The Journal of neuroscience : the official journal of the Society for Neuroscience
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Animals rely on environmental cues to identify potential rewards and select the best reward available. The orbitofrontal cortex (OFC) is proposed to encode sensory-specific representations of expected outcome. However, its contribution to the selection of a preferred outcome among different reward options is still unclear. ⋯ These results suggest a potential conflict between OFC (encoding pre-reversal contingencies) and other brain circuits (encoding the new contingencies). Remarkably, repeating the OFC inactivation before the reversal memory test restored normal behavior, confirming the hypothesis of a dominant impact of OFC on other decision-making circuits. These results indicate that the representations encoded in the OFC, while not essential to the expression of outcome preference, exert hierarchical control on downstream decision-making circuits.
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Patients with chronic daily headache and overuse of analgesics, triptans, or other acute headache compounds, are considered to suffer from medication-overuse headache (MOH). This implies that medication overuse is the cause of headache chronification. It remains a key question why only two-thirds of patients with chronic migraine-like headache and overuse of pain medication improve after detoxification, whereas the remainder continue to have chronic headache. ⋯ Another striking result is the correlation of treatment response with the amount of orbitofrontal gray matter. Thus, we demonstrate adaptive gray matter changes within the pain modulatory system in patients with MOH who responded to detoxification, probably reflecting neuronal plasticity. Decreased gray matter in the orbitofrontal cortex at baseline may be predictive of poor response to treatment.
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Neuropeptide Y (NPY) neurons in both the arcuate nucleus of the hypothalamus (ARH) and the dorsomedial hypothalamus (DMH) have been implicated in food intake and obesity. However, while ARH NPY is highly expressed in the lean animal, DMH NPY mRNA expression is observed only after diet-induced obesity (DIO). Furthermore, while ARH NPY neurons are inhibited by leptin, the effect of this adipokine on DMH NPY neurons is unknown. ⋯ This study demonstrates novel and important findings. First, NPY and CART are coexpressed in the same neurons within the DMH, and second, leptin stimulates DMH NPY neurons. These studies suggest that during the progression of DIO, there is an unknown signal that drives the expression of the orexigenic NPY signal within the DMH, and that the chronic hyperleptinemia increases the activity of these NPY/CART neurons.
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Systemic inflammatory events often precipitate acute cognitive dysfunction in elderly and demented populations. Delirium is a highly prevalent neuropsychiatric syndrome that is characterized by acute inattention and cognitive dysfunction, for which prior dementia is the major predisposing factor and systemic inflammation is a frequent trigger. Inflammatory mechanisms of delirium remain unclear. ⋯ Furthermore, the well tolerated COX inhibitor ibuprofen was protective against IL-1β-induced deficits. These data demonstrate that progressive microglial COX-1 expression and prostaglandin synthesis can underpin susceptibility to cognitive deficits, which can be triggered by systemic LPS-induced IL-1β. These data contribute to our understanding of how systemic inflammation and ongoing neurodegeneration interact to induce cognitive dysfunction and episodes of delirium.
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The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional μ-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. ⋯ During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on μ-opioid receptors.