Michela Campolo

Pain treatment using tDCS in a single patient: tele-medicine approach in non-invasive brain simulation.

Chronic pain often shows insufficient response to pharmacological treatments. Non-invasive brain stimulation (NIBS) of the motor cortex has been proposed as an alternative therapeutic approach [1]. Repetitive transcranial magnetic stimulation (rTMS) is a NIBS technique that could be used as a preoperative tool to predict the outcome of invasive motor cortex stimulation and could also serve as a therapeutic procedure in itself to treat pain disorders. This therapeutic procedure requires repeated rTMS sessions to be performed as well as a maintenance protocol [2]. RTMS devices used for pain treatment are not portable, so for the maintenance protocol the patients need to go to a specialized Hospital with available rTMS devices (and expertise). This is a potential limitation for the widespread use of rTMS in pain treatment. Other studies have also demonstrated the efficacy of transcranial direct current stimulation (tDCS) in relieving chronic pain syndromes [1]. TDCS is a NIBS technique that painlessly delivers electrical current of relatively low intensity through the skull to selected areas of the brain, inducing changes in the excitability of brain neurons and neuronal circuits [3]. The safety profile of tDCS is very high, with very low risk of seizures. Several double-blind studies on tDCS treatment for chronic pain have shown an analgesic effect of anodal tDCS applied over the primary motor cortex, typically with 20 min of stimulation during 5 consecutive days [4e7]. Again, some patients benefit from a maintenance protocol. TDCS devices are portable, which opens the possibility for patients e at least for the maintenance protocol e not to need to go to a specialized Hospital to receive the treatment. Here, we present a case of a patient treated in our Hospital using tDCS with good pain relief after 5 tDCS daily sessions, and with maintenance of the positive analgesic effects for more than one year with a single tDCS session every 7 days. The patient lives very far away from our Hospital and we decided to use modern information technology to start a Tele-NIBS treatment approach (Fig. 1).

tDCS Modulates Motor Imagery-Related BCI Features

Transcranial Direct Current Stimulation (tDCS) induces selective modulation of cortical excitability. This technique, as well as Brain–Computer Interfaces (BCIs), has been proposed as a supporting tool for neurorehabilitation. Here we show evidence that tDCS in SCI patients and control subjects modulates spectral features related to motor-imagery, yielding consistent discrimination. This suggests that tDCS can have beneficial effects for BCI-assisted neurorehabilitation.

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.

Evidence of neurophysiological improvement of early manifestations of small-fiber dysfunction after liver transplantation in a patient with familial amyloid neuropathy

Highlights • Detecting signs of neuropathy helps therapeutic decisions in familial amyloidosis.• Psychophysical thermal testing may be the only test showing damage in small fibers.• Quantitative signs of improvement may remain a few years after liver transplantation.

Clinical utility of contact heat evoked potentials (CHEPs) in a case of mentalis nerve lesion

Highlights • Assessment of lesions presenting with neuropathic pain requires specific techniques.• Brainstem reflexes may not be sufficient to demonstrate a neuropathic lesion.• Reduced size of nociceptive evoked potentials was the only abnormality found in a case of facial pain.

Platform Session – Electromyography: Preconscious and conscious responses to thermoalgesic stimulation in healthy subjects and patients with small fibre polyneuropathy

Introduction Functional evaluation of small fibers is still a challenging task for neurophysiologists. Adelta fibers function may be evaluated by nociceptive evoked potentials but there is no known neurophysiological method to evaluate a potential dysfunction of unmyelinated type C fibers. We have used a quantitative psychophysical method to demonstrate disturbance in pain and temperature assessment in patients with small fiber polyneuropathy (SFPNP). Methods In 16 healthy volunteers and 16 patients with SFPNP, we applied the thermode of a Thermotest (Somedic, Sweden), already heated at either 41, 43 and 45 °C, over the skin of the ventral forearm for the subjects to mark the first preconscious pain sensation, and the later conscious evaluation of the temperature sensation on an electronic VAS system consisting of graded manipulandum lever of 10 cm long. Subjects were warned that the thermode could be either hot, cold or at neutral temperature and instructed to continue marking their sensation during 40 s after the initial sensation. Only the results of heat stimulation are reported here. We measured two aspects: The first initial straight lever displacement, which indicated the reaction to the first sensation, and the degree of adaptation to the thermode temperature during 40 s. Results The initial reaction was larger in healthy subjects than in patients but the maximum level of pain was not different between healthy subjects and patients. Adaptation was present in all temperatures in healthy subjects, with a decrease of the sensation of more than 20% of the maximum level at 20 s. In contrast, patients expressed significantly less adaptation at all temperatures, with only 12% ± 5% decrease at 40 s. Conclusion Patients with SFPNP have reduced initial sensation and late adaptation to constant temperature stimuli. Our results show a quantitative novel method for the assessment of functions of temperature and pain fibers.

