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.

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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.

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.

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