Luca Bonini

Functional organization of inferior parietal lobule convexity in the macaque monkey: electrophysiological characterization of motor, sensory and mirror responses and their correlation with cytoarchitectonic areas

The general view on the functional role of the monkey inferior parietal lobule (IPL) convexity mainly derives from studies carried out more than two decades ago and does not account for the functional complexity suggested by more recent neuroanatomical findings. We investigated this issue by recording multi‐ and single units in the IPL convexity of two monkeys and characterizing their somatosensory, visual and motor responses, using a naturalistic (ethologically relevant) approach. These properties were then matched with IPL cytoarchitectonic parcellation. A further aim of this study was to describe the general properties and the localization of IPL mirror neurons, until now not investigated in detail. Results showed that each studied cytoarchitectonic subdivision of the IPL (PF, PFG, PG) is characterized by specific sensory and motor properties. A key feature of the recorded motor neurons is that of coding goal‐directed motor acts. Motor responses are somatotopically organized in a rostro‐caudal fashion, with mouth, hand and arm represented in PF, PFG and PG, respectively, with a certain degree of overlap between adjacent representations. In each subdivision the motor activity is associated with specific somatosensory and visual responses, suggesting that each area organizes motor acts in different space sectors. Mirror neurons have been found mainly in area PFG and their general features appear to be very similar to those of ventral premotor mirror neurons. The present data suggest that the IPL plays an important role in both action organization and action understanding and should be considered part of the motor system.

Grasping Neurons of Monkey Parietal and Premotor Cortices Encode Action Goals at Distinct Levels of Abstraction during Complex Action Sequences

Natural actions are formed by distinct motor acts, each of which is endowed with its own motor purpose (i.e., grasping), chained together to attain the final action goal. Previous studies have shown that grasping neurons of parietal area PFG and premotor area F5 can code the goal of simple actions in which grasping is embedded. While during simple actions the target is usually visible, directly cueing the final goal, during complex action sequences is often concealed and has to be kept in mind to shape action unfolding. The aim of this study was to assess the relative contribution of sensory-cued or memory-driven information about the final goal to PFG and F5 grasping neurons activity. To this purpose, we trained two monkeys to perform complex action sequences, each including two successive grasping acts, aimed at specific final goals (eating or placing). We recorded 122 PFG and 89 F5 neurons. Forty-seven PFG and 26 F5 neurons displayed action goal selectivity only during the late phase of the action, when sensory information cueing the action goal became available. Reward contingency did not affect neuronal selectivity. Notably, 17 PFG neurons reflected the final goal from the early phase of action unfolding, when only memory-driven information was available. Crucially, when monkeys were prevented from obtaining such information before action onset, neurons lost their early selectivity. Our findings suggest that external sensory cues and individuals motor intention integrate at different level of abstraction within a large anatomo-functional network, encompassing parietal and premotor cortices.

Association between salt sensitivity and insulin concentrations in patients with hypertension

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

Evolution of mirror systems: a simple mechanism for complex cognitive functions

Mirror neurons (MNs) were first discovered in monkeys and subsequently in humans and birds. While MNs are deemed to play a number of high‐level cognitive functions, here we propose that they serve a unitary form of sensorimotor recognition of others’ behavior. We caution that this basic function should not be confounded with the higher order functions that stem from the wider cortical systems in which MNs are embedded. Depending on the species, MNs function at different levels of motor event recognition, from motor goals to fine grained movements, thus contributing to social learning and imitative phenomena. Recent studies show that MNs coding has a prospective nature, suggesting that MNs also play a role in anticipating and predicting the behavior of others during social interactions. The presence of mirroring mechanisms in subcortical structures related to visceromotor reactions and the large diffusion of imitative phenomena among animals suggest that MN systems may be more ancient and widespread than previously thought.

Anatomo‐functional organization of the ventral primary motor and premotor cortex in the macaque monkey

The ventral agranular frontal cortex of the macaque monkey is formed by a mosaic of anatomically distinct areas. Although each area has been explored by several neurophysiological studies, most of them focused on small sectors of single areas, thus leaving to be clarified which is the general anatomo‐functional organization of this wide region. To fill this gap, we studied the ventral convexity of the frontal cortex in two macaque monkeys (Macaca nemestrina) using intracortical microstimulation and extracellular recording. Functional data were then matched with the cytoarchitectonic parcellation of the recorded region. The results demonstrated the existence of a dorso‐ventral functional border, encompassing the anatomical boundary between areas F4 and F1, and a rostro‐caudal anatomo‐functional border between areas F5 and F4. The ventral subdivision of areas F4 and F1 was highly electrically excitable, represented simple mouth movements and lacked visual properties; in contrast, their dorsal counterpart showed a higher stimulation threshold, represented forelimb and mouth motor acts and hosted different types of visual properties. The data also showed that area F5 was scarcely excitable, and displayed various motor specificity (e.g. for the type of grip) and complex visual (i.e. mirror responses) properties. Overall, the posterior areas F4 and F1 appear to be involved in organizing and controlling goal‐directed mouth motor acts and simple movements within different parts of the external (dorsal sector) and internal (ventral sector) space, whereas area F5 code motor acts at a more abstract level, thus enabling the emergence of higher order socio‐cognitive functions.

