Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning.

Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A-hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

Multiple, random spot urine sampling for estimating urinary sodium excretion.

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%.Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection.

Machine learning methods detect arm movement impairments in a patient with parieto-occipital lesion using only early kinematic information.

Patients with lesions of the parieto-occipital cortex typically misreach visual targets that they correctly perceive (optic ataxia). Although optic ataxia was described more than 30 years ago, distinguishing this condition from physiological behavior using kinematic data is still far from being an achievement. Here, combining kinematic analysis with machine learning methods, we compared the reaching performance of a patient with bilateral occipitoparietal damage with that of 10 healthy controls. They performed visually guided reaches toward targets located at different depths and directions. Using the horizontal, sagittal, and vertical deviation of the trajectories, we extracted classification accuracy in discriminating the reaching performance of patient from that of controls. Specifically, accurate predictions of the patient's deviations were detected after the 20% of the movement execution in all the spatial positions tested. This classification based on initial trajectory decoding was possible for both directional and depth components of the movement, suggesting the possibility of applying this method to characterize pathological motor behavior in wider frameworks.

Distress in Infants and Young Children: Don't Blame Acid Reflux.

OBJECTIVE: The role of gastroesophageal reflux (GER) causing distress in infants is controversial but acid inhibitors are often empirically prescribed. We evaluated the relation between distress assessed by the Face, Legs, Activity, Cry, Consolability (FLACC) scale and GER in infants. METHODS: We analyzed multiple intraluminal impedance-pH (MII-pH) monitoring tracings of infants with persistent unexplained fussiness or distress. Symptoms occurring during investigation were scored by parents using the FLACC scale and were grouped as "distress" episodes. RESULTS: We recruited 62 children (ages 15 days to 23 months, median age 3.5 months). During MII-pH, 452 episodes of distress were registered: 217 (48%) were temporally associated with GER and 235 (52%) were not, with no difference in the median value of FLACC between the 2 groups. Infants with abnormal acid exposure index had a significantly lower FLACC compared with the group with acid reflux index <7% (P < 0.001). When associated with symptoms, GER occurred significantly more often before than simultaneously or after an episode of distress (P = 0.001). Age, proximal extension, and duration of GER did not correlate with FLACC scores. Episodes of distress associated with nonacid reflux presented a significant higher FLACC compared with the ones with acid content (FLACC 6 vs 5, P = 0.011). In infants, episodes of distress do not significantly correlate with GER. CONCLUSIONS: No difference in infant distress was noted between proximal and distal GER. Non-acid reflux is perceived at least as painful than acid GER. Our results stress that acid inhibitors should not be started in infants presenting distress unless a clear association with acid GER is demonstrated.

Trans-saccadic adaptation of perceived size independent of saccadic adaptation.

Systematic shortening or lengthening of target objects during saccades modifies saccade amplitudes and perceived size of the objects. These two events are concomitant when size change during the saccade occurs asymmetrically, thereby shifting the center of mass of the object. In the present study, we asked whether or not the two are necessarily linked. We tested human participants in symmetrical systematic shortening and lengthening of a vertical bar during a horizontal saccade, aiming to not modify the saccade amplitude. Before and after a phase of trans-saccadic changes of the target bar, participants manually indicated the sizes of various vertically oriented bars by open-loop grip aperture. We evaluated the effect of trans-saccadic changes of bar length on manual perceptual reports and whether this change depended on saccade amplitude. As expected, we did not induce any change in horizontal or vertical components of saccade amplitude, but we found a significant difference in perceived size after the lengthening experiment compared to after the shortening experiment. Moreover, after the lengthening experiment, perceived size differed significantly from pre-lengthening baseline. These findings suggest that a change of size perception can be induced trans-saccadically, and its mechanism does not depend on saccadic amplitude change.

Interplay Between Grip and Vision in the Monkey Medial Parietal Lobe.

We aimed at understanding the relative contribution of visual information and hand shaping to the neuronal activity of medial posterior parietal area V6A, a newly added area in the monkey cortical grasping circuit. Two Macaca fascicularis performed a Reach-to-Grasp task in the dark and in the light, grasping objects of different shapes. We found that V6A contains Visual cells, activated only during grasping in the light; Motor neurons, equally activated during grasping in the dark and in the light; Visuomotor cells, differently activated while grasping in the dark and in the light. Visual, Motor, and Visuomotor neurons were moderately or highly selective during grasping, whereas they reduced their selectivity during object observation without performing grasping. The use of the same experimental design employed in the dorsolateral grasping area AIP by other authors allowed us to compare the grasp-related properties of V6A and AIP. From these data and from the literature a frame emerges with many similarities between medial grasping area V6A and lateral grasping area AIP: both areas update and control prehension, with V6A less sensitive than AIP to fine visual details of the objects to be grasped, but more involved in coordinating reaching and grasping.

