Mixed selectivity in monkey anterior intraparietal area during visual and motor processes.

Classical studies suggest that the anterior intraparietal area (AIP) contributes to the encoding of specific information such as objects and actions of self and others, through a variety of neuronal classes, such as canonical, motor and mirror neurons. However, these studies typically focused on a single variable, leaving it unclear whether distinct sets of AIP neurons encode a single or multiple sources of information and how multimodal coding emerges. Here, we chronically recorded monkey AIP neurons in a variety of tasks and conditions classically employed in separate experiments. Most cells exhibited mixed selectivity for observed objects, executed actions, and observed actions, enhanced when this information came from the monkey's peripersonal working space. In contrast with the classical view, our findings indicate that multimodal coding emerges in AIP from partially-mixed selectivity of individual neurons for a variety of information relevant for planning actions directed to both physical objects and other subjects.

Morphological variations on vital systems in a conjoined twin.

Conjoined twins (CTs), popularly referred to as Siamese twins, are a rare anomaly due to monochorionic and monoamniotic twin pregnancies. Dicephalus dibrachius dipus, a type of parapagus conjoined twin which is characterized by possessing two arms, two legs, a single trunk and two heads, epidemiologically, is an even rarer occurrence of CTs. In this article, a rare, well-preserved anatomical specimen of a dicephalus dibrachius dipus conjoined twin is presented. This study was conducted in a specimen which is part of the collection of the Embryology Museum of the institution by donation and approved by the Research Ethics Committee (REC). The female conjoined twins were born at full-term by cesarean section in the 1970s and died hours after birth. A thorough anatomical description was made through observational analysis, computed tomography and 3D reconstructed images. Major abnormalities were observed in the cardiovascular, respiratory and digestive systems. The internal anatomy exhibited a heart with three atria, two ventricles, two aortic arches, two pulmonary arteries, one innominate venous trunk and a respiratory system with two tracheas and four lungs. No other report was similar to our three atria heart description. This article provides a thorough anatomical description of all systems, which is valuable information for further studies on CTs.

Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions.

Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly understood. Here, we directly compared the response properties of putative pyramidal neurons (PNs) and GABAergic fast-spiking neurons (FSNs) during spontaneous licking and forelimb movements in male mice. Recordings centered on the face/mouth motor field of the anterolateral motor cortex (ALM) revealed that FSNs fire longer than PNs and earlier for licking, but not for forelimb movements. Computational analysis revealed that FSNs carry vastly more information than PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most FSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs than PNs. Finally, optogenetic silencing of a subset of FSNs reduced spontaneous licking movement. These data suggest that a global rise of inhibition contributes to the initiation and execution of spontaneous motor actions.SIGNIFICANCE STATEMENT Our study contributes to clarifying the causal role of fast-spiking neurons (FSNs) in driving initiation and execution of specific, spontaneous movements. Within the face/mouth motor field of mice premotor cortex, FSNs fire before pyramidal neurons (PNs) with a specific activation pattern: they reach their peak of activity earlier than PNs during the initiation of licking, but not of forelimb, movements; duration of FSNs activity is also greater and exhibits less selectivity for the movement type, as compared with that of PNs. Accordingly, FSNs appear to carry more redundant information than PNs. Optogenetic silencing of FSNs reduced spontaneous licking movement, suggesting that FSNs contribute to the initiation and execution of specific spontaneous movements, possibly by sculpting response selectivity of nearby PNs.

Combined use of minimal screw synthesis and external articulated fixation is effective for the management of supra-intercondyloid humeral fractures in the elderly? A retrospective study.

