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Transcranial Random Noise Stimulation Does Not Improve Behavioral and Neurophysiological Measures in Patients with Subacute Vegetative-Unresponsive Wakefulness State (VS-UWS).

ABSTRACT: Background: The absence of efficient treatments capable to promote central nervous system recovery in patients in vegetative state (VS) due to a severe acquired brain injury highlights the need of exploring alternative neuromodulatory treatments that can lead to neurobehavioral gains. Some encouraging preliminary observations suggest that transcranial direct current stimulation could be effective in disorders of consciousness (DoC) patients, especially when applied on the dorsolateral prefrontal cortex (DLPFC) in patients with minimally conscious state (MCS) but not in those with VS. Objective: The primary aim of the present study was to verify if the application of transcranial random noise stimulation (tRNS) on the DLPFC might favor improvements of consciousness recovery in subacute VS-UWS. Methods: Nine patients with DoC due to traumatic brain injury (n = 1), anoxia (n = 3), and vascular damage (n = 5), have undergone a randomized, double-blind, sham-controlled, neuromodulatory trial with tRNS of bilateral DLPFC. All patients were in a post-acute phase and the DoC onset ranged from 30 days to 4 months. The diagnosis of DoC was based on internationally established criteria from the Multi-Society Task Force on PVS, and classified as VS or MCS using the JFK Coma Recovery Scale-Revised scores (CRS-R). We used CRS-R, Synek Scale, Ad-Hoc semi-quantitative scale and the Clinical Global Impression-Improvement scale to measure behavioral and electrophysiological changes during tRNS intervention. All patients were also treated with daily conventional rehabilitation treatment. Results: No significant differences emerged between active and sham groups regarding improvements of level of consciousness, as well as on electroencephalographic data. Only one patient showed emergence from VS-UWS, evolving from VS to MCS after the tRNS stimulation, at a distance of 3 weeks from the enrolment into the study. Conclusion: Repeated applications of tRNS of the DLPFC, even if applied in a subacute phase of VS-UWS state, did not modify behavioral and neurophysiological outcomes differently than sham stimulation.

SUBMITTER: Mancuso M

PROVIDER: S-EPMC5681535 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transcranial Random Noise Stimulation Does Not Improve Behavioral and Neurophysiological Measures in Patients with Subacute Vegetative-Unresponsive Wakefulness State (VS-UWS).

Mancuso Mauro M Abbruzzese Laura L Canova Stefania S Landi Giulia G Rossi Simone S Santarnecchi Emiliano E

Frontiers in human neuroscience 20171106

<b>Background:</b> The absence of efficient treatments capable to promote central nervous system recovery in patients in vegetative state (VS) due to a severe acquired brain injury highlights the need of exploring alternative neuromodulatory treatments that can lead to neurobehavioral gains. Some encouraging preliminary observations suggest that transcranial direct current stimulation could be effective in disorders of consciousness (DoC) patients, especially when applied on the dorsolateral pre ...[more]

PMID: 29163104

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Project description:Proficiency in arithmetic learning can be achieved by using a multitude of strategies, the most salient of which are procedural learning (applying a certain set of computations) and rote learning (direct retrieval from long-term memory). Here we investigated the effect of transcranial random noise stimulation (tRNS), a non-invasive brain stimulation method previously shown to enhance cognitive training, on both types of learning in a 5-day sham-controlled training study, under two conditions of task difficulty, defined in terms of item repetition. On the basis of previous research implicating the prefrontal and posterior parietal cortex in early and late stages of arithmetic learning, respectively, sham-controlled tRNS was applied to bilateral prefrontal cortex for the first 3 days and to the posterior parietal cortex for the last 2 days of a 5-day training phase. The training involved learning to solve arithmetic problems by applying a calculation algorithm; both trained and untrained problems were used in a brief testing phase at the end of the training phase. Task difficulty was manipulated between subjects by using either a large ("easy" condition) or a small ("difficult" condition) number of repetition of problems during training. Measures of attention and working memory were acquired before and after the training phase. As compared to sham, participants in the tRNS condition displayed faster reaction times and increased learning rate during the training phase; as well as faster reaction times for both trained and untrained (new) problems, which indicated a transfer effect after the end of training. All stimulation effects reached significance only in the "difficult" condition when number of repetition was lower. There were no transfer effects of tRNS on attention or working memory. The results support the view that tRNS can produce specific facilitative effects on numerical cognition--specifically, on arithmetic learning. They also highlight the importance of task difficulty in the neuromodulation of learning, which in the current study due to the manipulation of item repetition might have being mediated by the memory system.

Project description:Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way.

Project description:IntroductionBehavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness.MethodsHence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject's own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN ('SON effect', primary endpoint assessed by temporal clustering permutation tests).ResultsPatients were either coma (n = 38), unresponsive wakefulness syndrome (UWS, n = 30) or minimally conscious state (MCS, n = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a 'SON effect'. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients (p = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients (p = 0.013 for comparison between groups). Among the 72 survivors' patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome.DiscussionAbout 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome.

Project description:BackgroundTranscranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation, which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared with other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of transcranial random noise stimulation.MethodsDepressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham transcranial random noise stimulation over 4 weeks in a double-blinded, parallel group randomized-controlled trial. Transcranial random noise stimulation was delivered for 30 minutes with a direct current offset of 2 mA and a random noise range of 2 mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale. Neuroplasticity, neuropsychological, and safety outcomes were analyzed as secondary measures.ResultsSixty-nine participants were randomized, of which 3 discontinued treatment early, leaving 66 (sham n = 34, active n = 32) for per-protocol analysis. Depression severity scores reduced in both groups (Montgomery-Asperg Depression Rating Scale reduction in sham = 7.0 [95% CI = 5.0-8.9]; and active = 5.2 [95% CI = 3.2-7.3]). However, there were no differences between active and sham groups in the reduction of depressive symptoms or the number of participants meeting response (sham = 14.7%; active = 3.1%) and remission criteria (sham = 5.9%; active = 0%). Erythema, paresthesia, fatigue, and dizziness/light-headedness occurred more frequently in the active transcranial random noise stimulation group. Neuroplasticity, neuropsychological, and acute cognitive effects were comparable between groups.ConclusionOur results do not support the use of transcranial random noise stimulation with the current stimulation parameters as a therapeutic intervention for the treatment of depression.Clinical trial registration at clinicaltrialsgov/NCT01792414.

Project description:BackgroundDual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors.MethodsWe conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2-4?weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2?mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS.ResultsStroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in ?-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS.ConclusionsTask-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related ?-activity.

Dataset Information

Transcranial Random Noise Stimulation Does Not Improve Behavioral and Neurophysiological Measures in Patients with Subacute Vegetative-Unresponsive Wakefulness State (VS-UWS).

Publications

Transcranial Random Noise Stimulation Does Not Improve Behavioral and Neurophysiological Measures in Patients with Subacute Vegetative-Unresponsive Wakefulness State (VS-UWS).

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