Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Prefrontal tDCS modulates autonomic responses in COVID-19 inpatients.

BACKGROUND: maladaptive changes in the autonomic nervous system (ANS) have been observed in short and long-term phases of COVID-19 infection. Identifying effective treatments to modulate autonomic imbalance could be a strategy for preventing and reducing disease severity and induced complications. OBJECTIVE: to investigate the efficacy, safety, and feasibility of a single session of bihemispheric prefrontal tDCS on indicators of cardiac autonomic regulation and mood of COVID-19 inpatients. METHODS: patients were randomized to receive a single 30-min session of bihemispheric active tDCS over the dorsolateral prefrontal cortex (2 mA; n = 20) or sham (n = 20). Changes in time [post-pre intervention] in heart rate variability (HRV), mood, heart rate, respiratory rate, and oxygen saturation were compared between groups. Additionally, clinical worsening indicators and the occurrence of falls and skin injuries were evaluated. The Brunoni Adverse Effects Questionary was employed after the intervention. RESULTS: there was a large effect size (Hedges' g = 0.7) of intervention on HRV frequency parameters, suggesting alterations in cardiac autonomic regulation. An increment in oxygen saturation was observed in the active group but not in the sham after the intervention (P = 0.045). There were no group differences regarding mood, incidence and intensity of adverse effects, no occurrence of skin lesions, falls, or clinical worsening. CONCLUSIONS: a single prefrontal tDCS session is safe and feasible to modulate indicators of cardiac autonomic regulation in acute COVID-19 inpatients. Further research comprising a thorough assessment of autonomic function and inflammatory biomarkers is required to verify its potential to manage autonomic dysfunctions, mitigate inflammatory responses and enhance clinical outcomes.

Reorganization of thalamocortical connections in congenitally blind humans.

Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the impaired microstructure of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals, whereas those connecting with the temporal cortex showed greater volume and increased connectivity. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.

Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae.

BACKGROUND: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. METHODS: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. RESULTS: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e' ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. CONCLUSIONS: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.

Poststroke consequences upon optimization properties of postural sway during upright stance: a cross-sectional study.

BACKGROUND: The understanding of human postural control has advanced with the introduction of optimization process modeling. These models, however, only provide control parameters, rather than analytical descriptors of optimization processes. Here, we use a newly developed direct (pattern) search algorithm to investigate changes in postural optimization process in poststroke individuals. OBJECTIVE: This cross-sectional study investigated the optimization properties of postural stability during upright standing in poststroke individuals. METHODS: Twenty-nine poststroke and 15 healthy age-matched individuals underwent posturography with a force platform while standing for 60 s for acquisition of center-of-pressure data. Poststroke individuals were grouped depending on their weight-bearing (WB) pattern and their balance capability assessed through Berg Balance Scale (BBS). The optimization properties of postural stability were computed assuming the minimization of postural sway as cost function. RESULTS: The asymmetric WB poststroke group showed larger convergence rate toward the local minimum of postural sway than the symmetric WB group. Additionally, the low-balance capability group exhibited smaller values for averaged local minima and global minimum of postural sway coordinates compared with high-balance capability group. Significant correlations were found for BBS and the local minima and global minimum (Pearson's r ranged 0.378-0.424, P < 0.05). CONCLUSIONS: In summary, the optimization properties describing postural dynamic stability, steadiness, and global reference are altered in poststroke individuals with asymmetric WB pattern and low-balance capability.

Predicting Upcoming Events Occurring in the Space Surrounding the Hand.

