Nitric oxide-mediated cortical activation: a diffuse wake-up system

Nitric oxide (NO) has been implicated in some of the central pathways engaged in the regulation of the sleep–wake cycle. The existence of nitric oxide synthase (NOS) in the cholinergic basal forebrain (BF) cells projecting to the cortex suggests a role for NO in the activation induced by the BF during arousal. We tested, in the anesthetized cat, the hypothesis that inhibition of NOS would decrease the ability of BFcholinergic fibers to induce cortical activation. In control conditions,BFstimulation evoked an awake-likeEEGpattern (i.e., a decrease in the low-frequency– high-amplitude oscillatory activity and an increase in the high-frequency–low-amplitude activity). After blocking NOS activity, the capacity of BF stimulation to induce cortical activation was strongly impaired. Furthermore, voltammetric measurements of NO levels revealed an increase in cortical NO after BF stimulation, also blocked by systemic NOS inhibition. These results indicate that the blockade of NOS activity significantly reduces the ability of BF stimulation to induce changes in the EEG pattern and suggest a role for NO in the BF–cholinergic system implicated in arousal mechanisms

Suppression of V1 feedback produces a shift in the topographic representation of receptive fields of LGN cells by unmasking latent retinal drives

[Abstract] In awake monkeys, we used repetitive transcranial magnetic stimulation (rTMS) to focally inactivate visual cortex while measuring the responsiveness of parvocellular lateral geniculate nucleus (LGN) neurons. Effects were noted in 64/75 neurons, and could be divided into 2 main groups: (1) for 39 neurons, visual responsiveness decreased and visual latency increased without apparent shift in receptive field (RF) position and (2) a second group (n = 25, 33% of the recorded cells) whose excitability was not compromised, but whose RF position shifted an average of 4.5°. This change is related to the retinotopic correspondence observed between the recorded thalamic area and the affected cortical zone. The effect of inactivation for this group of neurons was compatible with silencing the original retinal drive and unmasking a second latent retinal drive onto the studied neuron. These results indicate novel and remarkable dynamics in thalamocortical circuitry that force us to reassess constraints on retinogeniculate transmission

A simple, repeated rTMS protocol effectively removes auditory verbal hallucinations in a single patient study

Letter to the Edito

Endocannabinoid CB1 receptors modulate visual output from the thalamus

[Abstract] Rationale Endocannabinoids have emerged as a modulatory brain system affecting different types of synapses, broadly distributed throughout the CNS, which explain the diverse psychophysical effects observed following activation of the endocannabinoid system. Objectives and methods The present study aimed to characterize the effect of CB1-mediated activity in the visual thalamus. In vivo single-unit extracellular recordings were performed in anaesthetized adult pigmented rats, measuring visual and spontaneous activity, combined with application of CB1 receptor agonists (anandamide, 2-AG, and O2545) and one antagonist, AM251. Results CB1 receptors activation revealed two cellular populations, with excitatory effects on ∼28% of cells and inhibitory in ∼72%, actions which were blocked by the antagonist AM251. The agonist action significantly altered both spontaneous and visual activity, shifting the signal-tonoise ratio (S/N), with accompanying changes in the variability within the visual response. Increased responses by agonist application were accompanied by a decrease in S/N and an increase in variability, while those cells inhibited by the agonist showed an increase in S/N and a decrease in variability. There was no obvious correlation between the two effects and any other response property suggesting a more general role in modulating all information passing from LGN to cortex. Conclusions Our data support a role for CB1 at the level of the thalamus acting as a dynamic modulator of visual information being sent to the cortex, apparently maintaining the salience of the signal within upper and lower boundaries. This may account for some of the behavioral effects of cannabis.Ministerio de Ciencia e Innovación; BFU2009-08169Xunta de Galicia; 2007/000140-

M1 inhibition dependency on slowing of muscle relaxation after brief and fast fatiguing repetitive movements: preliminary results

[Abstract] This work presents preliminary results on the association between central and peripheral expressions of muscle fatigue induced by unresisted repetitive movements. We tested cortico-spinal excitability and intra-cortical inhibition right at the end of 30 s of maximal rate finger tapping (ft) or after 10 s of rest; the contractile properties of the muscle were also tested. This procedure was repeated 12 times. In half of the repetitions, the evaluation was done during induced muscle isquemia. In all cases ft rate decreased during the 30 s of task. Isquemia produced a slowing of muscle contractile properties in all cases, after ft as well as after 10 s of rest post-ft. Intracortical inhibition increased immediately after ft, but recovered after 10 s, regardless the presence of muscle isquemia. Our results suggest that the increment of inhibition in M1 after fatiguing repetitive movements is central in origin, and not an adaptation to the slowed contractility of the muscle.Ministerio de Economía y Competitividad; DEP2017-87601-

Bursting thalamic responses in awake monkey contribute to visual detection and are modulated by corticofugal feedback

