Yonghui Li

Brain anatomical network and intelligence

Intuitively, higher intelligence might be assumed to correspond to more efficient information transfer in the brain, but no direct evidence has been reported from the perspective of brain networks. In this study, we performed extensive analyses to test the hypothesis that individual differences in intelligence are associated with brain structural organization, and in particular that higher scores on intelligence tests are related to greater global efficiency of the brain anatomical network. We constructed binary and weighted brain anatomical networks in each of 79 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Based on their IQ test scores, all subjects were divided into general and high intelligence groups and significantly higher global efficiencies were found in the networks of the latter group. Moreover, we showed significant correlations between IQ scores and network properties across all subjects while controlling for age and gender. Specifically, higher intelligence scores corresponded to a shorter characteristic path length and a higher global efficiency of the networks, indicating a more efficient parallel information transfer in the brain. The results were consistently observed not only in the binary but also in the weighted networks, which together provide convergent evidence for our hypothesis. Our findings suggest that the efficiency of brain structural organization may be an important biological basis for intelligence.

Altered Anatomical Network in Early Blindness Revealed by Diffusion Tensor Tractography

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. Diffusion MRI studies have revealed the efficient small-world properties and modular structure of the anatomical network in normal subjects. However, no previous study has used diffusion MRI to reveal changes in the brain anatomical network in early blindness. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 17 early blind subjects and 17 age- and gender-matched sighted controls. We established the existence of structural connections between any pair of the 90 cortical and sub-cortical regions using deterministic tractography. Compared with controls, early blind subjects showed a decreased degree of connectivity, a reduced global efficiency, and an increased characteristic path length in their brain anatomical network, especially in the visual cortex. Moreover, we revealed some regions with motor or somatosensory function have increased connections with other brain regions in the early blind, which suggested experience-dependent compensatory plasticity. This study is the first to show alterations in the topological properties of the anatomical network in early blindness. From the results, we suggest that analyzing the brains anatomical network obtained using diffusion MRI data provides new insights into the understanding of the brains re-organization in the specific population with early visual deprivation.

Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats

RationaleAnatomical studies have shown that the paraventricular nucleus of the thalamus (PVT) innervates areas of the forebrain involved in the expression and regulation of emotional behaviors including fear and anxiety. In addition, the PVT is densely innervated by fibers containing orexin-A (OXA) and orexin-B (OXB), peptides that are well-known for their arousal effects on behavior.ObjectivesIn this study, we investigate whether microinjections of orexin receptor agonists and antagonists in the PVT region alter expression of anxiety-like behaviors in the rat as measured in the elevated plus maze.ResultsWe report that microinjections of OXA and OXB in the PVT region elicited anxiety-like response as indicated by a reduction in open arm time and entries. In addition, OXA and OXB produced changes in ethological measures indicative of an anxiety state. Central administrations of antagonists for corticotropin releasing factor (CRF) or the opioid kappa receptors attenuated the anxiogenic effects produced by microinjections of OXA in the PVT region. We also provide evidence that endogenously released orexins act at the PVT to produce anxiety by showing that microinjections of TCSOX229, an orexin-2 receptor antagonist, in the PVT region attenuated the anxiogenic effects produced by a previous exposure to footshock stress.ConclusionsThis study indicates that endogenously released orexins act on the PVT to regulate anxiety levels through mechanisms involving the brain kappa and CRF receptors.

Effect of 5-aza-2-deoxycytidine microinjecting into hippocampus and prelimbic cortex on acquisition and retrieval of cocaine-induced place preference in C57BL/6 mice

The long lasting addiction-related abnormal memory is one of the most important foundations for relapse. DNA methylation may be a possible mechanism for persistence of such memory. Here we injected the DNA methyltransferases (DNMTs) inhibitor, 5-aza-2-deoxycytidine (5-aza) into hippocampus CA1 area and prelimbic cortex during the stages of acquisition and expression of cocaine-induced place preference in C57BL/6 mice. Results showed that in CA1 DNA methylation inhibitors could restrain acquisition but had no impact on expression of the cocaine-induced conditioned place preference (CPP). On the contrary, in prelimbic cortex, 5-aza had no effect on acquisition but blocked expression. Our results indicated that DNA methylation in hippocampus is required for learning; while DNA methylation in prelimbic cortex is necessary for memory retrieval. The present finding is consistent with the role of the hippocampus as a structure contributing to cocaine-induced memory acquisition, and prelimbic cortex, a part of prefrontal cortex as an area responsible for cocaine-induced memory retrieval. In conclusion, DNA methylation does play an important role in drug-induced learning and memory although the detailed effect still calls for further research.

Changes in emotional behavior produced by orexin microinjections in the paraventricular nucleus of the thalamus.

The paraventricular nucleus of the midline thalamus (PVT) innervates areas of the extended amygdala known to play a key role in the expression of emotional behaviors. In this study, microinjections of orexins (hypocretins), which have excitatory actions on neurons in the PVT, in the midline thalamus were used to investigate if the PVT modulates the expression of emotional behavior in the open field. First, the approach-avoidance tendency (number and duration of visit to the center area) associated with novelty was examined in orexin treated rats before and after placing a novel object in the center of the open field. Second, the expression of ethological behaviors (rearing, locomotion, freezing, and grooming) in the open field was used to determine the effects of orexins on emotionality. Microinjections of orexin-A (OXA) or orexin-B (OXB) in the PVT decreased exploration of the center area and the novel object indicating that the center area and the object had more aversive properties in orexin treated rats. Both OXA and OXB microinjections in the PVT increased the expression of freezing and grooming behaviors which are indicative of a negative emotional state. The results indicate that microinjections of orexins in the PVT made the test situation more aversive and produced avoidance behaviors. This suggests that orexins may act at the PVT to modulate behaviors associated with a negative emotional state.

