Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions

Abstract

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05–0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

Biooriented Synthesis of Ibuprofen-Clubbed Novel Bis-Schiff Base Derivatives as Potential Hits for Malignant Glioma: In Vitro Anticancer Activity and In Silico Approach

“…In the spectrum, broad singlet signals in the region 4.70−4.65 were allotted to that of methylene protons, while in the upfield region of the spectrum, the methyl protons were seen at 0.80−0.89 ppm. Similar to this, the broad band 13 C NMR spectrum of these product compounds showed signals for methyl, methylene, methine, and quaternary carbons, which were further solved by its distortionless enhancement by the polarization transfer (DEPT) spectrum. In the downfield region of the spectrum, signals resonated in the region 177.9−170.1 were assigned to carbonyl carbon atoms.…”

“…In the last step, the Schiff base hydrazide was refluxed with different aromatic aldehydes in a catalytic amount of acetic acid in absolute ethanol to obtain bis-Schiff base derivatives of ibuprofen (Scheme 1). The synthesized derivatives were structurally deduced through various spectroscopic techniques including HR-ESI-MS, 1 H NMR, and 13 C NMR. Finally, we screened the obtained derivatives for their anticancer activity using a malignant glioma U87 cancerous cell line as well as a human embryonic kidney Hek293 cell line as a control.…”

“…2D interactions of all of the compounds with casein kinase-2 receptor (Figure S1); drug likeness of the compounds (Table S1); and 1 H NMR, 13…”

“…In the current study, we have successfully synthesized 21 novel bis-Schiff base derivatives based on the commercially available drug ibuprofen in better yields. Structures of these derivatives were deduced through modern spectroscopic techniques including HR-ESI-MS, 1 H NMR, and 13 C NMR. At last, these derivatives were evaluated for their anticancer activity using normal human embryonic kidney HEK293 cell and U87malignant glioma (ATCC-HTB-14) as a cancer cell line.…”

“…There exists a significant disparity between the supply and demand of new anticancer drugs . Current anticancer agents have notable post-treatment adverse effects because they lack selectivity. , Consequently, there is an urgent need to invent and develop new selective anticancer therapies that cause fewer side effects and have multiple modes of action. , The link between inflammation and cancer was first suggested by Rudolf Virchow who noticed the presence of leukocytes in tumor cells. , It is now widely recognized that chronic inflammation increases the risk of cancer. During the inflammation process, various growth factors, including epidermal growth factor (EGF) and fibroblast growth factor (FGF), are released, which stimulate cell proliferation and in turn cause cancer. , The biosynthesis of prostaglandins during inflammation is primarily facilitated by the enzyme cyclooxygenase (COX).…”