Bilateral Representation of Sensorimotor Responses in Benign Adult Familial Myoclonus Epilepsy: An MEG Study

Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30–50 ms and 30–100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus.

Epidural unilateral stimulation with “Adaptive Stim” option in treatment of type II CRPS

CRPS is a type of severe pain syndrome and can be triggered by previous surgery or trauma. CRPS type II is associated with a confirmed nerve injury. We want to present to your attention a case report of successful treatment of CRPS type II using unilateral epidural stimulation.

Current-dependent Ocular Tilt Reaction in STN-DBS: evidence for a putative incerto-interstitial pathway?

Objective: To report a patient with Parkinson’s disease presenting with a combined vestibular, oculomotor and postural syndrome dependent of deep brain stimulation (DBS) of the subthalamic nucleus. Methods: In a systematic monopolar review, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fiber tracts were segmented on MRI using both individual and normative structural and connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. Results: Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and subsequently body retropulsion could be elicited, consistent with an irritative effect on the Interstitial Nucleus of Cajal (INC). Symptom-associated VTA was found to overlap with the dorsal zona incerta (dZI) and the lateral ipsilateral vestibulothalamic tract (IVTT), while lying in close proximity to the medial IVTT and rather distant to the INC proper. As described in non-human primates, a ZI-to-INC, “incerto-interstitial” tract (IIT) with contact to the medial-uppermost portion of the VTA could be traced. By ways of directional current steering laterally to both tracts, therapeutic response could be preserved while vestibular side effects were minimized. Conclusion: Unilateral stimulation of mesencephalic vestibular-related circuitry induces an ipsilateral vestibular, oculomotor and postural roll-plane syndrome, which converts into a combined pitch-plane syndrome, when functional activation expands to the bilateral INC. The phenomenology of the roll-plane syndrome in this patient points to an activation of INC neurons by DBS, hypothetically via a potentially aberrant incerto-interstitial pathway. Directional current steering proved useful in managing this rare side effect.

The effects of direct current stimulation and random noise stimulation on attention networks

Attention is a complex cognitive process that selects specific stimuli for further processing. Previous research suggested the existence of three attentional networks: alerting, orienting and executive. However, one important topic is how to enhance the efficiency of attentional networks. In this context, understanding how this system behaves under two different modulatory conditions, namely transcranial direct current stimulation (tDCS) and transcranial Random Noise Stimulation (tRNS), will provide important insights towards the understanding of the attention network system. Twenty-seven healthy students took part on a randomized single-blinded crossover study, testing the effects that involved three modalities of unilateral stimulation (tRNS, anodal tDCS, and sham) over the DLPFC, during the performance of the attention network test (ANT) in three different conditions: standard, speed and accuracy. Results showed that tRNS was able to increase attention during more complex situations, namely by increasing alerting and decreasing conflict effect in the executive network. Under the Speed condition, tRNS increased efficiency of the alerting network, as well as under the more demanding conflict network, tRNS overall increased the performance when comparing to sham. No statistical significant effects of tDCS were observed. These results are compatible with the attention requiring the synchronization of pre-existing networks, rather the reinforcement or creation of new pathways.

Examinations of Bilateral Epileptiform Activities in Hippocampal Slices Obtained From Young Mice

Bilateral interconnections through the hippocampal commissure play important roles in synchronizing or spreading hippocampal seizure activities. Intact hippocampi or bilateral hippocampal slices have been isolated from neonatal or immature rats (6–7 or 12–21 days old, respectively) and the mechanisms underlying the bilateral synchrony of hippocampal epileptiform activities have been investigated. However, the feasibility of examining bilateral epileptiform activities of more developed hippocampal circuitry in vitro remains to be explored. For this, we prepared bilateral hippocampal slices from C57 black mice, a strain commonly used in neuroscience and for genetic/molecular modifications. Young mice (21–24-day-old) were used in most experiments. A 600-μm-thick slice was obtained from each mouse by horizontal vibratome sectioning. Bilateral dorsal hippocampal and connecting dorsal hippocampal commissure (DHC) tissues were preserved in the slice and extrahippocampal tissues were removed. Slices were recorded in a submerged chamber mainly at a room temperature (21–22°C). Bilateral CA3 areas were monitored by extracellular recordings, and unilateral electrical stimulation was used to elicit CA3 synaptic field potentials. The unilateral stimulation could elicit population spikes in the contralateral CA3 area. These contralateral spikes were attenuated by inhibiting synaptic transmission with cobalt-containing medium and were abolished when a cut was made at the DHC. Self-sustained and bilaterally correlated epileptiform potentials were observed following application of 4-aminopyradine and became independent after the DHC cut. Bilateral hippocampal activities were detectable in some slices of adult mice and/or at 35–36°C, but with smaller amplitudes and variable waveforms compared to those observed from slices of young mice and at the room temperature. Together, these observations suggested that examining bilateral epileptiform activities in hippocampal slices of young mice is feasible. The weaknesses and limitations of this preparation and our experimentation are discussed.

