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Neural populations, rather than single neurons, may be the fundamental unit of cortical computation. Analysing chronically recorded neural population activity is challenging not only because of the high dimensionality of activity but also because of changes in the signal that may or may not be due to neural plasticity. Hidden Markov models (HMMs) are a promising technique for analysing such data in terms of discrete latent states, but previous approaches have not considered the statistical properties of neural spiking data, have not been adaptable to longitudinal data, or have not modelled condition-specific differences. We present a multilevel Bayesian HMM addresses these shortcomings by incorporating multivariate Poisson log-normal emission probability distributions, multilevel parameter estimation and trial-specific condition covariates. We applied this framework to multi-unit neural spiking data recorded using chronically implanted multi-electrode arrays from macaque primary motor cortex during a cued reaching, grasping and placing task. We show that, in line with previous work, the model identifies latent neural population states which are tightly linked to behavioural events, despite the model being trained without any information about event timing. The association between these states and corresponding behaviour is consistent across multiple days of recording. Notably, this consistency is not observed in the case of a single-level HMM, which fails to generalise across distinct recording sessions. The utility and stability of this approach is demonstrated using a previously learned task, but this multilevel Bayesian HMM framework would be especially suited for future studies of long-term plasticity in neural populations., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The ventral part of lateral prefrontal cortex (VLPF) of the monkey receives strong visual input, mainly from inferotemporal cortex. It has been shown that VLPF neurons can show visual responses during paradigms requiring to associate arbitrary visual cues to behavioral reactions. Further studies showed that there are also VLPF neurons responding to the presentation of specific visual stimuli, such as objects and faces. However, it is largely unknown whether VLPF neurons respond and differentiate between stimuli belonging to different categories, also in absence of a specific requirement to actively categorize or to exploit these stimuli for choosing a given behavior. The first aim of the present study is to evaluate and map the responses of neurons of a large sector of VLPF to a wide set of visual stimuli when monkeys simply observe them. Recent studies showed that visual responses to objects are also present in VLPF neurons coding action execution, when they are the target of the action. Thus, the second aim of the present study is to compare the visual responses of VLPF neurons when the same objects are simply observed or when they become the target of a grasping action. Our results indicate that: (1) part of VLPF visually responsive neurons respond specifically to one stimulus or to a small set of stimuli, but there is no indication of a "passive" categorical coding; (2) VLPF neuronal visual responses to objects are often modulated by the task conditions in which the object is observed, with the strongest response when the object is target of an action. These data indicate that VLPF performs an early passive description of several types of visual stimuli, that can then be used for organizing and planning behavior. This could explain the modulation of visual response both in associative learning and in natural behavior.

Although it is established that F5 neurons can distinguish between nonsocial goals such as bringing food to the mouth for eating or placing it in a container, it is not clear whether they discriminate between social and nonsocial goals. Here, we recorded single-unit activity in the ventral premotor cortex of two female macaques and used a simple reach-to-grasp motor task in which a monkey grasped an object with a precision grip in three conditions, which only differed in terms of their final goal, that is, a subsequent motor act that was either social (placing in the experimenter's hand ["Hand" condition]) or nonsocial (placing in a container ["Container" condition] or bringing to the mouth for eating ["Mouth" condition]). We found that, during the execution of the grasping motor act, the response of a sizable proportion of F5 motor neurons was modulated by the final goal of the action, with some having a preference for the social goal condition. Our results reveal that the representation of goal-directed actions in ventral premotor cortex is influenced by contextual information not only extracted from physical cues but also from cues endowed with biological or social value. Our study suggests that the activity of grasping neurons in the premotor cortex is modulated by social context.

