Margherita Russo

Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients

PURPOSE Disorders of consciousness (DOC) diagnosis relies on the presence or absence of purposeful motor responsiveness, which characterizes the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS), respectively. Functional neuroimaging studies have raised the question of possible residual conscious awareness also in clinically-defined UWS patients. The aim of our study was to identify electrophysiological parameters, by means of a transcranial magnetic stimulation approach, which might potentially express the presence of residual networks sustaining fragmentary behavioral patterns, even when no conscious behavior can be observed. METHODS We enrolled 25 severe DOC patients, following post-anoxic or traumatic brain injury and 20 healthy individuals (HC) as control group. Baseline electrophysiological evaluation evidenced, in comparison to HC, a partial preservation of cortical effective connectivity and excitability in clinically defined MCS, whereas these components were absent in clinically defined UWS. Then, we applied an anodal transcranial direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex. RESULT a-tDCS was able to boost cortical connectivity and excitability in all HC, MCS, and to unmask such excitability/connectivity in some UWS patients. CONCLUSION a-tDCS could be useful in identifying residual connectivity markers in clinically-defined UWS, who may lack of purposeful behavior as a result of a motor-output failure.

A Single Session of Repetitive Transcranial Magnetic Stimulation Over the Dorsolateral Prefrontal Cortex in Patients With Unresponsive Wakefulness Syndrome: Preliminary Results.

Background. The level of consciousness is regulated by the activation of the frontal parietal network since a disruption within this interregional cortical connectivity is associated with a consciousness breakdown. Objective. The primary aim of the present study was to examine the feasibility and the safety of a single session of repetitive transcranial magnetic stimulation (rTMS), delivered over the dorsolateral prefrontal cortex (DLPFC), in patients with unresponsive wakefulness syndrome (UWS). As a secondary aim, we investigated the efficacy of rTMS over DLPFC on cortico-cortical connectivity as tested with paired-pulse and dual-coil TMS techniques. Methods. We enrolled 10 healthy and 10 postanoxic UWS subjects. After clinical assessment, subjects underwent a single/paired pulse TMS paradigm evaluating the inhibitory and facilitatory intracortical circuits. In addition, several interregional interactions between primary motor, dorsal and ventral premotor, supplementary motor, and posterior parietal cortex areas were investigated by means of dual-coil TMS technique. These parameters were evaluated at baseline, immediately after, and 60 minutes after a protocol of 10-Hz rTMS delivered at the level of the DLPFC. Results. rTMS over DLPFC did not cause any adverse events. We showed that rTMS over DLPFC did not induce, at group level, any clinical improvement or intra-/intercortical connectivity changes. Interestingly, in 3 patients rTMS induced a significant, although transient, clinical improvement associated with a short-lasting reshaping of brain connectivity. Conclusions. We demonstrated that a single session of 10-Hz rTMS over the right DLPFC may transiently improve consciousness and partially restore the connectivity within several cortical areas in some patients with UWS.

Cortical connectivity modulation induced by cerebellar oscillatory transcranial direct current stimulation in patients with chronic disorders of consciousness: A marker of covert cognition?

OBJECTIVE Although some patients suffering from unresponsive wakefulness syndrome (UWS) may retain some capacity for covert cognition, it is difficult to directly demonstrate this property by means of tasks needing patient active cooperation and preserved top-down attention processes. Instead, specific passive paradigms may allow identifying a residual θ and γ band functional connectivity within fronto-parietal networks (FPN), which may sustain covert cognitive processes. METHODS We attempted to highlight such networks in a sample of minimally conscious state (MCS) and UWS patients by means of a cerebellar 5 Hz oscillatory transcranial direct current stimulation (otDCS), in order to modulate the FPN functional connectivity. RESULTS We found a FPN θ and γ power modulation and coherence increase, which were paralleled by a transient coma recovery scale-revised score amelioration, only in MCS individuals. CONCLUSIONS Our data show a functional link between the FPN coherent θ and γ oscillations and the cerebellar-cerebral output. Moreover, our data highlighted a residual FPN functional connectivity, which is a fundamental prerequisite for objectifying every aware processes and the potential to cognitive processes (covert cognition). SIGNIFICANCE Our otDCS cerebellar-cerebral connectivity modulation may be a useful approach in improving chronic disorders of consciousness differential diagnosis and ameliorating the level of consciousness.

Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis

OBJECTIVE The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. SETTING Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. SUBJECTS AND METHODS We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. RESULTS One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. CONCLUSIONS Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.

Switched capacitor arrays analog memory for sparse data sampling

Abstract We present the design and the test performed on ADeLinel, a Full-Custom Analog Memory for sparse data sampling. It has been designed as an array of switched capacitors. It is only one channel of 8 cells. The control part of the ADeLine chip is custom designed for the size reduction, high speed performance and low power dissipation. The memory has been integrated in double poly, double metal AMS 0.8 μm CMOS. It has 3.5 V input and output swings, a linearity within ± 6 mV in a 2 V range and 11 bits of resolution.

Who May Benefit From Armeo Power Treatment? A Neurophysiological Approach to Predict Neurorehabilitation Outcomes

The Armeo Power, a rehabilitation exoskeleton that allows early treatment of motor disabilities, provides intelligent arm support in a large 3‐dimensional work space, thus enabling patients to perform intensive, repetitive, and goal‐oriented exercises. This device could efficiently induce new connections and facilitate plasticity phenomena potentiation. Knowledge of the potential brain plasticity reservoir after brain damage constitutes a prerequisite for an optimal rehabilitation strategy.

Constrained Spherical Deconvolution Tractography Reveals Cerebello-Mammillary Connections in Humans.

According to the classical view, the cerebellum has long been confined to motor control physiology; however, it has now become evident that it exerts several non-somatic features other than the coordination of movement and is engaged also in the regulation of cognition and emotion. In a previous diffusion-weighted imaging-constrained spherical deconvolution (CSD) tractography study, we demonstrated the existence of a direct cerebellum-hippocampal pathway, thus reinforcing the hypothesis of the cerebellar role in non-motor domains. However, our understanding of limbic-cerebellar interconnectivity in humans is rather sparse, primarily due to the intrinsic limitation in the acquisition of in vivo tracing. Here, we provided tractographic evidences of connectivity patterns between the cerebellum and mammillary bodies by using whole-brain CSD tractography in 13 healthy subjects. We found both ipsilateral and contralateral connections between the mammillary bodies, cerebellar cortex, and dentate nucleus, in line with previous studies performed in rodents and primates. These pathways could improve our understanding of cerebellar role in several autonomic functions, visuospatial orientation, and memory and may shed new light on neurodegenerative diseases in which clinically relevant impairments in navigational skills or memory may become manifest at early stages.

Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand

Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand.

Non-invasive brain stimulation, a tool to revert maladaptive plasticity in neuropathic pain

Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of maladaptive plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions.