Brain regions involved in the learning and application of reward rules in a two-deck gambling task

Decision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision-making, involves learning a reward-punishment rule over multiple trials. Patients with damage to ventromedial prefrontal cortex (VMPFC) show deficits learning these rules, although this performance deficit is not exclusively associated with VMPFC damage. In this study, we used functional Magnetic Resonance Imaging (fMRI) to study the roles of prefrontal cortex regions involved in rule learning and rule application in healthy adults using an adapted version of the Iowa Gambling Task. Participants (N = 20) were asked to infer rules over series of 16 trials in a two-deck card game. Rewards were given on each trial and punishment was unpredictable. For half of the series, those decks that gave high rewards were also better decks in the long run. For the other half of the series, the decks that gave low rewards were better decks in the long run. Behaviorally, participants started to differentiate between advantageous and disadvantageous decks after approximately four/six trials, and learning occurred faster for high-reward decks. Lateral PFC (lat-PFC) and Anterior Cingulate Coretex (ACC)/pre-supplementary motor area (pre-SMA) were most active for early decisions, whereas medial orbital frontal cortex (med-OFC) was most active for decisions made later in the series. These results suggest that lat-PFC and ACC/pre-SMA are important for directing behavior towards long-term goals, whereas med-OFC represents reward values towards which behavior should be directed.     

Young's modulus of collagen at slow displacement rates

Collagen is a key structural component of extracellular matrix and its mechanical properties, particularly its stiffness, have been shown to influence cell function. This study explores the mechanical behavior of type I collagen gels at low rates relevant to that of cell motion. The Young's modulus, E, was obtained for collagen samples of concentrations 1.3, 2 and 3 mg/ml at varying crosshead displacement rates: 0.01, 0.1 and 1 mm/min. Local strain measurement in the gage section were used for both the strain and strain rate determination. The power law models for the modulus at these low strain rates show that the values converge as the displacement rate approaches a quasistatic state. This study provides data that was unavailable in the past on the Young's modulus of collagen at rates relevant to the cell.     

Rapamycin causes regression of astrocytomas in tuberous sclerosis complex

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs. Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro. We sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC. METHODS: Five subjects with clinically definite TSC and either subependymal giant cell astrocytomas (n = 4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at standard immunosuppressive doses (serum levels 5-15 ng/ml) from 2.5 to 20 months. All lesions demonstrated growth on serial neuroimaging studies. Magnetic resonance imaging scans were performed before and at regular intervals following initiation of therapy. RESULTS: All lesions exhibited regression and, in one case, necrosis. Interruption of therapy resulted in regrowth of subependymal giant cell astrocytomas in one patient. Resumption of therapy resulted in further regression. Treatment was well tolerated. INTERPRETATION: Oral rapamycin therapy can induce regression of astrocytomas associated with TSC and may offer an alternative to operative therapy of these lesions.     

Factors associated with the identification of child mental health problems in primary care—a systematic review

Background: Although common and often with long-lasting effects, child mental health problems (MHPs) are still under-recognized and under-treated. A better understanding of the factors associated with the identification of MHPs in primary care may improve the recognition of MHPs.

Objectives: To review studies on factors associated with the identification of child MHPs in primary care.

Methods: Six leading databases were systematically searched until 1 October 2018. Two independent researchers selected articles and extracted data on study characteristics and factors associated with MHP identification. Inclusion criteria were the investigation of factors associated with MHP identification by primary care professionals (PCPs) in children aged 0–18 years.

Results: Of the 6215 articles identified, 26 were included. Prevalence rates of PCP-identified MHPs varied between 7 and 30%. PCPs identified 26–60% of children with an increased risk of MHPs as indicated by MHP assessment tools, but associated factors were investigated in relatively few studies. MHPs were more often identified in children with a family composition other than married parents, with worse mental health symptoms, prior MHPs, among boys in elementary school, when contact with PCPs was related to parental psychosocial concerns or routine health check-ups, when PCPs were recently trained in MHPs or when PCPs felt less burdened treating MHPs.

Conclusion: MHP identification varied substantially between studies and PCPs and was related to several child, family and practice factors. Future studies should systematically investigate factors associated with MHP identification by PCPs and specifically in children with an increased risk of MHPs according to mental health assessment tools.     

Sexual and reproductive health and human rights of women living with HIV: a global community survey

Objective

To determine the sexual and reproductive health priorities of women living with human immunodeficiency virus (HIV) and to allow the values and preferences of such women to be considered in the development of new guidelines.

