Early sleep after action observation and motor imagery training boosts improvements in manual dexterity.

The systematic observation and imagination of actions promotes acquisition of motor skills. Furthermore, studies demonstrated that early sleep after practice enhances motor learning through an offline stabilization process. Here, we investigated behavioral effects and neurodynamical correlates of early sleep after action observation and motor imagery training (AO + MI-training) on motor learning in terms of manual dexterity. Forty-five healthy participants were randomized into three groups receiving a 3 week intervention consisting of AO + MI-training immediately before sleeping or AO + MI-training at least 12 h before sleeping or a control stimulation. AO + MI-training implied the observation and motor imagery of transitive manual dexterity tasks, whereas the control stimulation consisted of landscape video-clips observation. Manual dexterity was assessed using functional tests, kinematic and neurophysiological outcomes before and after the training and at 1-month follow-up. AO + MI-training improved manual dexterity, but subjects performing AO + MI-training followed by early sleep had significantly larger improvements than those undergoing the same training at least 12 h before sleeping. Behavioral findings were supported by neurodynamical correlates during motor performance and additional sleep-dependent benefits were also detected at 1 month follow-up. These findings introduce a new approach to enhance the acquisition of new motor skills or facilitate recovery in patients with motor impairments.

Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI.

Brainstem nuclei play a pivotal role in many functions, such as arousal and motor control. Nevertheless, the connectivity of arousal and motor brainstem nuclei is understudied in living humans due to the limited sensitivity and spatial resolution of conventional imaging, and to the lack of atlases of these deep tiny regions of the brain. For a holistic comprehension of sleep, arousal and associated motor processes, we investigated in 20 healthy subjects the resting-state functional connectivity of 18 arousal and motor brainstem nuclei in living humans. To do so, we used high spatial-resolution 7 Tesla resting-state fMRI, as well as a recently developed in-vivo probabilistic atlas of these nuclei in stereotactic space. Further, we verified the translatability of our brainstem connectome approach to conventional (e.g. 3 Tesla) fMRI. Arousal brainstem nuclei displayed high interconnectivity, as well as connectivity to the thalamus, hypothalamus, basal forebrain and frontal cortex, in line with animal studies and as expected for arousal regions. Motor brainstem nuclei showed expected connectivity to the cerebellum, basal ganglia and motor cortex, as well as high interconnectivity. Comparison of 3 Tesla to 7 Tesla connectivity results indicated good translatability of our brainstem connectome approach to conventional fMRI, especially for cortical and subcortical (non-brainstem) targets and to a lesser extent for brainstem targets. The functional connectome of 18 arousal and motor brainstem nuclei with the rest of the brain might provide a better understanding of arousal, sleep and accompanying motor functions in living humans in health and disease.

MED1/BDNF/TrkB pathway is involved in thalamic hemorrhage-induced pain and depression by regulating microglia.

Central post-stroke pain (CPSP) and associated depression remain poorly understood and pharmacological treatments are unsatisfactory. Recently, microglia activation was suggested to be involved in CPSP pathophysiology. The goal of this study was to investigate the effectiveness of a co-ultramicronized combination of N-palmitoylethanolamide and luteolin (PEALut) in a mouse model of thalamic hemorrhage (TH)-induced CPSP. TH was established through the collagenase-IV injection in thalamic ventral-posterolateral-nucleus. PEALut effects in CPSP-associated behaviors were evaluated during a 28-days observation period. We found that repeated administrations of co-ultra PEALut significantly reduced mechanical hypersensitivity after TH, as compared to vehicle, by reducing the early microglial activation in the perilesional site. Moreover, PEALut prevented the development of depressive-like behavior (21 days post-TH). These effects were associated with the restoration of synaptic plasticity in LEC-DG pathway and monoamines levels found impaired in TH mice. Hippocampal MED1 and TrkB expressions were significantly increased in TH compared to sham mice 21 days post-TH, whereas BDNF levels were decreased. PEALut restored MED1/TrkB/BDNF expression in mice. Remarkably, we found significant overexpression of MED1 in the human autoptic brain specimens after stroke, indicating a translational potential of our findings. These results pave the way for better-investigating depression in TH- induced CPSP, together with the involvement of MED1/TrkB/BDNF pathway, proposing PEALut as an adjuvant treatment.