The desynchronization of alpha and beta oscillations (mu rhythm) in the central scalp EEG during action observation and action execution is thought to reflect neural mirroring processes. However, the extent to which mirror neurons (MNs) or other populations of neurons contribute to such EEG desynchronization is still unknown. Here, we provide the first evidence that, in the monkey, the neuronal activity recorded from the ventral premotor cortex (PMv) strongly contributes to the EEG changes occurring in the beta band over central scalp electrodes, during executed and observed actions. We simultaneously recorded scalp EEG and extracellular activity, Multi Unit Activity (MUA) and Local Field Potentials (LFP), from area F5 of two macaques executing and observing grasping actions. We found that MUA highly correlates with an increase in high gamma LFP power and, interestingly, such LFP power increase also correlates to EEG beta - and in part also to alpha - desynchronization. In terms of timing of signal changes, the increase in high gamma LFP power precedes the EEG desynchronization, during both action observation and execution, thus suggesting a causal role of PMv neuronal activity in the modulation of the alpha and beta mu-rhythm. Lastly, neuronal signals from deeper layers of PMv exert a greater contribution than superficial layers to the EEG beta rhythm modulation, especially during the motor task. Our findings have clear implications for EEG studies in that they demonstrate that the activity of different populations of neurons in PMv contribute to the generation of the mu-rhythm., (Copyright © 2018. Published by Elsevier Inc.)

Prefrontal cortex is crucial for exploiting contextual information for the planning and guidance of behavioral responses. Among contextual cues, those provided by others' behavior are particularly important, in primates, for selecting appropriate reactions and suppressing the inappropriate ones. These latter functions deeply rely on the ability to understand others' actions. However, it is largely unknown whether prefrontal neurons are activated by action observation. To address this issue, we recorded the activity of ventrolateral prefrontal (VLPF) neurons of macaque monkeys during the observation of videos depicting biological movements performed by a monkey or a human agent, and object motion. Our results show that a population of VLPF neurons respond to the observation of biological movements, in particular those representing goal directed actions. Many of these neurons also show a preference for the agent performing the action. The neural response is present also when part of the observed movement is obscured, suggesting that these VLPF neurons code a high order representation of the observed action rather than a simple visual description of it.

Objective: (1) Assessing the performance of the algorithm in terms of sensitivity and positive predictive value, considering General Practitioners' (GPs) judgement as benchmark, and (2) describing adverse events (hospitalisation, death, and health services' consumption) of complex patients compared to the general population., Data Sources: (i) Tuscany administrative database containing health data (2013-5); (ii) lists of complex patients indicated by GPs; and (iii) annual health registry of Tuscany., Study Design: The present study is a validation study. It compares a list of complex patients extracted through an administrative algorithm (criteria of high health consumption) to a gold standard list of patients indicated by GPs. GPs' decision was subjective but fairly well reasoned. The study compares also adverse outcomes (Emergency Room visits, hospitalisation, and death) between identified complex patients and general population., Principal Findings: Considering GPs' judgement, the algorithm showed a sensitivity of 72.8% and a positive predictive value of 64.4%. The complex cases presented here have higher incidence rates/100,000 (death 46.8; ER visits 223.2, hospitalisations 110.87, laboratory tests 1284.01, and specialist examinations 870.37) compared to the general population., Conclusions: The final validated algorithm showed acceptable sensitivity and positive predictive value.

