An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions.

This study provides the first characterization of early developmental trajectories of corpus callosum (CC) segments in rhesus macaques using noninvasive MRI techniques and assesses long-term effects of neonatal amygdala or hippocampal lesions on CC morphometry. In Experiment 1, 10 monkeys (5 males) were scanned at 1 week-2 years of age; eight additional infants (4 males) were scanned once at 1-4 weeks of age. The first 8 months showed marked growth across all segments, with sustained, albeit slower, growth through 24 months. Males and females had comparable patterns of CC maturation overall, but exhibited slight differences in the anterior and posterior segments, with greater increases in the isthmus for males and greater increases in the rostrum for females. The developmental changes are likely a consequence of varying degrees of axonal myelination, redirection, and pruning. In Experiment 2, animals with neonatal lesions of the amygdala (n = 6; 3 males) or hippocampus (n = 6; 4 males) were scanned at 1.5 years post-surgery and compared to scans of six control animals from Experiment 1. Whereas amygdala damage yielded larger rostral and posterior body segments, hippocampal damage yielded larger rostrum and isthmus. These differences demonstrate that early perturbations to one medial temporal lobe structure may produce extensive and long-lasting repercussions in other brain areas. The current findings emphasize the complexity of neural circuitry putatively subserving neurodevelopmental disorders such as autism spectrum disorder and Williams syndrome, which are each characterized by malformations and dysfunction of complex neural networks that include regions of the medial temporal lobe.

Individual differences in impulsivity predict anticipatory eye movements.

Impulsivity is the tendency to act without forethought. It is a personality trait commonly used in the diagnosis of many psychiatric diseases. In clinical practice, impulsivity is estimated using written questionnaires. However, answers to questions might be subject to personal biases and misinterpretations. In order to alleviate this problem, eye movements could be used to study differences in decision processes related to impulsivity. Therefore, we investigated correlations between impulsivity scores obtained with a questionnaire in healthy subjects and characteristics of their anticipatory eye movements in a simple smooth pursuit task. Healthy subjects were asked to answer the UPPS questionnaire (Urgency Premeditation Perseverance and Sensation seeking Impulsive Behavior scale), which distinguishes four independent dimensions of impulsivity: Urgency, lack of Premeditation, lack of Perseverance, and Sensation seeking. The same subjects took part in an oculomotor task that consisted of pursuing a target that moved in a predictable direction. This task reliably evoked anticipatory saccades and smooth eye movements. We found that eye movement characteristics such as latency and velocity were significantly correlated with UPPS scores. The specific correlations between distinct UPPS factors and oculomotor anticipation parameters support the validity of the UPPS construct and corroborate neurobiological explanations for impulsivity. We suggest that the oculomotor approach of impulsivity put forth in the present study could help bridge the gap between psychiatry and physiology.

Impact of chronic subthalamic high-frequency stimulation on metabolic basal ganglia activity: a 2-deoxyglucose uptake and cytochrome oxidase mRNA study in a macaque model of Parkinson's disease.

The mechanisms of action of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) remain only partially understood. Hitherto, experimental studies have suggested that STN-HFS reduces the activity of STN neurons. However, some recent reports have challenged this view, showing that STN-HFS might also increase the activity of globus pallidus internalis (GPi) neurons that are under strong excitatory drive of the STN. In addition, most results emanate from studies applying acute STN-HFS, while parkinsonian patients receive chronic stimulation. Thus, the present study was designed to assess the effect of chronic (10 days) STN-HFS in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primate. For this purpose, 2-deoxyglucose (2-DG) uptake, a measure of global synaptic activity, was assessed in the basal ganglia and the motor thalamus after chronic unilateral STN-HFS. Cytochrome oxidase subunit 1 (COI) mRNA expression, a marker of efferent metabolic activity, was additionally assessed in the globus pallidus. Chronic STN-HFS (i) reversed abnormally decreased 2-DG uptake in the STN of parkinsonian nonhuman primates, (ii) reversed abnormally increased 2-DG accumulation in the GPi while COI mRNA expression was increased, suggesting global activation of GPi neurons, and (iii) reversed abnormally increased 2-DG uptake in the ventrolateral motor thalamus nucleus. The simultaneous decrease in 2-DG uptake and increase in COI mRNA expression are difficult to reconcile with the current model of basal ganglia function and suggest that the mechanisms by which STN-HFS exerts its clinical benefits are more complex than a simple reversal of abnormal activity in the STN and its targets.

Responses to affective stimuli in monkeys with entorhinal or perirhinal cortex lesions.

Recent efforts to define the functions of the primate rhinal (entorhinal and perirhinal) cortical areas have focused on their interaction with the hippocampus in the mediation of normal memory. Less is known on the functional meaning of their strong connections to the amygdala, a key substrate for emotion. A previous study (Meunier and Bachevalier, 2002) showed evidence that complete rhinal ablations yield changes in monkeys' behavioral responses to affectively salient stimuli. Here, we studied monkeys with separate entorhinal or perirhinal ablations in the same paradigm, where responses were triggered by four stimuli: an unfamiliar human, a conspecific stimulus, a toy snake, and a familiar (generally rewarded) junk object. The two separate lesions produced similar changes, and each replicated the effects of complete rhinal lesions (i.e., attenuated affiliation and enhanced defense). Failure to modulate responses based on previous experience (i.e., memory difficulties) may explain these affective changes. This interpretation does not account, however, for the sparing of some memory-dependent modulations of defense, nor for the lack of correlation between the animals' affective changes and their own recognition memory performance. Alternatively, rhinal damage may introduce a negative bias in the risk assessment of affectively salient stimuli, a proposal more compatible with Gray and McNaughton's (2000) anxiety-centered view of medial temporal functions, than with prominent mnemonic/perceptual functional models of the hippocampal/rhinal duo. Reconciling the two perspectives may improve our understanding of rhinal functions.