Stimulation In Healthy Subjects Research Articles

Examining aldosterone plasma concentration alterations post-ACTH stimulation in healthy subjects: a systematic literature review and meta-analysis on ACTH's role in aldosterone secretion.

Adrenocorticotropic hormone (ACTH), in addition to the renin-angiotensin-aldosterone axis, is a potent aldosterone stimulator, suggesting a potential contribution to conditions associated with increased ACTH concentrations. This study aims to systematically review and synthesize the scientific evidence of alterations of plasma aldosterone concentrations in response to ACTH stimulation during the cosyntropin (Synacthen) test and define the range of aldosterone response. A systematic search of PubMed, Medline, and Google Scholar databases according to PRISMA guidelines was performed. Only studies that assessed the alterations in plasma aldosterone concentrations following ACTH stimulation in healthy individuals were included. We incorporated studies that utilized the doses of 1μg, 250μg, 0.125μg/m2, or 0.5μg/m2 of ACTH. Out of 1599 initially assessed articles, 17 were deemed relevant to our research. The selected articles were assessed by two independent investigators based on the predetermined inclusion and exclusion criteria. Finally, eight full-text articles were included. The analyzed studies revealed a significant increase in plasma aldosterone concentrations in healthy subjects after ACTH stimulation, irrespective of the ACTH dose. The peak aldosterone concentration after the 250μg dose occurred at 30min, whereas smaller doses exhibited an earlier peak, at around 15min. On average, plasma aldosterone concentration increased by 125.5% after the 1μg and 0.5μg/m2 doses, and by 189.6% after 250μg. The presented evidence strongly supports the contribution of ACTH to aldosterone secretion regulation beyond the renin-angiotensin-aldosterone axis. Establishing a normal aldosterone response threshold following standardized ACTH stimulation could aid in identifying individuals with ACTH-dependent aldosterone hypersecretion and guide personalized and effective treatment strategies.

Low frequency oscillations reflect neurovascular coupling and disappear after cerebral death

Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

The headshake enhances oculomotor response to galvanic vestibular stimulation in healthy subjects

ObjectiveTo investigate whether a headshake applied during galvanic vestibular stimulation (GVS) can enhance GVS-induced nystagmus in healthy subjects. MethodsIn nineteen healthy participants, we evaluated an average slow-phase velocity (aSPV) of nystagmus in a head-still and after the headshake conditions, with/out the bitemporal 2 mA GVS. The GVS was applied also with polarity congruent (supporting) or incongruent (suppressing) to any preexisting spontaneous nystagmus. ResultsThe orientation of GVS-induced nystagmus depended on GVS polarity. In the head-still condition, the GVS-induced nystagmus in 14 subjects (74%) for congruent and in 12 subjects (63%) for incongruent GVS. During headshake, we recorded nystagmus in 16 subjects (84%) for congruent and 15 subjects (79%) for incongruent GVS. The aSPV of congruent GVS-induced nystagmus was higher (p = 0.0003) by 1.33 (SE 0.26) deg/s for headshake compared to head-still condition. The aSPV of incongruent GVS also induced higher nystagmus (p = 0.0014) by 1.24 (SE 0.28) deg/s for the headshake condition. ConclusionOur study adds a new principle to the knowledge of the central processing of a GVS response in healthy subjects. The GVS-safety profile of current up to 2 mA was sufficient to elicit a significant GVS nystagmus response in a head-still position in 63% and after a headshake in 79%. Compared to the GVS head-still condition, a headshake enhanced the GVS-induced nystagmus more than twice. SignificanceThe headshake helps to identify GVS-induced nystagmus, which can be weak or absent during the head-still condition.

Different Effect Sizes of Motor Skill Training Combined with Repetitive Transcranial versus Trans-Spinal Magnetic Stimulation in Healthy Subjects.