Grasping actions require the integration of two neural processes, one enabling the transformation of object properties into corresponding motor acts, and the other involved in planning and controlling action execution on the basis of contextual information. The first process relies on parieto-premotor circuits, whereas the second is considered to be a prefrontal function. Up to now, the prefrontal cortex has been mainly investigated with conditional visuomotor tasks requiring a learned association between cues and behavioural output. To clarify the functional role of the prefrontal cortex in grasping actions, we recorded the activity of ventrolateral prefrontal (VLPF) neurons while monkeys (Macaca mulatta) performed tasks requiring reaching-grasping actions in different contextual conditions (in light and darkness, memory-guided, and in the absence of abstract learned rules). The results showed that the VLPF cortex contains neurons that are active during action execution (movement-related neurons). Some of them showed grip selectivity, and some also responded to object presentation. Most movement-related neurons discharged during action execution both with and without visual feedback, and this discharge typically did not change when the action was performed with object mnemonic information and in the absence of abstract rules. The findings of this study indicate that a population of VLPF neurons play a role in controlling goal-directed grasping actions in several contexts. This control is probably exerted within a wider network, involving parietal and premotor regions, where the role of VLPF movement-related neurons would be that of activating, on the basis of contextual information, the representation of the motor goal of the intended action (taking possession of an object) during action planning and execution., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The observation of actions executed by others results in desynchronization of electroencephalogram (EEG) in the alpha and beta frequency bands recorded from the central regions in humans. On the other hand, mirror neurons, which are thought to be responsible for this effect, have been studied only in macaque monkeys, using single-cell recordings. Here, as a first step in a research programme aimed at understanding the parallels between human and monkey mirror neuron systems (MNS), we recorded EEG from the scalp of two monkeys during action observation. The monkeys were trained to fixate on the face of a human agent and subsequently to fixate on a target upon which the agent performed a grasping action. We found that action observation produced desynchronization in the 19-25 Hz band that was strongest over anterior and central electrodes. These results are in line with human data showing that specific frequency bands within the power spectrum of the ongoing EEG may be modulated by observation of actions and therefore might be a specific marker of MNS activity.

Mirror neurons (MNs) of the monkey ventral premotor cortex (area F5) are a class of cells that match the visual descriptions of others' actions with correspondent motor representations in the observer's brain. Several human studies suggest that one's own motor representations activated during action observation play a role in directing proactive eye movements to the site of the upcoming hand-target interaction. However, there are no data on the possible relationship between gaze behaviour and MN activity. Here we addressed this issue by simultaneously recording eye position and F5 MN activity in two macaques during free observation of a grasping action. More than half of the recorded neurons discharged stronger when the monkey looked at the action than when it did not look at it, but their firing rate was better predicted by 'when' rather than by 'how long' the monkey gazed at the location of the upcoming hand-target interaction. Interestingly, the onset of MN response was linked to the onset of the experimenter's movement, thus making motor representations potentially exploitable to drive eye movements. Furthermore, MNs discharged stronger and earlier when the gaze was 'proactive' compared with 'reactive', indicating that gaze behaviour influences MN activity. We propose that feedforward, automatic representations of other's actions could lead eye movements that, in turn, would provide the motor system with feedback information that enhances the neural representations of the ongoing action., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Grasping objects requires the selection of specific grip postures in relation to the objects' physical properties. Furthermore, grasping acts can be embedded in actions aimed at different goals, depending on the context in which the action is performed. Here we assessed whether information on grip and action type integrate at the single-neuron level within the parieto-frontal motor system. For this purpose, we trained three monkeys to perform simple grasp-to-eat and grasp-to-place actions, depending on contextual cues, in which different grip types were required in relation to target features. We recorded 173 grasping neurons: 86 from the inferior parietal area PFG and 87 from the ventral premotor area F5. Results showed that most neurons in both areas are selective for grip type, but the discharge of many of them, particularly in PFG, appears to differ in relation to action context. Kinematics data and control experiments indicated that neuronal selectivity appears more likely to depend on the action goal triggered by the context than on specific contextual elements. The temporal dynamics of grip and goal selectivity showed that grasping neurons reflect first "how" the object has to be grasped (grip), to guide and monitor the hand shaping phase, and then "why" the action is performed (goal), very likely to facilitate subsequent motor acts following grasping. These findings suggest that, in the parieto-frontal system, grip types and action goals are processed by both parallel and converging pathways, and area PFG appears to be particularly relevant for integrating this information for action organization.

