scholarly journals Distinct neocortical mechanisms underlie human SI responses to median nerve and laser evoked peripheral activation

2021 ◽  
Author(s):  
Ryan V. Thorpe ◽  
Christopher J. Black ◽  
David A. Borton ◽  
Li Hu ◽  
Carl Y. Saab ◽  
...  

AbstractMagneto- and/or electro-encephalography (M/EEG) are non-invasive clinically-relevant tools that have long been used to measure electromagnetic fields in somatosensory cortex evoked by non-painful and painful somatosensory stimuli. Two commonly applied stimulation paradigms that produce distinct responses in primary somatosensory cortex (SI) linked to non-painful and painful sensations are electrical median nerve (MN) stimulation and cutaneous laser-evoked (LE) stimulation to the dorsum of the hand, respectively. Despite their prevalence, the physiological mechanisms that produce stereotypic macroscale MN and LE responses have yet to be fully articulated, limiting their utility in understanding brain dynamics associated with non-painful or painful somatosensation. We examined the neocortical circuit mechanisms contributing to MN and LE responses in SI using the Human Neocortical Neurosolver (HNN) neural modeling software tool. HNN was specifically designed for biophysically principled interpretation of the cell and circuit origin of M/EEG signals (Neymotin et al., 2020). Detailed analysis of the timing and orientation of peaks in source localized SI current dipole responses from MN and laser-evoked (LE) stimulation showed that these features were robust and conserved across prior studies. The first peak in the MN response at ∼20 ms corresponds to outward-directed deep-to-superficial electrical current flow through the cortical laminae, while the initial LE response occurs later at ∼170 ms and is oriented in the opposite direction. Historically, these peaks have both been labeled N20 and N1, despite their opposite current orientations. Simulating the cellular and circuit-level mechanisms accounting for these and later peaks with HNN’s detailed laminar neocortical column model revealed that the MN response can be simulated with a sequence of layer-specific exogenous excitatory feedforward and feedback synaptic drive. This sequence was similar to that previously reported for tactile evoked responses (Jones et al., 2007; Neymotin et al., 2020), with the novel discovery of an early excitatory feedback input to superficial layers at ∼30 ms post-stimulus that facilitated generation of the MN response’s first prominent inward-oriented deflection, known historically as the P30. Simulations of the LE response revealed that the initial ∼170 ms inward-deflection required a burst of repetitive gamma-frequency (∼40 Hz) excitatory supragranular feedback drives, consistent with prior reports of LE gamma-frequency activity. These results make novel and detailed multiscale predictions about the dynamic laminar circuit mechanisms underlying temporal and spectral features of MN and LE responses in SI, and can guide further investigations in follow-up studies. Ultimately, these findings may help with the development of targeted therapeutics for pathological somatosensation, such as chronic and neuropathic pain.

1989 ◽  
Vol 62 (3) ◽  
pp. 711-722 ◽  
Author(s):  
T. Allison ◽  
G. McCarthy ◽  
C. C. Wood ◽  
P. D. Williamson ◽  
D. D. Spencer

1. The anatomic generators of human median nerve somatosensory evoked potentials (SEPs) in the 40 to 250-ms latency range were investigated in 54 patients by means of cortical-surface and transcortical recordings obtained during neurosurgery. 2. Contralateral stimulation evoked three groups of SEPs recorded from the hand representation area of sensorimotor cortex: P45-N80-P180, recorded anterior to the central sulcus (CS) and maximal on the precentral gyrus; N45-P80-N180, recorded posterior to the CS and maximal on the postcentral gyrus; and P50-N90-P190, recorded near and on either side of the CS. 3. P45-N80-P180 inverted in polarity to N45-P80-N180 across the CS but was similar in polarity from the cortical surface and white matter in transcortical recordings. These spatial distributions were similar to those of the short-latency P20-N30 and N20-P30 potentials described in the preceding paper, suggesting that these long-latency potentials are generated in area 3b of somatosensory cortex. 4. P50-N90-P190 was largest over the anterior one-half of somatosensory cortex and did not show polarity inversion across the CS. This spatial distribution was similar to that of the short-latency P25-N35 potentials described in the preceding paper and, together with our and Goldring et al. 1970; Stohr and Goldring 1969 transcortical recordings, suggest that these long-latency potentials are generated in area 1 of somatosensory cortex. 5. SEPs of apparently local origin were recorded from several regions of sensorimotor cortex to stimulation of the ipsilateral median nerve. Surface and transcortical recordings suggest that the ipsilateral potentials are generated not in area 3b, but rather in other regions of sensorimotor cortex perhaps including areas 4, 1, 2, and 7. This spatial distribution suggests that the ipsilateral potentials are generated by transcallosal input from the contralateral hemisphere. 6. Recordings from the periSylvian region were characterized by P100 and N100, recorded above and below the Sylvian sulcus (SS) respectively. This distribution suggests a tangential generator located in the upper wall of the SS in the second somatosensory area (SII). In addition, N125 and P200, recorded near and on either side of the SS, suggest a radial generator in a portion of SII located in surface cortex above the SS. 7. In comparison with the short-latency SEPs described in the preceding paper, the long-latency potentials were more variable and were more affected by intraoperative conditions.


