Cognitive Motivations of Free Riding and Cooperation and Impaired Strategic Decision Making in Schizophrenia During a Public Goods Game

Schizophrenia is generally characterized by various positive and negative symptoms that are accompanied by significant social dysfunction. Various researchers investigated the functional impairments in schizophrenia including impaired theory of mind (TOM), poor integration of affective and cognitive information, and malfunctioning of adaptive and strategic learning process. However, most of the studies were limited to simplified cognitive tests or computerized choice games that exclude real social interaction. The aim of the current study was to investigate human strategies based on the incentives and particularly the cognitive and emotional motivations of free riding. We examined the decision patterns of 41 healthy subjects (HSs) and 37 schizophrenia patients (SZ) during the public goods game (PGG), one of the games simulating human cooperation and free riding in group interactions. Strategic decision processes during the iterative binary PGG were assessed in terms of cognitive understanding, loss sensitivity, and TOM. We found that greed and loss sensitivity both motivated free-riding behavior in the HS, but that they were more vulnerable to greedy incentives than to possible loss. More significantly, the SZ clearly displayed a lower prevalence of free riding and distinct decision patterns from HS. Nonstrategic and unexpectedly low free ridings in the SZ likely arise from poor integration of cognitive and affective information. We suggest that loss sensitivity and TOM as well as cognitive understanding are involved in regulation of the free riding and cooperative behavior.     

A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement

Laing distal myopathy (LDM) is caused by mutations in the MYH7 gene, and known to have muscle weakness of distal limbs and neck flexors. Through whole exome sequencing, we identified a novel p.Ala1439Pro MYH7 mutation in a Korean LDM family. This missense mutation is located in more N-terminal than any reported rod domain LDM mutations. In the early stage of disease, the present patients showed similar clinical patterns to the previously described patients of LDM. However, in the later stage, fatty replacement and atrophy of paraspinal or proximal leg muscles was more severely marked than lower leg muscles, and asymmetric atrophies were observed in trapezius, subscapularis and adductor magnus muscles. Distal myopathy like LDM showed marked and predominant fatty infiltrations in paraspinal or proximal leg muscles with marked asymmetry. These observations expand the clinical spectrum of LDM with the MYH7 mutation.     

Which dyskinesia scale best detects treatment response?

Numerous scales assess dyskinesia in Parkinson's disease (PD), variably focusing on anatomical distribution, phenomenology, time, severity, and disability. No study has compared these scales and their relative ability to detect change related to an established treatment. We conducted a randomized placebo‐controlled trial of amantadine, assessing dyskinesia at baseline and at 4 and 8 weeks using the following scales: Unified Dyskinesia Rating Scale (UDysRS), Lang‐Fahn Activities of Daily Living Dyskinesia Rating Scale (LF), 26‐Item Parkinson's Disease Dyskinesia scale (PDD‐26), patient diaries, modified Abnormal Involuntary Movements Scale (AIMS), Rush Dyskinesia Rating Scale (RDRS), dyskinesia items from the Movement Disorder Society–sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), and Clinical Global Impression (severity and change: CGI‐S, CGI‐C). Scale order was randomized at each visit, but raters were aware of each scale as it was administered. Sensitivity to treatment was assessed using effect size. Sixty‐one randomized dyskinetic PD subjects (31 amantadine, 30 placebo) completed the study. Four of the 8 scales (CGI‐C, LF, PDD‐26, and UDysRS) detected a significant treatment. The UDysRS Total Score showed the highest effect size (η² = 0.138) for detecting treatment‐related change, with all other scales having effect sizes < 0.1. No scale was resistant to placebo effects. This study resolves 2 major issues useful for future testing of new antidyskinesia treatments: among tested scales, the UDysRS, having both subjective and objective dyskinesia ratings, is superior for detecting treatment effects; and the magnitude of the UDysRS effect size from amantadine sets a clear standard for comparison for new agents. © 2012 Movement Disorder Society     

Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type‐B and ‐C cells in adult subventricular zone

The neurotransmitter dopamine acts on the subventricular zone (SVZ) to regulate both prenatal and postnatal neurogenesis, in particular through D₃ receptor (D₃R) subtype. In this study, we explored the cellular mechanism(s) underlying D₃R‐mediated cell proliferation and tested if systemic delivery of a D₃R agonist would induce SVZ multipotent neural stem/precursor cell (NSC/NPC) proliferation in vivo. We found that treatment with the D₃R agonist, 7‐OH‐DPAT, enhances cell proliferation in a dose‐dependent manner in cultured SVZ neurospheres from wild‐type, but not D₃R knock‐out mice. Furthermore, D₃R activation also stimulates S‐phase and enhances mRNA and protein levels of cyclin D1 in wild‐type neurospheres, a process which requires cellular Akt and ERK1/2 signaling. Moreover, chronic treatment with low dose 7‐OH‐DAPT in vivo increases BrdU⁺ cell numbers in the adult SVZ, but this effect was not seen in D₃R KO mice. Additionally, we probed the cell type specificity of D₃R agonist‐mediated cell proliferation. We found that in adult SVZ, GFAP⁺ astrocytes, type‐B GFAP⁺/nestin⁺ and type‐C EGF receptor (EGFR⁺)/nestin⁺ cells express D₃R mRNA, but type‐A Doublecortin (Dcx)⁺ neuroblasts do not. Using flow cytometry and immunofluorescence, we demonstrated that D₃R activation increases GFAP⁺ type‐B and EGFR⁺ type‐C cell numbers, and the newly divided Dcx⁺ type‐A cells. However, BrdU⁺/Dcx⁺ cell numbers were decreased in D₃R KO mice compared to wildtype, suggesting that D₃R maintains constitutive NSC/NPCs population in the adult SVZ. Overall, we demonstrate that D₃R activation induces NSC/NPC proliferation through Akt and ERK1/2 signaling and increases the numbers of type‐B and ‐C NSC/NPCs in the adult SVZ. © 2013 Wiley Periodicals, Inc.     

Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low‐dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose‐dependent inhibition of 4‐AP‐evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl ‐threo‐beta‐benzyl‐oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization‐induced increase in [Ca²⁺]_C but did not alter 4‐AP‐mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca_v2.2 (N‐type) and Ca_v2.1 (P/Q‐type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]_C caused by Ca²⁺ entry through presynaptic voltage‐dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades. Synapse 67:568–579, 2013 . © 2013 Wiley Periodicals, Inc.     

The effects of primer precuring on the shear bond strength between gold alloy surfaces and metal brackets

The objective of this study was to investigate the effects of precuring of primer coated on bracket bases on the strength of bonds between metal brackets and gold alloy. Square type III gold alloy plates were sandblasted with 30 μm silicon dioxide. After silica coating, excessive particles were removed gently with air. Silane was then applied, and maxillary central incisor metal brackets were bonded to each conditioned alloy surface with Transbond XT. Half of the specimens were precured at the bracket base after primer coating and the other half was not precured before bonding to the alloy surface. After bracket positioning, samples were cured using a light emitting diode (LED) for 40 seconds. Shear bond strengths were tested and adhesive remnant index (ARI) was evaluated after 1 hour and 24 hours. The primer precuring and 24 hours group exhibited highest bond strength (12.53 MPa) and the no precuring and 1 hour group showed lowest bond strength (5.58 MPa). Precured groups showed lower ARI scores. Due to the shallow curing depth of LED light and inhibition of transillumination at the metal surface, primer precuring at the bracket base is required for secure bracket bonding on gold alloy surfaces using LED curing units.