The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) represents an increasingly popular tool to non-invasively probe cortical excitability in humans. TMSevoked brain potentials (TEPs) are composed of successive components re ecting the propagation of activity from the site of stimulation, thereby providing information on the state of brain networks.However, TMS also generates peripherally evoked sensory activity which contributes to TEP waveforms and hinders their interpretation.In the present study, we examined whether topographic analysis of TEPs elicited by stimulation of two distinct cortical targets can disentangle confounding signals from the genuine TMS-evoked cortical response. In 20 healthy subjects, TEPs were evoked by stimulation of the left primary motor cortex (M1) and the left angular gyrus (AG). Topographic dissimilarity analysis and microstate analysis were used to identify target-speci c TEP components. Furthermore, we explored the contribution of cortico-spinal activation by comparing TEPs elicited by stimulation below and above the threshold to evoke motor responses.We observed topographic dissimilarity between M1 and AG TEPs until approximately 80 ms poststimulus and identi ed early TEP components that likely re ect speci c TMS-evoked activity. Later components peaking at 100 and 180 ms were similar in both datasets and attributed to sensory-evoked activity. Analysis of sub-and supra-threshold M1 TEPs revealed a component at 17 ms that possibly re ects the cortico-spinal output of the stimulated area. Moreover, supra-threshold M1 activation in uenced the topography of almost all later components. Together, our results demonstrate the utility of topographic analysis for the evaluation and interpretation of TMS-evoked EEG responses.

Background Opioid analgesics remain widely used for pain treatment despite the related serious side effects. Some of those, such as opioid tolerance and opioid-induced hyperalgesia may be at least partially due to modulation of opioid receptors (OR) function at nociceptive synapses in the spinal cord dorsal horn. It was suggested that increased release of different chemokines under pathological conditions may play a role in this process. The goal of this study was to investigate the crosstalk between the µOR, transient receptor potential vanilloid 1 (TRPV1) receptor and C–C motif ligand 2 (CCL2) chemokine and the involvement of spinal microglia in the modulation of opioid analgesia. Methods Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) and dorsal root evoked currents (eEPSC) in spinal cord slices superficial dorsal horn neurons were used to evaluate the effect of µOR agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), CCL2, TRPV1 antagonist SB366791 and minocycline. Paw withdrawal test to thermal stimuli was combined with intrathecal (i.t.) delivery of CCL2 and DAMGO to investigate the modulation in vivo. Results Application of DAMGO induced a rapid decrease of mEPSC frequency and eEPSC amplitude, followed by a delayed increase of the eESPC amplitude, which was prevented by SB366791. Chemokine CCL2 treatment significantly diminished all the DAMGO-induced changes. Minocycline treatment prevented the CCL2 effects on the DAMGO-induced eEPSC depression, while mEPSC changes were unaffected. In behavioral experiments, i.t. injection of CCL2 completely blocked DAMGO-induced thermal hypoalgesia and intraperitoneal pre-treatment with minocycline prevented the CCL2 effect. Conclusions Our results indicate that opioid-induced inhibition of the excitatory synaptic transmission could be severely attenuated by increased CCL2 levels most likely through a microglia activation-dependent mechanism. Delayed potentiation of neurotransmission after µOR activation is dependent on TRPV1 receptors activation. Targeting CCL2 and its receptors and TRPV1 receptors in combination with opioid therapy could significantly improve the analgesic properties of opioids, especially during pathological states.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) represents an increasingly popular tool to non-invasively probe cortical excitability in humans. TMS-evoked brain potentials (TEPs) are composed of successive components reflecting the propagation of activity from the site of stimulation, thereby providing information on the state of brain networks. However, TMS also generates peripherally evoked sensory activity which contributes to TEP waveforms and hinders their interpretation. In the present study, we examined whether topographic analysis of TEPs elicited by stimulation of two distinct cortical targets can disentangle confounding signals from the genuine TMS-evoked cortical response. In 20 healthy subjects, TEPs were evoked by stimulation of the left primary motor cortex (M1) and the left angular gyrus (AG). Topographic dissimilarity analysis and microstate analysis were used to identify target-specific TEP components. Furthermore, we explored the contribution of cortico-spinal activation by comparing TEPs elicited by stimulation below and above the threshold to evoke motor responses. We observed topographic dissimilarity between M1 and AG TEPs until approximately 80 ms post-stimulus and identified early TEP components that likely reflect specific TMS-evoked activity. Later components peaking at 100 and 180 ms were similar in both datasets and attributed to sensory-evoked activity. Analysis of sub- and supra-threshold M1 TEPs revealed a component at 17 ms that possibly reflects the cortico-spinal output of the stimulated area. Moreover, supra-threshold M1 activation influenced the topography of almost all later components. Together, our results demonstrate the utility of topographic analysis for the evaluation and interpretation of TMS-evoked EEG responses.

Orienting attention in the space around us is a fundamental prerequisite for willed actions. On Earth, at 1 g, orienting attention requires the integration of vestibular signals and vision, although the specific vestibular contribution to voluntary and automatic components of visuospatial attention remains largely unknown. Here, we show that unweighting of the otolith organ in zero gravity during parabolic flight, selectively enhances stimulus-driven capture of automatic visuospatial attention, while weakening voluntary maintenance of covert attention. These findings, besides advancing our comprehension of the basic influence of the vestibular function on voluntary and automatic components of visuospatial attention, may have operational implications for the identification of effective countermeasures to be applied in forthcoming human deep space exploration and habitation, and on Earth, for patients’ rehabilitation.