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Early-Stage Repetitive Transcranial Magnetic Stimulation Altered Posterior-Anterior Cerebrum Effective Connectivity in Methylazoxymethanol Acetate Rats.

ABSTRACT: The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to investigate the potential mechanism of schizophrenia through the posterior-anterior cerebrum imbalance in methylazoxymethanol acetate (MAM) rats and to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an early-stage intervention. The rats were divided into four groups: the MAM-sham group, vehicle-sham group, MAM-rTMS group, and vehicle-rTMS group. The rTMS treatment was targeted in the visual cortex (VC) in adolescent rats. Granger Causality Analysis (GCA) was used to evaluate the effective connectivity between regions of interest. Results demonstrated a critical right VC-nucleus accumbens (Acb)-orbitofrontal cortex (OFC) pathway in MAM rats; significant differences of effective connectivity (EC) were found between MAM-sham and vehicle-sham groups (from Acb shell to OFC: t = -2.553, p = 0.021), MAM-rTMS and MAM-sham groups (from VC to Acb core: t = -2.206, p = 0.043; from Acb core to OFC: t = 4.861, p < 0.001; from Acb shell to OFC: t = 4.025, p = 0.001), and MAM-rTMS and vehicle-rTMS groups (from VC to Acb core: t = -2.482, p = 0.025; from VC to Acb shell: t = -2.872, p = 0.012; from Acb core to OFC: t = 4.066, p = 0.001; from Acb shell to OFC: t = 3.458, p = 0.004) in the right hemisphere. Results of the early-stage rTMS intervention revealed that right nucleus accumbens played the role as a central hub, and VC was a potentially novel rTMS target region during adolescent schizophrenia. Moreover, the EC of right nucleus accumbens shell and orbitofrontal cortex was demonstrated to be a potential biomarker. To our knowledge, this was the first resting-state fMRI study using GCA to assess the deficits of a visual-reward neural pathway and the effectiveness of rTMS treatment in MAM rats. More randomized controlled trials in both animal models and schizophrenia patients are needed to further elucidate the disease characteristics.

SUBMITTER: Guo H

PROVIDER: S-EPMC8176023 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer's disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function.MethodsThis study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed.ResultsCross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged.ConclusionThis study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum.Clinical trial registrationhttp://www.chictr.org.cn, ChiCTR2000034533.

Project description:A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation (rTMS) is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity (FNC) in resting functional networks (RSNs) and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography (EEG). For psychiatric comorbidities, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 (14) patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety (p < 0.05). In the analysis of RSNs, we found a higher synchronization between the sensorimotor network (SMN) and posterior default-mode network (pDMN) in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN (aDMN) and SMN after rTMS, while the FNC between the aDMN and dorsal attention network (DAN) was greater (p < 0.05, FDR corrected). Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN (r = -0.67, p = 0.0022), which was markedly different in the good and bad response groups treated with rTMS (p = 0.0115). Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy.

Project description:Lower- and higher-order visual cortices in the posterior brain, ranging from the medial- and lateral-occipital to fusiform regions, are suggested to support visual object recognition, whereas the frontal eye field (FEF) plays a role in saccadic eye movements which optimize visual processing. Previous studies using electrophysiology and functional MRI techniques have reported that tasks requiring visual object recognition elicited cortical activation sequentially in the aforementioned posterior visual regions and FEFs. The present study aims to provide unique evidence of direct effective connectivity outgoing from the posterior visual regions by measuring the early component (10-50 ms) of cortico-cortical spectral responses (CCSRs) elicited by weak single-pulse direct cortical electrical stimulation. We studied 22 patients who underwent extraoperative intracranial EEG recording for clinical localization of seizure foci and functionally-important brain regions. We used animations to visualize the spatiotemporal dynamics of gamma band CCSRs elicited by stimulation of three different posterior visual regions. We quantified the strength of CCSR-defined effective connectivity between the lower- and higher-order posterior visual regions as well as from the posterior visual regions to the FEFs. We found that effective connectivity within the posterior visual regions was larger in the feedforward (i.e., lower-to higher-order) direction compared to the opposite direction. Specifically, connectivity from the medial-occipital region was largest to the lateral-occipital region, whereas that from the lateral-occipital region was largest to the fusiform region. Among the posterior visual regions, connectivity to the FEF was largest from the lateral-occipital region and the mean peak latency of CCSR propagation from the lateral-occipital region to FEF was 26 ms. Our invasive study of the human brain using a stimulation-based intervention supports the model that the posterior visual regions have direct cortico-cortical connectivity pathways in which neural activity is transferred preferentially from the lower-to higher-order areas. The human brain has direct cortico-cortical connectivity allowing a rapid transfer of neural activity from the lateral-occipital region to the FEF.

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Early-Stage Repetitive Transcranial Magnetic Stimulation Altered Posterior-Anterior Cerebrum Effective Connectivity in Methylazoxymethanol Acetate Rats.

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