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Carron, R.

Publications and source records attributed to Carron, R..

6 recordsLinked to original sources

Non-invasive temporal interference electrical stimulation of the human hippocampus

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders however its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modelling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging (fMRI) and behaviour experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.

neuroscience↗

Modulation of Arabidopsis growth by volatile organic compounds from a root-derived bacterial community

Plant roots are surrounded by fluctuating biotic and abiotic factors. The living component - the microbiota - is actively shaped by the plant and plays an important role in overall plant health. While it has been shown that specialized metabolites exuded from the plant are involved in shaping host interactions with the microbiota, it is unclear how underground volatile organic compounds (VOCs) influence this communication. This is especially true for root-associated bacteria which are known to release VOCs that can influence plant growth. Using a simplified synthetic bacterial community (SynCom) representing the phylogenetic diversity of bacteria in the root microbiome, we set out to characterize plant growth and defense metabolites when subjected to bacterial VOCs (bVOCs). Moreover, by profiling the SynCom community composition after co-cultivation with the plant, we explored how members of the community influenced each other in our growth setup. Our findings reveal that plant growth promotion can occur via VOCs from a bacterial SynCom, but that the plant response differs for individual community members. In addition, we find that bVOCs are able to repress chemical defense responses in the plant, possibly to facilitate colonization. By removing key species from the SynCom, we find that complex bacteria-bacteria interactions are likely to underlie this phenomenon, and that bVOC-induced modulation of plant responses in the rhizosphere may be an emergent property of bacterial communities rather than depending on individual species.

plant biology↗

Focal Non-invasive Deep-brain Stimulation with Temporal Interference for the Suppression of Epileptic Biomarkers

Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 -165Hz, to various deep-seated targets such as for instance the Mesio-temporal lobe (MTL) which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs). In the current study, we use Temporal Interference stimulation to provide a non-invasive focal DBS (130 Hz) of the MTL, specifically the hippocampus, which increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. The method could potentially revolutionize how DBS, certainly in epilepsy, is performed, and we therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs TCS in human cadavers. Results show the better penetration of TI fields into the human hippocampus as compared with TCS. Finally, we provide evidence of the efficacy of the specific form of Pulse-width Modulated TI (PWM-TI), implemented with square waves, which is used in this study. One Sentence SummaryA non-invasive deep brain stimulation applied via temporal interference achieves the suppression of biomarkers of epilepsy in mice and is scaled to humans.

neuroscience↗

Magnetoencephalography can reveal deep brain network activities linked to memory processes

Recording from deep neural structures such as hippocampus non-invasively and yet with high temporal resolution remains a major challenge for human neuroscience. Although it has been proposed that deep neuronal activity might be recordable during cognitive tasks using magnetoencephalography (MEG), this remains to be demonstrated as the contribution of deep structures to MEG recordings may be too small to be detected or might be eclipsed by the activity of large-scale neocortical networks. In the present study, we disentangled mesial activity and large-scale networks from the MEG signals thanks to blind source separation (BSS). We then validated the MEG BSS components using intracerebral EEG signals recorded simultaneously in patients during their presurgical evaluation of epilepsy. In the MEG signals obtained during a memory task involving the recognition of old and new images, we identified with BSS a putative mesial component, which was present in all patients and all control subjects. The time course of the component selectively correlated with SEEG signals recorded from hippocampus and rhinal cortex, thus confirming its mesial origin. This finding complements previous studies with epileptic activity and opens new possibilities for using MEG to study deep brain structures in cognition and in brain disorders.

neuroscience↗

Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields

Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation noninvasively without surgically implanted devices is enabling for fundamental research and clinical translation. Here we demonstrate how relatively high frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. We validate this principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, we demonstrate how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve. Our method is simple, relying on repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.

neuroscience↗

Orientation of Temporal Interference for Non-Invasive Deep Brain Stimulation in Epilepsy

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on nonpenetrating surface electrodes, namely an orientation-tunable form of temporally-interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally-invasive temporally-interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue.

neuroscience↗