A Retrospective Study on tDCS Treatment in Patients with Drug-Resistant Chronic Pain.

Background. Transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has an analgesic effect superior to a placebo in chronic pain. Some years ago, tDCS was implemented at the Hospital Nacional of Paraplegics (Toledo, Spain) to treat patients with pharmacological resistance to chronic pain. Objective. The main objectives of this study with tDCS were (1) to confirm the safety of one-year treatment; (2) to estimate the number of patients after one year in treatment; (3) to describe the effects of tDCS on the pain intensity during one-year treatment; and (4) to identify factors related to treatment success. Methods. This was a retrospective study conducted at the National Hospital for Paraplegics with 155 patients with pharmacologically resistant chronic pain. Anodal tDCS was applied over the M1 for 20 min at 1.5 mA for 10 treatment sessions from Monday to Friday (Induction phase), followed by 2-3 sessions per month (Maintenance phase). Pain intensity was assessed using a Visual Analogue Scale (VAS). Results. Anodal tDCS on M1 confirmed the reduction in the pain intensity. Moreover, 58% of outpatients completed one year of treatment. Only the VAS values obtained during the baseline influenced the response to treatment. Patients with a very high VAS at the baseline were more likely to not respond adequately to tDCS treatment. Conclusions. Anodal tDCS over M1 is an adequate therapy (safe and efficient) to treat drug-resistant chronic pain. Moreover, pain intensity at the start of treatment could be a predictor of patients' continuity with tDCS for at least one year.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans.

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone treatment in incomplete chronic traumatic spinal cord injury.

STUDY DESIGN: This is a double blind phase II/III placebo-controlled randomized trial of the safety and efficacy of GH treatment in incomplete chronic traumatic spinal cord injury. OBJECTIVE: The aim of this study was to investigate the possibility to use exogenous GH administration for motor recovery in chronic traumatic incomplete human SCI. The objectives were to establish safety and efficacy of a combined treatment of subcutaneous GH (or placebo) and rehabilitation in this population. SETTING: Hospital Nacional de Parapléjicos METHODS: The pharmacological treatment was a subcutaneous daily dose of growth hormone (GH, Genotonorm 0.4 mg, Pfizer Pharmaceuticals) or placebo for one year. The pharmacological treatment was performed, during the first six months under hospitalization and supervised rehabilitation. RESULTS: The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo increases the ISNCSCI motor score. On the other hand, the motor-score increment was marginal (after one-year combined treatment, the mean increment of the motor-score was around 2.5 points). Moreover, we found that intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals (measured using SCIM III and WISCI II). CONCLUSIONS: It is important to highlight that our aim was to propose GH as a possible treatment to improve motor functions in incomplete SCI individuals. At least with the doses we used, we think that the therapeutic effects of this approach are not clinically relevant in most subjects with SCI.

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability.

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons.

Static Magnetic Field Stimulation over Parietal Cortex Enhances Somatosensory Detection in Humans.

The role of neuronal oscillations in human somatosensory perception is currently unclear. To address this, here we use noninvasive brain stimulation to artificially modulate cortical network dynamics in the context of neurophysiological and behavioral recordings. We demonstrate that transcranial static magnetic field stimulation (tSMS) over the somatosensory parietal cortex increases oscillatory power specifically in the alpha range, without significantly affecting bottom-up thalamocortical inputs indexed by the early cortical component of somatosensory evoked potentials. Critically, we next show that parietal tSMS enhances the detection of near-threshold somatosensory stimuli. Interestingly, this behavioral improvement reflects a decrease of habituation to somatosensation. Our data therefore provide causal evidence that somatosensory perception depends on parietal alpha activity.SIGNIFICANCE STATEMENT Artificially increasing alpha power by placing a powerful magnetic field over the somatosensory cortex overcomes the natural decline in detection probability of a repeated near-threshold sensory stimulus.

New Insights from Clinical Assessment of Upper Extremities in Cervical Traumatic Spinal Cord Injury.

Upper extremity function has a strong impact on the quality of life in cervical spinal cord-injured patients. Upper extremity function depends on many factors, such as muscle strength, level of lesion, and extension of the cord damage in its axial axis produced by the injury. These variables can be obtained by the International Standards for Neurological Classification of Spinal Cord Injury, which is the standard for the functional evaluation of traumatic spinal cord injury (SCI) patients. The aim of this study was to describe the relationship between upper limb muscle strength, level of injury, and axial damage with the functionality of upper limb measured using the Jebsen-Taylor Hand Function Test (JTHFT) and the 9 Hole Peg Test (9HPT) in cervical SCI. Twenty-nine patients were included in this study. Our results suggest that both the JTHFT and 9HPT can be similarly used to quantify functional impairment after cervical SCI. Moreover, our data suggest that the upper extremity motor score, JTHFT, and 9HPT strongly correlate with the American Spinal Injury Association (ASIA) impairment scale (graded from A to E), but not with the lesion level. Our findings can be of great importance for the clinician or researchers whose therapeutic interventions have as a main objective to improve upper limb functionality in patients with cervical SCI. We suggest that ASIA impairment scale, ASIA motor score, and functional tests (including JTHFT and/or 9HPT) could be used as outcome measures in cervical SCI clinical trials.

Static Magnetic Field Stimulation over the Visual Cortex Increases Alpha Oscillations and Slows Visual Search in Humans.

Transcranial static magnetic field stimulation (tSMS) was recently introduced as a promising tool to modulate human cerebral excitability in a noninvasive and portable way. However, a demonstration that static magnetic fields can influence human brain activity and behavior is currently lacking, despite evidence that static magnetic fields interfere with neuronal function in animals. Here we show that transcranial application of a static magnetic field (120-200 mT at 2-3 cm from the magnet surface) over the human occiput produces a focal increase in the power of alpha oscillations in underlying cortex. Critically, this neurophysiological effect of tSMS is paralleled by slowed performance in a visual search task, selectively for the most difficult target detection trials. The typical relationship between prestimulus alpha power over posterior cortical areas and reaction time (RT) to targets during tSMS is altered such that tSMS-dependent increases in alpha power are associated with longer RTs for difficult, but not easy, target detection trials. Our results directly demonstrate that a powerful magnet placed on the scalp modulates normal brain activity and induces behavioral changes in humans.