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"Levinthal, David"
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Who pushed Humpty Dumpty? : and other notorious nursery tale mysteries
Police detective Binky investigates the theft of a golden goose, the poisoning of Snow White, and other fairy tale crimes.
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Multiple areas of the cerebral cortex influence the stomach
The central nervous system both influences and is influenced by the gastrointestinal system. Most research on this gut–brain connection has focused on how ascending signals from the gut and its microbiome alter brain function. Less attention has focused on how descending signals from the central nervous system alter gut function. Here, we used retrograde transneuronal transport of rabies virus to identify the cortical areas that most directly influence parasympathetic and sympathetic control of the rat stomach. Cortical neurons that influence parasympathetic output to the stomach originated from the rostral insula and portions of medial prefrontal cortex, regions that are associated with interoception and emotional control. In contrast, cortical neurons that influence sympathetic output to the stomach originated overwhelmingly from the primary motor cortex, primary somatosensory cortex, and secondary motor cortex, regions that are linked to skeletomotor control and action. Clearly, the two limbs of autonomic control over the stomach are influenced by distinct cortical networks.
Journal Article
Motor, cognitive, and affective areas of the cerebral cortex influence the adrenal medulla
Modern medicine has generally viewed the concept of “psychosomatic” disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.
Journal Article
The mind–body problem
Which regions of the cerebral cortex are the origin of descending commands that influence internal organs? We used transneuronal transport of rabies virus in monkeys and rats to identify regions of cerebral cortex that have multisynaptic connections with a major sympathetic effector, the adrenal medulla. In rats, we also examined multisynaptic connections with the kidney. In monkeys, the cortical influence over the adrenal medulla originates from 3 distinct networks that are involved in movement, cognition, and affect. Each of these networks has a human equivalent. The largest influence originates from a motor network that includes all 7 motor areas in the frontal lobe. These motor areas are involved in all aspects of skeletomotor control, from response selection tomotor preparation and movement execution. The motor areas provide a link between body movement and the modulation of stress. The cognitive and affective networks are located in regions of cingulate cortex. They provide a link between how we think and feel and the function of the adrenal medulla. Together, the 3 networks can mediate the effects of stress and depression on organ function and provide a concrete neural substrate for some psychosomatic illnesses. In rats, cortical influences over the adrenal medulla and the kidney originate mainly from 2 motor areas and adjacent somatosensory cortex. The cognitive and affective networks, present in monkeys, are largely absent in rats. Thus, nonhuman primate research is essential to understand the neural substrate that links cognition and affect to the function of internal organs.
Journal Article
Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth
There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.
Journal Article
The Cyclic Vomiting Syndrome Threshold: A Framework for Understanding Pathogenesis and Predicting Successful Treatments
Cyclic vomiting syndrome (CVS) is an uncommon, idiopathic disorder defined by recurrent, sudden-onset attacks of repetitive retching and vomiting that are separated by symptom-free intervals. CVS was long regarded as a disorder primarily experienced by children but is now known to present de novo in adulthood. Adult CVS has garnered more research attention over the past 20 years, and these efforts have identified some acute and prophylactic treatments for this disorder. However, CVS still lacks a unifying disease model, and this has hindered the development of new therapies. Here adult CVS is reframed as a neurogenic disorder, driven by various endophenotypic factors that shape patterns of activity within the neural circuits required for disease expression. The concept of the \"CVS threshold\" is put forth in parallel with exploring the remarkable similarity of adult CVS with features of chronic migraine, epilepsy, and panic disorder. Because of such shared neural mechanisms and overlapping endophenotypes, many therapies that have been developed for these other disorders could also be useful in managing CVS. This review seeks to achieve three primary aims: (1) to develop a comprehensive, explanatory framework for adult CVS pathogenesis, (2) to use this framework for identifying potentially novel therapies for CVS, and (3) to describe future research directions that are needed to move the field forward.
Journal Article
Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis
Background
Nausea and vomiting are commonly associated with medication use. Dopaminergic agonists have been associated with these symptoms, but their impact in patients without Parkinson’s disease, such as those with restless legs syndrome (RLS), is not well characterized.
Aims
We sought to determine whether the non-ergoline dopamine agonist ropinirole is associated with nausea and vomiting in adults with RLS.
Methods
We conducted a systematic review using PUBMED, EMBASE, and clinical trial databases to identify placebo-controlled clinical trials of ropinirole for RLS treatment. We extracted data including dosing schedule and the proportion of patients reporting nausea and/or vomiting. We also determined hazard ratios (HR) using a random effects proportional hazard model.
Results
We extracted data from a pool of 13 studies. The prevalence of nausea in the ropinirole-treated RLS group (RLS-R;
N
= 1528) was 37.2% compared to 9.4% in the placebo-treated RLS group (RLS-P;
N
= 1395) (
p
< 0.0001). The prevalence of vomiting in the RLS-R group was 10.9% compared to 2.6% in the RLS-P group (
p
< 0.0001). Ropinirole use was associated with a higher risk of reporting nausea (HR 5.924 [4.410–7.959],
p
< 0.001) and experiencing vomiting (HR 4.628 [3.035–7.057],
p
< 0.0001). Nausea and vomiting represented nearly 50% of all adverse events reported.
Conclusions
Nausea and vomiting are quite common side effects in those using ropinirole for RLS. As RLS is more widely recognized and treated; the prevalence of ropinirole-induced nausea and vomiting could grow substantially. Ropinirole use should be considered as a cause of chronic nausea and vomiting.
Journal Article