behavior was related to increased functional connectivity between the right CPu and left CPu. Conclusion. This is the first study to show that systemic inflammation impairs mood function that is associated with an altered resting-state functional network based on ReHo analysis, providing evidence of the abnormal regional brain spontaneous activity which might be involved in inflammation-related neurobehavioral abnormalities.

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Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.691710 ◽

2021 ◽

Vol 13 ◽

Author(s):

Jung Yun Jang ◽

S. Duke Han ◽

Belinda Yew ◽

Anna E. Blanken ◽

Shubir Dutt ◽

...

Keyword(s):

Older Adults ◽

Functional Connectivity ◽

Orbitofrontal Cortex ◽

Resting State ◽

Neural Mechanism ◽

Resting State Fmri ◽

Brain Regions ◽

Anterior Cingulate ◽

Resting State Functional Connectivity ◽

The Right

Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold p < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, t = −5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, t = −5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, t = 4.99) and anterior prefrontal (123 voxels, t = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.

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A Connectome-Wide Functional Signature of Trait Anger

Clinical Psychological Science ◽

10.1177/21677026211030240 ◽

2021 ◽

pp. 216770262110302

Author(s):

M. Justin Kim ◽

Maxwell L. Elliott ◽

Annchen R. Knodt ◽

Ahmad R. Hariri

Keyword(s):

Functional Connectivity ◽

Visual Information ◽

Past Research ◽

Brain Regions ◽

Small Sample ◽

Trait Anger ◽

Frontal Pole ◽

Brain Correlates ◽

Small Sample Sizes ◽

The Right

Past research on the brain correlates of trait anger has been limited by small sample sizes, a focus on relatively few regions of interest, and poor test–retest reliability of functional brain measures. To address these limitations, we conducted a data-driven analysis of variability in connectome-wide functional connectivity in a sample of 1,048 young adult volunteers. Multidimensional matrix regression analysis showed that self-reported trait anger maps onto variability in the whole-brain functional connectivity patterns of three brain regions that serve action-related functions: bilateral supplementary motor areas and the right lateral frontal pole. We then demonstrate that trait anger modulates the functional connectivity of these regions with canonical brain networks supporting somatomotor, affective, self-referential, and visual information processes. Our findings offer novel neuroimaging evidence for interpreting trait anger as a greater propensity to provoked action, which supports ongoing efforts to understand its utility as a potential transdiagnostic marker for disordered states characterized by aggressive behavior.

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Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study

Cellular Physiology and Biochemistry ◽

10.1159/000453212 ◽

2016 ◽

Vol 40 (6) ◽

pp. 1626-1636 ◽

Cited By ~ 12

Author(s):

Tao Liu ◽

Jianjun Li ◽

Zhiqiang Zhang ◽

Qiang Xu ◽

Guangming Lu ◽

...

Keyword(s):

Functional Connectivity ◽

Long Range ◽

Short Range ◽

Anterior Cingulate ◽

Betel Quid ◽

Posterior Lobe ◽

Functional Connectivity Density ◽

Dorsolateral Prefrontal ◽

The Right ◽

Mri Study

Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD) have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD) maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI) data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy controls (HCs) (n = 32) in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC) and increased in the left cerebellum posterior lobe (CPL) and bilateral inferior parietal lobule (IPL) in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC), and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS) (r=-0.432, P=0.012), and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002) in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

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Aberrant Frontostriatal Connectivity in Negative Symptoms of Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sby165 ◽

2018 ◽

Vol 45 (5) ◽

pp. 1051-1059 ◽

Cited By ~ 10

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.

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Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: a case study

10.31234/osf.io/e9n8c ◽

2018 ◽

Author(s):

Christiane Oedekoven ◽

James L. Keidel ◽

Stuart Anderson ◽

Angus Nisbet ◽

Chris Bird

Keyword(s):

Functional Connectivity ◽

Episodic Memory ◽

Memory Performance ◽

Memory Task ◽

Structural Mri ◽

Brain Regions ◽

Left Hippocampus ◽

Cortical Regions ◽

The Right ◽

Encoding And Retrieval

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of lifelike events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis revealed that in controls the functional connectivity between these regions when watching the videos was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of multimodal representations of the contents of an event.