2010 ◽  
Vol 96 (19) ◽  
pp. 193109 ◽  
Author(s):  
Shin-ichi Amma ◽  
Yuki Tokumoto ◽  
Keiichi Edagawa ◽  
Naoya Shibata ◽  
Teruyasu Mizoguchi ◽  
...  

2014 ◽  
Vol 10 (1) ◽  
pp. 92-93 ◽  
Author(s):  
Bernardo Dell’Osso ◽  
A. Carlo Altamura

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that, by means of magnetic fields and low intensity electrical current, respectively, aim to interefere with and modulate cortical excitability, at the level of dorsolateral prefrontal cortex, in patients with major depression and poor response to standard antidepressants. While the clinical efficacy of TMS in major depression has been extensively investigated over the last 10 years, tDCS has attracted research interest only in the last years, with fewer randomized clinical trials (RCTs) in the field. Nevertheless, in spite of the different rationale and mechanism of action of the two techniques, tDCS recent acquisitions, in relation to the treatment of major depression, seem to parallel those previously obtained with TMS, in terms of treatment duration to achieve optimal benefit and patient's history of drug-resistance. After briefly introducing the two techniques, the article examines possible common pathways of clinical use for TMS and tDCS, emerging from recent RCTs and likely orienting future investigation with non invasive brain stimulation for the treatment of major depression.


2005 ◽  
Vol 863 ◽  
Author(s):  
C. L. Gan ◽  
C. Y. Lee ◽  
C. K. Cheng ◽  
J. Gambino

AbstractThe reliability of Cu M1-V1-M2-V2-M3 interconnects with SiN and CoWP cap layers was investigated. Similar to previously reported results, the reliability of CoWP capped structures is much better than identical SiN capped structures. However, it was also observed that the reliability of CoWP capped interconnects was independent of the direction of electrical current flow. This phenomenon is different from what was observed for SiN capped structures, where M2 lines with electron current flow in the upstream configuration (“via-below”) have about three times larger median-time-to-failure than identical lines in the downstream configuration (“viaabove”). This is because the Cu/SiN interface is the preferential void nucleation site and provides the fastest diffusion pathway in such an architecture. Failure analysis has shown that fatal partially-spanned voids usually had formed directly below the via for “via-above” configuration, and fully-spanned voids occurred in the lines above the vias for “via-below” configuration.On the other hand, failure analysis for CoWP-coated Cu structures showed that partiallyspanned voids below the via do not cause fatal failures in the downstream configuration. This is because the CoWP layer is conducting, and thus able to shunt current around the void. As a result, a large fully-spanning void is required to cause a failure, just like the upstream configuration. Thus the lifetime of an interconnect with a conducting cap layer is independent of whether the current is flowing upstream or downstream.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carolina Reis ◽  
Beatriz S. Arruda ◽  
Alek Pogosyan ◽  
Peter Brown ◽  
Hayriye Cagnan

AbstractEssential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. Patients are usually treated using medications which have limited effects on tremor and may cause side-effects. Surgical therapies are effective in reducing essential tremor, however, the invasive nature of these therapies together with the high cost, greatly limit the number of patients benefiting from them. Non-invasive therapies have gained increasing traction to meet this clinical need. Here, we test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Peripheral stimulation induced a subtle but significant modulation in five out of nine patients—this modulation consisted mainly of amplification rather than suppression of tremor amplitude. Modulatory effects of stimulation were more pronounced when patient’s tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects. This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation.


2011 ◽  
Vol 2 ◽  
pp. 727-733 ◽  
Author(s):  
Tchavdar N Todorov ◽  
Daniel Dundas ◽  
Anthony T Paxton ◽  
Andrew P Horsfield

We give a physical interpretation of the recently demonstrated nonconservative nature of interatomic forces in current-carrying nanostructures. We start from the analytical expression for the curl of these forces, and evaluate it for a point defect in a current-carrying system. We obtain a general definition of the capacity of electrical current flow to exert a nonconservative force, and thus do net work around closed paths, by a formal noninvasive test procedure. Second, we show that the gain in atomic kinetic energy over time, generated by nonconservative current-induced forces, is equivalent to the uncompensated stimulated emission of directional phonons. This connection with electron–phonon interactions quantifies explicitly the intuitive notion that nonconservative forces work by angular momentum transfer.


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