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity.

Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.

Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive-compulsive disorder.

Recent evidence suggests that presupplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting-state and response inhibition in obsessive-compulsive disorder (OCD). We performed resting-state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication-free OCD patients and 49 healthy control (HC) participants by using the stop-signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre-SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop-signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre-SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre-SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting-state functional connectivity of the regions belonging to the cortico-striato-thalamo-cortical circuit and the cingulo-opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre-SMA and IFG for the pathophysiology of motor response inhibition in OCD.

Crabp1 Modulates HPA Axis Homeostasis and Anxiety-like Behaviors by Altering FKBP5 Expression.

Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic-pituitary-adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders.

The anti-fatigue potential of water-soluble polysaccharides of Semen cassiae on BALB/c mice.

Fatigue syndrome is a major health problem that affects the voluntary activities of an individual. Particularly, exercise-induced fatigue has become a serious concern in people's health. Since polysaccharides from various medicinal plants have been reported for anti-fatigue effect, the current study deals with the anti-fatigue potential of water-soluble polysaccharides of the Chinese medicinal plant Semen cassiae (Cassia obtusifolia L.) in BALB/c mice. Water-soluble polysaccharides from Semen cassiae were extracted using aqueous solvent (water). An orthogonal test design was employed for the optimization of polysaccharide extraction. The conditions optimized through this design unveiled the raw materials to solvent ratio as 1:30. The optimal temperature and time duration were found to be 80°C and 3.5 h, respectively. The yield of soluble polysaccharides at these specified conditions was 5.42%. Strikingly, the water-soluble polysaccharide from S. cassiae exhibited strong anti-fatigue activity at 100 mg/kg in BALB/c mice. S. cassiae polysaccharide extended the weight-loaded swimming duration in BALB/c mice. In addition, it ameliorated the level of antioxidant enzymes (SOD, GPX) while decreased the blood urea nitrogen, creatine phosphokinase, triglyceride, lactic acid, lactate dehydrogenase, and malondialdehyde levels in blood serum. Moreover, the assessment of the immunomodulatory effect of S. cassia polysaccharides unveiled the enhancement of B-cell and T-cell lymphocytes, denoting the positive effect on physical immunity.

Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function.

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions.

Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep.

Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.

Mental individuation of imagined finger movements can be achieved using TMS-based neurofeedback.

Neurofeedback (NF) in combination with motor imagery (MI) can be used for training individuals to volitionally modulate sensorimotor activity without producing overt movements. However, until now, NF methods were of limited utility for mentally training specific hand and finger actions. Here we employed a novel transcranial magnetic stimulation (TMS) based protocol to probe and detect MI-induced motor activity patterns in the primary motor cortex (M1) with the aim to reinforce selective facilitation of single finger representations. We showed that TMS-NF training but not MI training with uninformative feedback enabled participants to selectively upregulate corticomotor excitability of one finger, while simultaneously downregulating excitability of other finger representations within the same hand. Successful finger individuation during MI was accompanied by strong desynchronization of sensorimotor brain rhythms, particularly in the beta band, as measured by electroencephalography. Additionally, informative TMS-NF promoted more dissociable EEG activation patterns underlying single finger MI, when compared to MI of the control group where no such feedback was provided. Our findings suggest that selective TMS-NF is a new approach for acquiring the ability of finger individuation even if no overt movements are performed. This might offer new treatment modality for rehabilitation after stroke or spinal cord injury.

Electroacupuncture Alleviates Neuroinflammation and Motor Dysfunction by Regulating Intestinal Barrier Function in a Mouse Model of Parkinson Disease.