[Abstract] The lateral geniculate nucleus is the gateway for visual information en route to the visual cortex. Neural activity is characterized by the existence of two firing modes: burst and tonic. Originally associated with sleep, bursts have now been postulated to be a part of the normal visual response, structured to increase the probability of cortical activation, able to act as a “wake-up” call to the cortex. We investigated a potential role for burst in the detection of novel stimuli by recording neuronal activity in the lateral geniculate nucleus (LGN) of behaving monkeys during a visual detection task. Our results show that bursts are often the neuron’s first response, and are more numerous in the response to attended target stimuli than to unattended distractor stimuli. Bursts are indicators of the task novelty, as repetition decreased bursting. Because the primary visual cortex is the major modulatory input to the LGN, we compared the results obtained in control conditions with those observed when cortical activity was reduced by TMS. This cortical deactivation reduced visual response related bursting by 90%. These results highlight a novel role for the thalamus, able to code higher order image attributes as important as novelty early in the thalamo-cortical conversation

Antagonist muscle co-activation during straight walking and its relation to kinematics: Insight from young, elderly and Parkinson's disease

[Abstract] Increased antagonist muscle co-activation of the lower limb during walking seems to be an adaptive process to the physiological changes of aging, in order to gain joint stability. In the healthy subjects this view seems to be reinforced by the fact that the co-activation index (CAI) increases when the gait is faster. The few reports on antagonist co-activation in Parkinson's disease (PD) patients indicate that they have larger co-activation than the healthy elderly, supporting the idea of the stabilization role of CAI during gait, as postural instability is a cardinal feature of PD. However it has also been reported that there is a reduction of the CAI when increasing velocity in PD or normal elderly. This questions the role of coactivation in stabilization during increased velocity. In this study we have analyzed the gait of healthy subjects (young and elderly), and PD patients (with and without freezing of gait, FOG) in order to better understand the relation between co-activation and gait kinematics, and to gain insight into the pathological changes associated with FOG in PD. We used Multiple Linear Regression models to study the relationship in shank muscles between CAI, velocity and cadence. Our results indicate that, for all groups of interest, the relationship between co-activation and the kinematics of gait is poor, due to the high degree of variability, questioning the explanatory value of the index

Differential responses of spinal motoneurons to fatigue induced by short-lasting repetitive and isometric tasks

[Abstract] Compared to isometric activities, the neural basis of fatigue induced by repetitive tasks has been scarcely studied. Recently, we showed that during short-lasting repetitive tasks at the maximal possible rate (finger tapping for 10 and 30 s), tapping rate and maximal voluntary contraction (MVC) force decrease at the end of finger tapping. We also observed larger silent periods (SP) induced by transcranial magnetic stimulation during MVC post finger tapping. However, if SP were induced by cervicomedullary stimulation (CMS) they remained unchanged. This suggested a supraspinal origin of fatigue for repetitive tasks. Nevertheless, CMS SP only partially explore spinal excitability; therefore, to evaluate a spinal origin of fatigue it is essential to know the features of the CMS-evoked potentials (CMEP). Herein, we evaluated (n = 15) the amplitude of the CMEP during MVC executed immediately (no gap) after a short-lasting finger tapping task; we also evaluated the compound muscle action potential (CMAP) so that the amplitude of the CMEP was expressed as a function of the CMAP amplitude. Indices of fatigue obtained during finger tapping were compared with those obtained during short-lasting maximal isometric tasks. While indices of excitability increased initially in both tasks, they decreased with the isometric task only when the task was prolonged to 30 s. We suggest that the inability to maintain increased levels of spinal excitability during task execution is a neurophysiological mark of fatigue. Our results suggest that the origin of fatigue induced by brief and fast repetitive tasks is not spinal.Galicia. Consellería de Educación; 2007/000140-

Hyperthermia-Induced Changes in EEG of Anesthetized Mice Subjected to Passive Heat Exposure

[Abstract] Currently, the role of hypothermia in electroencephalography (EEG) is well-established. However, few studies have investigated the effect of hyperthermia on EEG, an important physiological parameter governing brain function. The aim of this work was to determine how neuronal activity in anesthetized mice is affected when the temperature rises above the physiological threshold mandatory to maintain the normal body functions. In this study, a temperature-elevation protocol, from 37 to 42°C, was applied to four female mice of 2-3 months old while EEG was recorded simultaneously. We found that hyperthermia reduces EEG amplitude by 4.36% when rising from 37 to 38 degrees and by 24.33% when it is increased to 42 degrees. Likewise, increasing the body temperature produces a very large impact on the EEG spectral parameters, reducing the frequency power at the delta, theta, alpha, and beta bands. Our results show that hyperthermia has a global effect on the EEG, being able to change the electrical activity of the brain.This work was supported by the Ministerio de Economía, Industria y Competitividad, BFU2017-82296-P. XUGA: Grupos de Referencia Competitiva (ED431C 2018/24)Xunta de Galicia; ED431C 2018/2