Red LED photobiomodulation reduces pain hypersensitivity and improves sensorimotor function following mild T10 hemicontusion spinal cord injury.

BACKGROUND: The development of hypersensitivity following spinal cord injury can result in incurable persistent neuropathic pain. Our objective was to examine the effect of red light therapy on the development of hypersensitivity and sensorimotor function, as well as on microglia/macrophage subpopulations following spinal cord injury. METHODS: Wistar rats were treated (or sham treated) daily for 30 min with an LED red (670 nm) light source (35 mW/cm(2)), transcutaneously applied to the dorsal surface, following a mild T10 hemicontusion injury (or sham injury). The development of hypersensitivity was assessed and sensorimotor function established using locomotor recovery and electrophysiology of dorsal column pathways. Immunohistochemistry and TUNEL were performed to examine cellular changes in the spinal cord. RESULTS: We demonstrate that red light penetrates through the entire rat spinal cord and significantly reduces signs of hypersensitivity following a mild T10 hemicontusion spinal cord injury. This is accompanied with improved dorsal column pathway functional integrity and locomotor recovery. The functional improvements were preceded by a significant reduction of dying (TUNEL(+)) cells and activated microglia/macrophages (ED1(+)) in the spinal cord. The remaining activated microglia/macrophages were predominantly of the anti-inflammatory/wound-healing subpopulation (Arginase1(+)ED1(+)) which were expressed early, and up to sevenfold greater than that found in sham-treated animals. CONCLUSIONS: These findings demonstrate that a simple yet inexpensive treatment regime of red light reduces the development of hypersensitivity along with sensorimotor improvements following spinal cord injury and may therefore offer new hope for a currently treatment-resistant pain condition.

Noninvasive transorbital alternating current stimulation improves subjective visual functioning and vision-related quality of life in optic neuropathy.

BACKGROUND: Noninvasive repetitive transorbital alternating current stimulation (rtACS) can improve visual field size in patients with optic nerve damage, but it is not known if this is of subjective relevance. We now assessed patient reported outcomes to determine the association between visual field changes and vision-related quality of life (QoL). METHODS: Patients having visual field impairments long after optic nerve damage (mean lesion age 5.5 years) were randomly assigned to a rtACS (n = 24) or sham stimulation group (n = 18). Visual fields and patient reported outcome measures (vision-related QoL: National Eye Institute Visual Function Questionnaire, NEI-VFQ and health-related QoL: Short Form Health Survey, SF-36) were collected before and after a 10-day treatment course with daily sessions of 20 to 40 minutes. The primary outcome measure was the percent change from baseline of detection ability (DA) in defective visual field sectors as defined by computer-based high resolution perimetry (HRP). Secondary outcome parameters included further HRP parameters as well as static and kinetic perimetry results. Changes in QoL measures were correlated with changes in primary and secondary outcome measures in both groups. RESULTS: DA increase in the defective visual field was significantly larger after rtACS (41.1 ± 78.9%, M ± SD) than after sham stimulation (13.6 ± 26.3%), P < 0.05. While there was a significant increase of DA in the whole tested HRP visual field after rtACS (26.8 ± 76.7%, P < 0.05), DA in sham-stimulation patients remained largely unchanged (2.7 ± 20.2%, ns). Results of secondary outcome measures (static and kinetic perimetry) provided further evidence of rtACS efficacy. Improvements in NEI-VFQ subscale "general vision" were observed in both groups but were larger in the rtACS group (11.3 ± 13.5, Z = -3.21, P < 0.001) than in the sham group (4.2 ± 9.4, Z = -1.73, P < 0.05) with a significant difference between groups (Z = -1.71, P < 0.05). DA change and some NEI-VFQ domains were correlated (r = 0.29, P < 0.05), but no significant correlations were observed between DA and SF-36 results. CONCLUSIONS: rtACS facilitates vision restoration after unilateral, long-term optic nerve lesion as assessed both by objective DA changes and improvements in some NEI-VFQ subscales. Both were positively but low correlated, which suggests that factors other than visual field size also contribute to improved vision-related QoL.

Improvements in motor behavioral tests during deep brain stimulation of the subthalamic nucleus in rats with different degrees of unilateral parkinsonism.

Deep brain stimulation (DBS) improves motor performance in Parkinson's disease (PD) patients. To evaluate the effects of subthalamic nucleus (STN)-DBS on impaired motor behavior, we studied improvements in motor performance after delivery of unilateral stimulation to the STN in rats with mild and severe lesions of the nigrostriatal dopamine system caused by injecting 6-hydroxydopamine into the striatum. The rats were trained and performed motor behavioral tests including rotational behavior test, stepping test, and rotarod test before and after receiving DBS. We demonstrated that stimulation at a current strength of 200 microA, which stopped most of the D-amphetamine-induced rotational behaviors in these two groups, improved movement impairments in both the mild and severe groups and that the improvements in the mild group were significantly better than those in the severe group. More experimental and clinical studies are needed to evaluate the efficiency of STN-DBS for different stages of PD.

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation.

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation (P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.

Corticosterone treatment of the chick embryo affects light-stimulated development of the thalamofugal visual pathway.