Orexins in the midline thalamus are involved in the expression of conditioned place aversion to morphine withdrawal

Previous studies have implicated the bed nucleus of the stria terminalis, central nucleus of the amygdala and the shell of the nucleus accumbens (collectively called the extended amygdala) as playing an important role in mediating the aversive emotion associated with opioid withdrawal. The paraventricular nucleus of the thalamus (PVT) provides a very dense input to the extended amygdala, and the PVT is densely innervated by orexin neurons, which appear to be involved in producing some of the physical and emotional effects associated with morphine withdrawal. In the present study, we confirm that the PVT is densely innervated by orexin fibers, whereas the regions of the extended amygdala associated with the effects of morphine withdrawal are poorly innervated. Microinjections of the orexin-1 receptor (OX1R) antagonist SB334867 or the orexin-2 receptor (OX2R) antagonist TCSOX229 at doses of 5.0 or 15.0 microg into the PVT region did not affect the acquisition of the conditioned place aversion (CPA) nor the physical effects produced by naloxone-precipitated morphine withdrawal. In contrast, microinjections of TCSOX229 (15.0 microg) in the PVT region significantly attenuated the expression of naloxone-induced CPA while microinjections of SB334867 at the same dose had no effect. The results from these experiments indicate a role for OX2R in the PVT on the expression of CPA associated with morphine withdrawal. Orexins may mediate the aversive effects of morphine withdrawal by engaging the extended amygdala indirectly through the action of orexins on the PVT.

COMT Val158Met Modulates Association Between Brain White Matter Architecture and IQ

The intelligence quotient (IQ) is typically associated with the architecture of gray and white matter in specific brain regions, and this association appears to be genetically based. However, specific sources of genetic variation for the association have not been studied extensively. Using diffusion tensor imaging in 15 mental retardation patients and 80 healthy volunteers, we studied the association between white matter architecture and IQ and also investigated the effects of COMT val158met on this association. The results showed that fractional anisotropy (FA) values in the prefrontal lobe and the hippocampus formation were associated with IQ and that val158met may affect this association. Subjects who were val homozygous showed steeper slopes for regression of the FA value on IQ than met carriers. Our findings suggest that COMT val158met may contribute to intelligence by affecting the association between IQ and the white matter architecture in the prefrontal lobe and the hippocampal formation.

Orexin-A acts on the paraventricular nucleus of the midline thalamus to inhibit locomotor activity in rats

Orexins (hypocretins) are novel peptides that have been shown to play a role in control of behavioral arousal. The paraventricular nucleus of the midline thalamus (PVT) is one area of the brain that is the most densely innervated by orexin fibers. In addition, the PVT sends a dense projection to the nucleus accumbens, an area of the striatum involved in the regulation of locomotion. This study was done to determine the effect of microinjections of orexin-A (OXA) or the orexin receptor antagonist SB334867 in the PVT on locomotor activity (LA) in morphine-naïve and morphine-sensitized rats. Microinjections of OXA (3 microg/500 nl) in or near the PVT inhibited LA in rats tested in a novel and familiar environment as well as in rats expressing behavioral sensitization to repeated injections of morphine. In contrast, microinjections of SB334867 had no effect on LA in any of the test situations. Using an approach involving experimenter based analysis of ethological behaviors; we found that microinjections of OXA in the midline thalamus decreased LA while at the same time increasing the expression of grooming and freezing. These results suggest that OXA can act on the PVT and the midline thalamus to produce arousal independent of LA.

Working memory and affective decision-making in addiction: A neurocognitive comparison between heroin addicts, pathological gamblers and healthy controls

BACKGROUND Cognitive deficits are observed both in heroin dependence and in pathological gambling (PG) on various tasks. PG, as a non-substance addiction, is free of toxic consequences of drug use. Therefore a direct neurocognitive comparison of heroin addicts and pathological gamblers helps dissociate the consequences of chronic heroin use on cognitive function from the cognitive vulnerabilities that predispose addiction. METHODS A case-control design was used, comparing 58 abstinent heroin addicts, 58 pathological gamblers, and 60 healthy controls on working memory and affective decision-making functions. Working memory was assessed using the Self-ordered Pointing Test (SOPT). Affective decision-making was measured by the Iowa Gambling Task (IGT). RESULTS Heroin addicts performed significantly worse both on the IGT and on the SOPT, compared to healthy controls. Pathological gamblers performed worse on the IGT than healthy controls, but did not differ from controls on the SOPT. Years of heroin use were negatively correlated with working memory and affective decision-making performance in heroin addicts, while severity of gambling was not significantly correlated with any task performance in pathological gamblers. CONCLUSIONS Our findings indicate that deficits in affective decision-making shared by heroin dependence and PG putatively represent vulnerabilities to addiction and that working memory deficits detected only in heroin addicts may be identified as heroin-specific harmful effects.

Cerebellum Abnormalities in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures Revealed by Diffusion Tensor Imaging

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS.