Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans
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ABSTRACT:
SUBMITTER: Yaakub S
PROVIDER: S-EPMC10474159 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTranscranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear.MethodsWe apply low-intensity tFUS to modulate the movement-related cortical potential (MRCP) originating from human subjects practicing a voluntary foot tapping task. 64-channel electroencephalograph (EEG) is recorded concurrently and further used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI).ResultsThe ESI illustrates the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source is imaged and its source profile is further evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) is further assessed in modulating the MRCP. The ESI results show that tFUS significantly increases the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition, and further, a high UPRF enhances the MSPA more than a low UPRF does.ConclusionThe present results demonstrate the neuromodulatory effects of the low-intensity tFUS on enhancing the human voluntary movement-related cortical activities evidenced through the ESI.SignificanceThis work provides the first evidence of tFUS enhancing the human endogenous motor cortical activities through excitatory modulation.
| S-EPMC8046844 | biostudies-literature
Project description:Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.
| S-EPMC7058635 | biostudies-literature
Project description:The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions, but such relationships are reduced after sonication, specifically for the targeted areas. Dissociable and focal effects on neural activity could not be explained by auditory confounds.
| S-EPMC6520498 | biostudies-literature
Project description:To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting 'offline' changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions - supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.
| S-EPMC6372282 | biostudies-literature
Project description:Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.
| S-EPMC8481295 | biostudies-literature
Project description:The effects of transcranial focused ultrasound (FUS) stimulation of the primary somatosensory cortex and its thalamic projection (i.e., ventral posterolateral nucleus) on the generation of electroencephalographic (EEG) responses were evaluated in healthy human volunteers. Stimulation of the unilateral somatosensory circuits corresponding to the non-dominant hand generated EEG evoked potentials across all participants; however, not all perceived stimulation-mediated tactile sensations of the hand. These FUS-evoked EEG potentials (FEP) were observed from both brain hemispheres and shared similarities with somatosensory evoked potentials (SSEP) from median nerve stimulation. Use of a 0.5 ms pulse duration (PD) sonication given at 70% duty cycle, compared to the use of 1 and 2 ms PD, elicited more distinctive FEP peak features from the hemisphere ipsilateral to sonication. Although several participants reported hearing tones associated with FUS stimulation, the observed FEP were not likely to be confounded by the auditory sensation based on a separate measurement of auditory evoked potentials (AEP) to tonal stimulation (mimicking the same repetition frequency as the FUS stimulation). Off-line changes in resting-state functional connectivity (FC) associated with thalamic stimulation revealed that the FUS stimulation enhanced connectivity in a network of sensorimotor and sensory integration areas, which lasted for at least more than an hour. Clinical neurological evaluations, EEG, and neuroanatomical MRI did not reveal any adverse or unintended effects of sonication, attesting its safety. These results suggest that FUS stimulation may induce long-term neuroplasticity in humans, indicating its neurotherapeutic potential for various neurological and neuropsychiatric conditions.
| S-EPMC10361523 | biostudies-literature
Project description:ObjectiveTranscranial focused ultrasound (tFUS) is an emerging neuromodulation approach that has been demonstrated in animals but is difficult to translate to humans because of acoustic attenuation and scattering in the skull. Optimal dose delivery requires subject-specific skull porosity estimates which has traditionally been done using CT. We propose a deep learning (DL) estimation of skull porosity from T1-weighted MRI images which removes the need for radiation-inducing CT scans.ApproachWe evaluate the impact of different DL approaches, including network architecture, input size and dimensionality, multichannel inputs, data augmentation, and loss functions. We also propose back-propagation in the mask (BIM), a method whereby only voxels inside the skull mask contribute to training. We evaluate the robustness of the best model to input image noise and MRI acquisition parameters and propagate porosity estimation errors in thousands of beam propagation scenarios.Main resultsOur best performing model is a cGAN with a ResNet-9 generator with 3D 64×64×64 inputs trained with L1 and L2 losses. The model achieved a mean absolute error of 6.9% in the test set, compared to 9.5% with the pseudo-CT of Izquierdo et al. (38% improvement) and 9.4% with the generic pixel-to-pixel image translation cGAN pix2pix (36% improvement). Acoustic dose distributions in the thalamus were more accurate with our approach than with the pseudo-CT approach of both Burgos et al. and Izquierdo et al, resulting in near-optimal treatment planning and dose estimation at all frequencies compared to CT (reference).SignificanceOur DL approach porosity estimates with ~7% error, is robust to input image noise and MRI acquisition parameters (sequence, coils, field strength) and yields near-optimal treatment planning and dose estimates for both central (thalamus) and lateral brain targets (amygdala) in the 200-1000 kHz frequency range.