Gastrointestinal dysfunction is the main nonmotor characteristic of Parkinson disease (PD), manipulation of gastrointestinal function by altering gut-brain axis is a potentially novel entry point for the treatment of PD. Acupuncture has been reported to confer beneficial effects in the gastrointestinal diseases. Therefore, this study aimed to explore the effects and mechanism of acupuncture on the pathophysiology and gastrointestinal function of PD. A PD mouse model was established by rotenone, and electroacupuncture was used to regulate the gastrointestinal function. Rotenone was found to induce the types of brain pathologies and gastrointestinal dysfunction that are similar to those observed with PD. Electroacupuncture significantly increased the spontaneous activity of mice with PD and increased the expression of tyrosine hydroxylase, while reducing the expression of Iba-1 in substantia nigra (SN), suggesting that motor dysfunction and neurological damage was alleviated. In addition, electroacupuncture significantly reduced the deposition of α-synuclein in both colon and SN, reduced intestinal inflammation, and exerted protective effects on enteric nervous system and intestinal barrier. In conclusion, electroacupuncture confers beneficial effects on the gastrointestinal system of mice with PD and can alleviate neuroinflammation and neuropathic injury by inhibiting intestinal inflammation, promoting intestinal barrier repair and reducing α-synuclein deposition in the colon.

Revisiting the acute effects of resistance exercise on motor imagery ability.

Motor imagery (MI) shares psychological and physiological similarities with the physical practice of the same action. Yet, it remains unclear whether fatigue elicited by exercise impairs MI ability. Fourteen participants performed MI of a self-paced walking sequence of 22 m before and after a resistance exercise eliciting muscle fatigue from upper and lower limbs, selectively. We indexed MI ability using psychometric and behavioral methods. Electromyography of the quadriceps was also recorded during physical practice trials of the walking sequence. For both experimental conditions, we recorded improved temporal congruence between MI and physical practice of the walking sequence (9.89 %, 95 % CI [7.03, 12.75], p < 0.01). Vividness decreased immediately after the fatiguing exercise (6.35 %, 95 % CI [5.18, 7.51], p < 0.05), before rapidly returning to pre-fatigue values during recovery trials. The results challenge the hypothesis of an effect of acute fatigue elicited by a resistance exercise on MI ability, i.e. restricted to MI tasks focusing fatigued effectors. The beneficial effects of fatigue conditions on the psychometric and behavioral indexes of MI ability are discussed in the broader context of psychobiological fatigue models linking perceived exertion with the reallocation of attentional resources. The general perception of fatigue, rather than local muscle fatigue, appeared linked to the acute effects of resistance exercise on MI ability.

Dendritic calcium signals in rhesus macaque motor cortex drive an optical brain-computer interface.

Calcium imaging is a powerful tool for recording from large populations of neurons in vivo. Imaging in rhesus macaque motor cortex can enable the discovery of fundamental principles of motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). Surface two-photon imaging, however, cannot presently access somatic calcium signals of neurons from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and imaging system capable of chronic, motion-stabilized two-photon imaging of neuronal calcium signals from macaques engaged in a motor task. By imaging apical dendrites, we achieved optical access to large populations of deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm movement. Combining several technical advances, we developed an optical BCI (oBCI) driven by these dendritic signalswhich successfully decoded movement direction online. By fusing two-photon functional imaging with CLARITY volumetric imaging, we verified that many imaged dendrites which contributed to oBCI decoding originated from layer 5 output neurons, including a putative Betz cell. This approach establishes new opportunities for studying motor control and designing BCIs via two photon imaging.

The contemporary model of vertebral column joint dysfunction and impact of high-velocity, low-amplitude controlled vertebral thrusts on neuromuscular function.

