A Computational Modeling Study to Investigate the Use of Epicranial Electrodes to Deliver Interferential Stimulation to Subcortical Regions

Background: Epicranial cortical stimulation (ECS) is a minimally invasive neuromodulation technique that works by passing electric current between subcutaneous electrodes positioned on the skull. ECS causes a stronger and more focused electric field in the cortex compared to transcranial electric stimulation (TES) where the electrodes are placed on the scalp. However, it is unknown if ECS can target deeper regions where the electric fields become relatively weak and broad. Recently, interferential stimulation (IF) using scalp electrodes has been proposed as a novel technique to target subcortical regions. During IF, two high, but slightly different, frequencies are applied which sum to generate a low frequency field (i.e., 10 Hz) at a target subcortical region. We hypothesized that IF using ECS electrodes would cause stronger and more focused subcortical stimulation than that using TES electrodes.Objective: Use computational modeling to determine if interferential stimulation-epicranial cortical stimulation (IF-ECS) can target subcortical regions. Then, compare the focality and field strength of IF-ECS to that of interferential Stimulation-transcranial electric stimulation (IF-TES) in the same subcortical region.Methods: A human head computational model was developed with 19 TES and 19 ECS disk electrodes positioned on a 10–20 system. After tetrahedral mesh generation the model was imported to COMSOL where the electric field distribution was calculated for each electrode separately. Then in MATLAB, subcortical targets were defined and the optimal configurations were calculated for both the TES and ECS electrodes.Results: Interferential stimulation using ECS electrodes can deliver stronger and more focused electric fields to subcortical regions than IF using TES electrodes.Conclusion: Interferential stimulation combined with ECS is a promising approach for delivering subcortical stimulation without the need for a craniotomy.

Anatomical and Topographical Variations in the Distribution of Brain Metastases Based on Primary Cancer Origin and Molecular Subtypes: A Systematic Review

Background While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuro-imaging and spatial modeling analytics have facilitated further exploration into this field. Methods A systematic electronic database search for studies analyzing the distribution of brain metastases (BM) from any primary systematic cancer published January 1990-July 2020 was conducted using PRISMA guidelines. Results Two authors independently reviewed 1,957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8,227 BMs from 2,599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2 positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes, and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes. Conclusion The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.

Ultrasound in the Diagnosis of Perinatal Ischemic Strokes (Literature Review with Their Own Clinical Observations)

The issues of early diagnosis of perinatal arterial stroke (PAII) continue to be discussed in the domestic and foreign literature. Along with MRI, the ultrasound method allows to identify foci of ischemia of different localization and sizes in newborns. During ultrasound, we identified 29 cases of PAIA of different localization in children of different gestational and postnatal age. Analysis of our own and published data showed that up to 32 weeks of gestational development, AII develops in the lenticular-striar basin, and later in the cortical-subcortical region. Diagnostic capabilities of ultrasound in PAII can be significantly expanded by using ultrasound duplex scanning of brain vessels. Our observations showed that the nature of changes in Doppler parameters depends on the localization of the affected vascular basin and on the duration of cerebrovascular disorders

Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson’s Disease

Background: Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson’s disease (PD). Objective: To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Methods: Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Results: Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Conclusion: Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Functional parcellation of human brain using localized topo-connectivity mapping

<p>The analysis of connectivity between parcellated regions of cortex provides insights into the functional architecture of the brain at a systems level. However, there has been less progress in the derivation of functional structures from voxel-wise analyses at finer scales. We propose a novel method, called localized topo-connectivity mapping with singular-value-decomposition-informed filtering (or filtered LTM), to identify and characterize voxel-wise functional structures in the human brain using resting-state fMRI data. Here we describe its mathematical background and provide a proof-of-concept using simulated data that allow an intuitive interpretation of the results of filtered LTM. The algorithm has also been applied to 7T fMRI data as part of the Human Connectome Project to generate group-average LTM images. Functional structures revealed by this approach agree moderately well with anatomical structures identified by T₁-weighted images and fractional anisotropy maps derived from diffusion MRI. Moreover, the LTM images also reveal subtle functional variations that are not apparent in the anatomical structures. To assess the performance of LTM images, the subcortical region and occipital white matter were separately parcellated. Statistical tests were performed to demonstrate that the synchronies of fMRI signals in LTM-informed parcellations are significantly larger than those of random parcellations. Overall, the filtered LTM approach can serve as a tool to investigate the functional organization of the brain at the scale of individual voxels as measured in fMRI.</p>

Functional parcellation of human brain using localized topo-connectivity mapping

<p>The analysis of connectivity between parcellated regions of cortex provides insights into the functional architecture of the brain at a systems level. However, there has been less progress in the derivation of functional structures from voxel-wise analyses at finer scales. We propose a novel method, called localized topo-connectivity mapping with singular-value-decomposition-informed filtering (or filtered LTM), to identify and characterize voxel-wise functional structures in the human brain using resting-state fMRI data. Here we describe its mathematical background and provide a proof-of-concept using simulated data that allow an intuitive interpretation of the results of filtered LTM. The algorithm has also been applied to 7T fMRI data as part of the Human Connectome Project to generate group-average LTM images. Functional structures revealed by this approach agree moderately well with anatomical structures identified by T₁-weighted images and fractional anisotropy maps derived from diffusion MRI. Moreover, the LTM images also reveal subtle functional variations that are not apparent in the anatomical structures. To assess the performance of LTM images, the subcortical region and occipital white matter were separately parcellated. Statistical tests were performed to demonstrate that the synchronies of fMRI signals in LTM-informed parcellations are significantly larger than those of random parcellations. Overall, the filtered LTM approach can serve as a tool to investigate the functional organization of the brain at the scale of individual voxels as measured in fMRI.</p>

A Processing Pipeline for Quantifying Lenticulostriate Artery Vascular Volume in Subcortical Nuclei

Lenticulostriate arteries (LSAs) supply blood to the basal ganglia region. Its lesion causes lacunar stroke and resulting neurological syndromes. However, due to its small caliber and large individual variance, the evaluation of LSAs was limited to descriptive and objective measurements. In this study, we aimed to develop a post-processing method to quantify LSAs in subcortical regions and compare their vascular volume to conventional LSA measurements. A processing pipeline was designed to extract subcortical areas in individual spaces while screening out vessels. The vascular volume of LSAs in the subcortical region was calculated from time-of-flight-magnetic resonance angiography (TOF-MRA) at 7 Tesla. The reproducibility was tested to be good for the vascular volume (n = 5, ICCA = 0.84). Comparing the results to conventional measurements, the vascular volume was significantly correlated with the number of branches (r = 0.402, p &lt; 0.001) and the length (r = 0.246, p = 0.032) of LSAs. By applying the method to a group of healthy volunteers (n = 40), we found that most LSAs crossing through the putamen which thereby has the highest vascular density among subcortical nuclei. In general, we proposed a semi-automated processing pipeline for quantifying the vascular volume of LSAs in subcortical regions. The novel method was tested to be robust and provided reasonable results. This method revealed spatial relationships among the perforating arteries and basal ganglia. The vascular volume can be used to evaluated blood supply of subcortical regions, benefiting the radiologic evaluation of neurodegenerative diseases caused by small vascular lesions.

Aberrant Neurogliovascular Unit Dynamics in Cerebral Small Vessel Disease: A Rheological Clue to Vascular Parkinsonism

The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood–brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, metabolic waste, and clearance through the venous circulation. As a physiologically integrated neurogliovascular unit (NGVU) serving a particularly vulnerable cerebral white matter (from hypoxia, metabolic insults, infection, and inflammation), a likely insidious process over a lifetime could inflict microenvironment damages that may lead to pathological conditions. Two such conditions, cerebral small vessel disease (CSVD) and vascular parkinsonism (VaP), with poorly understood pathomechanisms, are frequently linked to this brain-wide NGVU. VaP is widely regarded as an atypical parkinsonism, described by cardinal motor manifestations and the presence of cerebrovascular disease, particularly white matter hyperintensities (WMHs) in the basal ganglia and subcortical region. WMHs, in turn, are a recognised imaging spectrum of CSVD manifestations, and in relation to disrupted NGVU, also include enlarged perivascular spaces. Here, in this narrative review, we present and discuss on recent findings that argue for plausible clues between CSVD and VaP by focusing on aberrant multicellular dynamics of a unique integrated NGVU—a crossroad of the immune–vascular–nervous system—which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets.

Different Functional Network Connectivity Patterns in Epilepsy: A Rest-State fMRI Study on Mesial Temporal Lobe Epilepsy and Benign Epilepsy With Centrotemporal Spike

The stark discrepancy in the prognosis of epilepsy is closely related to brain damage features and underlying mechanisms, which have not yet been unraveled. In this study, differences in the epileptic brain functional connectivity states were explored through a network-based connectivity analysis between intractable mesial temporal lobe epilepsy (MTLE) patients and benign epilepsy with centrotemporal spikes (BECT). Resting state fMRI imaging data were collected for 14 MTLE patients, 12 BECT patients and 16 healthy controls (HCs). Independent component analysis (ICA) was performed to identify the cortical functional networks. Subcortical nuclei of interest were extracted from the Harvard-Oxford probability atlas. Network-based statistics were used to detect functional connectivity (FC) alterations across intranetworks and internetworks, including the connectivity between cortical networks and subcortical nuclei. Compared with HCs, MTLE patients showed significant lower activity between the connectivity of cortical networks and subcortical nuclei (especially hippocampus) and lower internetwork FC involving the lateral temporal lobe; BECT patients showed normal cortical-subcortical FC with hyperconnectivity between cortical networks. Together, cortical-subcortical hypoconnectivity in MTLE suggested a low efficiency and collaborative network pattern, and this might be relevant to the final decompensatory state and the intractable prognosis. Conversely, cortical-subcortical region with normal connectivity remained well in global cooperativity, and compensatory internetwork hyperconnectivity caused by widespread cortical abnormal discharge, which might account for the self-limited clinical outcome in BECT. Based on the fMRI functional network study, different brain network patterns might provide a better explanation of mechanisms in different types of epilepsy.