Occipital tACS bursts during a visual task impact ongoing neural oscillation power, coherence and LZW complexity

Little is known about the precise neural mechanisms by which tACS affects the human cortex. Current hypothesis suggest that transcranial current stimulation (tCS) can directly enhance ongoing brain oscillations and induce long - lasting effects through the activation of synaptic plasticity mechanisms [1]. Entrainment has been demonstrated in in - vitro studies, but its presence in non-invasive human studies is still under debate [2,3]. Here, we aim to investigate the immediate and short-term effects of tACS bursts on the occipital cortex of participants engaged in a change – of - speed detection task, a task that has previously reported to have a clear physiology - behavior relationship, where trials with faster responses also have increased power in γ - oscillations (50 - 80 Hz) [4]. The dominant brain oscillations related to the visual task are modulated using multichannel tACS at 10 and 70 Hz within occipital cortex. We found that tACS stimulation at 10 Hz (tACS 10) enhanced both α (8 - 13 Hz) and γ oscillations, in hand with an increase in reaction time (RT) in the change – of - speed detection visual task. On the other hand, tACS at 70Hz desynchronized visual cortices, impairing both phase - locked and endogenous γ - power while increasing RT. While both tACS protocols seem to revert the relationship reported in [4], we argue that tACS produces a shift in attentional resources within visual cortex while leaving unaltered the resources required to conduct the task. This theory is supported by the fact that the correlation between fast RT and high γ- power trials is maintained for tACS sessions too. Finally, we measured cortical excitability by analyzing Event – Related - Potentials (ERP) Lempel – Ziv - Welch Complexity (LZW). In control sessions we observe that lower γ - LZW complexity correlates to faster reaction times. Both metrics are altered by tACS stimulation, as tACS 10 decreased amplitude of the P300 peak, while increasing γ- LZW complexity. To this end, our study highlights the nonlinear cross - frequency interaction between exogenous stimulation and endogenous brain dynamics, and proposes the use of complexity metrics, as LZW, to characterize excitability patterns of cortical areas in a behaviorally relevant timescale. These insights will hopefully contribute to the design of adaptive and personalized tACS protocols where cortical excitability can be characterized through complexity metrics. Additional Title Page Footnotes: We introduce a bursting tACS protocol to study semi-concurrent tACS effects in the visual system and their impact on behavior as measured by reaction time. Burst 10 Hz tACS (tACS10) applied to the visual cortex entrained γ-oscillations and increased RTs in a change-of-speed detection visual task more than 70 Hz tACS (tACS70) or Control conditions. Burst tACS10 also decreased amplitude of the P300 peak, while increasing α-power and γ-LZW complexity. Physiological and behavioral impact of occipital tACS10 and tACS70 was frequency-specific. tACS70 reduced γ-oscillations after 20min of tACS stimulation. Cognitive task may determine cortical excitation levels as measured by complexity metrics, as lower γ-LZW complexity correlates to faster reaction times.

Capítulo 11 – Efectos de los campos magnéticos estáticos sobre la corteza cerebral

La presente investigacion se realizo en el ambito hospitalario del Hospital Nacional de Paraplejicos donde se desarrollan nuevas tecnicas de diagnostico y tratamiento de enfermedades neurologicas, asi como el estudio de la fisiologia del sistema nervioso central. Las tecnicas de estimulacion cortical han evolucionado y, ademas de ser una herramienta que ayuda a valorar cambios de excitabilidad cortical, son tambien capaces de inducir cambios de actividad cortical aumentando o disminuyendo su excitabilidad, en funcion de los parametros utilizados, como por ejemplo la intensidad o frecuencia del estimulo. Actualmente, la estimulacion cortical no invasiva se propone como tratamiento paralelo, por ejemplo, a los tratamientos farmacologicos y/o a la rehabilitacion convencional en patologias tales como la depresion, el dolor neuropatico y el ictus Los campos magneticos estaticos se propone como una nueva tecnica de estimulacion cortical no invasiva capaces de modificar procesos fisiologicos del sistema nervioso central tanto en animales como en humanos. No obstante, existen zonas de la corteza cerebral donde nunca antes se ha estudiado el posible efecto de esta nueva estimulacion. La corteza parietal tiene como funcion principal la interpretacion de la informacion sensorial, asi como la asociacion e integracion del esquema corporal y los movimientos, por tanto resulta un area de especial interes para estudiar un posible efecto de los campos magneticos sobre ella. Con la finalidad de caracterizar un posible efecto de los campos magneticos estaticos sobre la corteza parietal desarrollamos un estudio electrifisiologico (con tecnicas de EEG y estimulacion electrica periferica) para evaluar un posible cambio en la frecuencia de los ritmo cerebrales y cambios en la amplitud de los potenciales evocados. Asimismo, se realizara un estudio de sensibilidad somatosensorial para caracterizar el posible efecto a nivel de comportamiento, aumento o disminucion de la sensibilidad.

P641: Tele-medicine approach in non-invasive brain simulation: case report in a pain patient

Objective: To study the effect of transcranial static magnetic field stimulation (tSMS) over the parietal cortex on the size of somatosensory evoked potentials (SEPs) in humans. Methods: SEPs were elicited by electrical stimulation of right median nerve at the wrist before, during and after tSMS (or sham) in 8 healthy subjects. tSMS was applied for 20 min to the left parietal cortex using a neodimium cylindric magnet with a diameter of 6 cm and height of 3 cm. Sham stimulation was obtained by applying for 20 min to the left parietal cortex a steel cylinder with a diameter of 6 cm and height of 3 cm. Results: Amplitudes of N20/P25 and P25/N30 following right median nerve stimulation were significantly modified for at least 10 min after the end of tSMS, whereas P14/N20 were unaffected. There was no effect on SEPs evoked by right median nerve stimulation after sham stimulation. Conclusions: tSMS over the sensorimotor cortex can induce a long-lasting changes in cortical components of SEPs. Significance: tSMS can modulate cortical somatosensory processing in humans.

Selective Enhancement of Motor Imagery Features Using Transcranial Direct Current Stimulation

Transcranial Direct Current Stimulation (tDCS) has been shown to selectively modulate cortical responses in memory, motor and perceptual tasks. Here we show that this type of stimulation results in targeted enhancement of brain patterns elicited during motor-imagery. Offline analysis suggest this may yield higher classification performance. Experiments with healthy subjects (N = 10) and patients with spinal cord injury (N = 9) supports the idea of using tDCS as a facilitator for using brain-computer interfacing (BCI) in the frame of motor rehabilitation.