| S-EPMC11275664 | biostudies-literature
Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.
| S-EPMC6146769 | biostudies-literature
Project description:Background and purposeTranscranial MR imaging-guided focused ultrasound is a promising novel technique to treat multiple disorders and diseases. Planning for transcranial MR imaging-guided focused ultrasound requires both a CT scan for skull density estimation and treatment-planning simulation and an MR imaging for target identification. It is desirable to simplify the clinical workflow of transcranial MR imaging-guided focused ultrasound treatment planning. The purpose of this study was to examine the feasibility of deep learning techniques to convert MR imaging ultrashort TE images directly to synthetic CT of the skull images for use in transcranial MR imaging-guided focused ultrasound treatment planning.Materials and methodsThe U-Net neural network was trained and tested on data obtained from 41 subjects (mean age, 66.4 ± 11.0 years; 15 women). The derived neural network model was evaluated using a k-fold cross-validation method. Derived acoustic properties were verified by comparing the whole skull-density ratio from deep learning synthesized CT of the skull with the reference CT of the skull. In addition, acoustic and temperature simulations were performed using the deep learning CT to predict the target temperature rise during transcranial MR imaging-guided focused ultrasound.ResultsThe derived deep learning model generates synthetic CT of the skull images that are highly comparable with the true CT of the skull images. Their intensities in Hounsfield units have a spatial correlation coefficient of 0.80 ± 0.08, a mean absolute error of 104.57 ± 21.33 HU, and a subject-wise correlation coefficient of 0.91. Furthermore, deep learning CT of the skull is reliable in the skull-density ratio estimation (r = 0.96). A simulation study showed that both the peak target temperatures and temperature distribution from deep learning CT are comparable with those of the reference CT.ConclusionsThe deep learning method can be used to simplify workflow associated with transcranial MR imaging-guided focused ultrasound.
| S-EPMC7661089 | biostudies-literature
Project description:Low intensity transcranial focused ultrasound (LIFU) is a promising method of non-invasive neuromodulation that uses mechanical energy to affect neuronal excitability. LIFU confers high spatial resolution and adjustable focal lengths for precise neuromodulation of discrete regions in the human brain. Before the full potential of low intensity ultrasound for research and clinical application can be investigated, data on the safety of this technique is indicated. Here, we provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of symptomology to other forms of non-invasive brain stimulation. Participants (N = 120) that were enrolled in one of seven human ultrasound neuromodulation studies in one laboratory at the University of Minnesota (2015-2017) were queried to complete a follow-up Participant Report of Symptoms questionnaire assessing their self-reported experience and tolerance to participation in LIFU research (Isppa 11.56-17.12 W/cm2) and the perceived relation of symptoms to LIFU. A total of 64/120 participant (53%) responded to follow-up requests to complete the Participant Report of Symptoms questionnaire. None of the participants experienced serious adverse effects. From the post-hoc assessment of safety using the questionnaire, 7/64 reported mild to moderate symptoms, that were perceived as 'possibly' or 'probably' related to participation in LIFU experiments. These reports included neck pain, problems with attention, muscle twitches and anxiety. The most common unrelated symptoms included sleepiness and neck pain. There were initial transient reports of mild neck pain, scalp tingling and headache that were extinguished upon follow-up. No new symptoms were reported upon follow up out to 1 month. The profile and incidence of symptoms looks to be similar to other forms of non-invasive brain stimulation.
| S-EPMC7101402 | biostudies-literature