Background: Fractures of the distal humerus are relatively rare and can be a source of disabling outcomes especially if not properly treated. Therefore, the objective of the treatment must be to obtain a stable synthesis that allows early mobilization, avoiding complications such as muscular hypotonotrophy, joint rigidity or delays in consolidation that may be due to prolonged immobilization of this joint. Although ORIF treatment of these fractures may intuitively appear to be the gold standard, there is still no consensus in the literature on which type of treatment is most suitable. Patients and method: We report in this retrospective case series analysis our experience on 31 elder patients (more than 65 years old), affected by a supra-intercondyloid humerus fracture, treated using a minimal internal fixation with cannulated screws combined with the use of an external articulated elbow fixator. This methodology is less invasive but allows a stable synthesis and an early mobilization.Clinical and radiographic examinations were performed for each patient at 1, 2, 3 and 6 months after surgery. At 6 months the residual joint excursion was evaluated and the data were collected. In addition, at 6 months, each patient underwent three different functional capacity assessment questionnaires: MAYO Elbow Performance score, The Disability of the ARM, Shoulder and Hand Score (QuickDASH) and Oxford Elbow Score. Results: The healing rate was 100% with no cases of non-union, despite the old age of our patients. The average range of motions obtained at 6 months from the surgery was 111° in flexion-extension and 157° in pronation-supination for the patient with an extra-articular fracture, 88° in flexion-extension and 153° in pronation-supination for the patients with a partial articular fracture and 85° in flexion-extension and 149° in pronation-supination for the patients with a complete articular fracture. Our results in the recovery of an arc of motion in flexion-extension are slightly less performing than the results obtained with an ORIF treatment. Indeed, according to literature the mean postoperative flexion arc in an ORIF treatment of distal humerus fractures in adults is 110°.The functional results obtained were satisfactory, with an average score at 6 months from the surgery of 95/100 (Mayo score) for the patients with an extra-articular fracture, 83.3/100 for the patients with a partial articular fracture and 79/100 for the patients with a complete articular fracture. Conclusion: The results obtained, in terms of range of motions, function, pain and healing and complications rate lead us to affirm that, in selected patients, this technique can represent a valid treatment and therefore a valid option that could be considered.

Mirror neurons 30 years later: implications and applications.

Mirror neurons (MNs) were first described in a seminal paper in 1992 as a class of monkey premotor cells discharging during both action execution and observation. Despite their debated origin and function, recent studies in several species, from birds to humans, revealed that beyond MNs properly so called, a variety of cell types distributed among multiple motor, sensory, and emotional brain areas form a 'mirror mechanism' more complex and flexible than originally thought, which has an evolutionarily conserved role in social interaction. Here, we trace the current limits and envisage the future trends of this discovery, showing that it inspired translational research and the development of new neurorehabilitation approaches, and constitutes a point of no return in social and affective neuroscience.

Use of a Plasma-Sprayed Titanium-Hydroxyapatite Femoral Stem in Hip Arthroplasty in Patients Older than 70 Years. Is Cementless Fixation a Reliable Option in the Elderly?

BACKGROUND: Although cementless implants are increasing in popularity, the use of cementless femoral stems for total hip arthroplasty (THA) and hip hemiarthroplasty (HH) in elderly patients remains controversial. The aim of this study was to report the outcomes of a cementless stem used in a large multicentric cohort of elderly patients receiving elective THA and HH for displaced femoral neck fracture. METHODS: A total of 293 patients (301 hips) aged 70 years or older (mean age, 78 years; range, 70-93) who received the same cementless plasma-sprayed porous titanium-hydroxyapatite stem were retrospectively evaluated after primary THA and HH to investigate stem survival, complications, and clinical and radiographic results. RESULTS: Cumulative stem survival was 98.5% (95% CI, 96.4-99.4%; 91 hips at risks) with revision due to any reason as the end-point at 10-year follow-up (mean 8.6 years, range 4-12). No stem was revised due to aseptic loosening. The mean Forgotten Joint Score was 98.7. Radiographically, the implants showed complete osseointegration, with slight stress-shieling signs in less than 10% of the hips. CONCLUSION: The use of cementless stems was proven to be a reliable and versatile option even in elderly patients for elective THA and HH for femoral neck fracture.

Parietal maps of visual signals for bodily action planning.

