Neurophysiological recordings from parietal areas of macaque brain during an instructed-delay reaching task.

Facilitating data sharing in scientific research, especially in the domain of animal studies, holds immense value, particularly in mitigating distress and enhancing the efficiency of data collection. This study unveils a meticulously curated collection of neural activity data extracted from six electrophysiological datasets recorded from three parietal areas (V6A, PEc, PE) of two Macaca fascicularis during an instructed-delay foveated reaching task. This valuable resource is now accessible to the public, featuring spike timestamps, behavioural event timings and supplementary metadata, all presented alongside a comprehensive description of the encompassing structure. To enhance accessibility, data are stored as HDF5 files, a convenient format due to its flexible structure and the capability to attach diverse information to each hierarchical sub-level. To guarantee ready-to-use datasets, we also provide some MATLAB and Python code examples, enabling users to quickly familiarize themselves with the data structure.

A focus on the multiple interfaces between action and perception and their neural correlates.

Successful behaviour relies on the appropriate interplay between action and perception. The well-established dorsal and ventral stream theories depicted two distinct functional pathways for the processes of action and perception, respectively. In physiological conditions, the two pathways closely cooperate in order to produce successful adaptive behaviour. As the coupling between perception and action exists, this requires an interface that is responsible for a common reading of the two functions. Several studies have proposed different types of perception and action interfaces, suggesting their role in the creation of the shared interaction channel. In the present review, we describe three possible perception and action interfaces: i) the motor code, including common coding approaches, ii) attention, and iii) object affordance; we highlight their potential neural correlates. From this overview, a recurrent neural substrate that underlies all these interface functions appears to be crucial: the parieto-frontal circuit. This network is involved in the mirror mechanism which underlies the perception and action interfaces identified as common coding and motor code theories. The same network is also involved in the spotlight of attention and in the encoding of potential action towards objects; these are manifested in the perception and action interfaces for common attention and object affordance, respectively. Within this framework, most studies were dedicated to the description of the role of the inferior parietal lobule; growing evidence, however, suggests that the superior parietal lobule also plays a crucial role in the interplay between action and perception. The present review proposes a novel model that is inclusive of the superior parietal regions and their relative contribution to the different action and perception interfaces.

Depth and direction effects in the prediction of static and shifted reaching goals from kinematics.

The kinematic parameters of reach-to-grasp movements are modulated by action intentions. However, when an unexpected change in visual target goal during reaching execution occurs, it is still unknown whether the action intention changes with target goal modification and which is the temporal structure of the target goal prediction. We recorded the kinematics of the pointing finger and wrist during the execution of reaching movements in 23 naïve volunteers where the targets could be located at different directions and depths with respect to the body. During the movement execution, the targets could remain static for the entire duration of movement or shifted, with different timings, to another position. We performed temporal decoding of the final goals and of the intermediate trajectory from the past kinematics exploiting a recurrent neural network. We observed a progressive increase of the classification performance from the onset to the end of movement in both horizontal and sagittal dimensions, as well as in decoding shifted targets. The classification accuracy in decoding horizontal targets was higher than the classification accuracy of sagittal targets. These results are useful for establishing how human and artificial agents could take advantage from the observed kinematics to optimize their cooperation in three-dimensional space.

Motor-like neural dynamics in two parietal areas during arm reaching.

The classical view on motor control makes a clear distinction between the role of motor cortex in controlling muscles and parietal cortex in processing movement plans and goals. However, the strong parieto-frontal connections argue against such clear-cut separation of function. Modern dynamical approaches revealed that population activity in motor cortex can be captured by a limited number of patterns, called neural states that are preserved across diverse motor behaviors. Whether such dynamics are also present in parietal cortex is unclear. Here, we studied neural dynamics in the primate parietal cortex during arm movements and found three main states temporally coupled to the planning, execution and target holding epochs. Strikingly, as reported recently in motor cortex, execution was subdivided into distinct, arm acceleration- and deceleration-related, states. These results suggest that dynamics across parieto-frontal areas are highly consistent and hint that parietal population activity largely reflects timing constraints while motor actions unfold.

Decoding of standard and non-standard visuomotor associations from parietal cortex.