Predicting upcoming sensorimotor events means creating forward estimates of the body and the surrounding world. This ability is a fundamental aspect of skilled motor behavior and requires an accurate and constantly updated representation of the body and the environment. To test whether these prediction mechanisms could be affected by a peripheral injury, we employed an action observation and electroencephalogram (EEG) paradigm to assess the occurrence of prediction markers in anticipation of observed sensorimotor events in healthy and brachial plexus injury (BPI) participants. Nine healthy subjects and six BPI patients watched a series of video clips showing an actor's hand and a colored ball in an egocentric perspective. The color of the ball indicated whether the hand would grasp it (hand movement), or the ball would roll toward the hand and touch it (ball movement), or no event would occur (no movement). In healthy participants, we expected to find distinct electroencephalographic activation patterns (EEG signatures) specific to the prediction of the occurrence of each of these situations. Cluster analysis from EEG signals recorded from electrodes placed over the sensorimotor cortex of control participants showed that predicting either an upcoming hand movement or the occurrence of a tactile event yielded specific neural signatures. In BPI participants, the EEG signals from the sensorimotor cortex contralateral to the dominant hand in the hand movement condition were different compared to the other conditions. Furthermore, there were no differences between ball movement and no movement conditions in the sensorimotor cortex contralateral to the dominant hand, suggesting that BPI blurred specifically the ability to predict upcoming tactile events for the dominant hand. These results highlight the role of the sensorimotor cortex in creating estimates of both actions and tactile interactions in the space around the body and suggest plastic effects on prediction coding following peripheral sensorimotor loss.

Discrimination of Meat Produced by Bos taurus and Bos indicus Finished under an Intensive or Extensive System.

Meat obtained under commercial conditions shows considerable variability, mostly due to genetic background and production system. In this study, meat physicochemical properties and fatty acid profiles were analysed to investigate the feasibility of using them as tools to discriminate between meats produced by different genetic groups and finishing systems. Samples of the Longissimus thoracis were collected from 160 commercial bulls of the B. taurus (n = 75) and B. indicus (n = 85) groups, finished either on pasture (n = 46) or with grain supplementation (n = 114) and analysed by standard procedures. Data were analysed by discriminant analysis using a stepwise procedure, to select the meat characteristics that better contribute to discriminate the various groups. Our results indicate that fatty acid profiles of meat had better discriminating ability than physicochemical properties, especially to identify meat from animals finished on grain or pasture. The overall discrimination of meat from different genetic groups was achieved with a slightly lower reliability. Nonetheless, our results show that reliability of allocation to genetic group can be improved if prior information on finishing system is considered. These results are of high importance because they can be incorporated as tools to assess the authenticity of beef, particularly in meat certification programs.

Postural Muscle Unit Plasticity in Stroke Survivors: Altered Distribution of Gastrocnemius' Action Potentials.

Neuromuscular adaptations are well-reported in stroke survivors. The death of motor neurons and the reinnervation of residual muscle fibers by surviving motor neurons, for example, seem to explain the increased density of muscle units after stroke. It is, however, unknown whether reinnervation takes place locally or extensively within the muscle. Here we combine intramuscular and surface electromyograms (EMGs) to address this issue for medial gastrocnemius (MG); a key postural muscle. While seven stroke survivors stood upright, two intramuscular and 15 surface EMGs were recorded from the paretic and non-paretic gastrocnemius. Surface EMGs were triggered with the firing instants of motor units identified through the decomposition of both intramuscular and surface EMGs. The standard deviation of Gaussian curves fitting the root mean square amplitude distribution of surface potentials was considered to assess differences in the spatial distribution of motor unit action potentials and, thus, in the distribution of muscle units between limbs. The median number of motor units identified per subject in the paretic and non-paretic sides was, respectively, 2 (range: 1-3) and 3 (1-4). Action potentials in the paretic gastrocnemius were represented at a 33% wider skin region when compared to the non-paretic muscle (Mann-Whitney; P = 0.014). Side differences in the representation of motor unit were not associated with differences in subcutaneous thickness (skipped-Spearman r = -0.53; confidence interval for r: -1.00 to 0.63). Current results suggest stroke may lead to the enlargement of the gastrocnemius muscle units recruited during standing. The enlargement of muscle units, as assessed from the skin surface, may constitute a new marker of neuromuscular plasticity following stroke.

Lower limb amputees undergo long-distance plasticity in sensorimotor functional connectivity.

Amputation in adults is associated with an extensive remapping of cortical topography in primary and secondary sensorimotor areas. Here, we used tactile residual limb stimulation and 3T functional magnetic resonance imaging in humans to investigate functional connectivity changes in the sensorimotor network of patients with long-term lower limb traumatic amputations with phantom sensation, but without pain. We found a pronounced reduction of inter-hemispheric functional connectivity between homologous sensorimotor cortical regions in amputees, including the primary (S1) and secondary (S2) somatosensory areas, and primary (M1) and secondary (M2) motor areas. We additionally observed an intra-hemispheric increased functional connectivity between primary and secondary somatosensory regions, and between the primary and premotor areas, contralateral to amputation. These functional connectivity changes in specialized small-scale sensory-motor networks improve our understanding of the functional impact of lower limb amputation in the brain. Our findings in a selective group of patients with phantom limb sensations, but without pain suggest that disinhibition of neural inputs following traumatic limb amputation disrupts sensorimotor topology, unbalancing functional brain network organization. These findings step up the description of brain plasticity related with phantom sensations by showing that pain is not critical for sensorimotor network changes after peripheral injury.

