Huntington's disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. While patients' performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients' performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.

Understanding the neural mechanisms of training-induced brain plasticity has significant implications for improving academic achievement. Previous studies suggest abacus-based mental calculation (AMC) training significantly improves individual's arithmetic capability, and the frontal-parietal network is suggested to be the key neural circuit underlying AMC. Yet, it remains unclear how AMC training shifts brain activation in this network and whether the training effect is transferable or not. The current study aimed to address these questions using a longitudinal design engaging an experimental group (20 days of AMC training) and a control group. The fMRI results indicated that AMC training increased sustained but reduced transient activation in the frontal-parietal network when the AMC group performed the training-related arithmetic task. More interestingly, similar pre- to post-training changes in activation were observed in two training-unrelated tasks. The control group, on the other hand, did not exhibit any pre- to post-training differences in brain activation on any of the three tasks. These findings extend the previous cross-sectional studies of AMC and suggest that AMC training induces functional changes in brain activation and such plasticity may be transferable beyond the AMC. The training effects on sustained and transient neural activity may also provide a new perspective to understand training-induced neural plasticity and related transfer effect.

Subjective well-being (SWB) is the eternal pursuit of all mankind. Individual differences in SWB may reflect the way of emotional processing. Neuroimaging studies have partly examined the neural mechanism of the individual differences in SWB using resting-state functional magnetic resonance imaging (rs-fMRI). However, few studies have investigated the relationship between the individual differences in SWB and brain functional connectivity during facial emotion processing task. Here, we applied negative facial emotion processing task-based fMRI to explore the brain functional basis of the individual differences in SWB. Results showed that SWB is positively correlated with the activation of right posterior cingulate cortex, left interior temporal gyrus and left angular gyrus for the comparison of negative stimulus and neutral stimulus, revealing that happy individuals may be more proactive to use attention transfer and behavioral inhibition strategies to decrease negative experiences during negative emotional processing. In addition, high SWB is associated with strong functional connectivity between high-level cognitive networks (e.g., frontal-parietal network) and low-level perceptual networks (e.g., sensorimotor network), and weak functional connectivity within default mode network and within low-level perceptual networks, indicating that the self-reflection, emotional regulation and cognitive control during negative facial emotion processing underlies the individual differences in SWB. These findings provide a novel insight to characterize the brain functional basis of the individual differences in SWB.

Accumulating evidence indicates a positive effect of abacus-based mental calculation (AMC) training on various cognitive functions including short-term memory (STM). Our previous work has shown AMC training-induced activation changes in the frontal-parietal network (FPN) using task fMRI. However, whether AMC training-induced functional plasticity in the same brain network can be detected at resting state remains unknown. The current study aimed to address this question using resting state functional connectivity in a longitudinal AMC training experiment engaging a training group (18 subjects, age = 21.439 ± 0.565) and a control group (18 subjects, age = 21.113 ± 1.140). Our results revealed that the average functional connectivity strength within the FPN showing task activation changes was significantly enhanced after training in the AMC group, whereas it remained stable in the control group. Further analysis indicated that such connectivity increase in the AMC group was primarily driven by the enhanced coupling of bilateral superior parietal lobules (SPL). In addition, a significant and positive correlation between letter forward memory span and SPL connectivity was found at post-training session in the AMC group. While the weakest quartile of SPL connections ranking by pre-training connectivity strength showed the largest effect of enhancement after training, it was the strongest quartile of SPL connectivity that correlated the most with memory span at post-training session. These findings suggest that AMC training may enhance bilateral SPL functional connectivity, through which AMC training might exert a transfer effect to improve short-term memory capacity.

The tachykinin peptide substance P (SP) is expressed by many interneurons and some projection neurons in the superficial dorsal horn of the spinal cord. We have recently shown that SP-expressing excitatory interneurons in lamina II correspond largely to a morphological class known as radial cells. However, little is known about their function, or their synaptic connectivity. Here we use a modification of the Brainbow technique to define the excitatory synaptic input to SP radial cells. We show that around half of their excitatory synapses (identified by expression of Homer) are from boutons with VGLUT2, which are likely to originate mainly from local interneurons. The remaining synapses presumably include primary afferents, which generally have very low levels of VGLUT2. Our results also suggest that the SP cells are preferentially innervated by a population of excitatory interneurons defined by expression of green fluorescent protein under control of the gene for gastrin-releasing peptide, and that they receive sparser input from other types of excitatory interneuron. We show that around 40% of lamina I projection neurons express Tac1, the gene encoding substance P. Finally, we show that silencing Tac1-expressing cells in the dorsal horn results in a significant reduction in reflex responses to cold and radiant heat, but does not affect withdrawal to von Frey hairs, or chloroquine-evoked itch.

Aging is associated with changes in numerous homeostatic functions, such as food intake, that are thought to be mediated by the hypothalamus. Orexin/hypocretin neurons of the hypothalamus regulate several physiological functions, including feeding, sleep and wakefulness. Evidence from both clinical and animal studies supports the notion that aging is associated with loss or dysregulation of the orexin system. Here, we used virus-mediated gene transfer to manipulate expression of orexin peptides in young and aged rats and examined behavioral and neurochemical correlates of food intake in these animals. Aged rats showed slower feeding latencies when presented with palatable food compared to young control rats, and these deficits were ameliorated by upregulation of orexin expression. Similarly, young animals treated with a virus designed to decrease preproorexin expression showed longer feeding latencies reminiscent of aged control rats. Feeding was also associated with increased acetylcholine, glutamate and GABA efflux in insular cortex of young control animals. Orexin upregulation did not restore deficits in feeding-elicited release of these neurotransmitters in aged rats, but did enhance basal neurotransmitter levels which may have contributed to the behavioral correlates of these genetic manipulations. These studies demonstrate that age-related deficits in behavioral and neurochemical measures of feeding are likely to be mediated, in part, by the orexin system. Because these same neurotransmitter systems have been shown to underlie orexin effects on cognition, treatments which increase orexin function may have potential for improving both physiological and cognitive manifestations of certain age-related disorders.

Alterations in central extended amygdala (EAc) function have been linked to anxiety, depression, and anxious temperament (AT), the early-life risk to develop these disorders. The EAc is composed of the central nucleus of the amygdala (Ce), the bed nucleus of the stria terminalis (BST), and the sublenticular extended amygdala (SLEA). Using a non-human primate model of AT and multimodal neuroimaging, the Ce and the BST were identified as key AT-related regions. Both areas are primarily comprised of GABAergic neurons and the lateral Ce (CeL) and lateral BST (BSTL) have among the highest expression of neuropeptides in the brain. Somatostatin (SST) is of particular interest because mouse studies demonstrate that SST neurons, along with corticotropin-releasing factor (CRF) neurons, contribute to a threat-relevant EAc microcircuit. Although the distribution of CeL and BSTL SST neurons has been explored in rodents, this system is not well described in non-human primates. In situ hybridization demonstrated an anterior-posterior gradient of SST mRNA in the CeL but not the BSTL of non-human primates. Triple-labeling immunofluorescence staining revealed that SST protein-expressing cell bodies are a small proportion of the total CeL and BSTL neurons and have considerable co-labeling with CRF. The SLEA exhibited strong SST mRNA and protein expression, suggesting a role for SST in mediating information transfer between the CeL and BSTL. These data provide the foundation for mechanistic non-human primate studies focused on understanding EAc function in neuropsychiatric disorders.