Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography.

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the neurophysiological effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10, 1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

Combined Medial And Lateral Bucket Handle Meniscus Tears With Associated Complete Anterior Cruciate Ligament Tear: A Case Report.

The majority of meniscal tears in bucket handles are associated with anterior cruciate ligament (ACL) impairment. Its a rare condition which is rarely encountered when the meniscus has a bucket handle on both sides of the compartment. Here we present the case of a 28-year- old male cricket player with a total ACL rupture, a double Posterior Cruciate ligament (PCL) sign on MRI (Magnetic Resonance Imaging), an uncommon occurrence of a complex bucket handle rupture of the medial meniscus with a double PCL sign. It was a complete ACL tear and displaced bucket handle medial meniscus that was also visible on the magnetic resonance imaging. In this report, double PCL sign was shown on MRI and that was confirmed during the arthroscopic procedure.

Automated real-time EEG sleep spindle detection for brain-state-dependent brain stimulation.

Sleep spindles are a hallmark electroencephalographic feature of non-rapid eye movement sleep, and are believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real-time with sensory or non-invasive brain-stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real-time is highly challenging due to their spontaneous and transient nature. Here, we present the real-time spindle detector, a robust multi-channel electroencephalographic signal-processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the real-time spindle detection method by streaming pre-recorded sleep electroencephalographic datasets to a real-time computer system running a Simulink® Real-Time™ implementation of the algorithm. Sleep spindles were detected with high levels of Sensitivity (~83%), Precision (~78%) and a convincing F1-Score (~81%) in reference to state-of-the-art offline algorithms (which reached similar or lower levels when compared with each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude and symmetry, and showed the typical time-frequency characteristics as well as a centroparietal topography. Spindles were detected close to their centre and reliably at the predefined target phase. The real-time spindle detection algorithm therefore empowers researchers to target spindles during human sleep, and apply the stimulation method and experimental paradigm of their choice.

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans.

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

The Brain Electrophysiological recording & STimulation (BEST) toolbox.

Non-invasive brain stimulation (NIBS) experiments involve many recurring procedures that are not sufficiently standardized in the community. Given the diversity in experimental design and experience of the investigators, automated but yet flexible data collection and analysis tools are needed to increase objectivity, reliability, and reproducibility of NIBS experiments. The Brain Electrophysiological recording and STimulation (BEST) Toolbox is a MATLAB-based, open-source software with graphical user interface that allows users to design, run, and share freely configurable multi-protocol, multi-session NIBS studies, including transcranial magnetic, electric, and ultrasound stimulation (TMS, tES, TUS). Interfacing with a variety of recording and stimulation devices, the BEST toolbox analyzes EMG and EEG data, and configures stimulation parameters on-the-fly to facilitate closed-loop protocols and real-time applications. Its functionality is continuously expanded and includes e.g., TMS motor hotspot search, threshold estimation, motor evoked potential (MEP) and TMS-evoked EEG potential (TEP) measurements, dose-response curves, paired-pulse and dual-coil TMS, rTMS interventions.

SHISA3, an antagonist of the Wnt/ß-catenin signaling, is epigenetically silenced and its ectopic expression suppresses growth in breast cancer.

Breast cancer (BC) is the foremost cause of cancer related deaths in women globally. Currently there is a scarcity of reliable biomarkers for its early stage diagnosis and theranostics monitoring. Altered DNA methylation patterns leading to the silencing of tumor suppressor genes are considered as an important mechanism underlying tumor development and progression in various cancer types, including BC. Very recently, epigenetic silencing of SHISA3, an antagonist of ß-catenin, has been reported in various types of tumor. However, the role of SHISA3 in BC has not been investigated yet. Therefore, we aimed at evaluating the contribution of SHISA3 in BC causation by analyzing its expression and methylation levels in BC cell lines (MDA-MB231, MCF-7 and BT-474) and in 103 paired BC tissue samples. The SHISA3 expression and methylation status was determined by qPCR and methylation specific PCR (MSP) respectively. The role of SHISA3 in BC tumorigenesis was evaluated by proliferation and migration assays after ectopic expression of SHISA3. The association between SHISA3 hypermethylation and clinicopathological parameters of BC patients was also studied. The downregulation of SHISA3 expression was found in three BC cell lines used and in all BC tissue samples. However, SHISA3 promoter region was hypermethylated in 61% (63/103) tumorous tissues in comparison to the 18% of their matched normal tissues. The 5-aza-2'-deoxycytidine treatment restored SHISA3 expression by reversing promoter hypermethylation in both MDA-MB231 and MCF-7 cells. Furthermore, ectopic expression of SHISA3 significantly reduced the proliferation and migration ability of these cells. Taken together, our findings for the first time reveal epigenetic silencing and tumor suppressing role of SHISA3 in BC. Henceforth, this study has identified SHISA3 as potentially powerful target for the development of new therapies against BC, as well as novel diagnostic and therapy response monitoring approaches.

Merkel cell polyomavirus DNA sequences in the blood of healthy population of Pakistan.

Aim: This study aimed at detecting and quantifying Merkel cell polyomavirus (MCPyV) viral loads in the peripheral blood of healthy Pakistani individuals. Patients & methods: A total of 221 whole blood samples obtained from healthy individuals were examined by qPCR. Results & conclusion: MCPyV was detected in the peripheral blood of 31.2% healthy individuals. The rate of MCPyV positivity decreased from young (36%), to middle (33.7%) and elder (25.3%) age groups. Our data revealed higher prevalence of MCPyV in women (43.93%) than men (25.80%). The MCPyV viral load was calculated in the range of 0.06 -11 copies/ng of isolated DNA. The MCPyV viral load increased from young (median = 3.35) to elder (median = 5.66) age groups. The MCPyV circulate at a higher frequency by residing dormant in certain blood cells, which might act as potential vehicles for the spread of MCPyV infection among general population.

Cutting efficiency of different dental materials utilized in an air abrasion system.

OBJECTIVES: The aim of the present study was to test cutting efficiency of different materials against conventional alumina in an air abrasion system. MATERIALS AND METHODS: The powder samples were divided into three groups: Group 1 - alumina (control), Group 2 - 45S5 bioactive glass, and Group 3 - hydroxyapatite. 30 microscope glass slides of 0.5 mm thickness were used as an alternative of human enamel and were also divided randomly into these three groups. The time taken by the abrasive particles to cut a hole through the microscope glass slide was recorded with a stop watch. In addition, morphology of the particles was observed through scanning electron microscopy (SEM). A t-test was used to compare the times taken to cut a hole through the microscope glass slides, and the level of significance was set at P < 0.05. RESULTS: The mean time taken to cut a hole through the microscope glass slide was 2.96 s and 23.01s for Groups 1 and 2, respectively, whereas powder of Group 3 did not cut after 120 s. The differences between cutting times of Groups 1 and 2 were statistically significant (P < 0.05). The SEM micrographs revealed coarse angular shape for particles of Groups 1 and 2 but Group 3 particles were with round ends and presence of smaller particles was also observed in Groups 2 and 3. CONCLUSION: The alumina particles demonstrated excellent cutting efficiency followed by 45S5 particles. The use of bioactive glass particles should be encouraged for cutting purposes whenever a shortage of time for practitioners is not a concern.