Posts Tagged transcranial stimulation

[ARTICLE] Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices

Transcranial focused ultrasound is an emerging technique for non-invasive neurostimulation. Compared to magnetic or electric non-invasive brain stimulation, this technique has a higher spatial resolution and can reach deep structures. In addition, both animal and human studies suggest that, potentially, different sites of the central and peripheral nervous system can be targeted by this technique. Depending on stimulation parameters, transcranial focused ultrasound is able to determine a wide spectrum of effects, ranging from suppression or facilitation of neural activity to tissue ablation. The aim is to review the state of the art of the human transcranial focused ultrasound neuromodulation literature, including the theoretical principles which underlie the explanation of the bioeffects on neural tissues, and showing the stimulation techniques and parameters used and their outcomes in terms of clinical, neurophysiological or neuroimaging results and safety.


Preliminary animal studies suggest that, potentially, different sites in the peripheral nervous system, from nerves (1) to spinal roots (2), and in the central nervous system, from superficial regions like primary motor cortex (3) or frontal eye field (4), to more deep areas like hippocampus (3), amygdala (5), or thalamus (6) can be targeted by focused ultrasound stimulation technique. In addition, animal studies showed that this technique has a high spatial resolution, useful also for mapping small brain areas, as shown by Fry (7) for the mapping of lateral geniculate nucleus, or by Ballantine et al. (2) for the stimulation of Edinger-Westphal nucleus.

Furthermore, a recent fMRI resting-state functional connectivity animal study (8), showed that the effect of tFUS neuromodulation can last for up to 2 h after stimulation, opening a new way to explore not only the online effect but also the long lasting effect of neuromodulation. The first human transcranial application of ultrasounds for neuromodulation was described by Hameroff et al. (9), with an unfocused transcranial ultrasound (tUS) continuous stimulation of posterior frontal cortex, applied on 31 patients affected by chronic pain. The first human application of focused transcranial ultrasound (tFUS) technique was described by Legon et al. (10). They targeted the primary somatosensory cortex of healthy volunteers, in a within-subjects, sham-controlled study. One of the most interesting results of tFUS applications was a case report of emergence from minimally conscious state, after low intensity non-invasive ultrasonic thalamic stimulation in a patient after acute brain injury (11). Following this first single evidence, a clinical trial is ongoing to explore the effect of thalamic low intensity focused ultrasound in acute brain injury patients (12).

Regarding peripheral nervous system neuromodulation, Bailey et al. (13) explored the ability of continuous US at 1.5 MHz in modulating the ulnar nerve stimulation response to magnetic stimulation (MS). This study showed no significant change in electromyographic response during magnetic plus US ulnar nerve stimulation. However, further studies are needed in order to explore different parameter of stimulation.

In recent years, the scientific community showed a progressive increasing interest on FUS neuromodulation, and some reviews have been published in order to summarize the state of the art on this topic (1418).

Mechanisms of Actions of US Neuromodulation

Focused ultrasound is a non-invasive, non-ionizing technique. In order to target a brain region, the first challenge is to let ultrasounds single waves to reach the target at the same time, without different acoustic reflection, refraction, and distortion due to the inhomogeneity of skull bone. This problem can be solved by time shifting each single ultrasound wave, according to the related skull bone acoustical properties, in order to let all the waves to reach the target at the same time (1922).

The mechanical interaction between US and neuronal membranes can modify the membrane gating kinetics through the action on mechanosensitive voltage-gated ion channels or neurotransmitter receptors (2325). The study of Tyler et al. (25) supports this hypothesis. Their study showed, on ex vivo mouse brains and hippocampal slice cultures, that low-intensity, low-frequency ultrasound (LILFU) is able to activate voltage-gated sodium and calcium channels. However, this can’t be the only mechanism of action, explaining the action potential induction, since in simulations, considering the role of membrane tension on activation of mechanically sensitive voltage gated channels, the resulting effect was too low to induce an excitation (2627).

In addition, the mechanical action of US is able to induce cavitation into the cellular membrane, by means of membrane pore formation, which changes the membrane permeability.

The bilayer sonophore model (28) was introduced to better explain the bioeffects of US, taking into consideration the biomechanical proprieties of US and of cell membranes. According to this model (28), the mechanical energy of US leads to periodic expansions and contractions of the membrane. In this model, the US bioeffect is dependent on the tension applied to the membrane. With a progressive increase in membrane stretch intensity, the bioeffect is mediated by different mechanisms. First by the activation of mechanosensitive proteins. Then, with an increase of intensity, there is a pore formation and with the maximum stretch that can be achieved with the technique a membrane rupture and irreversible lesion is obtained (28) (Figure 1).

Figure 1. Ultrasound gradually increases tension in the membrane. From the reference stage (S0), the stretch first activates mechanosensitive proteins (S1); growing tension might damage membrane proteins (S2) and then might induce pore formation (S3a, S3b) or cause membrane rupture [modified, with permission, from Krasovitski et al. (28)].


Continue —> Frontiers | Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices | Neurology

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[Abstract] Dual-tDCS and Upper Limb Rehabilitation Improves Retention of Motor Function in Chronic Stroke: A Pilot Study

Background: Single sessions of dual transcranial direct-current stimulation (dual-tDCS) with concurrent rehabilitation improves motor function in stroke survivors, which outlasts the stimulation period. However few studies have investigated the behavioural and neurophysiological adaptations following a multi-session intervention of dual-tDCS concurrent with rehabilitation.

Objective: This pilot study explored the immediate and lasting effects of 3-weeks of dual-tDCS and upper limb (UL) rehabilitation on motor function and corticospinal plasticity in chronic stroke survivors.

Methods: Fifteen chronic stroke survivors underwent 3-weeks of UL rehabilitation with sham or real dual-tDCS. UL motor function was assessed via the Motor Assessment Sale (MAS), Tardieu Scale and grip strength. Corticospinal plasticity was indexed by motor evoked potentials (MEPs), cortical silent period (CSP) and short-interval intracortical inhibition (SICI) recorded from the paretic and non-paretic ULs, using transcranial magnetic stimulation (TMS). Measures were taken at baseline, 48 hours post and 3-weeks following (follow-up) the intervention.

Results: MAS improved following both real-tDCS (62%) and sham-tDCS (43%, P < 0.001), however at 3-weeks follow-up, the real-tDCS condition retained these newly regained motor skills to a greater degree than sham-tDCS (real-tDCS 64%, sham-tDCS 21%, P = 0.002). MEP amplitudes from the paretic UL increased for real-tDCS (46%: P < 0.001) and were maintained at 3-weeks follow-up (38%: P = 0.03), whereas no changes were observed with sham-tDCS. No changes in MEPs from the non-paretic nor SICI from the paretic UL were observed for either group. SICI from the non-paretic UL was greater at follow-up, for real-tDCS (27%: P = 0.04). CSP from the non-paretic UL increased by 33% following the intervention for real-tDCS compared with sham-tDCS (P = 0.04), which was maintained at 3-weeks follow-up (24%: P = 0.04).

Conclusions: Dual-tDCS improved retention of gains in motor function, which appears to be modulated through intracortical inhibitory pathways in the contralesional primary motor cortex (M1). The findings provide preliminary evidence for the benefits of dual-tDCS during rehabilitation. Larger clinical trials are warranted to examine long term benefits of dual-tDCS in a stroke affected population.

Source: Frontiers | Dual-tDCS and Upper Limb Rehabilitation Improves Retention of Motor Function in Chronic Stroke: A Pilot Study | Frontiers in Human Neuroscience

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