OBJECTIVE: Neural signals can be decoded and used to move neural prostheses with the purpose of restoring motor function in patients with mobility impairments. Such patients typically have intact eye movement control and visual function, suggesting that cortical visuospatial signals could be used to guide external devices. Neurons in parietal cortex mediate sensory-motor transformations, encode the spatial coordinates for reaching goals, hand position and movements, and other spatial variables. We studied how spatial information is represented at the population level, and the possibility to decode not only the position of visual targets and the plans to reach them, but also conditional, non-spatial motor responses. APPROACH: The animals first fixated one of nine targets in 3D space and then, after the target changed color, either reached toward it, or performed a non-spatial motor response (lift hand from a button). Spiking activity of parietal neurons was recorded in monkeys during two tasks. We then decoded different task related parameters. MAIN RESULTS: We first show that a maximum-likelihood estimation (MLE) algorithm trained separately in each task transformed neural activity into accurate metric predictions of target location. Furthermore, by combining MLE with a Naïve Bayes classifier, we decoded the monkey's motor intention (reach or hand lift) and the different phases of the tasks. These results show that, although V6A encodes the spatial location of a target during a delay period, the signals they carry are updated around the movement execution in an intention/motor specific way. SIGNIFICANCE: These findings show the presence of multiple levels of information in parietal cortex that could be decoded and used in brain machine interfaces to control both goal-directed movements and more cognitive visuomotor associations.

Reduced neural representation of arm/hand actions in the medial posterior parietal cortex.

Several investigations at a single-cell level demonstrated that the medial posterior parietal area V6A is involved in encoding reaching and grasping actions in different visual conditions. Here, we looked for a "low-dimensional" representation of these encoding processes by studying macaque V6A neurons tested in three different tasks with a dimensionality reduction technique, the demixed principal component analysis (dPCA), which is very suitable for neuroprosthetics readout. We compared neural activity in reaching and grasping tasks by highlighting the portions of population variance involved in the encoding of visual information, target position, wrist orientation and grip type. The weight of visual information and task parameters in the encoding process was dependent on the task. We found that the distribution of variance captured by visual information in the three tasks did not differ significantly among the tasks, whereas the variance captured by target position and grip type parameters were significantly higher with respect to that captured by wrist orientation regardless of the number of conditions considered in each task. These results suggest a different use of relevant information according to the type of planned and executed action. This study shows a simplified picture of encoding that describes how V6A processes relevant information for action planning and execution.

Reference frames for reaching when decoupling eye and target position in depth and direction.

Spatial representations in cortical areas involved in reaching movements were traditionally studied in a frontoparallel plane where the two-dimensional target location and the movement direction were the only variables to consider in neural computations. No studies so far have characterized the reference frames for reaching considering both depth and directional signals. Here we recorded from single neurons of the medial posterior parietal area V6A during a reaching task where fixation point and reaching targets were decoupled in direction and depth. We found a prevalent mixed encoding of target position, with eye-centered and spatiotopic representations differently balanced in the same neuron. Depth was stronger in defining the reference frame of eye-centered cells, while direction was stronger in defining that of spatiotopic cells. The predominant presence of various typologies of mixed encoding suggests that depth and direction signals are processed on the basis of flexible coordinate systems to ensure optimal motor response.

Multiple representation of reaching space in the medial posterior parietal area V6A.

During foveal reaching, the activity of neurons in the macaque medial posterior parietal area V6A is modulated by both gaze and arm direction. In the present work, we dissociated the position of gaze and reaching targets, and studied the neural activity of single V6A cells while the eyes and reaching targets were arranged in different spatial configurations (peripheral and foveal combinations). Target position influenced neural activity in all stages of the task, from visual presentation of target and movement planning, through reach execution and holding time. The majority of neurons preferred reaches directed toward peripheral targets, rather than foveal. Most neurons discharged in both premovement and action epochs. In most cases, reaching activity was tuned coherently across action planning and execution. When reaches were planned and executed in different eye/target configurations, multiple analyses revealed that few neurons coded reaching actions according to the absolute position of target, or to the position of target relative to the eye. The majority of cells responded to a combination of both these factors. These data suggest that V6A contains multiple representations of spatial information for reaching, consistent with a role of this area in forming cross-reference frame representations to be used by premotor cortex.

Common neural substrate for processing depth and direction signals for reaching in the monkey medial posterior parietal cortex.