Background: Ovarian vein thrombosis (OVT) is a rare but potentially serious postpartum complication, which occurs in 0.05% to 0.18% of pregnancies and is diagnosed on the right side in 80% to 90% of the cases., Case Report: A 32-year-old woman presented at 15 days postpartum to our emergency department with severe abdominal pain, fever, and abdominal distension. Abdominal examination revealed right lower quadrant pain with rebound tenderness. The plain abdominal radiography evidenced a diffuse fecal stasis; abdominal ultrasound showed the presence of free fluid in the Douglas' pouch and between small bowel loops. Diagnosis of acute appendicitis was made. The patient immediately underwent explorative laparoscopy; at surgery, a woody tumoration consistent with right ovarian vein thrombosis was found. Laparoscopic ultrasound confirmed the diagnosis. Anticoagulation therapy and antibiotics were instituted. CT-scan confirmed the presence of thrombosis up to the vena cava. The patient was discharged on postoperative day 4. At 1-month follow-up, she remained stable and symptom free., Discussion: Even though postpartum ovarian vein thrombosis is rare, recognition and treatment is needed to institute adequate therapy and avoid potential serious sequelae. The diagnosis can be established by ultrasound, CT scan, and MRI examinations, although, as in the case described, the limitation of ultrasound includes obscuration of the gonadic vein by overlying bowel gas., Conclusion: OVT should be considered in any woman in the postpartum period with lower abdominal pain, fever, and leucocytosis.

Anthracyclines represent an established therapy for various hemopoietic and solid tumors; however the cardiotoxicity of these agents continues to limit their therapeutic potential in many cancer patients. Acute life-threatening cardiac toxicity which occurs immediately after a single dose of therapy is very rare under current treatment protocols. This form of toxicity occurs unexpectedly owing to a large variation in individual sensitivity. It may cause transient arrhythmias, hypotension, a pericarditis-myocarditis syndrome, or acute left ventricular failure. We report the case of a 43-year-old woman recently operated on for breast cancer, with acute life-threatening left ventricular failure associated with severe hyperglycemia, occurring a few hours after the first dose of anthracyclines for adjuvant chemotherapy. Severe regional wall motion abnormalities and a significant impaired systolic left ventricular function associated with high creatine phosphokinase-MB and troponin levels were observed. At discharge the regular insulin treatment was interrupted since glycemia was normalized, and complete recovery of the cardiac function was observed 1 month later. Differential diagnosis and the underlying pathogenetic mechanisms are discussed. This life-threatening event is rare, but considering the widespread use of anthracyclines in cancer treatment, it is important for the cardiologist to be aware of the potential acute cardiac toxicity of these agents for early diagnosis and management.

The authors report their experience with US in gynecologic emergencies through a retrospective study on 105 patients presenting with acute abdomen of suspected gynecologic nature. The series included 3 groups of patients: Group I: 59 patients all submitted to immediate surgery. The following pathologic conditions were observed: ectopic pregnancy (23 cases), torsion or hemorrhage from ovarian cysts (13 cases), pyosalpinx or tubo-ovarian abscess (9 cases), torsion of pedunculated uterine leiomyoma (7 cases), intraperitoneal bleeding from hemorrhagic corpus luteum (6 cases), hematocolpos and hematometra from imperforate hymen (3 cases). Two false positives, not included in this group, resulting from appendicular abscesses and misinterpreted as ovarian, were submitted to surgery in a gynecologic unit. Group II: 19 patients treated with medical therapy for the following conditions: torsion or hemorrhage from hyperstimulated ovary (10 cases), pyosalpinx or tubo-ovarian abscess (9 cases). Group III: 25 patients in whom neither US nor clinical examination revealed positive gynecologic findings. Both US and clinical follow-up were negative in these patients. The study was aimed at evaluating the role of US in identifying both lesion and peritoneal involvement, and in the diagnosis of nature. US proved a valuable tool in the first two diagnostic steps, allowing to confirm/dismiss active pathologic conditions, to indicate the medical/surgical treatment (immediate or delayed), to detect associated pathologies to study with further examinations. As for lesion nature, US alone proved poorly useful if not correlated with an accurate clinical history.