By injecting a single 60 microg dose of corticosterone into the eggs of domestic chicks on day 18 of incubation, we have shown that elevated levels of this hormone affect the development of asymmetry in the visual projections from the thalamus to the Wulst regions in the left and right hemispheres of the forebrain. In vehicle-treated (control) embryos this visual pathway develops asymmetry in response to light stimulation during the final stages of incubation, when the embryo is oriented so that its left eye is occluded by its body and its right eye can be stimulated by light entering through the egg shell. Pre-hatching exposure to light leads to more projections from the left side of the thalamus to the right Wulst than from the right side of the thalamus to the left Wulst, as confirmed here by injection of the tracers Fluorogold and Rhodamine into the left and right Wulst followed by counting the number of labelled cell bodies in the thalamus (asymmetry greater in males than females). The chicks injected with corticosterone pre-hatching did not develop any group bias for asymmetry in response to light exposure before hatching. They were random with respect to presence/absence of lateralization and, when present, the lateralization was not as strong as in the controls and its direction was random. The corticosterone-treated group had fewer projections from the left side of the thalamus to the right Wulst than did the controls. The results are considered with respect to maternal deposits of the hormone in the yolk and pre-hatching stress of the embryo.

Auditory M50 and M100 responses to broadband noise: functional implications.

The functional significance of the M50 and M100 auditory evoked fields remains unclear. Here we report auditory evoked field data from three different studies employing wide-band noise stimuli. We find that, for the same stimuli, the strength of the M100, as well as its lateralization, are task-modulated. The M50, in contrast, shows three properties: It is dramatically more pronounced for noise stimuli than for pure tones, does not seem to be task dependent, and, is significantly stronger in the left hemisphere in all task conditions. These contrasting patterns of activation shed light on the properties of the response-generating mechanisms and suggest roles in the process of auditory figure-ground segregation.

Shift in sound localization induced by rTMS of the posterior parietal lobe.

Neuroimaging studies in human subjects and single-unit recordings in monkeys have suggested the primate posterior parietal cortex (PPC) to be involved in auditory space perception. Here we tested this hypothesis by combining repetitive focal transcranial magnetic stimulation (rTMS) of the right PPC with a task of pointing to free-field-sound stimuli. After a period of 15 min rTMS at 1Hz, subjects exhibited an overall signed error in pointing by 2.5 degrees, directed to the left and downward, with reference to a baseline condition with "sham rTMS". No effects of rTMS on the general precision of sound localization (unsigned errors) were found. Thus, low-frequency offline rTMS may have specifically affected neuronal circuits transforming auditory spatial coordinates in both azimuth and elevation. This is in accordance with the view that the PPC may represent a neural substrate of the perceptual stability in spatial hearing.

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided.

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.

Light-dependent development of asymmetry in the ipsilateral and contralateral thalamofugal visual projections of the chick.

Light-exposure of the chick embryo induces development of asymmetry in the thalamofugal visual projections to the Wulst regions of the forebrain since the embryo is turned so that it occludes its left and not its right eye. This asymmetry can be reversed by occluding the embryo's right eye and exposing its left eye to light. Here we show that three sub-regions of the thalamus (two in the dorsolateral anterior thalami (DLA) and one more caudal) have differing asymmetries of contralateral and/or ipsilateral projections. Hence the effect of asymmetrical light stimulation is regionally specific within the thalamus. Lateralised light stimulation appears to promote the development of ipsilateral projections from DLA pars dorsolateralis pars anterioris and contralateral projections from the caudal regions (the nucleus superficialis parvocellularis especially) but it may suppress the development of contralateral projections from the nucleus dorsolateralis anterior thalami pars lateralis rostralis. We also show that the light stimulation causes lateralised expression of c-fos and receptors for neurotransmitters.

Exposure to different wavelengths of light and the development of structural and functional asymmetries in the chicken.

The thalamofugal visual projections of the chick are known to develop in response to stimulation by light prior to hatching, and asymmetry in the number of projections develops as a consequence of the embryo being oriented in the egg so that it occuludes its left eye. The right eye only is stimulated by light and this causes the visual projections connected to the right eye to develop in advance of those connected to the left. We have now found that exposure of embryos, from day 19 of incubation to hatching, to red (peak transmission at 670 nm) or green (peak at 500 nm) light is as effective as broad-spectrum (white) light in establishing asymmetry in these projections. The intensities of the light to which the embryos were exposed in each case were equivalent, achieved in part by removing the air sac end of the egg shell. The thalamofugal visual projections, therefore, develop in response to light stimulation but appear to have no wavelength specificity. This result is consistent with the apparent lack of involvement of the thalamofugal visual pathway in colour vision. However, functional asymmetry, tested as left-right eye differences in categorising grain from pebbles, was found to be less marked in the chicks that had been exposed to green light compared to those that had been exposed to 'while' light, and it was absent in those exposed to red light or incubated in the dark. Thus, there is wavelength specificity for the development of the behavioural asymmetry, which suggests involvement of colour-coded neurons outside the thalamofugal visual pathway, probably in the tectofugal pathway. Exposure of the embryos to red and green light alternating at 30 min intervals is as effective as "white' light for establishing both the structural and functional asymmetry.