Independent Component and Graph Theory Analyses Reveal Normalized Brain Networks on Resting-State Functional MRI After Working Memory Training in People With HIV.

BACKGROUND: Cognitive training may partially reverse cognitive deficits in people with HIV (PWH). Previous functional MRI (fMRI) studies demonstrate that working memory training (WMT) alters brain activity during working memory tasks, but its effects on resting brain network organization remain unknown. PURPOSE: To test whether WMT affects PWH brain functional connectivity in resting-state fMRI (rsfMRI). STUDY TYPE: Prospective. POPULATION: A total of 53 PWH (ages 50.7 ± 1.5 years, two women) and 53 HIV-seronegative controls (SN, ages 49.5 ± 1.6 years, six women). FIELD STRENGTH/SEQUENCE: Axial single-shot gradient-echo echo-planar imaging at 3.0 T was performed at baseline (TL1), at 1-month (TL2), and at 6-months (TL3), after WMT. ASSESSMENT: All participants had rsfMRI and clinical assessments (including neuropsychological tests) at TL1 before randomization to Cogmed WMT (adaptive training, n = 58: 28 PWH, 30 SN; nonadaptive training, n = 48: 25 PWH, 23 SN), 25 sessions over 5-8 weeks. All assessments were repeated at TL2 and at TL3. The functional connectivity estimated by independent component analysis (ICA) or graph theory (GT) metrics (eigenvector centrality, etc.) for different link densities (LDs) were compared between PWH and SN groups at TL1 and TL2. STATISTICAL TESTS: Two-way analyses of variance (ANOVA) on GT metrics and two-sample t-tests on FC or GT metrics were performed. Cognitive (eg memory) measures were correlated with eigenvector centrality (eCent) using Pearson's correlations. The significance level was set at P < 0.05 after false discovery rate correction. RESULTS: The ventral default mode network (vDMN) eCent differed between PWH and SN groups at TL1 but not at TL2 (P = 0.28). In PWH, vDMN eCent changes significantly correlated with changes in the memory ability in PWH (r = -0.62 at LD = 50%) and vDMN eCent before training significantly correlated with memory performance changes (r = 0.53 at LD = 50%). DATA CONCLUSION: ICA and GT analyses showed that adaptive WMT normalized graph properties of the vDMN in PWH. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: 1.

Theta-burst transcranial magnetic stimulation induced functional connectivity changes between dorsolateral prefrontal cortex and default-mode-network.

Functional connectivity (FC) is fundamental to brain function and has been implicated in many neuropsychological and neuropsychiatric disorders. It is then of great scientific and clinical interest to find a non-invasive approach to modulate FC. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulational tool that can affect the target region and remote brain areas. While the distributed effects of TMS are postulated to be through either structural or functional connectivity, an understudied but of great scientific interest question is whether TMS can change the FC between these regions. The purpose of this study was to address this question in normal healthy brain using TMS with continuous theta burst stimulation (cTBS) pulses, which are known to have long-lasting inhibition function. FC was calculated from resting state fMRI before and after real and control (SHAM) stimulation. Compared to SHAM, the repetitive TMS (rTMS) reduces FC between the cTBS target: the left dorsolateral prefrontal cortex (lDLPFC) and brain regions within the default mode network (DMN), proving the effects of rTMS on FC. The reduction of FC might be the results of the inhibitory effects of cTBS rTMS.

Reduced brain entropy by repetitive transcranial magnetic stimulation on the left dorsolateral prefrontal cortex in healthy young adults.

Entropy indicates system irregularity and the capacity for information processing. Recent research has identified interesting voxel-wise entropy distribution patterns in normal brain and its changes due to aging and brain disorders. A question of great scientific and clinical importance is whether brain entropy (BEN) can be modulated using non-invasive neuromodulations. The purpose of this study was to address this open question using high-frequency repetitive transcranial magnetic stimulation (rTMS). BEN was calculated from resting state fMRI at each voxel acquired before and after applying 20 Hz rTMS or SHAM (control) stimulation. As compared to SHAM, 20 Hz rTMS reduced BEN in medial orbito-frontal cortex and subgenial anterior cingulate cortex (MOFC/sgACC), suggesting a reduced information processing therein, probably as a result of the enhanced top-down regulation by the left DLPFC rTMS. No significant changes were observed to the functional connectivity (FC) between the left DLPFC (the target site) to the rest of the brain, suggesting that rTMS may not affect FC though it might use FC to transfer its effects or the ad hoc information. Our data proved that rTMS can modulate BEN and BEN can be used to monitor rTMS effects.

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex.

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn't produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution.

Caffeine Caused a Widespread Increase of Resting Brain Entropy.

Entropy is an important trait of brain function and high entropy indicates high information processing capacity. We recently demonstrated that brain entropy (BEN) is stable across time and differs between controls and patients with various brain disorders. The purpose of this study was to examine whether BEN is sensitive to pharmaceutical modulations with caffeine. Both cerebral blood flow (CBF) and resting fMRI were collected from sixty caffeine-naïve healthy subjects before and after taking a 200 mg caffeine pill. Our data showed that caffeine reduced CBF in the whole brain but increased BEN across the cerebral cortex with the highest increase in lateral prefrontal cortex, the default mode network (DMN), visual cortex, and motor network, consistent with the beneficial effects of caffeine (such as vigilance and attention) on these areas. BEN increase was correlated to CBF reduction only in several regions (-0.5 < r < -0.4), indicating a neuronal nature for most of the observed BEN alterations. In summary, we showed the first evidence of BEN alterations due to caffeine ingestion, suggesting BEN as a biomarker sensitive to pharmaceutical brain function modulations.

Smoking Cessation With 20 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) Applied to Two Brain Regions: A Pilot Study.

Chronic smoking impairs brain functions in the prefrontal cortex and the projecting meso-cortical limbic system. The purpose of this pilot study is to examine whether modulating the frontal brain activity using high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve smoking cessation and to explore the changing pattern of the brain activity after treatment. Fourteen treatment-seeking smokers were offered a program involving 10 days of rTMS treatment with a follow-up for another 25 days. A frequency of 20 Hz rTMS was sequentially applied on the left dorso-lateral prefrontal cortex (DLPFC) and the superior medial frontal cortex (SMFC). The carbon monoxide (CO) level, withdrawal, craving scales, and neuroimaging data were collected. Ten smokers completed the entire treatment program, and 90% of them did not smoke during the 25-day follow-up time. A significant smoking craving reduction and resting brain activity reduction measured by the cerebral blood flow (CBF) and brain entropy (BEN) were observed after 10 days of 20 Hz rTMS treatments compared to the baseline. Although limited by sample size, these pilot findings definitely showed a high potential of multiple-target high-frequency rTMS in smoking cessation and the utility of fMRI for objectively assessing the treatment effects.