Many psychophysical studies suggest that target depth and direction during reaches are processed independently, but the neurophysiological support to this view is so far limited. Here, we investigated the representation of reach depth and direction by single neurons in area V6A of the medial posterior parietal cortex (PPC) of macaques, while a fixation-to-reach task in 3-dimensional (3D) space was performed. We found that, in a substantial percentage of V6A neurons, depth and direction signals jointly influenced fixation, planning, and arm movement-related activity. While target depth and direction were equally encoded during fixation, depth tuning became stronger during arm movement planning, execution, and target holding. The spatial tuning of fixation activity was often maintained across epochs, and depth tuning persisted more than directional tuning across epochs. These findings support for the first time the existence of a common neural substrate for the encoding of target depth and direction during reaches in the PPC. Present results also highlight the presence of several types of V6A cells that process independently or jointly signals about eye position and arm movement planning and execution in order to control reaches in 3D space. A conceptual framework for the processing of depth and direction for reaching is proposed.

Body-centered, mixed, but not hand-centered coding of visual targets in the medial posterior parietal cortex during reaches in 3D space.

The frames of reference used by neurons in posterior parietal cortex (PPC) to encode spatial locations during arm reaching movements is a debated topic in modern neurophysiology. Traditionally, target location, encoded in retinocentric reference frame (RF) in caudal PPC, was assumed to be serially transformed to body-centered and then hand-centered coordinates rostrally. However, recent studies suggest that these transformations occur within a single area. The caudal PPC area V6A has been shown to represent reach targets in eye-centered, body-centered, and a combination of both RFs, but the presence of hand-centered coding has not been yet investigated. To examine this issue, 141 single neurons were recorded from V6A in 2 Macaca fascicularis monkeys while they performed a foveated reaching task in darkness. The targets were presented at different distances and lateralities from the body and were reached from initial hand positions located at different depths. Most V6A cells used body-centered, or mixed body- and hand-centered coordinates. Only a few neurons used pure hand-centered coordinates, thus clearly distinguishing V6A from nearby PPC regions. Our findings support the view of a gradual RF transformation in PPC and also highlight the impact of mixed frames of reference.

The human homologue of macaque area V6A.

In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al., 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al., 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field is mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighboring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A.

Three-dimensional eye position signals shape both peripersonal space and arm movement activity in the medial posterior parietal cortex.

Research conducted over the last decades has established that the medial part of posterior parietal cortex (PPC) is crucial for controlling visually guided actions in human and non-human primates. Within this cortical sector there is area V6A, a crucial node of the parietofrontal network involved in arm movement control in both monkeys and humans. However, the encoding of action-in-depth by V6A cells had been not studied till recently. Recent neurophysiological studies show the existence in V6A neurons of signals related to the distance of targets from the eyes. These signals are integrated, often at the level of single cells, with information about the direction of gaze, thus encoding spatial location in 3D space. Moreover, 3D eye position signals seem to be further exploited at two additional levels of neural processing: (a) in determining whether targets are located in the peripersonal space or not, and (b) in shaping the spatial tuning of arm movement related activity toward reachable targets. These findings are in line with studies in putative homolog regions in humans and together point to a role of medial PPC in encoding both the vergence angle of the eyes and peripersonal space. Besides its role in spatial encoding also in depth, several findings demonstrate the involvement of this cortical sector in non-spatial processes.

Human v6: the medial motion area.

Cortical-surface-based functional Magnetic Resonance Imaging mapping techniques and wide-field retinotopic stimulation were used to verify the presence of pattern motion sensitivity in human area V6. Area V6 is highly selective for coherently moving fields of dots, both at individual and group levels and even with a visual stimulus of standard size. This stimulus is a functional localizer for V6. The wide retinotopic stimuli used here also revealed a retinotopic map in the middle temporal cortex (area MT/V5) surrounded by several polar-angle maps that resemble the mosaic of small areas found around macaque MT/V5. Our results suggest that the MT complex (MT+) may be specialized for the analysis of motion signals, whereas area V6 may be more involved in distinguishing object and self-motion.

Mare's colostrum globules stimulate fibroblast growth in vitro: a biochemical study.

The wound repair function of mare's milk and colostrum was investigated. Mare's colostrum improved wound healing in vivo; thus fibroblast growth activation by mare's milk and colostrum was examined. As expected, colostrum was more effective than milk. To establish the biochemical nature of the bioactive molecules involved, colostrum was fractionated into whey, casein, and fat globules, and the efficacy of these fractions on fibroblast proliferation was studied. The fat globule fraction provided the strongest stimulation; its composition was studied and compared with the less-active milk fat globule fraction. The lipid pattern highlighted several differences between mare's colostrum and milk; in particular, total lipid, linoleic acid, linolenic acid, ganglioside, and glycolipid contents were higher in colostrum. A proteomic investigation revealed some differences between the protein composition of colostrum and milk fat globules. Adipophylin and lactadherin were significantly overexpressed in colostrum fat globules. The role of specific lipids on skin wound repair and that of the epidermal growth factor-like domain, embedded within the lactadherin molecule and probably released in conditions stimulating proteolysis, are discussed.

Efficacy of two different platinum- or anthracycline-containing chemotherapy regimens for the treatment of small cell lung cancer.

The records of 190 consecutive patients referred to our department to be treated for small cell lung cancer were retrospectively evaluated, and the outcomes were compared on the basis of their first-line treatment. 113 patients were treated with 4-6 courses of cyclophosphamide, epidoxorubicin and etoposide (CEVP16), 77 with 4-6 courses of carboplatin and etoposide (CBE). 72 patients had limited disease and 118 extensive disease. Response rates were 58.4% for CEVP16 and 28.6% for CBE (p=0.0001), with no significant difference in the time to progression (255 vs 246 days, p=0.21). Overall survival was 334 days and 212 days, and the 1-year survival rate was 46% and 22.1%, respectively (p=0.0018). In patients with limited disease, overall survival was 434 days and 249 days (p=0.08) in both treatment group respectively and 281 and 208 days in those with extensive disease, respectively (p=0.02). No difference in side effects was observed between the two groups of patients. Our data suggest a role for anthracycline-containing regimens as first-line treatment of small cell lung cancer.

Real-time supervisor system based on trinary logic to control experiments with behaving animals and humans.

A new method is presented based on trinary logic able to check the state of different control variables and synchronously record the physiological and behavioral data of behaving animals and humans. The basic information structure of the method is a time interval of defined maximum duration, called time slice, during which the supervisor system periodically checks the status of a specific subset of input channels. An experimental condition is a sequence of time slices subsequently executed according to the final status of the previous time slice. The proposed method implements in its data structure the possibility to branch like an if-else cascade and the possibility to repeat parts of it recursively like the while-loop. Therefore its data structure contains the most basic control structures of programming languages. The method was implemented using a real-time version of LabVIEW programming environment to program and control our experimental setup. Using this supervision system, we synchronously record four analog data channels at 500 Hz (including eye movements) and the time stamps of up to six neurons at 100 kHz. The system reacts with a resolution within 1 ms to changes of state of digital input channels. The system is set to react to changes in eye position with a resolution within 4 ms. The time slices, experimental conditions, and data are handled by relational databases. This facilitates the construction of new experimental conditions and data analysis. The proposed implementation allows continuous recording without an inter-trial gap for data storage or task management. The implementation can be used to drive electrophysiological experiments of behaving animals and psychophysical studies with human subjects.

Biphenotypic acute leukemia: a case report.

We describe an uncommon case of acute leukemia in which leukemic blasts expressed myeloid antigens and cyCD79alpha molecule. In this 49-year old male patient, two distinct blast populations were detected in peripheral blood and bone marrow samples: one of small size resembling lymphoblasts and another with pink cytoplasmic granules resembling myeloblasts. Cytochemical reaction for myeloperoxidase was negative in both cell types. Conventional cytogenetic analysis showed a normal karyotype (46 XY) in all metaphases studied, while gene rearrangement analysis by seminested PCR of the immunoglobulin heavy chain (Ig-H) and T-cell-gamma chain (TCR-gamma) receptor, showed a germline configuration of the TCR and clonal rearrangement of Ig-H chain genes. Multicolour cytofluorimetric analysis showed that bone marrow and peripheral blood blasts expressed CD19, CD79alpha bright, CD22 and terminal deoxynucleotidyl transferase (TdT) as lymphoid markers, CD13, CD117, CD15 as myeloid markers, CD34, HLA-DR as stem cell markers. CD33 myeloid antigen was expressed by 50% of the blastic population. No differences in the immunophenotypic profile were detected in the two blast populations which were identified by morphology. According to EGIL (European Group of Immunological Classification of Leukemias) and WHO (World Health Organization) criteria, a diagnosis of biphenotypic acute leukemia (BAL) was made. The patient was treated with AML induction therapy followed by autologous stem cell transplantation, but relapse free survival was 6 months. The patient died a few weeks later due to unresponsiveness to salvage chemotherapy regimens. We conclude that patients with BAL should have a risk stratification with treatment tailored to their immunophenotype and gene rearrangement profiles.