Repetitive transcranial magnetic stimulation (rTMS) is used to enhance motor training (MT) performance. The use of rTMS is limited under certain conditions, such as after a stroke with severe damage to the corticospinal tract. This raises the question as to whether repetitive trans-spinal magnetic stimulation (rSMS) can also be used to improve MT. A direct comparison of the effect size between rTMS and rSMS on the same MT is still lacking. Before conducting the study in patients, we determined the effect sizes of different stimulation approaches combined with the same motor training in healthy subjects. Two experiments (E1 and E2) with 96 subjects investigated the effect size of combining magnetic stimulation with the same MT. In E1, high-frequency rTMS, rSMS, and spinal sham stimulation (sham-spinal) were applied once in combination with MT, while one group only received the same MT (without stimulation). In E2, rTMS, rSMS, and sham-spinal were applied in combination with MT over several days. In all subjects, motor tests and motor-evoked potentials were evaluated before and after the intervention period. rTMS had the greatest effect on MT, followed by rSMS and then sham-spinal. Daily stimulation resulted in additional training gains. This study suggests that rSMS increases excitability and also enhances MT performance. This current study provides a basis for further research to discover whether patients who cannot be treated effectively with rTMS would benefit from rSMS.

Long-term bilateral change in pain and sensitivity to high-frequency cutaneous electrical stimulation in healthy subjects depends on stimulus modality: a dermatomal examination.

Contradictory changes in pain and sensitivity at long-term following cutaneous 100 Hz high frequency stimulation (HFS) have been previously observed. Thus, we aimed to document long-lasting changes in multimodal sensitivity following HFS, and factors influencing them. Long-lasting changes were assessed with mechanical [brush, von Frey filament (588.2 mN)] and thermal [heat (40°C)/cold (25°C)] bedside sensory testing, and electrical TS (0.2 ms single electrical stimuli), at the homotopic (ipsilateral C6 dermatome), adjacent heterotopic (ipsilateral C5 and C7 dermatomes) and contralateral (contralateral C6 dermatomes) dermatomal sites in a single testing session. TS were applied before and after application of 100 Hz HFS at the ipsilateral C6 dermatome. Subjects rated their sensation and pain intensity to TS, and completed questionnaires related to pain descriptors and quality of life. Long-lasting changes in mechanical and cold sensitivity was detected up to 45 min after HFS at homotopic C6 dermatome, and a temporary increase in cold sensitivity at 20 min in the contralateral C6 dermatome (p < 0.05). A slow development of bilateral depotentiation to electrical pain TS was also detected from 40 min after HFS (p < 0.05). Higher HFS-induced mechanical and cold sensitivity was identified in women (p < 0.05). Age and quality of life were associated with pain intensity (p < 0.05). Long-term unilateral and bilateral changes in sensation and pain following electrical HFS have been found. These findings may suggest a new insight into the development of persistent pain mechanisms. Further studies are now needed.

Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects.

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.

A randomized vagus nerve stimulation study demonstrates that serum aldosterone levels decrease with age in women, but not in men

In this randomized, sham-controlled study, we explored the effects of acute transcutaneous vagus nerve stimulation (tVNS) on serum aldosterone in 20 younger (21–26 years) and 19 older (40–70 years) healthy participants. Blood samples were collected on two different days before and after a 20-min application of active tVNS at the inner tragus or sham stimulation of the earlobe. Irrespective of the stimulation mode, aldosterone levels decreased from pre- to post-stimulation in both the young (active: β = − 1.610 (− 2.855, − 0.365), p = 0.022; sham: β = − 0.857 (− 2.102, 0.388), p = 0.257) and the old cohort (active: β = − 1.969 (− 3.234, − 0.703), p = 0.005; sham: β = − 1.334 (− 2.600, − 0.069), p = 0.063). Although this decline was significant during active tVNS, the difference in estimated β-coefficients between active and sham stimulation was not statistically significant in either cohort. Nevertheless, aldosterone concentrations showed a significant interaction effect between sex and age (p = 0.001). Among all study participants, younger women (23.3 ± 1.6 years) had the highest mineralocorticoid levels (pre active: 172.1 ± 102.0 pg/ml, pre sham: 214.3 ± 82.3 pg/ml), whereas the lowest were observed in older females (59.4 ± 9.4 years) (pre active: 104.9 ± 85.8 pg/ml, pre sham: 81.1 ± 53.8 pg/ml). This post hoc analysis did not suggest that active auricular tVNS reduces serum aldosterone levels compared to sham stimulation in healthy subjects. However, serum aldosterone levels differed among subjects depending on their age and sex, irrespective of tVNS.

