Martine Meunier

Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys

Object memory processes, evaluated in rhesus monkeys by delayed nonmatching-to-sample with trial-unique stimuli and object reversal learning, were more severely impaired by orbital frontal than by anterior cingulate lesions. Spatial memory processes, assessed by spatial delayed response and spatial reversal learning, showed a weak trend in the opposite direction, though on these tasks neither lesion produced a serious loss. Comparison of the present results with those of earlier studies on the effects of various limbic system lesions suggests that object memory processes, including object recognition and object-reward association, are served by a circuit consisting mainly of the rhinal cortex, orbitofrontal cortex, and the magnocellular division of the medial dorsal thalamic nucleus. Although both the rhinal and orbitofrontal components of this circuit appear to participate in both functions, evidence from the present and earlier studies suggests that the orbitofrontal component is the more important one for associative memory, i.e. the formation across trials of associations between particular objects or classes of objects and reward, whereas the rhinal component is the more critical one for recognition memory, i.e. the storage and retrieval within trials of the representations of particular objects.

Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys

All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibres of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala with those induced by fibre‐sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of defence, aggression, submission and approach responses. In unoperated controls, defence and approach behaviours were elicited by all four stimuli, ‘social’ and inanimate alike, whereas aggression and submission responses occurred only in the presence of the two ‘social’ stimuli. Furthermore, all defence reactions were reduced with an attractive inanimate item, while freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioural changes as those with aspiration lesions, i.e. reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two‐thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, because some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fibre damage.

Conditional visuo-motor learning in primates : a key role for the basal ganglia

Sensory guidance of behavior often involves standard visuo-motor mapping of body movements onto objects and spatial locations. For example, looking at and reaching to grasp a glass of wine requires the mapping of the eyes and hand to the location of the glass in space, as well as the formation of a hand configuration appropriate to the shape of the glass. But our brain is far more than just a standard sensorimotor mapping machine. Through evolution, the brain of advanced mammals, in particular human and non-human primates, has acquired a formidable capacity to construct non-standard, arbitrary mapping using associations between external events and behavioral responses that bear no direct relationship. For example, we have all learned to stop at a red traffic light and to go at a green one, or to wait for a specific tone before dialing a phone number and to hang up when hearing a busy signal. These arbitrary associations are acquired through experience, thereby providing primates with a rich and flexible sensorimotor repertoire. Understanding how they are learned, and how they are recalled and used when the context requires them, has been one of the challenging issues for cognitive neuroscience. Valuable insights have been gained over the last two decades through the convergence of multiple complementary approaches. Human neuropsychology and experimental lesions in monkeys have identified a network of brain structures important for conditional sensorimotor associations, whereas imaging studies in healthy human subjects and electrophysiological recordings in awake monkeys have sought to identify the different functional processes underlying the overall function. The present review focuses on the contribution of a network linking the prefrontal cortex, basal ganglia, and dorsal premotor cortex, with special emphasis on results from recording experiments in monkeys. We will first review data pointing to a specific contribution of each component of the network to the performance of well-learned arbitrary visuo-motor associations, as well as data suggesting how novel associations are formed. Then we will propose a model positing that each component of the fronto-striatal network makes a specific contribution to the formation and/or execution of sensorimotor associations. In this model, the basal ganglia are thought to play a key role in linking the sensory, motor, and reward information necessary for arbitrary mapping.

Hand position modulates saccadic activity in the frontal eye field.

Recent neurophysiological studies have begun to uncover the neuronal correlates of eye hand coordination. This study was designed to test whether the frontal eye field (FEF) saccadic activity is modulated by hand position. Single neurons were recorded in two macaque monkeys performing visually guided saccades while holding their hand at given locations on a touchscreen. To determine the relative contributions of hand vision and its proprioception, monkeys executed the task with or without vision of the hand. We found that saccadic activity of more than half of the neuronal sample (54%; n=130) was dependent on hand position relative to the saccade end point. Both visual and proprioceptive signals contributed to this modulation. These data demonstrate that the oculomotor function of the FEF takes into account hand position in space.

Prehension movements in the macaque monkey: effects of perturbation of object size and location

While the neural bases of prehension have been extensively studied in monkeys, a few kinematic studies have examined their prehension behavior. Recently (Roy et al. 2000, 2002), we have described the kinematics of reaching and grasping in freely behaving monkeys under normal conditions by applying the high-resolution recording techniques (Optotrak® system) and behavioral paradigms used in humans. Here we determined whether online movement reorganization observed in monkeys following sudden changes of either object size or location at movement onset is similar to that observed in humans. We found that changing object size led to rapid on-flight re-calibration of the different movement parameters, eventually preserving the unitary aspect of the movement with a minor time cost. By contrast, a shift in object location triggered a massive time-consuming reorganization. Re-directed movements appeared as a concatenation of two sub-movements: a first one directed to the initial object and a second one directed to the new object location. These findings first complement our earlier studies in providing further evidence of the similarities between monkey and human prehension. Second, they suggest that the two components of prehension, reaching and grasping, interact through coordination mechanisms that are more efficient to correct for size than for location perturbation. This difference may reflect a hierarchical organization in which reaching would be the subordinate of grasping in both primate species.

Stimulus similarity and encoding time influence incidental recognition memory in adult monkeys with selective hippocampal lesions

Recognition memory impairment after selective hippocampal lesions in monkeys is more profound when measured with visual paired-comparison (VPC) than with delayed nonmatching-to-sample (DNMS). To clarify this issue, we assessed the impact of stimuli similarity and encoding duration on the VPC performance in monkeys with hippocampal lesions and sham-operated controls. The novelty preference was compared for pictures of dissimilar vs. similar objects and for encoding duration of 30, 10, 5, and 1 sec. The novelty preference was spared after hippocampal lesions with dissimilar (colored or black and white [BW]) stimuli and an encoding time ≥10 sec, but declined with similar stimuli or a short encoding time of 1 or 5 sec. Therefore, the severe VPC impairment reported earlier after hippocampal damage cannot be attributed to the long encoding time used (30 sec) relative to DNMS (1-5 sec). However, it may result, at least in part, from the poorer distinctiveness of the stimuli typically used for VPC (BW slides of pictures of equal size and brightness of objects differing in shape) relative to the actual objects used for DNMS, differing in shape, color, size, brightness, and texture. This conclusion fits well with current models that view the hippocampus as a comparator capable of individualizing the representations of highly overlapping inputs.

Could LC-NE-Dependent Adjustment of Neural Gain Drive Functional Brain Network Reorganization?

The locus coeruleus-norepinephrine (LC-NE) system is thought to act at synaptic, cellular, microcircuit, and network levels to facilitate cognitive functions through at least two different processes, not mutually exclusive. Accordingly, as a reset signal, the LC-NE system could trigger brain network reorganizations in response to salient information in the environment and/or adjust the neural gain within its target regions to optimize behavioral responses. Here, we provide evidence of the co-occurrence of these two mechanisms at the whole-brain level, in resting-state conditions following a pharmacological stimulation of the LC-NE system. We propose that these two mechanisms are interdependent such that the LC-NE-dependent adjustment of the neural gain inferred from the clustering coefficient could drive functional brain network reorganizations through coherence in the gamma rhythm. Via the temporal dynamic of gamma-range band-limited power, the release of NE could adjust the neural gain, promoting interactions only within the neuronal populations whose amplitude envelopes are correlated, thus making it possible to reorganize neuronal ensembles, functional networks, and ultimately, behavioral responses. Thus, our proposal offers a unified framework integrating the putative influence of the LC-NE system on both local- and long-range adjustments of brain dynamics underlying behavioral flexibility.