Effects of increased intensity of intermittent training in runners with differing VO2 kinetics.

The purpose of this study was to test the hypothesis that athletes having a slower oxygen uptake ( VO(2)) kinetics would benefit more, in terms of time spent near VO(2max), from an increase in the intensity of an intermittent running training (IT). After determination of VO(2max), vVO(2max) (i.e. the minimal velocity associated with VO(2max) in an incremental test) and the time to exhaustion sustained at vVO(2max) ( T(lim)), seven well-trained triathletes performed in random order two IT sessions. The two IT comprised 30-s work intervals at either 100% (IT(100%)) or 105% (IT(105%)) of vVO(2max) with 30-s recovery intervals at 50% of vVO(2max) between each repeat. The parameters of the VO(2) kinetics (td(1), tau(1), A(1), td(2), tau(2), A(2), i.e. time delay, time constant and amplitude of the primary phase and slow component, respectively) during the T(lim) test were modelled with two exponential functions. The highest VO(2) reached was significantly lower ( P<0.01) in IT(100%) run at 19.8 (0.9) km(.)h(-1) [66.2 (4.6) ml(.)min(-1.)kg(-1)] than in IT(105%) run at 20.8 (1.0) km(.)h(-1) [71.1 (4.9) ml(.)min(-1.)kg(-1)] or in the incremental test [71.2 (4.2) ml(.)min(-1.)kg(-1)]. The time sustained above 90% of VO(2max) in IT(105%) [338 (149) s] was significantly higher ( P<0.05) than in IT(100%) [168 (131) s]. The average T(lim) was 244 (39) s, tau(1) was 15.8 (5.9) s and td(2) was 96 (13) s. tau(1) was correlated with the difference in time spent above 90% of VO(2max) ( r=0.91; P<0.01) between IT(105%) and IT(100%). In conclusion, athletes with a slower VO(2) kinetics in a vVO(2max) constant-velocity test benefited more from the 5% rise of IT work intensity, exercising for longer above 90% of VO(2max) when the IT intensity was increased from 100 to 105% of vVO(2max).

Early- and late-responding cells to saccadic eye movements in the cortical area V6A of macaque monkey.

The cortical area V6A, located in the dorsal part of the anterior bank of the parieto-occipital sulcus, contains retino- and craniocentric visual neurones together with neurones sensitive to gaze direction and/or saccadic eye movements, somatosensory stimulation and arm movements. The aim of this work was to study the dynamic characteristics of V6A saccade-related activity. Extracellular recordings were carried out in six macaque monkeys performing a visually guided saccade task with the head restrained. The task was performed in the dark, in both the dark and light, and sometimes in the light only. The discharge of certain neurones during saccades is due to their responsiveness to visual stimuli. We used a statistical method to distinguish responses due to visual stimulation from those responsible for saccadic control. Out of 597 V6A neurones tested, 66 (11%) showed responses correlated with saccades; 26 of 66 responded also to visual stimulation and 31 of 66 did not; the remaining 9 were not visually tested. We calculated the response latency to saccade onset and its inter-trial variance in 24 of 66 neurones. Saccade neurones could respond before, during or after the saccade. Neurones responding before saccade-onset or during saccades had much higher latency variance than neurones responding after saccades. The early-responding cells had a mean latency (+/-SD) of -64+/-62 ms, while the late-responding cells a mean latency of +89+/-20 ms. The responses to saccadic eye movements were directionally sensitive and varied with the amplitude of the saccade. Responses of late-responding cells disappeared in complete darkness. We suggest that the activity of early-responding cells represents the intended saccadic eye movement or the shift of attention towards another part of the visual space, whereas that of late-responding cells is a visual response due to retinal stimulation during saccades.

Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.