The posterior parietal cortex (PPC) has long been understood as a high-level integrative station for computing motor commands for the body based on sensory (i.e., mostly tactile and visual) input from the outside world. In the last decade, accumulating evidence has shown that the parietal areas not only extract the pragmatic features of manipulable objects, but also subserve sensorimotor processing of others' actions. A paradigmatic case is that of the anterior intraparietal area (AIP), which encodes the identity of observed manipulative actions that afford potential motor actions the observer could perform in response to them. On these bases, we propose an AIP manipulative action-based template of the general planning functions of the PPC and review existing evidence supporting the extension of this model to other PPC regions and to a wider set of actions: defensive and locomotor actions. In our model, a hallmark of PPC functioning is the processing of information about the physical and social world to encode potential bodily actions appropriate for the current context. We further extend the model to actions performed with man-made objects (e.g., tools) and artifacts, because they become integral parts of the subject's body schema and motor repertoire. Finally, we conclude that existing evidence supports a generally conserved neural circuitry that transforms integrated sensory signals into the variety of bodily actions that primates are capable of preparing and performing to interact with their physical and social world.

Largely shared neural codes for biological and nonbiological observed movements but not for executed actions in monkey premotor areas.

The neural processing of others' observed actions recruits a large network of brain regions (the action observation network; AON) in which frontal motor areas are thought to play a crucial role. As the discovery of mirror neurons (MNs) in the ventral premotor cortex, it has been assumed that their activation was conditional upon the presentation of biological rather than nonbiological motion stimuli, supporting a form of direct visuomotor matching. Nonetheless, nonbiological observed movements have rarely been used as control stimuli to evaluate visual specificity, thereby leaving the issue of similarity among neural codes for executed actions and biological or nonbiological observed movements unresolved. Here, we addressed this issue by recording from two nodes of the AON that are attracting increasing interest, namely, the ventrorostral part of the dorsal premotor area F2 and the mesial presupplementary motor area F6 of macaques while they 1) executed a reaching-grasping task, 2) observed an experimenter performing the task, and 3) observed a nonbiological effector moving in the same context. Our findings revealed stronger neuronal responses to the observation of biological than nonbiological movement, but biological and nonbiological visual stimuli produced highly similar neural dynamics and relied on largely shared neural codes, which in turn remarkably differed from those associated with executed actions. These results indicate that, in highly familiar contexts, visuomotor remapping processes in premotor areas hosting MNs are more complex and flexible than predicted by a direct visuomotor matching hypothesis.NEW & NOTEWORTHY Pioneering studies on mirror neurons (MNs) in premotor areas emphasized the absence of response to the sight of nonbiological moving objects, suggesting a match between execution and observation activities. This study shows that although premotor neurons can discriminate between biological and nonbiological observed movements, these visual stimuli rely on largely shared neural codes, which differ strongly from those associated with executed actions.

Local and system mechanisms for action execution and observation in parietal and premotor cortices.

The action observation network (AON) includes a system of brain areas largely shared with action execution in both human and nonhuman primates. Yet temporal and tuning specificities of distinct areas and of physiologically identified neuronal classes in the encoding of self and others' action remain unknown. We recorded the activity of 355 single units from three crucial nodes of the AON, the anterior intraparietal area (AIP), and premotor areas F5 and F6, while monkeys performed a Go/No-Go grasping task and observed an experimenter performing it. At the system level, during task execution, F6 displays a prevalence of suppressed neurons and signals whether an action has to be performed, whereas AIP and F5 share a prevalence of facilitated neurons and remarkable target selectivity; during task observation, F5 stands out for its unique prevalence of facilitated neurons and its stronger and earlier modulation than AIP and F6. By applying unsupervised clustering of spike waveforms, we found distinct cell classes unevenly distributed across areas, with different firing properties and carrying specific visuomotor signals. Broadly spiking neurons exhibited a balanced amount of facilitated and suppressed activity during action execution and observation, whereas narrower spiking neurons showed more mutually facilitated responses during the execution of one's own and others' action, particularly in areas AIP and F5. Our findings elucidate the time course of activity and firing properties of neurons in the AON during one's own and others' action, from the system level of anatomically distinct areas to the local level of physiologically distinct cell classes.

Stable readout of observed actions from format-dependent activity of monkey's anterior intraparietal neurons.

Humans accurately identify observed actions despite large dynamic changes in their retinal images and a variety of visual presentation formats. A large network of brain regions in primates participates in the processing of others' actions, with the anterior intraparietal area (AIP) playing a major role in routing information about observed manipulative actions (OMAs) to the other nodes of the network. This study investigated whether the AIP also contributes to invariant coding of OMAs across different visual formats. We recorded AIP neuronal activity from two macaques while they observed videos portraying seven manipulative actions (drag, drop, grasp, push, roll, rotate, squeeze) in four visual formats. Each format resulted from the combination of two actor's body postures (standing, sitting) and two viewpoints (lateral, frontal). Out of 297 recorded units, 38% were OMA-selective in at least one format. Robust population code for viewpoint and actor's body posture emerged shortly after stimulus presentation, followed by OMA selectivity. Although we found no fully invariant OMA-selective neuron, we discovered a population code that allowed us to classify action exemplars irrespective of the visual format. This code depends on a multiplicative mixing of signals about OMA identity and visual format, particularly evidenced by a set of units maintaining a relatively stable OMA selectivity across formats despite considerable rescaling of their firing rate depending on the visual specificities of each format. These findings suggest that the AIP integrates format-dependent information and the visual features of others' actions, leading to a stable readout of observed manipulative action identity.

Author Correction: Differential neural dynamics underlying pragmatic and semantic affordance processing in macaque ventral premotor cortex.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Connectional gradients underlie functional transitions in monkey pre-supplementary motor area.

The pre-supplementary motor area F6 is involved in a variety of functions in multiple domains, from planning/withholding goal-directed actions in space to rule-based cognitive processes and social interactions. Yet, the neural machinery underlying this functional heterogeneity remains unclear. Here, we measured local population dynamics in different rostro-caudal sites of cytoarchitectonically verified area F6 in two monkeys during spatial, contextual and motor processes, both in individual and social conditions. Then, we correlated multimodal population tuning with local anatomical connectivity revealed by neural tracer injections into the functionally characterized sites. We found stronger tuning for object position relative to the monkey in the rostral portion of area F6 than in its caudal part, which in turn exhibits stronger tuning to self and other's (observed) action. Functional specificities were associated with a rostro-caudal transition in connectivity strength from lateral prefrontal cortex, pregenual anterior cingulate cortex and associative striatum (rostrally), to dorso-ventral premotor areas and the motor putamen (caudally). These findings suggest that the functional heterogeneity of the pre-supplementary area F6 is accounted for by gradual transitions in functional properties grounded on local cortico-cortical and cortico-striatal connectional specificities.

Refinement techniques in non-human primate neuroscientific research.

Non-human primates (NHP) are widely considered an essential model for biomedical research because of their close genetic, anatomo-functional and cognitive similarities to humans. These same reasons also raise particular ethical concerns for the unavoidable harm caused to these animals, in particular to those involved in neuroscientific studies. Besides reducing the number of animals needed to the absolute minimum, it is therefore essential to implement procedures allowing, at the same time, to minimize the harm to the animals and maximize the quality and ecological validity of the data. Technological progresses have made possible, for example, to self-train monkeys in their home cage with positive reinforcement techniques and to adopt various types of telemetric systems for wirelessly recording neuronal activity in freely behaving animals. Example of full application of these techniques are still very limited in the literature, but different recent international projects and pioneering studies are paving the way for turning to the use of new technologies to get a more "ethically acceptable" NHP neuroscientific research.

Differential neural dynamics underling pragmatic and semantic affordance processing in macaque ventral premotor cortex.

Premotor neurons play a fundamental role in transforming physical properties of observed objects, such as size and shape, into motor plans for grasping them, hence contributing to "pragmatic" affordance processing. Premotor neurons can also contribute to "semantic" affordance processing, as they can discharge differently even to pragmatically identical objects depending on their behavioural relevance for the observer (i.e. edible or inedible objects). Here, we compared the response of monkey ventral premotor area F5 neurons tested during pragmatic (PT) or semantic (ST) visuomotor tasks. Object presentation responses in ST showed shorter latency and lower object selectivity than in PT. Furthermore, we found a difference between a transient representation of semantic affordances and a sustained representation of pragmatic affordances at both the single neuron and population level. Indeed, responses in ST returned to baseline within 0.5 s whereas in PT they showed the typical sustained visual-to-motor activity during Go trials. In contrast, during No-go trials, the time course of pragmatic and semantic information processing was similar. These findings suggest that premotor cortex generates different dynamics depending on pragmatic and semantic information provided by the context in which the to-be-grasped object is presented.

Anterior Intraparietal Area: A Hub in the Observed Manipulative Action Network.

Current knowledge regarding the processing of observed manipulative actions (OMAs) (e.g., grasping, dragging, or dropping) is limited to grasping and underlying neural circuitry remains controversial. Here, we addressed these issues by combining chronic neuronal recordings along the anteroposterior extent of monkeys' anterior intraparietal (AIP) area with tracer injections into the recorded sites. We found robust neural selectivity for 7 distinct OMAs, particularly in the posterior part of AIP (pAIP), where it was associated with motor coding of grip type and own-hand visual feedback. This cluster of functional properties appears to be specifically grounded in stronger direct connections of pAIP with the temporal regions of the ventral visual stream and the prefrontal cortex, as connections with skeletomotor related areas and regions of the dorsal visual stream exhibited opposite or no rostrocaudal gradients. Temporal and prefrontal areas may provide visual and contextual information relevant for manipulative action processing. These results revise existing models of the action observation network, suggesting that pAIP constitutes a parietal hub for routing information about OMA identity to the other nodes of the network.

Agent-based representations of objects and actions in the monkey pre-supplementary motor area.

Information about objects around us is essential for planning actions and for predicting those of others. Here, we studied pre-supplementary motor area F6 neurons with a task in which monkeys viewed and grasped (or refrained from grasping) objects, and then observed a human doing the same task. We found "action-related neurons" encoding selectively monkey's own action [self-type (ST)], another agent's action [other-type (OT)], or both [self- and other-type (SOT)]. Interestingly, we found "object-related neurons" exhibiting the same type of selectivity before action onset: Indeed, distinct sets of neurons discharged when visually presented objects were targeted by the monkey's own action (ST), another agent's action (OT), or both (SOT). Notably, object-related neurons appear to signal self and other's intention to grasp and the most likely grip type that will be performed, whereas action-related neurons encode a general goal attainment signal devoid of any specificity for the observed grip type. Time-resolved cross-modal population decoding revealed that F6 neurons first integrate information about object and context to generate an agent-shared signal specifying whether and how the object will be grasped, which progressively turns into a broader agent-based goal attainment signal during action unfolding. Importantly, shared representation of objects critically depends upon their location in the observer's peripersonal space, suggesting an "object-mirroring" mechanism through which observers could accurately predict others' impending action by recruiting the same motor representation they would activate if they were to act upon the same object in the same context.

Cortical and subcortical connections of parietal and premotor nodes of the monkey hand mirror neuron network.

Mirror neurons (MNs) are a class of cells originally discovered in the monkey ventral premotor cortex (PMv) and inferior parietal lobule (IPL). They discharge during both action execution and action observation and appear to play a crucial role in understanding others' actions. It has been proposed that the mirror mechanism is based on a match between the visual description of actions, encoded in temporal cortical regions, and their motor representation, provided by PMv and IPL. However, neurons responding to action observation have been recently found in other cortical regions, suggesting that the mirror mechanism relies on a wider network. Here we provide the first description of this network by injecting neural tracers into physiologically identified IPL and PMv sectors containing hand MNs. Our results show that these sectors are reciprocally connected, in line with the current view, but IPL MN sectors showed virtually no direct connection with temporal visual areas. In addition, we found that PMv and IPL MN sectors share connections with several cortical regions, including the dorsal and mesial premotor cortex, the primary motor cortex, the secondary somatosensory cortex, the mid-dorsal insula and the ventrolateral prefrontal cortex, as well as subcortical structures, such as motor and polysensory thalamic nuclei and the mid-dorsal claustrum. We propose that each of these regions constitutes a node of an "extended network", through which information relative to ongoing movements, social context, environmental contingencies, abstract rules, and internal states can influence MN activity and contribute to several socio-cognitive functions.