Decoding Information for Grasping from the Macaque Dorsomedial Visual Stream.

Neurodecoders have been developed by researchers mostly to control neuroprosthetic devices, but also to shed new light on neural functions. In this study, we show that signals representing grip configurations can be reliably decoded from neural data acquired from area V6A of the monkey medial posterior parietal cortex. Two Macaca fascicularis monkeys were trained to perform an instructed-delay reach-to-grasp task in the dark and in the light toward objects of different shapes. Population neural activity was extracted at various time intervals on vision of the objects, the delay before movement, and grasp execution. This activity was used to train and validate a Bayes classifier used for decoding objects and grip types. Recognition rates were well over chance level for all the epochs analyzed in this study. Furthermore, we detected slightly different decoding accuracies, depending on the task's visual condition. Generalization analysis was performed by training and testing the system during different time intervals. This analysis demonstrated that a change of code occurred during the course of the task. Our classifier was able to discriminate grasp types fairly well in advance with respect to grasping onset. This feature might be important when the timing is critical to send signals to external devices before the movement start. Our results suggest that the neural signals from the dorsomedial visual pathway can be a good substrate to feed neural prostheses for prehensile actions.SIGNIFICANCE STATEMENT Recordings of neural activity from nonhuman primate frontal and parietal cortex have led to the development of methods of decoding movement information to restore coordinated arm actions in paralyzed human beings. Our results show that the signals measured from the monkey medial posterior parietal cortex are valid for correctly decoding information relevant for grasping. Together with previous studies on decoding reach trajectories from the medial posterior parietal cortex, this highlights the medial parietal cortex as a target site for transforming neural activity into control signals to command prostheses to allow human patients to dexterously perform grasping actions.

Vision for Prehension in the Medial Parietal Cortex.

In the last 2 decades, the medial posterior parietal area V6A has been extensively studied in awake macaque monkeys for visual and somatosensory properties and for its involvement in encoding of spatial parameters for reaching, including arm movement direction and amplitude. This area also contains populations of neurons sensitive to grasping movements, such as wrist orientation and grip formation. Recent work has shown that V6A neurons also encode the shape of graspable objects and their affordance. In other words, V6A seems to encode object visual properties specifically for the purpose of action, in a dynamic sequence of visuomotor transformations that evolve in the course of reach-to-grasp action.We propose a model of cortical circuitry controlling reach-to-grasp actions, in which V6A acts as a comparator that monitors differences between current and desired hand positions and configurations. This error signal could be used to continuously update the motor output, and to correct reach direction, hand orientation, and/or grip aperture as required during the act of prehension.In contrast to the generally accepted view that the dorsomedial component of the dorsal visual stream encodes reaching, but not grasping, the functional properties of V6A neurons strongly suggest the view that this area is involved in encoding all phases of prehension, including grasping.

Reaching and grasping actions and their context shape the perception of object size.

Humans frequently estimate the size of objects to grasp them. In fact, when performing an action, our perception is focused towards the visual properties of the object that enable us to successfully execute the action. However, the motor system is also able to influence perception, but only a few studies have reported evidence for action-induced visual perception modifications. Here, we aimed to look for a feature-specific perceptual modulation before and after a reaching or a grasping action. Human participants were instructed to either reach for or grasp two-dimensional bars of different size and to perform a size perceptual task before and after the action in two contexts: in one where they knew the subsequent type of movement and in the other where they did not know. We found significant modifications of perceived size of stimuli more pronounced after grasping than after reaching. The mere knowledge of the subsequent action type significantly affected the size perception before the movement execution, with consistent results in both manual and verbal reports. These data represent direct evidence that, in natural conditions without manipulation of visual information, the action type and the action context dynamically modulate size perception, by shaping it according to relevant information required to recognize and interact with objects.

Adaptation of Saccades and Perceived Size after Trans-Saccadic Changes of Object Size.