Observing Grasping Actions Directed to Emotion-Laden Objects: Effects upon Corticospinal Excitability.

The motor system is recruited whenever one executes an action as well as when one observes the same action being executed by others. Although it is well established that emotion modulates the motor system, the effect of observing other individuals acting in an emotional context is particularly elusive. The main aim of this study was to investigate the effect induced by the observation of grasping directed to emotion-laden objects upon corticospinal excitability (CSE). Participants classified video-clips depicting the right-hand of an actor grasping emotion-laden objects. Twenty video-clips differing in terms of valence but balanced in arousal level were selected. Motor evoked potentials (MEPs) were then recorded from the first dorsal interosseous using transcranial magnetic stimulation (TMS) while the participants observed the selected emotional video-clips. During the video-clip presentation, TMS pulses were randomly applied at one of two different time points of grasping: (1) maximum grip aperture, and (2) object contact time. CSE was higher during the observation of grasping directed to unpleasant objects compared to pleasant ones. These results indicate that when someone observes an action of grasping directed to emotion-laden objects, the effect of the object valence promotes a specific modulation over the motor system.

Electroconvulsive therapy in obsessive-compulsive disorder: a chart review and evaluation of its potential therapeutic effects.

In a chart review of patients with obsessive-compulsive disorder (OCD) attending a university clinic, ECT was prescribed for five subjects (1.2%), only because of severe intervening manic (N=1) or depressive episodes (N=4). Although affective symptoms improved in four of the five patients, OCD symptoms remained unchanged (N=3) or transiently worsened (N=2).

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex.

Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke.

Balance Impairments after Brachial Plexus Injury as Assessed through Clinical and Posturographic Evaluation.

OBJECTIVE: To investigate whether a sensorimotor deficit of the upper limb following a brachial plexus injury (BPI) affects the upright balance. DESIGN: Eleven patients with a unilateral BPI and 11 healthy subjects were recruited. The balance assessment included the Berg Balance Scale (BBS), the number of feet touches on the ground while performing a 60 s single-leg stance and posturographic assessment (eyes open and feet placed hip-width apart during a single 60 s trial). The body weight distribution (BWD) between the legs was estimated from the center of pressure (COP) lateral position. The COP variability was quantified in the anterior-posterior and lateral directions. RESULTS: BPI patients presented lower BBS scores (p = 0.048) and a higher frequency of feet touches during the single-leg stance (p = 0.042) compared with those of the healthy subjects. An asymmetric BWD toward the side opposite the affected arm was shown by 73% of BPI patients. Finally, higher COP variability was observed in BPI patients compared with healthy subjects for anterior-posterior (p = 0.020), but not for lateral direction (p = 0.818). CONCLUSIONS: This study demonstrates that upper limb sensorimotor deficits following BPI affect body balance, serving as a warning for the clinical community about the need to prevent and treat the secondary outcomes of this condition.

Motor imagery modulation of postural sway is accompanied by changes in the EMG-COP association.

Motor imagery (MI) performed in an upright stance promotes increases in postural sway without changes in usual amplitude measures of calf muscle EMG. However, postural muscle activity can also be determined from the temporal association between EMG and center of pressure (COP) displacements. In this study we investigated whether the MI modulation of postural sway is accompanied by changes in EMG-COP association. Surface EMG from the lateral gastrocnemius (LG) muscle and COP coordinates were collected from 12 subjects while they imagined themselves performing a rising on tiptoes movement via kinesthetic or visual imagery. As a control condition subjects were requested to imagine singing a song. The standard deviation of the forward-backward COP sway and the coefficient of variation of the EMG were calculated and compared across tasks. The degree of association between COP sways and LG activity was evaluated through a cross-correlation function. Kinesthetic imagery promoted a larger COP displacement than both visual and control imagery (p<0.02). No difference in EMG amplitude was observed across imagery tasks (p=0.08). Crucially, we found a stronger EMG-COP association during kinesthetic imagery compared to control imagery (p=0.02), whereas the EMG-COP association in visual imagery was not different from that observed during kinesthetic or control imagery (p>0.19). In conclusion, kinesthetic imagery resulted in a higher EMG-COP temporal association. Subliminal fringe mechanisms may account for the imagery effects on muscle activity and postural sway during upright stance.

