Type 1 vanilloid receptors (VR1) have been identified recently in the brain, in which they serve as yet primarily undetermined purposes. The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are ligands for VR1, and AEA has been shown to afford protection against ouabain-induced in vivo excitotoxicity, in a manner that is only in part dependent on the type 1 cannabinoid (CB1) receptor. In the present study, we assessed whether VR1 is involved in neuroprotection by AEA and by arvanil, a hydrolysis-stable AEA analog that is a ligand for both VR1 and CB1. Furthermore, we assessed the putative involvement of lipoxygenase metabolites of AEA in conveying neuroprotection. Using HPLC and gas chromatography/mass spectroscopy, we demonstrated that rat brain and blood cells converted AEA into 12-hydroxy- N -arachidoylethanolamine (12-HAEA) and 15-hydroxy- N -arachidonoylethanolamine (15-HAEA) and that this conversion was blocked by addition of the lipoxygenase inhibitor nordihydroguaiaretic acid....

The importance of the basal ganglia in controlling motor function is well known. However, neuroimaging studies have failed to show either movement-rate dependence or different activation patterns caused by self-initiated (SI) and externally triggered (ET) movements in the basal ganglia–thalamo-motor loop. We herein report the functional magnetic resonance image (fMRI) mapping of sequential left-hand finger movements at five different rates under SI and ET conditions. Significant movement-rate dependence was found in the whole right basal ganglia–thalamo-motor loop only during the SI task. Network analysis also showed strong interactions within this loop during SI movement, whereas interactions were present only from the premotor cortex to the putamen via the sensorimotor cortex during the ET task. Furthermore, psychophysiological interaction analysis confirmed the different modulation between the two tasks in the putamen. fMRI provides evidence that the basal ganglia–thalamo-motor loop plays a key role in ...

Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram (EEG)/magnetoencephalogram and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG–fMRI data acquired before and after alpha-frequency transcranial alternating current stimulation ( α -tACS) and observed that α -tACS tightened the dynamic coupling between spontaneous fluctuations in alpha power and DMN connectivity (especially, in the posterior DMN, between the posterior c...

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on inten...

The human brain activity related to strategies for navigating in space and how it changes with practice was investigated with functional magnetic resonance imaging. Subjects used two different strategies to solve a place-learning task in a computer-generated virtual environment. One-half of the subjects used spatial landmarks to navigate in the early phase of training, and these subjects showed increased activation of the right hippocampus. The other half used a nonspatial strategy and showed, with practice, sustained increased activity within the caudate nucleus during navigation. Activation common to both groups was observed in the posterior parietal and frontal cortex. These results provide the first evidence for spontaneous variability and shift in neural mechanisms during navigation in humans.

Intrinsic connectional architecture of the brain is a crucial element in understanding the governing principle of brain organization. To date, enormous effort has been focused on addressing this issue in humans by combining resting-state functional magnetic resonance imaging (rsfMRI) with other techniques. However, this research area is significantly underexplored in animals, perhaps because of confounding effects of anesthetic agents used in most animal experiments on functional connectivity. To bridge this gap, we have systematically investigated the intrinsic connectional architecture in the rodent brain by using a previously established awake-animal imaging model. First, group independent component analysis was applied to the rsfMRI data to extract elementary functional clusters of the brain. The connectional relationships between these clusters, as evaluated by partial correlation analysis, were then used to construct a graph of whole-brain neural network. This network exhibited the typical features o...

Central pain is neuropathic pain resulting from a lesion of the CNS, such as a stroke [poststroke central pain (CPSP)]. Lesions involving the posterior thalamus lead to reduction or loss of sensation and to CPSP, although the responsible nuclei have not been identified. We now examine the hypotheses that thalamic lesions must extend posterior to the ventral caudal nucleus (Vc) and include ventral medial posterior nucleus (VMpo), to result in loss of cold sensibility and CPSP. Patients with small thalamic strokes associated with CPSP were evaluated by atlas-based mapping of magnetic resonance imaging scans, and by somatosensory testing. All lesions involved posterior Vc; two lesions also involved nuclei posterior to Vc, but not VMpo. All patients tested had alterations of cold pain sensation and tactile sensation, as measured by von Frey hairs. Three patients had altered cool sensation, and the patient with the least involvement of Vc had normal cool thresholds, suggesting that a critical volume of Vc must ...

The growing field of social neuroscience is reliant on the development of robust, ecologically valid paradigms for simulating social interaction and measuring social cognition in highly controlled laboratory settings. Perspective taking is a key component of social cognition, and accordingly several paradigms aimed at measuring perspective taking exist. A relatively novel paradigm is the ball detection task, in which participants and a virtual agent form independent beliefs about the presence of a target stimulus behind an occluder. Previous studies have shown that incongruent trials (in which the participant's and the agent's beliefs differ) affect participant reaction times and elicit increased neural activity in the so-called mentalizing network. This paradigm has important advantages over previous ones, in that experimental conditions can be fully randomized, and ceiling effects are not found even for adult populations. Here, we combined this paradigm with a stress induction and a nonstressful control ...

Fractal analysis has been used to quantify a wide range of complex and irregularly shaped objects in basic biology and medicine. In this study we measured the white matter (WM) fractal dimension (FD) based on human MR brain images. Coronal MR head images were collected from 6 healthy young (26.8±3.4) and 6 elderly (74.2±2.6) subjects using a 1.5T Siemens Vision scanner and a three-dimensional Turboflash imaging sequence (TR/TE = 11.4/4.4ms, flip angle = 10°). Slice thickness was 2 mm, in-plane resolution was 1 x 1 mm2. The head images were then resampled via trilinear interpolation to be 1 mm in thickness. The brain was segmented from the resampled head images using the BET tool in the FSL package. The WM was then segmented from the brain images using the FSL FAST tool and recorded as a binary (black & white) images. A 3-D thinning method was applied to the binary images to obtain skeletons of the WM. A box-counting dimension was adopted to define the FD of the WM skeleton which repeatedly meshed different...

Individual differences in pain sensitivity and reactivity are well recognized but the underlying mechanisms are likely to be diverse. The phenomenon of stress-induced analgesia is well documented in animal research and individual variability in the stress response in humans may produce corresponding changes in pain. We assessed the magnitude of the acute stress response of 16 chronic back pain (CBP) patients and 18 healthy individuals exposed to noxious thermal stimulations administered in a functional magnetic resonance imaging experiment and tested its possible contribution to individual differences in pain perception. The temperature of the noxious stimulations was determined individually to control for differences in pain sensitivity. The two groups showed similar significant increases in reactive cortisol across the scanning session when compared with their basal levels collected over 7 consecutive days, suggesting normal hypothalamic–pituitary–adrenal axis reactivity to painful stressors in CBP patie...