The Effects of Sex, Women’s Body Composition and Monthly Cycle Phases on the Sensory Threshold of Upper Limb to Transcutaneous Electrical Nerve Stimulation in Healthy Subjects

Neuromuscular excitability plays an essential role in electrotherapy treatment. The vast majority of these treatments are procedures that change the sensitivity to sensory stimuli, especially pain, with the use of an electric current. The aim of this study was to assess changes in the sensory threshold in response to transcutaneous electrical nerve stimulation (TENS), taking into account certain personal factors, such as sex, body composition, and phases of the menstrual cycle. The study involved 205 women and 49 men aged 19–33 years. Sensory threshold was examined by TENS stimulation (a biphasic current waveform, 100 Hz and 100 µs) and body composition using a TANITA analyzer. The mean sensitivity threshold in women was lower than in men (mean ± SD, F: 8.78 ± 2.11 mA vs. M: 11.20 ± 3.29 mA, p &lt; 0.001). There were no significant differences in sensory threshold during the different phases of a woman’s monthly cycle. The taller the woman, the higher the sensory threshold (B ± SE, 0.15 ± 0.07, p = 0.036), while those with a higher percentage of body fat and a higher total water content had a lower sensory threshold (fat: B ± SE, −0.25 ± 0.07, p &lt; 0.001; water: B ± SE, −0.20 ± 0.07, p = 0.003). In conclusion, the sensory threshold in women was lower than in men. In women aged 19–33 years, the phases of the monthly cycle did not affect the sensory threshold; however, being taller and having less body fat and a lower water content increased the sensory threshold.

Motor evoked potentials recorded from muscles versus nerves after lumbar stimulation in healthy subjects and patients with disc-root conflicts.

The study aimed to describe properties and to prove diagnostic usefulness of motor evoked potentials (MEPs) recordings from muscles versus nerves of lower extremities when induced at lumbar levels with magnetic field. Methodologically similar MEPs recordings from muscles and nerves of lower extremities were performed once in healthy volunteers (N = 43) and patients with disc-root conflicts at lumbar spine levels (N = 43, proven in MRI studies). Simultaneous electroneurographic (ENG) recordings following stimulation of peroneal nerves verified neural impulses transmission in motor fibers peripherally and at L5 ventral roots. ENG studies in patients proven only moderate axonal type of peroneal nerves injury. The mean values of MEPs amplitudes recorded from nerves were significantly different from those recorded in anatomically related muscles, both in controls (1179.6 ± 451.2 vs 1718.3 ± 481.3) and patients (495.6 ± 275.9 vs 1218.2 ± 465.5) (p = 0.0009-0.0000012); they are about 30% and 51% smaller, respectively. In both groups of subjects, latencies of MEPs recorded from nerves were shorter at about 3.0 ms and characterized by a slightly longer duration (3.0-5.0 ms) than those recorded from muscles. Results revealed positive correlations between decrease of amplitudes in sEMG and MEPs recordings from lower extremities muscles indicating consequences of pathology in neural transmission from spinal centers. Results of this study point to clear-cut characteristics of MEPs induced oververtebrally with the magnetic field in parameters recorded in healthy subjects and patients with consequences of chronic L4-L5 low back pain, which can be easily implemented in clinical practice. Non-invasive method of MEPs recorded from nerves can be helpful for diagnosing of patients with visible atrophic changes in muscles and simultaneous symptoms of only slight pathology in transmission of nerve impulses peripherally.

Modulation of Mind Wandering Using Monaural Beat Stimulation in Subjects With High Trait-Level Mind Wandering.

Mind wandering (MW) refers to a state when attention shifts from the task at hand or current situation toward thoughts, feelings, and imaginations. This state is often accompanied by a decline in mood, and patients suffering from major depression exhibit more perseverative MW. Hence, although the directionality of the relationship between mood and MW is still under investigation, it may be useful to explore possible avenues to reduce MW. In an earlier pilot study, we investigated MW during auditory beat stimulation in healthy subjects using thought-probes during a sustained attention to response task (SART). We found evidence for reduced MW during monaural 5 Hz beats compared to silence, sine tones, and binaural 5 Hz beats. Moreover, the data tentatively suggested that this reduction was particularly pronounced in subjects with high levels of MW during silence. In the current study, we therefore asked whether MW can be reduced by monaural theta beats in subjects with high trait-levels of MW, as indicated by an online MW questionnaire. Preselected subjects performed a SART task with thought-probes assessing the propensity to mind wander, meta-awareness, and the temporal orientation of MW. Stimulation conditions comprised monaural theta beats, as well as silence (headphones on), and sine tones as control conditions. Our main hypothesis stating that the propensity to mind wander during monaural theta beats is reduced compared to both control conditions was only partly confirmed. Indeed, MW was significantly diminished during exposure to the theta beats compared to sine tones. However, reduced MW during theta beats versus silence was only observed in a subgroup using stricter inclusion criteria. Considering possible reasons for this outcome, our data suggest that the preselection procedure was suboptimal and that beat effects are modulated by the individual responses to auditory stimulation in general.

Classification of Schizophrenia EEG Based on Gamma-Band Brain Network

Gamma-band (40-Hz) activity is critical for cortico-cortical transmission and the integration of information across neural networks during sensory and cognitive processing. Patients with schizophrenia show selective reductions in the capacity to support synchronized gamma-band oscillations in response to auditory stimulation presented 40-Hz. Despite widespread application of this 40-Hz auditory steady-state response (ASSR) as a translational electroencephalographic biomarker for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not been fully characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n = 426) and healthy comparison subjects (n = 293). Both groups showed multiple ASSR source interactions that were broadly distributed across brain regions. Schizophrenia patients showed distinct, hierarchically sequenced connectivity abnormalities. During the response onset interval, patients exhibited abnormal increased connectivity from the inferior frontal gyrus to the superior temporal gyrus, followed by decreased connectivity from the superior temporal to the middle cingulate gyrus. In the later portion of the ASSR response (300–500 ms), patients showed significantly increased connectivity from the superior temporal to the middle frontal gyrus followed by decreased connectivity from the left superior frontal gyrus to the right superior and middle frontal gyri. These findings highlight both the orchestration of distributed multiple sources in response to simple gamma-frequency stimulation in healthy subjects as well as the patterns of deficits in the generation and maintenance of gamma-band oscillations across the temporo-frontal sources in schizophrenia patients.

FV 8. The effect of repeated blocks of intermittant theta burst stimulation (iTBS) over the dorsolateral prefrontal cortex (dlPFC) on fronto-striatal connectivity. A 18F-DesmethoxyFallypride (DMFP) Positron Emission Tomography study (PET)

Background. Frontostriatal networks are neural pathways formed between frontal lobe regions and striatum that is involved in cognitive and behavioural processes. Transcranial Magnetic Stimulation (TMS) is able to modulate connectivity in the human brain and it is widely used for clinical purposes to treat depression patients. This exploratory PET and TMS multimodal study would contribute to better understand the role of striatal dopaminergic neurotransmission in the fronto-striatal area. Objective. The main objective of the study is to investigate the fronto-striatal connectivity by measuring the release of dopamine in the striatum in response to an excitatory intermittent theta burst stimulation (iTBS) of the left-dlPFC. A PET measurement was performed by using the 18F-DesmethoxyFallypride (DMFP) radioligand, that is a high affinity receptor-antagonist which competes with endogenous Dopamine neurotransmitters for D2/D3 receptor binding. Methods. The study was conducted on 23 healthy participants, who underwent iTBS sham (control) and verum stimulations on separate days. The PET scan lasted 120 mins, consisting of 4 iTBS stimulations delivered to the left-DLPFC at 30 mins interval. In verum stimulation, 90% of resting motor threshold (rMT) was used as the stimulation intensity. The excitatory iTBS protocol is delivered in a sequence of trains (burst of 10 pulses in 2 secs having inter train interval of 8 secs), with a total duration of 190 secs. PET dynamic data was analysed using reference region method in which cerebellum was used as the reference region (due to lack of D2-D3 receptors). Binding Potentials (BP) are the main outcome measure representing the ligand binding which is inversely proportional to the Dopamine (DA) levels.Mean Binding Potentials in the sub-regions of the striatum (Nucleus Caudate and Putamen) were compared between the sham and verum stimulation using analysis of variance (ANOVA). Results. iTBS stimulation of the left DLPFC increased the dopamine release (as reflected by BPs) in the striatum areas (putamen and nucleus caudate) in the verum stimulation, as compared to sham stimulation.Although the increase in dopamine release did not differ between the first block of stimulation, we observed significant increase after two, three and fourth blocks of stimulation. Conclusion. Our data suggest that the efficiency of iTBS protocol can effectively enhance fronto-striatal connectivity by applying a higher number of stimuli (i.e., 3rd & 4th TMS block but not 1st-& 2nd block). This minimal time stimulation protocol can be used as a therapy for treating Depression patients by presenting it in the repeated blocks of short intervals. This scheme could prevent the long stimulation protocols, and be less painful. Fig. 1. Figure represents the statistically significant main effect of TMS . The verum stimulation shows a reduction of 8.6% [18F]DMFP Binding Potential as compared to the sham stimulation. Fig. 2. Percentage reduction in [18F] desmethoxyfallypride-binding potentials extracted from the difference of sham and verum stimulation in healthy subjects. Dose-dependent iTBS aftereffects seem to be more pronounced at 3rd block and 4th block respectively as compared to 1st and 2nd block of TMS.

