We quantified the electric permittivity of single bacterial cells at microwave frequencies and nanoscale spatial resolution by means of near-field scanning microwave microscopy. To this end, calibrated complex admittance images have been obtained at ∼19 GHz and analyzed with a methodology that removes the nonlocal topographic cross-talk contributions and thus provides quantifiable intrinsic dielectric images of the bacterial cells. Results for single Escherichia coli cells provide a relative electric permittivity of ∼4 in dry conditions and ∼20 in humid conditions, with no significant loss contributions. Present findings, together with the ability of microwaves to penetrate the cell membrane, open an important avenue in the microwave label-free imaging of single cells with nanoscale spatial resolution.

have received compensation from Neuroelecrics Inc., manufacturers of the tested device. G. Ruffini is a shareholder of Neuroelectrics. R. Salvador, M. C. Biagi, and L. Dubreuil-Vall are employed by Neuroelectrics. A. Pascual-Leone serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Magstim Inc., Nexstim, and Cognito and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and MRI. A. Rotenberg is cofounder and serves on the scientific advisory board of Neuromotion. He is also presently or has recently participated on the advisory boards of Epihunter, Gamify, Neurorex, and Roche. He has had research support from Brainsway, CRE Medical, Kintai, Neuroelectrics, Roche, Sage, and Takeda. The remaining authors have no conflicts of interest to disclose. H. L. Kaye and D. San-Juan contributed equally. Funding was provided by a grant from the Massachusetts Life Sciences Center and by Neuroelectrics.

Lift-mode electrostatic force microscopy (EFM) is one of the most convenient imaging modes to study the local dielectric properties of non-planar samples. Here we present the quantitative analysis of this imaging mode. We introduce a method to quantify and subtract the topographic crosstalk from the lift-mode EFM images, and a 3D numerical approach that allows for extracting the local dielectric constant with nanoscale spatial resolution free from topographic artifacts. We demonstrate this procedure by measuring the dielectric properties of micropatterned SiO 2 pillars and of single bacteria cells, thus illustrating the wide applicability of our approach from materials science to biology.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that can cause dementia (Alzheimer's disease-related dementia, ADRD) with growing cognitive disability and vast physical, emotional, and financial pressures not only on the patients but also on caregivers and families. Loss of memory is an early and very debilitating symptom in AD patients and a relevant predictor of disease progression. Data from rodents, as well as human studies, suggest that dysregulation of specific brain oscillations, particularly in the hippocampus, is linked to memory deficits. Animal and human studies demonstrate that non-invasive brain stimulation (NIBS) in the form of transcranial alternating current stimulation (tACS) allows to reliably and safely interact with ongoing oscillatory patterns in the brain in specific frequencies. We developed a protocol for patient-tailored home-based tACS with an instruction program to train a caregiver to deliver daily sessions of tACS that can be remotely monitored by the study team. We provide a discussion of the neurobiological rationale to modulate oscillations and a description of the study protocol. Data of two patients with ADRD who have completed this protocol illustrate the feasibility of the approach and provide pilot evidence on the safety of the remotely-monitored, caregiver-administered, home-based tACS intervention. These findings encourage the pursuit of a large, adequately powered, randomized controlled trial of home-based tACS for memory dysfunction in ADRD.

Major depressive disorder (MDD) is a worldwide cause of disability in older age, especially during the covid pandemic. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has shown encouraging efficacy for treatment of depression. Here, we investigate the feasibility of an innovative protocol where tDCS is administered within the homes of older adults with MDD (patient participants) with the help of a study companion (i.e. caregiver). We further analyze the feasibility of a remotely-hosted training program that provides the knowledge and skills to administer tDCS at home, without requiring them to visit the lab. We also employed a newly developed multi-channel tDCS system with real-time monitoring designed to guarantee the safety and efficacy of home-based tDCS. Patient participants underwent a total of 37 home-based tDCS sessions distributed over 12 weeks. The protocol consisted of three phases each lasting four weeks: an acute phase, containing 28 home-based tDCS sessions, a taper phase containing nine home-based tDCS sessions, and a follow up phase, with no stimulation sessions. We found that the home-based, remotely-supervised, study companion administered, multi-channel tDCS protocol for older adults with MDD was feasible and safe. Further, the study introduces a novel training program for remote instruction of study companions in the administration of tDCS. Future research is required to determine the translatability of these findings to a larger sample.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04799405?term=NCT04799405&draw=2&rank=1, identifier NCT04799405.

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Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here we propose a quantitative meta-analysis of the neural substrate of DoC emerging from functional magnetic resonance (fMRI) and positron emission tomography (PET) studies. We also map the relevant networks of resulting areas to highlight similarities with Resting State Networks (RSNs) and hypothesize potential therapeutic solutions leveraging network-targeted noninvasive brain stimulation. Available literature was reviewed and analyzed through the activation likelihood estimate (ALE) statistical framework to describe resting-state or task-dependent brain activation patterns in DoC patients. Results show that task-related activity is limited to temporal regions resembling the auditory cortex, whereas resting-state fMRI data reveal a diffuse decreased activation affecting two subgroups of cortical (angular gyrus, middle frontal gyrus) and subcortical (thalamus, cingulate cortex, caudate nucleus) regions. Clustering of their cortical functional connectivity projections identify two main altered functional networks, related to decreased activity of (i) the default mode and frontoparietal networks, as well as (ii) the anterior salience and visual/auditory networks. Based on the strength and topography of their connectivity profile, biophysical modeling of potential brain stimulation solutions suggests the first network as the most feasible target for tES, tDCS neuromodulation in DoC patients.

Transcranial current stimulation (tCS or tES) protocols yield results that are highly variable across individuals. Part of this variability results from differences in the electric field (E-field) induced in subjects’ brains during stimulation. The E-field determines how neurons respond to stimulation, and it can be used as a proxy for predicting the concurrent effects of stimulation, like changes in cortical excitability, and, ultimately, its plastic effects. While the use of multichannel systems with small electrodes has provided a more precise tool for delivering tCS, individually variable anatomical parameters like the shape and thickness of tissues affect the E-field distribution for a specific electrode montage. Therefore, using the same montage parameters across subjects does not lead to the homogeneity of E-field amplitude over the desired targets. Here we describe a pipeline that leverages individualized head models combined with montage optimization algorithms to reduce the variability of the E-field distributions over subjects in tCS. We will describe the different steps of the pipeline – namely, MRI segmentation and head model creation, target specification, and montage optimization – and discuss their main advantages and limitations.