First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

Background With the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior. Methods Twelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed. Results Compared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area. Conclusions TPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

Impaired Topographic Organization in Patients With Idiopathic Blepharospasm

Background: Idiopathic blepharospasm (BSP) is a common adult-onset focal dystonia. Neuroimaging technology can be used to visualize functional and microstructural changes of the whole brain.Method: We used resting-state functional MRI (rs-fMRI) and graph theoretical analysis to explore the functional connectome in patients with BSP. Altogether 20 patients with BSP and 20 age- and gender-matched healthy controls (HCs) were included in the study. Measures of network topology were calculated, such as small-world parameters (clustering coefficient [Cp], the shortest path length [Lp]), network efficiency parameters (global efficiency [Eglob], local efficiency [Eloc]), and the nodal parameter (nodal efficiency [Enod]). In addition, the least absolute shrinkage and selection operator (LASSO) regression was adopted to determine the most critical imaging features, and the classification model using critical imaging features was constructed.Results: Compared with HCs, the BSP group showed significantly decreased Eloc. Imaging features of nodal centrality (Enod) were entered into the LASSO method, and the classification model was constructed with nine imaging nodes. The area under the curve (AUC) was 0.995 (95% CI: 0.973–1.000), and the sensitivity and specificity were 95% and 100%, respectively. Specifically, four imaging nodes within the sensorimotor network (SMN), cerebellum, and default mode network (DMN) held the prominent information. Compared with HCs, the BSP group showed significantly increased Enod in the postcentral region within the SMN, decreased Enod in the precentral region within the SMN, increased Enod in the medial cerebellum, and increased Enod in the precuneus within the DMN.Conclusion: The network model in BSP showed reduced local connectivity. Baseline connectomic measures derived from rs-fMRI data may be capable of identifying patients with BSP, and regions from the SMN, cerebellum, and DMN may provide key insights into the underlying pathophysiology of BSP.

Characterization of Spinal Sensorimotor Network Using Transcutaneous Spinal Stimulation during Voluntary Movement Preparation and Performance

Transcutaneous electrical spinal stimulation (TSS) can be used to selectively activate motor pools based on their anatomical arrangements in the lumbosacral enlargement. These spatial patterns of spinal motor activation may have important clinical implications, especially when there is a need to target specific muscle groups. However, our understanding of the net effects and interplay between the motor pools projecting to agonist and antagonist muscles during the preparation and performance of voluntary movements is still limited. The present study was designed to systematically investigate and differentiate the multi-segmental convergence of supraspinal inputs on the lumbosacral neural network before and during the execution of voluntary leg movements in neurologically intact participants. During the experiments, participants (N = 13) performed isometric (1) knee flexion and (2) extension, as well as (3) plantarflexion and (4) dorsiflexion. TSS consisting of a pair pulse with 50 ms interstimulus interval was delivered over the T12-L1 vertebrae during the muscle contractions, as well as within 50 to 250 ms following the auditory or tactile stimuli, to characterize the temporal profiles of net spinal motor output during movement preparation. Facilitation of evoked motor potentials in the ipsilateral agonists and contralateral antagonists emerged as early as 50 ms following the cue and increased prior to movement onset. These results suggest that the descending drive modulates the activity of the inter-neuronal circuitry within spinal sensorimotor networks in specific, functionally relevant spatiotemporal patterns, which has a direct implication for the characterization of the state of those networks in individuals with neurological conditions.

Aberrant Interhemispheric Functional Connectivity in Diabetic Retinopathy Patients

Background: Accumulating lines of evidence demonstrated that diabetic retinopathy (DR) patients trigger abnormalities in brain’s functional connectivity (FC), whereas the alterations of interhemispheric coordination pattern occurring in DR are not well understood. Our study was to investigate alterations of interhemispheric coordination in DR patients.Methods: Thirty-four DR individuals (19 males and 15 females: mean age: 52.97 ± 8.35 years) and 37 healthy controls (HCs) (16 males and 21 females; mean age: 53.78 ± 7.24 years) were enrolled in the study. The voxel-mirrored homotopic connectivity (VMHC) method was conducted to investigate the different interhemispheric FC between two groups. Then, the seed-based FC method was applied to assess the different FCs with region of interest (ROI) in the brain regions of decreased VMHC between two groups.Results: Compared with HC groups, DR groups showed decreased VMHC values in the bilateral middle temporal gyrus (MTG), lingual/calcarine/middle occipital gyrus (LING/CAL/MOG), superior temporal gyrus (STG), angular (ANG), postcentral gyrus (PosCG), inferior parietal lobule (IPL), and precentral gyrus (PreCG). Meanwhile, altered FC includes the regions of auditory network, visual network, default mode network, salience network, and sensorimotor network. Moreover, a significant positive correlation was observed between the visual acuity-oculus dexter (OD) and zVMHC values in the bilateral LING/CAL/MOG (r = 0.551, p = 0.001), STG (r = 0.426, p = 0.012), PosCG (r = 0.494, p = 0.003), and IPL (r = 0.459, p = 0.006) in DR patients.Conclusion: Our results highlighted that DR patients were associated with substantial impairment of interhemispheric coordination in auditory network, visual network, default mode network, and sensorimotor network. The VMHC might be a promising therapeutic target in the intervention of brain functional dysfunction in DR patients.

Neural Networks Implicated in Autobiographical Memory Training

Training of autobiographical memory has been proposed as intervention to improve cognitive functions. The neural substrates for such improvements are poorly understood. Several brain networks have been previously linked to autobiographical recollections, including the default mode network (DMN) and the sensorimotor network. Here we tested the hypothesis that different neural networks support distinct aspects of memory improvement in response to training on a group of 59 subjects. We found that memory training using olfactory cues increases resting-state intra-network DMN connectivity, and this associates with improved recollection of cue-specific memories. On the contrary, training decreased resting-state connectivity within the sensorimotor network, a decrease that correlated with improved ability for voluntary recall. Moreover, only the decrease in sensorimotor connectivity associated with the training-induced decrease in the TNFα factor, an immune modulation previously linked to improved cognitive performance. We identified functional and biochemical factors that associate with distinct memory processes improved by autobiographical training. Pathways which connect autobiographical memory to both high level cognition and somatic physiology are discussed.

The Empowering Effect of Embodied Awareness Practice on Body Structural Map and Sensorimotor Activity: The Case of Feldenkrais Method

While outcomes of embodied awareness practices in terms of improved posture and flexibility, movement efficiency, and well-being are often reported, systematic investigations of such training effects and of the actual nature, extent, and neurofunctional correlates of learning mechanisms thought to lie at the core of such practices are very limited. The present study focused on the Feldenkrais method (FM), one of the most established embodied awareness practices, and aimed at investigating the neurofunctional outcomes of the somatic learning process at the core of the method by testing the modulations induced by a standardized FM protocol on the complexity of practicers’ body structural map and on the activity of their sensorimotor network during different movement-related tasks (i.e., gestures observation, execution, and imagery). Twenty-five participants were randomly divided into an experimental group—which completed a 28-session FM protocol based on guided group practice—and a control group, and underwent pre-/post-training psychometric and electrophysiological assessment. Data analysis highlighted, at the end of the FM protocol, a significant increase of EEG markers of cortical activation (task-related mu desynchronization) in precentral regions during action observation and in central regions during action execution and imagery. Also, posterior regions of the sensorimotor network showed systematic activation during all the action-related tasks.

TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease: A Proof-of-Concept Six Years Prospective Study

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge.Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level.Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)].Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD.Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.