CGRP release in an experimental human trigeminal pain model.

BackgroundMigraine and trigemino-autonomic cephalalgia attacks are associated with an increase of α-calcitonin-gene related peptide levels in the ipsilateral jugular vein. It is however unknown whether trigeminal pain stimulation in healthy subjects without headache disorders also induces increase of calcitonin-gene related peptide levels.FindingsWe measured α-calcitonin-gene related peptide levels in eight healthy subjects after subcutaneous injection of capsaicin in the forehead and in the mandibular region and after injection of sodium chloride in the forehead. We observed a significant increase of α-calcitonin-gene related peptide level only after injection of capsaicin in the forehead (i.e. first trigeminal branch). We also observed trigemino-autonomic activation (lacrimation, rhinorrhea etc.) only after injection of capsaicin in the forehead.ConclusionIncrease of α-calcitonin-gene related peptide levels do not only occur in primary headache attacks but also after experimental trigeminal pain of the first branch. This finding suggests that α-calcitonin-gene related peptide elevation is, at least an additional, unspecific effect of first trigeminal branch stimulation following pain activation and not a specific mechanism of idiopathic headache disorders.

Innate Muscle Patterns Reproduction During Afferent Somatosensory Input With Vojta Therapy in Healthy Adults. A Randomized Controlled Trial.

Vojta therapy describes stereotypic widespread motor responses as a pattern of tonic muscle contractions during a peripherical pressure stimulation. The present work proposes to characterize the responses at muscles level to a specific tactile input based on Vojta therapy, assessed by sEMG, compared to a sham stimulation in healthy subjects. Surface electromyography (sEMG) signal was acquired with dipolar electrodes placed at wrist extensors of both forearms, right tibialis anterior, and top part of rectus abdominus, ground channel placed over the right olecranon. It was amplified and digitized by a 4-channel hub Biosignalsplux device (Plux Wireless Biosignals S.A., Lisboa, Portugal), sampled at 1000 Hz with 16-bit per channel. A continuous 10-minute record of the sEMG signal from the four electrodes were registered. Resting EEG during the first minute before the stimulation period was recorded by 64 active electrodes. Statistically significant differences were showed between sham and experimental group. Experimental group participants were subjected to cluster analysis based on their muscle activation patterns, generating three different models of activation. Differences in the previous resting cortical activity in left superior frontal area were found between clusters that activated limb muscles and the cluster that did not. Vojta specific stimulation area activates innate muscle responses assessed by sEMG in healthy subjects, compared to a sham stimulation. This characterization might be helpful to the prescription and application of Vojta therapy in an individual-basis for non-neurophysiologically damaged adult subjects.

Excitatory and inhibitory responses to cervical root magnetic stimulation in healthy subjects

ObjectivesTo characterize direct and reflex hand muscle responses to cervical root magnetic stimulation (CRMS) in healthy volunteers during sustained voluntary contraction. MethodsIn 18 healthy volunteers, we recorded from the first dorsal interosseous (FDI) muscle the responses to CRMS of progressively increasing intensity and level of muscle contraction. The compound muscle action potential (CMAP) and the silent period (SP) were compared to those obtained with plexus, midarm and wrist stimulation. Additionally, in a smaller number of subjects, we obtained the peristimulus time histogram (psth) of single motor unit firing in the FDI, examined the effects of vibration and recorded the modulation of sustained EMG activity in muscles of the lower limbs. ResultsIncreasing CRMS intensity led to larger CMAP with no relevant changes in SP1 or SP2, except for lower amplitude of the burst interrupting the silent period (BISP). Increasing the level of muscle contraction led to reduced CMAP, shorter SP duration and increased BISP amplitude. The psth analysis showed the underlying changes in the motor unit firing frequency that corresponded to the changes seen in the CMAP and the SP with surface recordings. Progressively distal stimulation led to CMAPs of shorter latency and increased amplitude, SPs of longer latency and shorter duration, and a BISP of longer latency. Vibration led to reduction of the SP. CRMS induced SPs in muscles of the lower limb. ConclusionsCRMS induces excitatory and inhibitory responses in hand muscles, fitting with the expected behavior of mixed nerve stimulation at very proximal sites. SignificanceCharacterization of the effects of CRMS on hand muscles is of physiological and potentially clinical applicability, as it is a painless and reliable procedure.