PURPOSE: There is growing evidence that vertebral column function and dysfunction play a vital role in neuromuscular control. This invited review summarises the evidence about how vertebral column dysfunction, known as a central segmental motor control (CSMC) problem, alters neuromuscular function and how spinal adjustments (high-velocity, low-amplitude or HVLA thrusts directed at a CSMC problem) and spinal manipulation (HVLA thrusts directed at segments of the vertebral column that may not have clinical indicators of a CSMC problem) alters neuromuscular function. METHODS: The current review elucidates the peripheral mechanisms by which CSMC problems, the spinal adjustment or spinal manipulation alter the afferent input from the paravertebral tissues. It summarises the contemporary model that provides a biologically plausible explanation for CSMC problems, the manipulable spinal lesion. This review also summarises the contemporary, biologically plausible understanding about how spinal adjustments enable more efficient production of muscular force. The evidence showing how spinal dysfunction, spinal manipulation and spinal adjustments alter central multimodal integration and motor control centres will be covered in a second invited review. RESULTS: Many studies have shown spinal adjustments increase voluntary force and prevent fatigue, which mainly occurs due to altered supraspinal excitability and multimodal integration. The literature suggests physical injury, pain, inflammation, and acute or chronic physiological or psychological stress can alter the vertebral column's central neural motor control, leading to a CSMC problem. The many gaps in the literature have been identified, along with suggestions for future studies. CONCLUSION: Spinal adjustments of CSMC problems impact motor control in a variety of ways. These include increasing muscle force and preventing fatigue. These changes in neuromuscular function most likely occur due to changes in supraspinal excitability. The current contemporary model of the CSMC problem, and our understanding of the mechanisms of spinal adjustments, provide a biologically plausible explanation for how the vertebral column's central neural motor control can dysfunction, can lead to a self-perpetuating central segmental motor control problem, and how HVLA spinal adjustments can improve neuromuscular function.

Neuronal figure-ground responses in primate primary auditory cortex.

Figure-ground segregation, the brain's ability to group related features into stable perceptual entities, is crucial for auditory perception in noisy environments. The neuronal mechanisms for this process are poorly understood in the auditory system. Here, we report figure-ground modulation of multi-unit activity (MUA) in the primary and non-primary auditory cortex of rhesus macaques. Across both regions, MUA increases upon presentation of auditory figures, which consist of coherent chord sequences. We show increased activity even in the absence of any perceptual decision, suggesting that neural mechanisms for perceptual grouping are, to some extent, independent of behavioral demands. Furthermore, we demonstrate differences in figure encoding between more anterior and more posterior regions; perceptual saliency is represented in anterior cortical fields only. Our results suggest an encoding of auditory figures from the earliest cortical stages by a rate code.

Contribution of the brain-derived neurotrophic factor and neurometabolites to the motor performance.

Individual motor performance ability is affected by various factors. Although the key factor has not yet completely been elucidated, the brain-derived neurotrophic factor (BDNF) genotype as well as neurometabolites may become contibuting factors depending on the learning stage. We investigated the effects of the Met allele of the BDNF gene and those of the neurometabolites on visuomotor learning. In total, 43 healthy participants performed a visuomotor learning task consisting of 10 blocks using the right index finger (Val66Val, n = 15; Val66Met, n = 15; and Met66Met, n = 13). Glutamate plus glutamine (Glx) concentrations in the primary motor cortex, primary somatosensory cortex (S1), and cerebellum were evaluated using 3-T magnetic resonance spectroscopy in 19 participants who participated in the visuomotor learning task. For the learning stage, the task error (i.e., learning ability) was significantly smaller in the Met66Met group compared with that observed in the remaining groups, irrespective of the learning stage (all p values < 0.003). A significant difference was observed between the Val66Val and Met66Met groups in the learning slope (i.e., learning speed) in the early learning stage (p = 0.048) but not in the late learning stage (all p values> 0.54). Moreover, positive correlations were detected between the learning slope and Glx concentrations in S1 only in the early learning stage (r = 0.579, p = 0.009). The BDNF genotype and Glx concentrations in S1 partially contribute to interindividual variability on learning speed in the early learning stage.

Thalamic control of cortical dynamics in a model of flexible motor sequencing.

The neural mechanisms that generate an extensible library of motor motifs and flexibly string them into arbitrary sequences are unclear. We developed a model in which inhibitory basal ganglia output neurons project to thalamic units that are themselves bidirectionally connected to a recurrent cortical network. We model the basal ganglia inhibitory patterns as silencing some thalamic neurons while leaving others disinhibited and free to interact with cortex during specific motifs. We show that a small number of disinhibited thalamic neurons can control cortical dynamics to generate specific motor output in a noise-robust way. Additionally, a single "preparatory" thalamocortical network can produce fast cortical dynamics that support rapid transitions between any pair of learned motifs. If the thalamic units associated with each sequence component are segregated, many motor outputs can be learned without interference and then combined in arbitrary orders for the flexible production of long and complex motor sequences.