The Extended Mirror Neuron Network Anatomy, Origin, and Functions

Mirror neurons (MNs) are a fascinating class of cells originally discovered in the ventral premotor cortex (PMv) and, subsequently, in the inferior parietal lobule (IPL) of the macaque, which become active during both the execution and observation of actions. In this review, I will first highlight the mounting evidence indicating that mirroring others’ actions engages a broad system of reciprocally connected cortical areas, which extends well beyond the classical IPL-PMv circuit and might even include subcortical regions such as the basal ganglia. Then, I will present the most recent findings supporting the idea that the observation of one’s own actions, which might play a role in the ontogenetic origin and tuning of MNs, retains a particular relevance within the adult MN system. Finally, I will propose that both cortical and subcortical mechanisms do exist to decouple MN activity from the motor output, in order to render it exploitable for high-order perceptual, cognitive, and even social functions. The findings reviewed here provide an original framework for envisaging the main challenges and experimental directions of future neurophysiological and neuroanatomical studies of the monkey MN system.

Application of floating silicon-based linear multielectrode arrays for acute recording of single neuron activity in awake behaving monkeys.

Abstract One of the fundamental challenges in behavioral neurophysiology in awake animals is the steady recording of action potentials of many single neurons for as long as possible. Here, we present single neuron data obtained during acute recordings mainly from premotor cortices of three macaque monkeys using a silicon-based linear multielectrode array. The most important aspect of these probes, compared with similar models commercially available, is that, once inserted into the brain using a dedicated insertion device providing an intermediate probe fixation by means of vacuum, they can be released and left floating in the brain. On the basis of our data, these features appear to provide (i) optimal physiological conditions for extracellular recordings, (ii) good or even excellent signal-to-noise ratio depending on the recorded brain area and cortical layer, and (iii) extreme stability of the signal over relatively long periods. The quality of the recorded signal did not change significantly after several penetrations into the same restricted cortical sector, suggesting limited tissue damage due to probe insertion. These results indicate that these probes offer several advantages for acute neurophysiological experiments in awake monkeys, and suggest the possibility to employ them for semichronic or even chronic studies.

A modified mark test for own-body recognition in pig-tailed macaques (Macaca nemestrina)

Classic mirror self-recognition mark tests involve familiarizing the subject with its mirror image, surreptitiously applying a mark on the subject’s eyebrow, nose, or ear, and measuring self-directed behaviors toward the mark. For many non-human primate species, however, direct gaze at the face constitutes an aggressive and threatening signal. It is therefore possible that monkeys fail the mark test because they do not closely inspect their faces in a mirror and hence they have no expectations about their physical appearance. In the current study, we prevented two pig-tailed macaques (Macaca nemestrina) from seeing their own faces in a mirror, and we adopted a modified version of the classic mark test in which monkeys were marked on the chest, a body region to which they normally have direct visual access but that in the current study was visible only via a mirror. Neither monkey tried to touch the mark on its chest, possibly due to a failure to understand the mirror as a reflective surface. To further the monkeys’ understanding of the mirror image, we trained them to reach for food using the mirror as the only source of information. After both monkeys had learned mirror-mediated reaching, we replicated the mark test. In this latter phase of the study, only one monkey scratched the red dye on the chest once. The results are consistent with other findings suggesting that monkeys are not capable of passing a mark test and imply that face and body recognition rely on the same cognitive abilities.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

OBJECTIVE Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. APPROACH Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. MAIN RESULTS Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. SIGNIFICANCE With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects

Grasping relies on a network of parieto-frontal areas lying on the dorsolateral and dorsomedial parts of the hemispheres. However, the initiation and sequencing of voluntary actions also requires the contribution of mesial premotor regions, particularly the pre-supplementary motor area F6. We recorded 233 F6 neurons from 2 monkeys with chronic linear multishank neural probes during reaching–grasping visuomotor tasks. We showed that F6 neurons play a role in the control of forelimb movements and some of them (26%) exhibit visual and/or motor specificity for the target object. Interestingly, area F6 neurons form 2 functionally distinct populations, showing either visually-triggered or movement-related bursts of activity, in contrast to the sustained visual-to-motor activity displayed by ventral premotor area F5 neurons recorded in the same animals and with the same task during previous studies. These findings suggest that F6 plays a role in object grasping and extend existing models of the cortical grasping network.