Neural network dynamics underlying gamma synchronization deficits in schizophrenia

Gamma-band (40-Hz) activity is critical for cortico-cortical transmission and the integration of information across neural networks during sensory and cognitive processing. Patients with schizophrenia show selective reductions in the capacity to support synchronized gamma-band oscillations in response to auditory stimulation presented 40-Hz. Despite widespread application of this 40-Hz auditory steady-state response (ASSR) as a translational electroencephalographic biomarker for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not been fully characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n = 426) and healthy comparison subjects (n = 293). Both groups showed multiple ASSR source interactions that were broadly distributed across brain regions. Schizophrenia patients showed distinct, hierarchically sequenced connectivity abnormalities. During the response onset interval, patients exhibited abnormal increased connectivity from the inferior frontal gyrus to the superior temporal gyrus, followed by decreased connectivity from the superior temporal to the middle cingulate gyrus. In the later portion of the ASSR response (300–500 ms), patients showed significantly increased connectivity from the superior temporal to the middle frontal gyrus followed by decreased connectivity from the left superior frontal gyrus to the right superior and middle frontal gyri. These findings highlight both the orchestration of distributed multiple sources in response to simple gamma-frequency stimulation in healthy subjects as well as the patterns of deficits in the generation and maintenance of gamma-band oscillations across the temporo-frontal sources in schizophrenia patients.

Opposite modulations of corticospinal excitability by intermittent and continuous peripheral electrical stimulation in healthy subjects

Peripheral electrical stimulation (PES) modulates the excitability of the corticospinal tract (CST). This modulation of CST excitability depends on the PES intensity, defined by the amplitude and the width of each pulse, the total pulse number, the stimulation frequency, and the intervention duration. Another key PES parameter is the stimulation pattern; little is known about how PES pattern affects CST excitability, as previous studies did not control other PES parameters. Here, we investigated the effect of the net difference in PES pattern on CST excitability. We use three controlled PESs, intermittent PES (30 Hz) (stimulation trains at 30 Hz with pauses), continuous PES (12 Hz) (constant stimulation at 12 Hz without pauses), and continuous PES (30 Hz) with the same stimulation frequency as the intermittent PES (30 Hz), to compare the effect of the stimulation frequency. The motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) of healthy subjects were recorded before and after these three types of PESs in separate sessions. We found that intermittent PES (30 Hz) increased MEP amplitudes, whereas continuous PES (12 and 30 Hz) decreased amplitudes. A significant change in subcortical SEP component occurred during continuous PES (12 and 30 Hz), but not intermittent PES (30 Hz), whereas cortical SEP components showed similar behavior in three types of PESs. We conclude that (1) opposing modulations of CST excitability were induced by the differences in the PES pattern, and (2) these modulations appear to be mediated through different processes in the sensorimotor system. Our findings suggest the possibility that it may be preferable to select the PES pattern in therapeutic interventions based on the putative desired effect and the neural structure being targeted.

A direct comparison of the electrophysiological effects of transcranial direct and alternating current stimulation in healthy subjects

ObjectiveDespite the clinical effectiveness of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), the comparability of these interventions in neurophysiological aspects have not been thoroughly investigated. Thus, we aimed to directly compare the electrophysiological effects of single-session tDCS and gamma-tACS in healthy subjects, matching the intervention protocol as closely as possible. Methods: This was a randomized, double-blinded, and active-controlled study. Sixty healthy college students were enrolled in the study. Both tACS with, at 40 Hz frequency, and tDCS have the same current intensity (2 mA, 30 min) within the same target area (right and left dorsolateral prefrontal cortex). Resting-state electroencephalography (EEG) was recorded before and after single-session stimulation. ResultsSignificant differences in theta, alpha, low-beta, and gamma frequencies were found between tDCS, tACS, and the sham groups. Low-beta source activity of the middle temporal gyrus was decreased only after an intervention with tACS. Conclusion: The present study indicates that tDCS and tACS resulted in an increased range of frequency activity, including slow- and fast-wave bands. Specifically, tDCS modulates the frontal region, while tACS modulates neural oscillations at the fronto-central, parietal, and temporal areas. The tACS also decreased low-beta source activity in the middle temporal gyrus. Identifying the common and unique EEG patterns of tDCS and tACS may help shed light on their potential clinical benefits and distinctive neuropathology in various clinical symptoms.

