Prehensile kinematics of the marmoset monkey: Implications for the evolution of visually-guided behaviors.

Throughout the primate lineage, there is a wide diversity of prehensile capacity that is thought to stem from individual species foraging patterns. While many studies have explored primates with precise hand grips, such as higher apes, few have considered primates that lack opposition movements. The New World marmoset monkey occupies an intriguing niche, displaying adept control of their hand movements yet their absence of opposable digits results in relatively imprecise grasping actions when compared with those observed in Old World monkeys, apes, and humans. The marmoset monkey offers a unique composition of ancestral primate corticospinal organization combined with skilled hand use to explore the evolution and development of visually-guided actions. In this study, four adult marmosets were trained to perform a series of visually-guided tasks, designed to assess their control over locating and retrieving objects of differing dimensions. Two of these animals received a neonatal lesion of the inferior pulvinar (unilateral), a thalamic nucleus previously demonstrated to be involved in visuomotor development. The kinematics of their reaching and grasping patterns were recorded for offline analysis. Predictive modeling revealed that maximum grip aperture, time to reach peak velocity and hand use were reliable predictors of distinguishing between cohorts. A consistent feature observed across all tasks was that they do not precisely scale their grip according to the dimensions of the target object which may be attributed to their lack of independent digit control. Therefore, the marmoset monkey represents a previously understudied position in the evolution of primate reach and grasp behavior.

Neural Correlates of the Antinociceptive Effects of Stimulating the Anterior Pretectal Nucleus in Rats.

Stimulation-evoked antinociception (SEA) from the anterior pretectal nucleus (APtN) activates mechanisms that descend to the spinal cord through the dorsolateral funiculus, but the encephalic route followed by the descending pathways from the APtN is not completely known. This study evaluated the changes in the SEA from the APtN in the Wistar rat tail-flick test after lidocaine-induced neural block or N-methyl-d-aspartate-induced neurotoxic lesion of the deep mesencephalic nucleus (DpMe), tegmental pedunculopontine nucleus (PPTg), or lateral paragigantocellular nucleus (LPGi). The SEA from the APtN was less intense after neural block of the contralateral DpMe or PPTg or the ipsilateral LPGi, but was not changed by the neural block of the ipsilateral DpMe or PPTg or the contralateral LPGi. Antinociception did not occur when APtN stimulation was carried out 5 minutes after lidocaine or 6 days after N-methyl-d-aspartate injections into the contralateral DpMe and the ipsilateral LPGi, or into the contralateral PPTg and the ipsilateral LPGi. We conclude that the SEA from the APtN activates 2 descending pain inhibitory pathways, one relaying in the ipsilateral LPGi and another relaying sequentially in the contralateral DpMe and PPTg. PERSPECTIVE: The antinociceptive effect of the APtN stimulation involves 2 descending pathways: one relaying in the ipsilateral LPGi and another descending contralaterally via relays in the DpMe and PPTg.

Pharmacological modulation of pulvinar resting-state regional oscillations and network dynamics in major depression.

The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment.

Short-term plasticity of gray matter associated with leptin deficiency and replacement.

CONTEXT: Leptin affects neurogenesis, neuronal growth, and viability. We previously reported that leptin supplementation increased gray matter (GM) concentration in the anterior cingulate gyrus (ACG), cerebellum, and inferior parietal lobule, areas that are also involved in food intake. OBJECTIVE: The aim of this study was to report the changes in brain structure at different states of leptin supplementation. DESIGN: We conducted a nonrandomized trial. SETTING AND PATIENTS: We studied three adults with congenital leptin deficiency due to a mutation in the leptin gene. INTERVENTION: Patients received treatment with recombinant methionyl human leptin, with annual 11- to 36-d periods of treatment withholding followed by treatment restoration over 3 yr. MAIN OUTCOME MEASURES: GM concentration (by voxel-based morphometry analysis of magnetic resonance scans) was correlated with body mass index (BMI) and leptin supplementation. RESULTS: Annually withholding leptin supplementation for several weeks increased BMI and reversed the original effects of leptin in the cerebellum and ACG. The changes in the ACG were consistent with an indirect effect of leptin mediated through increased BMI. In the cerebellum, where leptin receptors are most dense, GM changes appeared to be direct effects of leptin. Leptin restoration did not lead to recovery of GM in the short term but did lead to an unexpected GM increase in the posterior half of the left thalamus, particularly the pulvinar nucleus. CONCLUSION: These findings provide the first in vivo evidence of remarkably plastic, reversible, and regionally specific effects of leptin on human brain morphology. They suggest that leptin may have therapeutic value in modulating plasticity-dependent brain functions.