When saccadic eye movements consistently fail to land on the intended target, saccade accuracy is maintained by gradually adapting the amplitude of successive saccades to the same target. Such saccadic adaptation is usually induced by systematically displacing a small visual target during the execution of the saccade. However, saccades are normally performed to extended objects. Here we report changes in saccade amplitude when the size of a target object is systematically changed during a saccade. Moreover, we find that this manipulation also affected the visual perception of the size of that object. Human subjects were tested in shortening and lengthening adaptation where they had to make saccades to targets of different sizes, which were each shortened or lengthened during saccade execution, respectively. In both experiments, a preadaptation and postadaptation phase required manually indicating the horizontal size of each target by grip aperture and, in a further experiment, a verbal size report. We evaluated the effect of change in visual perception on saccade and on the two modalities of judgment. We observed that (1) saccadic adaptation can be induced by modifying target object size and (2) this gradual change in saccade amplitude in the direction of the object size change evokes a concomitant change in perceived object size. These findings suggest that size is a relevant signal for saccadic system and its trans-saccadic manipulation entails considerable changes at multiple levels of sensorimotor performance.

Object affordance modulates visual responses in the macaque medial posterior parietal cortex.

Area V6A is a visuomotor area of the dorsomedial visual stream that contains cells modulated by object observation and by grip formation. As different objects have different shapes but also evoke different grips, the response selectivity during object presentation could reflect either the coding of object geometry or object affordances. To clarify this point, we here investigate neural responses of V6A cells when monkeys observed two objects with similar visual features but different contextual information, such as the evoked grip type. We demonstrate that many V6A cells respond to the visual presentation of objects and about 30% of them by the object affordance. Given that area V6A is an early stage in the visuomotor processes underlying grasping, these data suggest that V6A may participate in the computation of object affordances. These results add some elements in the recent literature about the role of the dorsal visual stream areas in object representation and contribute in elucidating the neural correlates of the extraction of action-relevant information from general object properties, in agreement with recent neuroimaging studies on humans showing that vision of graspable objects activates action coding in the dorsomedial visual steam.

Saccadic adaptation shapes visual space in macaques.

Saccadic eye movements are an integral part of many visually guided behaviors. Recent research in humans has shown that processes which control saccades are also involved in establishing perceptual space: A shift in object localization during fixation occurred after saccade amplitudes had been shortened or lengthened by saccadic adaptation. We tested whether similar effects can be established in nonhuman primates. Two trained macaque monkeys localized briefly presented stimuli on a touch screen by indicating the memorized target position with the hand on the screen. The monkeys performed this localization task before and after saccade amplitudes were modified through saccadic adaptation. During localization trials they had to maintain fixation. Successful saccadic adaptation led to a concurrent shift of the touched position on the screen. This mislocalization occurred for both adaptive shortening and lengthening of saccade amplitude. We conclude that saccadic adaptation has the potential to influence localization performance in monkeys, similar to the results found in humans.

rTMS over the human medial parietal cortex impairs online reaching corrections.

Indirect correlational evidence suggests that the posteromedial sector of the human parietal cortex (area hV6A) is involved in reaching corrections. We interfered with hV6A functions using repetitive transcranial magnetic stimulation (rTMS) while healthy participants performed reaching movements and in-flight adjustments of the hand trajectory in presence of unexpected target shifts. rTMS over hV6A specifically altered action reprogramming, causing deviations of the shifted trajectories, particularly along the vertical dimension (i.e., distance). This study provides evidence of the functional relevance of hV6A in action reprogramming while a sudden event requires a change in performance and shows that hV6A also plays a role in state estimation during reaching. These findings are in line with neurological data showing impairments in actions performed along the distance dimension when lesions occur in the dorsal posterior parietal cortex.

Vision for action in the macaque medial posterior parietal cortex.

Area V6A encodes hand configurations for grasping objects (Fattori et al., 2010). The aim of the present study was to investigate whether V6A cells also encode three-dimensional objects, and the relationship between object encoding and grip encoding. Single neurons were recorded in V6A of two monkeys trained to perform two tasks. In the first task, the monkeys were required to passively view an object without performing any action on it. In the second task, the monkeys viewed an object at the beginning of each trial and then they needed to grasp that object in darkness. Five different objects were used. Both tasks revealed that object presentation activates ∼60% of V6A neurons, with about half of them displaying object selectivity. In the Reach-to-Grasp task, the majority of V6A cells discharged during both object presentation and grip execution, displaying selectivity for either the object or the grip, or in some cases for both object and grip. Although the incidence of neurons encoding grips was twofold that of neurons encoding objects, object selectivity in single cells was as strong as grip selectivity, indicating that V6A cells were able to discriminate both the different objects and the different grips required to grasp them. Hierarchical cluster analysis revealed that clustering of the object-selective responses depended on the task requirements (view only or view to grasp) and followed a visual or a visuomotor rule, respectively. Object encoding in V6A reflects representations for action, useful for motor control in reach-to-grasp.