Physiological response to Vibro-Acoustic stimulation in healthy subjects: a preliminary study.

Over the last decade Vibro-Acoustic Therapy (VAT) was used for several clinical applications. This paper investigates the use of AcusticA®, an innovative VAT solution represented by a wooden chaise longue that follows the construction principles of a "musical instrument that stimulates the whole body" in relation to the sound frequencies produced by the music tracks. Ten healthy young subjects were enrolled for this study. Wearable sensors were used to monitor the human physiological response during the VAT session but also during a traditional acoustic therapy (AT) to highlight similarity and differences of those stimulations. Signals from heart activity, brain activity and electrodermal activity were analyzed to investigate the response during the non-stimulated and the stimulated phases. Additionally, two supervised classification algorithms were used to investigate whether the extracted instances could be grouped into two different groups. The results identify a trend of the attention and meditation features extracted from brain activity, which pointed out the relax efficacy of the VAT.Clinical Relevance - There are not significant differences (p<0.05) in the physiological response between the VAT and the AT stimulation, but during the VAT the alpha coefficients were significant different during the stimulated phase. Finally, the classification algorithms were able to classify the groups with an accuracy equal to 100% in the best case.

S143. NEURAL MECHANISMS OF ROBOT-INDUCED HALLUCINATIONS IN HEALTHY PARTICIPANTS AND SYMPTOMATIC HALLUCINATIONS OF NEUROLOGICAL AND PSYCHIATRIC ORIGIN

BackgroundThe ability to recognize whether sensory consequences have been self-generated or externally produced is an important element of motor control and self-monitoring. Deficits in self-monitoring have been proposed to cause abnormal bodily experiences and psychotic symptoms such as hallucinations. A recent study designed a robotic system that applies sensorimotor stimulation in healthy subjects and safely induces mild presence hallucinations (PH) and passivity experiences (Blanke et al., 2014). PH are defined as the sensation that someone is close by when actually no one is present and passivity experiences are characterized by perceptions or beliefs that an external agent is controlling one’s actions, perceptions, and/or thoughts. Although, both symptoms occur in schizophrenia and Parkinson’s disease, their neural mechanisms are unknown.MethodsHere, we first investigated the neural mechanisms of PH and passivity experiences in 25 healthy subjects. We developed a new MR-compatible robotic system able to generate the aforementioned sensorimotor conflicts, while recording subjects’ brain activity using fMRI. In addition, we applied lesion network mapping to 11 neurological patients with symptomatic PH and compared both populations to find a common PH network. In a final step, we investigated the relevance of the PH network by analyzing the connectivity of the PH network in resting state fMRI data from 58 psychotic patients.ResultsWe first evaluated the regions associated with the general sensorimotor conflict, which revealed the left sensorimotor area, the left putamen, the right inferior parietal lobule and the right cerebellum. Then, we analyzed the regions that were more activated during the condition eliciting PH and passivity experiences and found the inferior frontal gyrus (IFG), the insula, the superior medial gyrus and the middle temporal gyrus (MTG). Comparison of these two networks with the symptomatic PH network in neurological patients highlighted the IFG, the MTG and the vPMc. The resting state analysis within those regions in psychotic patients revealed no global differences between the groups but a functional connectivity decrease between MTG and IFG (bilaterally) specific for psychotic patients experiencing passivity experiences.DiscussionCollectively, we showed that through the use of a robotic system generating sensorimotor conflicts, the neural correlates of induced-PH and passivity experiences can be studied in healthy subjects in a controlled manner. In addition, we found two networks associated with induced-PH and passivity experience. Of these regions, three were also recruited in patients with PH of neurological origin, forming the PH network. MTG-IFG connectivity in the PH network was altered selectively in psychotic patients with passivity experiences, revealing the relevance of the neural mechanisms of PH and passivity experiences in psychosis.