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.

Visual cortex repetitive transcranial magnetic stimulation (rTMS) reversing neurodevelopmental impairments in adolescents with major psychiatric disorders (MPDs): A cross‐species translational study

“…In our quest to explore the subtle frontal‐posterior imbalance, our early experiment has suggested that central carbon metabolism disturbance and mitochondrial dysfunction may underlie the ReHo alterations 15 . Furthermore, in a prior fMRI study, we identified the nucleus accumbens as a central hub, transmitting rTMS effectiveness from posterior to frontal cortex 51 . Additionally, a separate structural MRI study hinted at the significance of hippocampus volume reversal in neuromodulation (under revision) 52 .…”

“… 15 Furthermore, in a prior fMRI study, we identified the nucleus accumbens as a central hub, transmitting rTMS effectiveness from posterior to frontal cortex. 51 Additionally, a separate structural MRI study hinted at the significance of hippocampus volume reversal in neuromodulation (under revision). 52 Our previous research has already highlighted the potential of this objective neuroimaging biomarker in guiding neurotherapeutic approaches for MPDs.…”

A Neuroimaging-based Precision Medicine Framework for Depression

“…Decreased GABA may underlie neural mechanisms for increased ALFF in posterior regions in atypical depression [45]. Of note, both human and animal neuroimaging studies have observed excitatory effects of high-frequency rTMS and inhibitory effects of low-frequency rTMS on OCC [38, 46, 47]. Hence, in attempt to dampen the increases in posterior ALFF, we delivered low-frequency rTMS to the OCC in atypical depression.…”

Cerebral blood flow changes induced by high-frequency repetitive transcranial magnetic stimulation combined with cognitive training in Alzheimer's disease

“…Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that has been shown to induce short ("on-line") and long ("off-line") effects in different ways (2). The application of magnetic pulses to a target location in the brain repetitively generates long-lasting beneficial effects persisting for several weeks or even months after treatment (3)(4)(5)(6). rTMS has been approved by regulatory agencies as a therapeutic tool for a number of neuropsychiatric disorders, such as drug-resistant depression and obsessivecompulsive disorder (7,8).…”