Eye position encoding in three-dimensional space: integration of version and vergence signals in the medial posterior parietal cortex.

Eye position signals are pivotal in the visuomotor transformations performed by the posterior parietal cortex (PPC), but to date there are few studies addressing the influence of vergence angle upon single PPC neurons. In the present study, we investigated the influence on single neurons of the medial PPC area V6A of vergence and version signals. Single-unit activity was recorded from V6A in two Macaca fascicularis fixating real targets in darkness. The fixation targets were placed at eye level and at different vergence and version angles within the peripersonal space. Few neurons were modulated by version or vergence only, while the majority of cells were affected by both signals. We advance here the hypothesis that gaze-modulated V6A cells are able to encode gazed positions in the three-dimensional space. In single cells, version and vergence influenced the discharge with variable time course. In several cases, the two gaze variables influence neural discharges during only a part of the fixation time, but, more often, their influence persisted through large parts of it. Cells discharging for the first 400-500 ms of fixation could signal the arrival of gaze (and/or of spotlight of attention) in a new position in the peripersonal space. Cells showing a more sustained activity during the fixation period could better signal the location in space of the gazed objects. Both signals are critical for the control of upcoming or ongoing arm movements, such as those needed to reach and grasp objects located in the peripersonal space.

The influence of action on perception spans different effectors.

Perception and action are fundamental processes that characterize our life and our possibility to modify the world around us. Several pieces of evidence have shown an intimate and reciprocal interaction between perception and action, leading us to believe that these processes rely on a common set of representations. The present review focuses on one particular aspect of this interaction: the influence of action on perception from a motor effector perspective during two phases, action planning and the phase following execution of the action. The movements performed by eyes, hands, and legs have a different impact on object and space perception; studies that use different approaches and paradigms have formed an interesting general picture that demonstrates the existence of an action effect on perception, before as well as after its execution. Although the mechanisms of this effect are still being debated, different studies have demonstrated that most of the time this effect pragmatically shapes and primes perception of relevant features of the object or environment which calls for action; at other times it improves our perception through motor experience and learning. Finally, a future perspective is provided, in which we suggest that these mechanisms can be exploited to increase trust in artificial intelligence systems that are able to interact with humans.

Biases in the spectral amplitude distribution of a natural scene modulate horizontal size perception.

Introduction: Visual perception is a complex process that involves the analysis of different spatial and temporal features of the visual environment. One critical aspect of this process is adaptation, which allows the visual system to adjust its sensitivity to specific features based on the context of the environment. Numerous theories highlight the significance of the visual scene and its spectral properties in perceptual and adaptation mechanisms. For example, size perception is known to be influenced by the spatial frequency content of the visual scene. Nonetheless, several inquiries still exist, including how specific spectral properties of the scene play a role in size perception and adaptation mechanisms. Methods: In this study, we explore aftereffects on size perception following adaptation to a natural scene with a biased spectral amplitude distribution. Twenty participants had to manually estimate the horizontal size of a projected rectangle after adaptation to three visually biased conditions: vertical-biased, non-biased, and horizontal-biased. Size adaptation aftereffects were quantified by comparing the perceptual responses from the non-biased condition with the vertical- and horizontal-biased conditions. Results: We found size perception shifts which were contingent upon the specific orientation and spatial frequency distribution inherent in the amplitude spectra of the adaptation stimuli. Particularly, adaptation to vertical-biased produced a horizontal enlargement, while adaptation to horizontal-biased generated a decrease in the horizontal size perception of the rectangle. On average, size perception was modulated by 5-6%. Discussion: These findings provide supporting evidence for the hypothesis that the neural mechanisms responsible for processing spatial frequency channels are involved in the encoding and perception of size information. The implications for neural mechanisms underlying spatial frequency and size information encoding are discussed.

Is the medial posterior parietal area V6A a single functional area?