Subsecond Ensemble Dynamics of Orexin Neurons Link Sensation and Action.

Hypothalamic hypocretin/orexin neurons have been initially conceptualized as slow, modulatory controllers of behavior. Furthermore, their behavioral effects have been assumed to be a secondary consequence of their impact on arousal. However, cellular-resolution calcium imaging and optogenetic studies show that orexin neurons regulate self-generated and sensory-evoked movement on rapid, subsecond timescales. Orexin cell activity rapidly and transiently peaks before and during movements. Optogenetic prevention of this activation reduces the probability of locomotion initiation, and optogenetic mimicry of orexin cell activation rapidly causes locomotion. Neural ensemble calcium imaging experiments reveal that the same orexin cells whose activity underlies movement initiation display subsecond-latency responses to diverse sensory stimuli. These findings establish orexin neurons as rapid and strong sensorimotor controllers that are in many ways operationally similar to classic subcortical movement controllers, such as midbrain dopamine neurons. While a scientific definition of "arousal" is still lacking, the subsecond-scale sensorimotor control by orexin neurons could be viewed as reminiscent of a motor rather than an arousal system.

Arrabidaea chica Verlot fractions reduce MIA-induced osteoarthritis progression in rat knees.

This study aims to investigate the activity of n-hexane, ethyl acetate and butanol fractions obtained from Arrabidaea chica Verlot against MIA-induced osteoarthritis (OA). The antinociceptive potentials of each fraction were evaluated through a cyclooxygenase (COX) 1 and 2 inhibition test and an in vivo OA-model. In addition, toxicity assessments in the liver, spleen and kidney, as well as radiographic and histopathological knee analyses, were performed. The chemical composition of the n-hexane fraction was elucidated, and a molecular docking protocol was carried out to identify which compounds are associated with the detected bioactivity. The n-hexane A. chica fraction preferentially inhibits COX-2, with 90% inhibition observed at 10 µg/mL. The fractions also produced significant improvements in OA incapacity, motor activity and hyperalgesia parameters and in radiological knee conditions. However, concerning the histopathological evaluations, these improvements were only significant in the hexane and ethyl acetate fraction treatments, which resulted in better average scores, suggesting that these fractions slow OA-promoted joint injury progression. Histopathological organ analyses indicate that the fractions are not toxic to animals. Twenty compounds were identified in the n-hexane fraction, comprising fatty acids, terpenes and phytosterols. In silico analyses indicate the presence of favourable interactions between some of the identified compounds and the COX-2 enzyme, mainly concerning alpha-tocopherol (Vitamin E), squalene and beta-sitosterol. The findings indicate that A. chica fractions display analgesic, anti-inflammatory properties, are non-toxic and are able to slow OA progression, and may, therefore, be prioritized as natural products in OA human clinical trials.

The superior parietal lobule of primates: a sensory-motor hub for interaction with the environment.

The superior parietal lobule of the macaque monkey occupies the postero-medial part of the parietal lobe and plays a crucial role in the integration of different sources of information (from visual, motor and somatosensory brain regions) for the purpose of high-level cognitive functions, as perception for action. This region encompasses the intraparietal sulcus and the parieto-occipital sulcus and includes also the precuneate cortex in the mesial surface of the hemisphere. It hosts several areas extensively studied in the macaque: PE, PEip, PEci anteriorly and PEc, MIP, PGm and V6A posteriorly. Recently studies based on functional MRI have suggested putative human homologue of some of the areas of the macaque superior parietal lobule. Here we review the anatomical subdivision, the cortico-cortical and thalamo-cortical connections of the macaque superior parietal lobule compared with their functional properties and the homology with human organization in physiological and lesioned situations. The knowledge of this part of the macaque brain could help in understanding pathological conditions that in humans affect the normal behaviour of arm-reaching actions and can inspire brain computer interfaces performing in more accurate ways the sensorimotor transformations needed to interact with the surrounding environment.