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Resting State Functional Connectivity Predicts Future Changes in Sedentary Behavior

10.1101/2021.01.26.428161 ◽

2021 ◽

Author(s):

Timothy P. Morris ◽

Aaron Kucyi ◽

Sheeba Arnold Anteraper ◽

Maiya Rachel Geddes ◽

Alfonso Nieto-Castañon ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Exercise Intervention ◽

Supplementary Motor Area ◽

Anterior Insula ◽

Motor Area ◽

Anterior Cingulate ◽

Sedentary Behaviors ◽

Resting State Functional Connectivity ◽

The Right

AbstractInformation about a person’s available energy resources is integrated in daily behavioral choices that weigh motor costs against expected rewards. It has been posited that humans have an innate attraction towards effort minimization and that executive control is required to overcome this prepotent disposition. With sedentary behaviors increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths, understanding the predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. In 64 healthy older adults participating in a 6-month aerobic exercise intervention, we use neuroimaging (resting state functional connectivity), baseline measures of executive function and accelerometer measures of time spent sedentary to predict future changes in objectively measured time spent sedentary in daily life. Using cross-validation and bootstrap resampling, our results demonstrate that functional connectivity between 1) the anterior cingulate cortex and the supplementary motor area and 2) the right anterior insula and the left temporoparietal/temporooccipital junction, predict changes in time spent sedentary, whereas baseline cognitive, behavioral and demographic measures do not. Previous research has shown activation in and between the anterior cingulate and supplementary motor area as well as in the right anterior insula during effort avoidance and tasks that integrate motor costs and reward benefits in effort-based decision making. Our results add important knowledge toward understanding mechanistic associations underlying complex sedentary behaviors.

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Exploring Cortical Attentional System by Using fMRI during a Continuous Perfomance Test

Computational Intelligence and Neuroscience ◽

10.1155/2010/329213 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 31

Author(s):

M. G. Tana ◽

E. Montin ◽

S. Cerutti ◽

A. M. Bianchi

Keyword(s):

Performance Test ◽

Continuous Performance Test ◽

Blood Oxygen Level Dependent ◽

Brain Regions ◽

Brain Network ◽

Anterior Cingulate ◽

Visual Object ◽

Bold Response ◽

Object Processing ◽

The Right

Functional magnetic resonance imaging (fMRI) was performed in eight healthy subjects to identify the localization, magnitude, and volume extent of activation in brain regions that are involved in blood oxygen level-dependent (BOLD) response during the performance of Conners' Continuous Performance Test (CPT). An extensive brain network was activated during the task including frontal, temporal, and occipital cortical areas and left cerebellum. The more activated cluster in terms of volume extent and magnitude was located in the right anterior cingulate cortex (ACC). Analyzing the dynamic trend of the activation in the identified areas during the entire duration of the sustained attention test, we found a progressive decreasing of BOLD response probably due to a habituation effect without any deterioration of the performances. The observed brain network is consistent with existing models of visual object processing and attentional control and may serve as a basis for fMRI studies in clinical populations with neuropsychological deficits in Conners' CPT performance.

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Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans

Neural Plasticity ◽

10.1155/2016/1245259 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Nobuaki Mizuguchi ◽

Shintaro Uehara ◽

Satoshi Hirose ◽

Shinji Yamamoto ◽

Eiichi Naito

Keyword(s):

Task Performance ◽

Motor Skill ◽

Brain Activity ◽

Motor Task ◽

Brain Regions ◽

Anterior Cingulate ◽

Cerebellar Hemisphere ◽

Intensive Training ◽

Performance Variability ◽

The Right

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

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