Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging (fMRI) signal covariations between the midbrain periaqueductal gray matter (PAG), rostral ventromedial medulla (RVM), and spinal trigeminal nucleus (SpV) are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 minutes, we recorded ongoing pain intensity in 24 PTN participants, and classified them as fluctuating (n=13) or stable (n=11). Using a PAG seed, we identified connections between the PAG and emotional-affective...

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....

It has been suggested that learning is associated with a transient and highly selective increase in brain gray matter in healthy young volunteers. It is not clear whether and to what extent the aging brain is still able to exhibit such structural plasticity. We built on our original study, now focusing on healthy senior citizens. We observed that elderly persons were able to learn three-ball cascade juggling, but with less proficiency compared with 20-year-old adolescents. Similar to the young group, gray-matter changes in the older brain related to skill acquisition were observed in area hMT/V5 (middle temporal area of the visual cortex). In addition, elderly volunteers who learned to juggle showed transient increases in gray matter in the hippocampus on the left side and in the nucleus accumbens bilaterally.

Introduction: Lifestyle choices contribute to nearly all of the 10 leading causes of death in the United States, and Alzheimer’s disease (AD) is no exception. Links from AD to metabolic and inflammatory diseases give dietary and lifestyle contributions ...

Plexiform neurofibromas in patients with neurofibromatosis type I (NF1) typically involve deep or named nerves, can become very large, may cause serious functional impairment and have a risk of malignant progression. In developing an animal model to study plexiform neurofibromas, we have shown that human NF1 neurofibrosarcoma-derived Schwann cells (SC) can be successfully xenografted into the sciatic nerves of scid mice. The histogenesis of engrafted neurofibrosarcoma SC was consistent with that of established human plexiform neurofibromas. The tumors invaded and degenerated the host nerve structure and proliferated in a slow, sustained manner without apparent malignancy. In addition, we observed angiogenic markers in xenografted nerves. We performed MRI to study the formation and progression of these tumors in our model. Using a 17.6 tesla, 89mm bore magnet we performed H-1 MRI at 750MHz on excised, fixed xenografted mouse sciatic nerves. We then compared the T1 weighted images to immunostaining of the sa...

In this experiment we address the pharmacological modulation of repetition priming, a basic form of learning, using event-related functional magnetic resonance imaging. We measured brain activity in a word-stem completion paradigm in which, before study, volunteers were given either placebo, lorazepam (2 mg orally), or scopolamine (0.4 mg, i.v.). Relative to placebo, both drugs attenuated the behavioral expression of priming. Repetition was associated with a decreased neuronal response in left extrastriate, left middle frontal, and left inferior frontal cortices in the placebo group. Both drugs abolished these “repetition suppression” effects. By showing a concurrence of behavioral and neuronal modulations, the results suggest that GABAergic and cholinergic systems influence the neuronal plasticity necessary for repetition priming.

Animal studies have shown that motor skill learning and sensorimotor skill reacquisition after experimental stroke are associated with functional and structural changes in the affected-limb representation in sensorimotor cortex. While studies in stroke patients have demonstrated functional plasticity of the paretic limb representation in sensorimotor cortex, no study has examined whether structural remodeling also occurs. Therefore, 9 chronic stroke patients with a range of residual right-sided upper limb paresis and 9 age- and gender-matched normal controls underwent functional and structural MRI to evaluate for functional and structural plasticity, respectively. Functional MRI was conducted during unilateral punctate tactile stimulation to the middle finger. MRI data were analyzed using cortical surface-based tools including an automated procedure for measuring cortical thickness. Activation during right (affected side of patients) finger stimulation was greater (p < 0.025) in patients as compared to con...

Motor compensation after stroke is a behavior in which the non-paretic limb performs tasks normally accomplished by the paretic limb. For example, stroke survivors with right hemiparesis often bear weight exclusively on the left leg when rising from a c...

The action observation network(AON) is comprised of motor regions (inferior frontal gyrus, ventral premotor cortex, and posterior parietal cortex) that are active when we make an action and when we see someone else make a similar action. Previous studie...

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained human participants of both sexes in an orientation discrimination task, while using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to separately examine training-induced changes in working memory (WM) representation. fMRI decoding revealed orientation-specific neural patterns during the delay period in primary visual cortex (V1) before, but not after, training, whereas neurodisruption of V1 during the delay period led to behavioral deficits in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represented WM content after, but not before, training. These results suggest that training do...