Three macaque monkeys and 13 healthy human volunteers underwent diffusion tensor MRI with a 3 Tesla scanner for diffusion tract tracing (DTT) reconstruction of callosal bundles from different areas. In six macaque monkeys and three human subjects, the length of fiber tracts was obtained from histological data and combined with information on the distribution of axon diameter, so as to estimate callosal conduction delays from different areas. The results showed that in monkeys, the spectrum of tract lengths obtained with DTT closely matches that estimated from histological reconstruction of axons labeled with an anterogradely transported tracer. For each sector of the callosum, we obtained very similar conduction delays regardless of whether conduction distance was obtained from tractography or from histological analysis of labeled axons. This direct validation of DTT measurements by histological methods in monkeys was a prerequisite for the computation of the callosal conduction distances and delays in humans, which we had previously obtained by extrapolating the length of callosal axons from that of the monkey, proportionally to the brain volumes in the two species. For this analysis, we used the distribution of axon diameters from four different sectors of the corpus callosum. As in monkeys, in humans the shortest callosal conduction delays were those of motor, somatosensory, and premotor areas; the longer ones were those of temporal, parietal, and visual areas. These results provide the first histological validation of anatomical data about connection length in the primate brain based on DTT imaging.

Parkinson’s disease (PD) patients have impairment of facial expressivity (hypomimia) and difficulties in interpreting the emotional facial expressions produced by others, especially for aversive emotions. We aimed to evaluate the ability to produce facial emotional expressions and to recognize facial emotional expressions produced by others in a group of PD patients and a group of healthy participants in order to explore the relationship between these two abilities and any differences between the two groups of participants. Twenty non-demented, non-depressed PD patients and twenty healthy participants (HC) matched for demographic characteristics were studied. The ability of recognizing emotional facial expressions was assessed with the Ekman 60-faces test (Emotion recognition task). Participants were video-recorded while posing facial expressions of 6 primary emotions (happiness, sadness, surprise, disgust, fear and anger). The most expressive pictures for each emotion were derived from the videos. Ten healthy raters were asked to look at the pictures displayed on a computer-screen in pseudo-random fashion and to identify the emotional label in a six-forced-choice response format (Emotion expressivity task). Reaction time (RT) and accuracy of responses were recorded. At the end of each trial the participant was asked to rate his/her confidence in his/her perceived accuracy of response. For emotion recognition, PD reported lower score than HC for Ekman total score (p<0.001), and for single emotions sub-scores happiness, fear, anger, sadness (p<0.01) and surprise (p = 0.02). In the facial emotion expressivity task, PD and HC significantly differed in the total score (p = 0.05) and in the sub-scores for happiness, sadness, anger (all p<0.001). RT and the level of confidence showed significant differences between PD and HC for the same emotions. There was a significant positive correlation between the emotion facial recognition and expressivity in both groups; the correlation was even stronger when ranking emotions from the best recognized to the worst (R = 0.75, p = 0.004). PD patients showed difficulties in recognizing emotional facial expressions produced by others and in posing facial emotional expressions compared to healthy subjects. The linear correlation between recognition and expression in both experimental groups suggests that the two mechanisms share a common system, which could be deteriorated in patients with PD. These results open new clinical and rehabilitation perspectives.

The statistical structure of intrinsic parietal and parieto-frontal connectivity in monkeys was studied through hierarchical cluster analysis. Based on their inputs, parietal and frontal areas were grouped into different clusters, including a variable number of areas that in most instances occupied contiguous architectonic fields. Connectivity tended to be stronger locally: that is, within areas of the same cluster. Distant frontal and parietal areas were targeted through connections that in most instances were reciprocal and often of different strength. These connections linked parietal and frontal clusters formed by areas sharing basic functional properties. This led to five different medio-laterally oriented pillar domains spanning the entire extent of the parieto-frontal system, in the posterior parietal, anterior parietal, cingulate, frontal, and prefrontal cortex. Different information processing streams could be identified thanks to inter-domain connectivity. These streams encode fast hand reaching and its control, complex visuomotor action spaces, hand grasping, action/intention recognition, oculomotor intention and visual attention, behavioral goals and strategies, and reward and decision value outcome. Most of these streams converge on the cingulate domain, the main hub of the system. All of them are embedded within a larger eye–hand coordination network, from which they can be selectively set in motion by task demands.

The parietal mechanisms for online control of hand trajectory were studied by combining single-cell recording and reversible inactivation of superior parietal area 5 (PE/PEc; SPL) of monkeys while these made reaches and saccades to visual targets, when the target position changed unexpectedly. Neural activity was modulated by hand position, speed, and movement direction, and by pre- and/or postsaccadic signals. After bilateral muscimol injection, an increase in the hand reaction- and movement-time toward both the first and second targets was observed. This caused an increase in the time necessary for the trajectory correction, and therefore an elongation of the hand-path toward the first target location. Furthermore, hand trajectories were different in shape than control ones. An elongation of the eye reaction time to both first and second targets was also observed, which could partially explain the deficit of planning and correction of hand movement. These results identify the superior parietal lobule as a crucial node in the online control of hand and eye movement and highlight the role of the eye impairment in the emergence of the reaching disorder so far regarded as the hallmark of optic ataxia.

Experiencing an adverse childhood and parental neglect is a risk factor for depression in the adult population. Patients with a history of traumatic childhood develop a subtype of depression that is characterized by earlier onset, poor treatment response and more severe symptoms. The long-lasting molecular mechanisms that are engaged during early traumatic events and determine the risk for depression are poorly understood. In this study, we altered adult depression-like behavior in mice by applying juvenile isolation stress. We found that this behavioral phenotype was associated with a reduction in the levels of the deacetylase sirtuin1 (SIRT1) in the brain and in peripheral blood mononuclear cells. Notably, peripheral blood mRNA expression of SIRT1 predicted the extent of behavioral despair only when depression-like behavior was induced by juvenile—but not adult—stress, implicating SIRT1 in the regulation of adult behavior at early ages. Consistent with this hypothesis, pharmacological modulation of SIRT1 during juvenile age altered the depression-like behavior in naive mice. We also performed a pilot study in humans, in which the blood levels of SIRT1 correlated significantly with the severity of symptoms in major depression patients, especially in those who received less parental care during childhood. On the basis of these novel findings, we propose the involvement of SIRT1 in the long-term consequences of adverse childhood experiences.