Altered Dynamic Amplitude of Low-frequency Fluctuations in Patients with Postpartum Depression

Background Postpartum depression (PPD) is a common mood disorder with increasing incidence year by year. However, the dynamic changes in local neural activity remain unclear. In this study, we utilized the dynamic amplitude of low-frequency (dALFF) to investigate the abnormal temporal variability of local neural activity. Methods Twenty-four patients with PPD and nineteen healthy postpartum women controls (HCs) matched for age, education level and body mass index were examined by resting-state functional magnetic resonance imaging (rs-fMRI). A sliding-window method was used to assess the dALFF, and a k-means clustering method was used to identify dALFF states. Two-sample t-test was used to compare the differences of dALFF variability and state metrics between PPD and HCs. Pearson correlation analysis was used to analyze the relationship between dALFF variability, states metrics and clinical severity. Results (1) Patients with PPD had lower variance of dALFF than HCs in the cognitive control network, cerebellar network, and sensorimotor network. (2) Four dALFF states were identified, and the number of transitions between the four dALFF states increased in the patients compared with that in HCs. (3) Multiple dALFF states were found to be correlated with the severity of depression. The variance of dALFF in the right middle frontal gyrus was negatively correlated with the Edinburgh postnatal depression scale score. Conclusion This study provides new insights into the brain dysfunction of PPD from the perspective of dynamic local brain activity, and highlights its important role in understanding the neurophysiological mechanisms of PPD.

Altered brain network functional connectivity patterns in patients with vestibular migraine diagnosed according to the diagnostic criteria of the Bárány Society and the International Headache Society

Background Vestibular migraine (VM) is considered one of the most common causes of episodic central vestibular disorders, the mechanism of VM is currently still unclear. The development of functional nuclear magnetic resonance (fMRI) in recent years offers the possibility to explore the altered functional connectivity patterns in patients with VM in depth. The study aimed to investigate altered patterns of brain network functional connectivity in patients with VM diagnosed based on the diagnostic criteria of the Bárány Society and the International Headache Society, and hope to provide a scientific theoretical basis for understanding whether VM is a no-structural central vestibular disease, i.e., functional central vestibular disease with altered brain function. Methods Seventeen patients with VM who received treatment in our hospital from December 2018 to December 2020 were enrolled. Eight patients with migraine and 17 health controls (HCs) were also included. Clinical data of all patients were collected. Blood pressure, blood routine tests and electrocardiography were conducted to exclude other diseases associated with chronic dizziness. Videonystagmography, the vestibular caloric test, the video head impulse test and vestibular-evoked myogenic potentials were measured to exclude peripheral vestibular lesions. MRI was utilized to exclude focal lesions and other neurological diseases. All subjects underwent fMRI. The independent component analysis was performed to explore changes in intra- and inter-network functional connectivity in patients with VM. Results Among 17 patients with VM, there were 7 males and 10 females with an average age of 39.47 ± 9.78 years old. All patients had a history of migraine. Twelve (70.6%) patients had recurrent spontaneous vertigo, 2 (11.7%) patients had visually induced vertigo, and 3 (17.6%) patients had head motion-induced vertigo. All 17 patients with VM reported worsening of dizziness vertigo during visual stimulation. The migraine-like symptoms were photophobia or phonophobia (n = 15, 88.2%), migraine-like headache (n = 8, 47.1%), visual aura during VM onset (n = 7, 41.2%). 5 (29.4%) patients with VM had hyperactive response during the caloric test, and 12 (70.6%) patients had caloric test intolerance. Eleven (64.7%) patients had a history of motion sickness. Totally 13 independent components were identified. Patients with VM showed decreased functional connectivity in the bilateral medial cingulate gyrus and paracingulate gyrus within sensorimotor network (SMN) compared with HCs. They also showed weakened functional connectivity between auditory network (AN) and anterior default mode network (aDMN) compared with HCs, and enhanced functional connectivity between AN and the salience network (SN) compared with patients with migraine. Conclusion Patients with vestibular migraine showed obvious altered functional connectivity in the bilateral medial cingulate gyrus and paracingulate gyrus within the SMN. The median cingulate and paracingulate gyri may be impaired, the disinhibition of sensorimotor network and vestibular cortical network may result in a hypersensitivity state (photophobia/phonophobia). Altered functional connectivity between AN and DMN, SN may lead to increased sensitivity to vestibular sensory processing.