Positive Clinical Neuroscience: Explorations in Positive Neurology

Disorders of the brain and its sensory organs have traditionally been associated with deficits in movement, perception, cognition, emotion, and behavior. It is increasingly evident, however, that positive phenomena may also occur in such conditions, with implications for the individual, science, medicine, and for society. This article provides a selective review of such positive phenomena – enhanced function after brain lesions, better-than-normal performance in people with sensory loss, creativity associated with neurological disease, and enhanced performance associated with aging. We propose that, akin to the well-established field of positive psychology and the emerging field of positive clinical psychology, the nascent fields of positive neurology and positive neuropsychology offer new avenues to understand brain-behavior relationships, with both theoretical and therapeutic implications

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

C-tactile afferent stimulating touch carries a positive affective value

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major—smile muscle, positive affect & corrugator supercilii—frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly

Ethical Considerations in Crowdfunding

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Practice Inquiry: Clinical Uncertainty as a Focus for Small-Group Learning and Practice Improvement

PROBLEM: Many primary care physicians in nonacademic settings lack a collegial forum for engaging the clinical uncertainties inherent in their work. PROGRAM DESCRIPTION: “Practice Inquiry” is proposed as a set of small-group, practice-based learning and improvement (PBLI) methods designed to help clinicians better manage case-based clinical uncertainty. Clinicians meet regularly at their offices/clinics to present dilemma cases, share clinical experience, review evidence for blending with experience, and draw implications for practice improvement. From 2001 through 2005, Practice Inquiry was introduced to sites in the San Francisco Bay Area as a demonstration effort. Meeting rosters, case logs, a feedback survey, and meeting field notes documented implementation and provided data for a formative, qualitative evaluation. PROGRAM EVALUATION: Of the 30 sites approached, 14 held introductory meetings. As of summer 2006, 98 clinicians in 11 sites continue to hold regularly scheduled group meetings. Of the 118 patient cases presented in the seven oldest groups, clinician–patient relationship and treatment dilemmas were most common. Clinician feedback and meeting transcript data provided insights into how busy practitioners shared cases, developed trust, and learned new knowledge/skills for moving forward with patients. DISCUSSION: Ongoing clinician involvement suggests that Practice Inquiry is a feasible, acceptable, and potentially useful set of PBLI methods. Two of the Practice Inquiry’s group learning tasks received comparatively less focus: integrating research evidence with clinical experience and tracking dilemma case outcomes. Future work should focus on reducing the methodological limitations of a demonstration effort and examining factors affecting clinician participation. Set-aside work time for clinicians, or other equally potent incentives, will be necessary for the further elaboration of these PBLI methods aimed at managing uncertainty

The role of routine post-natal abdominal ultrasound for newborns in a resource-poor setting: a longitudinal study

<p>Abstract</p> <p>Background-</p> <p>Neonatal abdominal ultrasound is usually performed in Nigeria to investigate neonatal symptoms rather than as a follow up to evaluate fetal abnormalities which were detected on prenatal ultrasound. The role of routine obstetric ultrasonography in the monitoring of pregnancy and identification of fetal malformations has partly contributed to lowering of fetal mortality rates. In Nigeria which has a high maternal and fetal mortality rate, many pregnant women do not have ante-natal care and not infrequently, women also deliver their babies at home and only bring the newborns to the clinics for immunization. Even when performed, most routine obstetric scans are not targeted towards the detection of fetal abnormalities.</p> <p>The aim of the present study is to evaluate the benefit of routinely performing abdominal scans on newborns with a view to detecting possible abnormalities which may have been missed ante-natally.</p> <p>Methods-</p> <p>This was a longitudinal study of 202 consecutive, apparently normal newborns. Routine clinical examination and abdominal ultrasound scans were performed on the babies by their mother's bedside, before discharge. Neonates with abnormal initial scans had follow-up scans.</p> <p>Results-</p> <p>There were 108 males and 94 females. There were 12 (5.9%) abnormal scans seen in five male and seven female neonates. Eleven of the twelve abnormalities were in the kidneys, six on the left and five on the right. Three of the four major renal anomalies- absent kidney, ectopic/pelvic kidney and two cases of severe hydronephrosis were however on the left side. There was one suprarenal abnormality on the right suspected to be a possible infected adrenal haemorrage. Nine of the abnormal cases reported for follow- up and of these, two cases had persistent severe abnormalities.</p> <p>Conclusions-</p> <p>This study demonstrated a 5.9% incidence of genito urinary anomalies on routine neonatal abdominal ultrasound in this small population. Routine obstetric USS is very useful but inadequate availability of skilled personnel and cost implications create great challenges in poor resource settings like Nigeria. However, awareness should be created so that parents who can afford such investigations can make informed decisions.</p

Activation of cGMP-Dependent Protein Kinase Stimulates Cardiac ATP-Sensitive Potassium Channels via a ROS/Calmodulin/CaMKII Signaling Cascade

) channels, an ion channel critical for stress adaptation in the heart; however, the underlying mechanism remains largely unknown. The present study was designed to address this issue. channels was confirmed in intact ventricular cardiomyocytes, which was ROS- and CaMKII-dependent. Kinetically, PKG appeared to stimulate these channels by destabilizing the longest closed state while stabilizing the long open state and facilitating opening transitions. channels and contribute to cardiac protection against ischemia-reperfusion injury

Glycine Inhibitory Dysfunction Turns Touch into Pain through PKCgamma Interneurons

Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. During tactile allodynia, activation of the sensory fibers which normally detect touch elicits pain. Here we provide a new behavioral investigation into the dynamic component of tactile allodynia that developed in rats after segmental removal of glycine inhibition. Using in vivo electrophysiological recordings, we show that in this condition innocuous mechanical stimuli could activate superficial dorsal horn nociceptive specific neurons. These neurons do not normally respond to touch. We anatomically show that the activation was mediated through a local circuit involving neurons expressing the gamma isoform of protein kinase C (PKCγ). Selective inhibition of PKCγ as well as selective blockade of glutamate NMDA receptors in the superficial dorsal horn prevented both activation of the circuit and allodynia. Thus, our data demonstrates that a normally inactive circuit in the dorsal horn can be recruited to convert touch into pain. It also provides evidence that glycine inhibitory dysfunction gates tactile input to nociceptive specific neurons through PKCγ-dependent activation of a local, excitatory, NMDA receptor-dependent, circuit. As a consequence of these findings, we suggest that pharmacological inhibition of PKCγ might provide a new tool for alleviating allodynia in the clinical setting