The visuomotor medial posterior parietal area V6A has been recently subdivided into two cytoarchitectonic sectors called V6Ad and V6Av (Luppino et al., 2005). The aim of the present study was to recognize whether these two cortical sectors show different functional profiles. Fourteen hemispheres from eight animals (Macaca fascicularis) were included in this study, for a total of 3828 extracellularly recorded neurons assigned to areas V6Ad or V6Av on cytoarchitectural basis. The sensitivity of recorded neurons to sensory- and motor-related activities was checked with a series of functional tests performed on behaving animals. We found that cells sensitive to visual stimuli were more represented in V6Av and cells sensitive to somatosensory stimuli were more represented in V6Ad. Visual cells directly encoding spatial locations (real-position cells) were present only in V6Av. Cells encoding basic visual and somatic properties as well as different aspects of reaching and grasping activities were present in both sectors of V6A, although with different incidence. Cells that had reach-related activity enhanced by visual feedback and grasping neurons activated by whole-hand prehension were more concentrated in V6Av. Conversely, reaching neurons inhibited by visual feedback and grasping neurons activated by precision grip were more represented in V6Ad. Although V6Av and V6Ad show partly different functional profiles, our data support the idea that V6A is a single functional area involved in the control of reach-to-grasp movements, with the dorsal sector (V6Ad) more involved in the somatomotor control and the ventral sector (V6Av) in the visual control of reaching and grasping actions.

Eye position effects in saccadic adaptation in macaque monkeys.

The saccadic amplitude of humans and monkeys can be adapted using intrasaccadic target steps in the McLaughlin paradigm. It is generally believed that, as a result of a purely retinal reference frame, after adaptation of a saccade of a certain amplitude and direction, saccades of the same amplitude and direction are all adapted to the same extent, independently from the initial eye position. However, recent studies in humans have put the pure retinal coding in doubt by revealing that the initial eye position has an effect on the transfer of adaptation to saccades of different starting points. Since humans and monkeys show some species differences in adaptation, we tested the eye position dependence in monkeys. Two trained Macaca fascicularis performed reactive rightward saccades from five equally horizontally distributed starting positions. All saccades were made to targets with the same retinotopic motor vector. In each session, the saccades that started at one particular initial eye position, the adaptation position, were adapted to shorter amplitude, and the adaptation of the saccades starting at the other four positions was measured. The results show that saccades that started at the other positions were less adapted than saccades that started at the adaptation position. With increasing distance between the starting position of the test saccade and the adaptation position, the amplitude change of the test saccades decreased with a Gaussian profile. We conclude that gain-decreasing saccadic adaptation in macaques is specific to the initial eye position at which the adaptation has been induced.

Severe lactic acidosis and persistent diastolic hypotension following standard dose of intermittent nebulized salbutamol in a child: a case report.

BACKGROUND: Salbutamol is a selective ß2-receptor agonist widely used to treat asthma in both emergency and outpatient settings. However, it has been associated with a broad spectrum of side effects. Lactic acidosis and diastolic hypotension are rarely reported together following intermittent salbutamol nebulization in children, even less so at standard therapeutic doses. CASE PRESENTATION: We present the case of a 12-year-old Italian boy, 34 kg body weight, who experienced a serious drug reaction during a moderate asthma exacerbation with associated dehydration (blood urea nitrogen/creatinine 0.25), following intermittent inhaled (0.2 mg at 3-hour intervals-overall 1.4 mg in 24 hours before arrival) and nebulized treatment (3.25 mg at 20-minute intervals in 60 minutes, overall 11.25 mg in our emergency department). The patient developed hyperglycemia (peak concentration 222 mg/dL), hypokalemia (lowest concentration 2.6 mEq/L), electrocardiogram alterations (corrected QT interval 467 ms), long-lasting arterial hypotension despite fluid boluses (lowest value 87/33 mmHg), and elevated blood lactate levels (peak concentration 8.1 mmol/L), following the third nebulized dose. Infections, liver dysfunction, and toxicity following other medications were ruled out. The aforementioned alterations improved within 24 hours after discontinuation of salbutamol. CONCLUSIONS: We reinforce the message that even the use of intermittent nebulized salbutamol for acute moderate asthma can lead to severe transient complications in children. Then, healthcare providers should pay attention not only in emergency settings, to achieve prompt recognition and proper management of this adverse reaction. Careful reassessment could prevent similar reactions.