Methods

A core team created a global reference group of 14 women living with HIV and together they developed a global community online survey. The survey, which contained mandatory and optional questions, was based on an appreciative enquiry approach in which the life-cycle experiences of women living with HIV were investigated. The same set of questions was also used in focus group discussions led by the global reference group.

Findings

The study covered 945 women (832 in the survey and 113 in the focus groups) aged 15–72 years in 94 countries. Among the respondents to the optional survey questions, 89.0% (427/480) feared or had experienced gender-based violence, 56.7% (177/312) had had an unplanned pregnancy, 72.3% (227/314) had received advice on safe conception and 58.8% (489/832) had suffered poor mental health after they had discovered their HIV-positive status.

Conclusion

The sexual and reproductive health needs and rights of women living with HIV are complex and require a stronger response from the health sector. The online survey placed the voices of women living with HIV at the start of the development of new global guidelines. Although not possible in some contexts and populations, a similar approach would merit replication in the development of guidelines for many other health considerations.     

The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients.

OBJECTIVES: To measure the effect of baclofen on the transmission in different spinal pathways to soleus motoneurones in spastic multiple sclerosis patients. METHODS: Baclofen was administered orally in 14 and intrathecally in 8 patients. H(max)/M(max), presynaptic inhibition by biceps femoris tendon tap of femoral nerve stimulation, depression of the soleus H-reflex following previous activation of the Ia afferents from the soleus muscle (i.e. postactivation depression), disynaptic reciprocal Ia inhibition of the soleus H-reflex and the number of backpropagating action potentials in primary afferents, which may be a sign of presynaptic inhibition, were examined. RESULTS: Baclofen depressed the soleus H(max)/M(max) ratio significantly following oral and intrathecal baclofen. None of the two tests of presynaptic inhibition, or the postactivation depression or the disynaptic reciprocal Ia inhibition of the soleus H-reflex were affected by baclofen administration. Also the action potentials of the primary afferents were unchanged during baclofen administration. CONCLUSIONS: The antispastic effect of baclofen is not caused by an effect on the transmitter release from Ia afferents or on disynaptic reciprocal Ia inhibition. One possible explanation of the depression of the H-reflex by baclofen is suggested to be a direct depression of motoneuronal excitability.     

Cardiac arrhythmias six months following traumatic spinal cord injury

ObjectiveTo investigate the incidence of cardiac arrhythmias at six months following traumatic spinal cord injury (SCI) and to compare the prevalence of arrhythmias between participants with cervical and thoracic SCI.DesignA prospective observational study using continuous twenty-four-hour Holter monitoring.SettingInpatient rehabilitation unit of a university research hospital and patient home setting.ParticipantsFifty-five participants with acute traumatic SCI were prospectively included. For each participant, the SCI was characterized according to the International Standards for Neurological Classification of SCI by the neurological level and severity according to the American Spinal Injury Association Impairment Scale.Outcome measuresComparisons between demographic characteristics and arrhythmogenic occurrences as early as possible after SCI (4 ± 2 days) followed by 1, 2, 3, 4 weeks and 6 month time points of Holter monitoring.ResultsBradycardia (heart rate [HR] <50 bpm) was present in 29% and 33% of the participants with cervical (C1–C8) and thoracic (T1–T12) SCI six months after SCI, respectively. The differences in episodes of bradycardia between the two groups were not significant (P < 0.54). The mean maximum HR increased significantly from 4 weeks to 6 months post-SCI (P < 0.001), however mean minimum and maximum HR were not significantly different between the groups at the six-month time point. There were no differences in many arrhythmias between recording periods or between groups at six months.ConclusionsAt the six-month timepoint following traumatic SCI, there were no significant differences in occurrences of arrhythmias between participants with cervical and thoracic SCI compared to the findings observed in the first month following SCI.     

Evaluating denoising strategies in resting‐state functional magnetic resonance in traumatic brain injury (EpiBioS4Rx)

Resting‐state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high‐quality data, one should mitigate fMRI‐related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise‐related signal (i.e., in‐scanner movement and physiological noise) in functional connectivity (FC) of traumatic brain injury (TBI) patients. We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 TBI patients from the Epilepsy Bioinformatics Study for Anti‐epileptogenic Therapy clinical trial. Pipelines were evaluated by three quality control (QC) metrics across three exclusion regimes based on the participant''s head movement profile. While no pipeline eliminated noise effects on FC, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high‐motion participants were excluded, the choice of denoising pipeline becomes secondary ‐ although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data‐driven methods performed comparatively worse. In this study, we report the first large‐scale evaluation of denoising pipelines aimed at reducing noise‐related FC in a clinical population known to be highly susceptible to in‐scanner motion and significant anatomical abnormalities. If resting‐state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as TBI datasets.