Motor imagery modulation of body sway is task-dependent and relies on imagery ability.

In this study we investigate to what extent the effects of motor imagery on postural sway are constrained by movement features and the subject's imagery ability. Twenty-three subjects were asked to imagine three movements using the kinesthetic modality: rising on tiptoes, whole-body forward reaching, and whole-body lateral reaching. After each task, subjects reported the level of imagery vividness and were subsequently grouped into a HIGH group (scores ≥3, "moderately intense" imagery) or a LOW group (scores ≤2, "mildly intense" imagery). An eyes closed trial was used as a control task. Center of gravity (COG) coordinates were collected, along with surface EMG of the deltoid (medial and anterior portion) and lateral gastrocnemius muscles. COG variability was quantified as the amount of fluctuations in position and velocity in the forward-backward and lateral directions. Changes in COG variability during motor imagery were observed only for the HIGH group. COG variability in the forward-backward direction was increased during the rising on tiptoes imagery, compared with the control task (p = 0.01) and the lateral reaching imagery (p = 0.02). Conversely, COG variability in the lateral direction was higher in rising on tiptoes and lateral reaching imagery than during the control task (p < 0.01); in addition, COG variability was higher during the lateral reaching imagery than in the forward reaching imagery (p = 0.02). EMG analysis revealed no effects of group (p > 0.08) or task (p > 0.46) for any of the tested muscles. In summary, motor imagery influences body sway dynamics in a task-dependent manner, and relies on the subject' imagery ability.

Modulation of the response to a somatosensory stimulation of the hand during the observation of manual actions.

Observation of hand movements has been repeatedly demonstrated to increase the excitability of the motor cortical representation of the hand. Little attention, however, has been devoted to its effect on somatosensory processing. Movement execution is well known to decrease somatosensory cortical excitability, a phenomenon termed 'gating'. As executed and observed actions share common cortical representations, we hypothesized that action observation (hand movements) should also modulate the cortical response to sensory stimulation of the hand. Seventeen healthy subjects participated in these experiments in which electroencephalographic (EEG) recordings of the somatosensory steady-state response (SSSR) were obtained. The SSSR provides a continuous measure of somatosensory processing. Recordings were made during a baseline condition and five observation conditions in which videos showed either a: (1) hand action; (2) passive stimulation of a hand; (3) static hand; (4) foot action; or (5) static object. The method employed consisted of applying a continuous 25 Hz vibratory stimulation to the index finger during the six conditions and measuring potential gating effects in the SSSR within the 25 Hz band (corresponding to the stimulation frequency). A significant effect of condition was found over the contralateral parietal cortex. Observation of hand actions resulted in a significant gating effect when compared to baseline (average gating of 22%). Observation of passive touch of the hand also gated the response (17% decrease). In conclusion, the results show that viewing a hand performing an action or being touched interferes with the processing of somatosensory information arising from the hand.

Re-emergence of hand-muscle representations in human motor cortex after hand allograft.

The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex.

A freezing-like posture to pictures of mutilation.

Postural sway and heart rate were recorded in young men viewing emotionally engaging pictures. It was hypothesized that they would show a human analog of "freezing" behavior (i.e., immobility and heart rate deceleration) when confronted with a sustained block of unpleasant (mutilation) images, relative to their response to pleasant/arousing (sport action) or neutral (objects) pictures. Volunteers stood on a stabilometric platform during picture viewing. Significantly reduced body sway was recorded during the unpleasant pictures, along with increased mean power frequency (indexing muscle stiffness). Heart rate during unpleasant pictures also showed the expected greater deceleration. This pattern resembles the "freezing" and "fear bradycardia" seen in many species when confronted with threatening stimuli, mediated by neural circuits that promote defensive survival.