Bilateral T12 Dorsal Root Ganglion Stimulation for the Treatment of Low Back Pain With 20-Hz and 4-Hz Stimulation, a Retrospective Study.

OBJECTIVES: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S. MATERIALS AND METHODS: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation. RESULTS: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation. CONCLUSIONS: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.

The Na/Ca Exchange as a Target for Antitumor Effect of 4Hz Pulsing Magnetic Field.

The correlation between cell hydration and proliferation is one of the controversial subjects in the present cancer research because the detailed mechanism(s) of correlation between these two cell parameters are not evaluated yet. The fact that magnetic fields have antitumor effects and our previous data that the effect of 4 Hz pulsing magnetic field (PMF) is realized by the activation of Cyclic guanosine monophosphate (cGMP)-dependent Na/Ca exchange allow us to suggest that through the study of PMF effects on cell hydration and proliferation in soft tissues of sarcoma-180 tumor-carrying mice compared with those of healthy ones will be possible to evaluate the character of correlation between cell hydration and proliferation in norm and pathology. The daily 30-min PMF (0.2 mT) exposed on tumor-carrying mice has lifetime prolongation, time-dependent depression of tumor growth, decrease of thermal threshold, and lactate concentration in blood. In the initial (6 days) period tumorigenesis PMF leads to dehydration in spleen cells, which is accompanied by the activation of cell proliferation, while in late periods of tumorigenesis it leads to cell hydration accompanied with proliferation. We are suggesting that PMF-induced overhydration and the increase of cell proliferation in cancer tissue as a consequence of high [Ca]i-induced activation of Ca-calmoduline-NO-cGMP pathway leads to the activation of FNa/Ca exchange, while its antitumor effect expressed in initial period of tumorigenesis is due to the activation of cGMP-dependent FNa/Ca, where because of low [Ca]i, it brings to cell dehydration as a result of reactivation of Na/K pump.

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice.

Introduction: Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. Methods: We recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks. Results: Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. Discussion: These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

Cerebellar control of fear learning via the cerebellar nuclei-Multiple pathways, multiple mechanisms?

Fear learning is mediated by a large network of brain structures and the understanding of their roles and interactions is constantly progressing. There is a multitude of anatomical and behavioral evidence on the interconnection of the cerebellar nuclei to other structures in the fear network. Regarding the cerebellar nuclei, we focus on the coupling of the cerebellar fastigial nucleus to the fear network and the relation of the cerebellar dentate nucleus to the ventral tegmental area. Many of the fear network structures that receive direct projections from the cerebellar nuclei are playing a role in fear expression or in fear learning and fear extinction learning. We propose that the cerebellum, via its projections to the limbic system, acts as a modulator of fear learning and extinction learning, using prediction-error signaling and regulation of fear related thalamo-cortical oscillations.

Distributed cell assemblies spanning prefrontal cortex and striatum.

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10 ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony.

Prefrontal-hippocampal coupling by theta rhythm and by 2-5 Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus.

Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4-8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2-5 Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC-HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2-5 Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC-HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2-5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel thalamo-cortical network by which PFC-to-HC coupling occurs via a 2-5 Hz oscillation and is mediated through the nRe.