Pulvinar inactivation disrupts selection of movement plans.

The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions.

Effects of inactivation of the lateral pulvinar on response properties of second visual area cells in Cebus monkeys.

1. In the present study, we investigated the influence of the pulvinar nucleus upon response properties of single cells in the second visual area (V2) of Cebus monkeys. The method used consisted of the inactivation of a portion of the lateral pulvinar by GABA injections while studying the response properties of cells in V2 at the same visuotopic location as that of the inactivation. 2. After GABA injection in the pulvinar, most cells in V2 (67%) showed changes in spontaneous and/or stimulus-driven activities. Contrary to the effect found with inactivation of the striate cortex, which promotes a reduction in the response of V2 neurons, we found that the main effect of pulvinar inactivation was an increment in stimulus-driven responses of V2 cells (39% of units studied). A reduction of responses was observed in 27% of units. 3. A change in orientation and/or direction selectivity was found in 91% of cells after inactivation of the pulvinar. Most commonly, the orientation selectivity of a neuron was decreased during pulvinar inactivation. 4. The inactivation results indicate that the pulvinar projections have a modulatory effect on the activity of V2 cells.

Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans.

Subjects sedated by noradrenergic alpha2 agonists can switch rapidly from a state of extremely low to almost full consciousness following phasic increases in arousal or cognitive demand. Such flexibility is not displayed by traditional sedatives, such as the benzodiazepine diazepam. Experimentally, the phasic modulation of alpha2 effect by arousing or distracting stimuli can counteract the deleterious cognitive effects of alpha2 agonists. We used behavioural and fMRI indices of brain function to investigate the phasic modulatory effect that presentation of loud white noise would have on attentional dysfunction induced by administration of dexmedotomidine, an alpha2 agonist. Dexmedotomidine and midazolam were compared to placebo during performance of a target detection task, which was presented in the presence or absence of white noise. Compared to placebo, both dexmedotomidine and midazolam impaired task performance. This impairment was significantly attenuated by presentation of white noise in the dexmedotomidine condition only. This functional improvement corresponded to selective increase in activity of left medial pulvinar nucleus of the thalamus. This regional increase is suggested to index increases in phasic arousal, which counteract dexmedotomidine's detrimental attentional effects. Finally, despite sedating subjects to equivalent degrees, dexmedotomidine and midazolam had strikingly different regional effects on task-induced brain activity. Therefore, for the same level of sedation, the behavioural and anatomical attributes identifying the quality of sedation can vary.

Pulvinar participates in synchronizing neural assemblies in the visual cortex, in cats.

It has been proposed that the perception of a coherent image necessitates two processes, that is, an ensemble of neurons which synchronizes discharges of individual cells and stimulus-specific gamma-band (gamma) neuronal oscillations which may serve as carrier signals for a temporal code. We tested the hypothesis that cortical gamma-oscillations and synchronization depend upon the interactions between the lateral posterior-pulvinar complex of the thalamus (LP-P) and visual cortex. Local reversible inactivation of the LP-P was achieved by pressure injections of gamma-aminobutyric acid (GABA). In the majority of cases the LP-P depression decreased the strength of the synchronization and oscillations. Also, the results demonstrate that the occurrence of stimulus-dependent oscillations and the synchronization of neuronal responses are two distinct processes and consequently they may occur or disappear independently of each other.