The Effect of Unilateral and Bilateral Electrical Stimulation of the Brain on Improving the Balance of the Elderly

Objectives: This study aimed to investigate the effect of unilateral and bilateral electrical stimulation of the brain on balance in the elderly. Methods & Materials: Thirty-six elderly in Ilam City, Iran, participated in the study. In the pretest, the static balance was taken, and then the participants were randomly divided into three groups: unilateral brain stimulation, bilateral brain stimulation, and sham. The intervention took in 3 sessions. In the unilateral stimulation group, the anode electrode was positioned at the O point, and the cathode was above the left ophthalmic cavity (FP1). In the bilateral stimulation group, the anode electrode was positioned at O1, and the cathode was positioned at O2. The intensity of stimulation was 2 mA, and the duration of treatment was 15 minutes per session. In the control group, the anode and cathode electrodes were placed on the O and FP1 points, respectively, but the excitation current was stopped after 30 seconds. After the last training session, the posttest was performed. The obtained data were analyzed using 1-way ANOVA. Results: The Results showed no statistically significant difference between the three groups in the pretest phase (P<0.535). But at posttest, there was a difference between groups (P<0.002). Post-hoc test Results showed a difference between unilateral stimulation with the control group (P=0.001) and bilateral stimulation with the control group (P=0.005). But there was no significant difference between the unilateral stimulation group and the bilateral stimulation group (P=0.599). Conclusion: Unilaterally and bilaterally, cerebellar stimulation can be improved in the elderly.

When Left Is One and Right Is Double: An Experimental Investigation of Visual Allesthesia after Right Parietal Damage

Illusory visual phenomena, such as palinopsia, polyopsia or allesthesia, are rare manifestations of posterior cortical damage. Symptoms are characterized by illusory perceptions, ranging from isolated stationary objects to scenes and moving persons. Such illusions may appear while the original object is still in view, or become manifest with a delay and last for minutes, hours or even days. Some authors have suggested a disinhibited cortical response underlying visual illusions, but experimental studies supporting this hypothesis are lacking. Here, we examined a rare patient who after focal right parietal injury consistently reported a second stimulus on the left when briefly shown a target in his right hemifield. The patient perceived the illusory stimulus as less intense, and therefore concluded that it must have a different shape than the original stimulus. A masking experiment revealed that the frequency of the illusion was inversely related to the visibility of the original stimulus, suggesting that it depended on early, feedforward visual processing. We propose that illusory perceptions reflect the interplay of two physiological processes: a fast and automatic activation of contralateral, homotopic visual cortex after unilateral stimulation, and the lack of top-down inhibition following damage to the posterior parietal cortex.

The Effects of Deep Brain Stimulation on Speech Intelligibility in Persons With Essential Tremor

Purpose The aim of this study was to investigate how deep brain stimulation (DBS) of the caudal zona incerta (cZi) affects speech intelligibility in persons with essential tremor. Method Thirty-five participants were evaluated: off stimulation, on chronic stimulation optimized to alleviate tremor, and during unilateral stimulation at increasing amplitude levels. At each stimulation condition, the participants read 10 unique nonsense sentences from the Swedish Test of Intelligibility. Two listeners, blinded to stimulation condition, transcribed all recorded sentences orthographically in a randomized procedure. A mean speech intelligibility score for each patient and stimulation condition was computed, and comparisons were made between scores off and on stimulation. Results Chronic cZi-DBS had no significant effect on speech intelligibility, and there was no difference in outcome between bilateral and unilateral treatments. During unilateral stimulation at increasing amplitudes, nine participants demonstrated deteriorating speech intelligibility. These nine participants were on average older and had more superior contacts activated during the evaluation compared with the participants without deterioration. Conclusions Chronic cZi-DBS, optimized for tremor suppression, does not generally affect speech intelligibility in persons with essential tremor. Furthermore, speech intelligibility may be preserved in many individuals, even when stimulated at high amplitudes. Adverse effects of high-amplitude unilateral stimulation observed in this study were associated with stimulation originating from a more superior location, as well as with the participants' age. These results, highlighting age and stimulation location as contributing to speech intelligibility outcomes, were, however, based on a limited number of individuals experiencing adverse effects with high-amplitude stimulation and should, therefore, be interpreted with caution.