The authors report their experience with US and CT in 31 cases of inflammatory aneurysms out of a study population of 200 patients with abdominal aortic aneurysms. The work started with a case that had not been diagnosed at US, either due to the operator's poor knowledge of this pathologic condition or because of improper examination technique. The authors stress the importance of a high-frequency probe and proper gain settings which are often necessary for a good visualization of the anterior aortic wall. The correct diagnosis of the inflammatory nature of the aneurysm has been assessed by US ever since, in all cases except for very obese and meteoric patients. In our series, US diagnostic accuracy was 78%, versus 33% reported in literature. US was not accurate in evaluating adjacent structures involvement within fibrous tissues (ureteral narrowing, caval narrowing)--which CT did. Neither US nor CT exhibited reliable diagnostic accuracy in demonstrating enteric involvement within fibrous tissues.

The authors describe the different types of postoperative carcinoma recurrences, as seen on CT examinations of the chest, in 38 patients who underwent different surgical procedures for bronchogenic carcinoma (12 pneumonectomies, 22 lobectomies, 2 segmentectomies, and 2 atypical resections). The recurrences were classified as follows: 1) recurrence in the bronchial stump; 2) lymph node enlargement; 3) recurrence in the thoracic wall; 4) recurrence in the residual lobe; 5) pleural effusion; 6) nodule in the contralateral lung. The CT findings, correlated with those from plain chest radiographs and clinical symptoms, indicate a higher incidence of recurrences in the hilar region, either in the bronchial stump or as node enlargement. In the discussion, the problems faced after total and subtotal resection are separately analyzed. While after pneumonectomy plain chest radiographs fail to demonstrate the recurrence in most cases, so that CT is nearly always mandatory, after subtotal resection the diagnostic accuracy of conventional radiology appears higher since the residual parenchyma offers good natural contrast. Nevertheless, after subtotal resection, greater difficulties arise at a deeper radiological analysis due to lobar reassessment, the features of which are to be known.

Our purpose is to define the morphological patterns of interstitial lung disease on CT and to evaluate the diagnostic impact of high-resolution technique (HRCT). Sixty-six consecutive patients with proven interstitial lung disease were considered in our study. The basic morphological patterns include: a) large reticular pattern (10-25 mm); b) small reticular pattern (2-3 mm); c) intermediate reticular pattern (5-10 mm) with cystic dilatation of distal airspaces; d) nodular pattern; e) high-density parenchymal areas. Topography of the involved areas (peripheral, middle and axial compartments), and lesion distribution with reference to the secondary pulmonary lobule (centrilobular, perilobular, panlobular, bronchovasal) are additional diagnostic criteria. The identification and correlation of these three parameters proved very useful in limiting the range of diagnostic possibilities to interstitial disease, obviously considering clinical data. In our series a correct CT diagnosis was obtained in 57 of 66 cases (86.36%). In 24 of them (36.34%) diagnosis corrected a previous erroneous or generic clinical suspicion. Our data suggest that HRCT is indicated in interstitial lund disease when neither clinical nor radiographic findings allow a specific diagnosis to be made.

Sonography has recently gained attention as a non-invasive technique improving the diagnostic accuracy of conventional radiology as regards the pathologic conditions of the maxillary sinus. Eighty-two patients with various pathologies of the maxillary sinus--i.e. acute/chronic sinusitis, mucocele, mucopyocele, polyp, and carcinoma--were submitted to US after preliminary conventional radiographs and before CT and surgical treatment (both performed in selected cases only). US proved useful in detecting liquid exudate, mucosal hypertrophy, and lesions of the anterior wall, while it was not as accurate in detecting lesions of the posterior wall (unless fluid was present) and in establishing the nature of a solid lesion. The last two conditions are those where CT is mainly indicated.