Pre-frontal stimulation does not reliably increase reward responsiveness.

Depression is the leading cause of disability worldwide and its effects can be fatal, with over 800,000 people dying by suicide each year. Neuromodulatory treatments such as transcranial magnetic stimulation (TMS) are being used to treat depression. Despite its endorsement by two regulatory bodies: NICE (2016) and the FDA (2008), there are major questions about the treatment efficacy and biological mechanisms of TMS. Ahn et al.'s (2013) justified the use of TMS in a clinical context in an important study indicating that excitatory TMS increases reward responsiveness. A pseudo-replication of this study by Duprat et al., (2016) also found a similar effect of active TMS, but only with the addition of an exploratory covariate to the analyses-trait reward responsiveness. Here we replicate Ahn et al.'s (2013) key study, and to test the reliability of the effects, and their dependency on trait reward responsiveness as described by Duprat et al., (2016). Using excitatory and sham TMS, we tested volunteers using the probabilistic learning task to measure their reward responsiveness both before and after stimulation. We also examined affect (positive, negative) following stimulation. Irrespective of TMS, the task was shown to be sensitive to reward responsiveness. However, we did not show TMS to be effective in increasing reward responsiveness and we did not replicate Ahn et al., (2013) or Duprat et al., (2016)'s key findings for TMS efficacy, where we provide evidence favouring the null. Moreover, exploratory analyses suggested following active stimulation, positive affect was reduced. Given our findings, we question the basic effects, which support the use of TMS for depression, particularly considering potential deleterious effects of reduced positive affect in patients with depression.

Disease-modifying agents in the Sonya Slifka Longitudinal Multiple Sclerosis Study.

BACKGROUND: Although experts recommend that people with multiple sclerosis (MS) should begin treatment with disease-modifying agents (DMAs) as soon as possible after diagnosis and continue indefinitely, many do not use these agents or discontinue them prematurely. Since DMAs reduce relapse rates and slow disease progression, and since even benign relapses and course can lead to axonal damage and permanent neurologic impairment, it is important that all appropriate candidates have access to treatment. We used a population-based sample of people with MS to determine rates, predictors, and reasons for use, non-use, and discontinuation of DMAs. METHODS: We collected data from 2156 people with MS on their use of and experience with DMAs. We used chi-squared tests to compare current, past, and never users of any DMA and ever users of individual DMAs, and logistic regression to identify predictors of use. RESULTS: One-half of the participants were using a DMA at the time of the interview; 12.2% had used previously, but stopped. Reasons for never using and reasons for stopping were at odds with expert recommendations. Characterization of users, and of their experiences by type of DMA, was consistent with current knowledge of these agents. Seeing a neurologist for usual MS care was an important factor in starting and persisting with DMA therapy. CONCLUSIONS: Dissemination of expert opinion about, and management strategies for, use of DMAs to non-neurologic professionals and patients and their families might help more people who are appropriate candidates for DMA therapy to start and continue treatment.

Access to and utilization of neurologists by people with multiple sclerosis.

OBJECTIVE: This study examined access to and use of neurologists among a broad, national sample of people with multiple sclerosis (MS); identified demographic, economic, and clinical factors associated with access and use; and examined differences in treatment and management of MS. METHODS: We used computer-assisted telephone interviews to collect data from 2,156 people with MS on demographics, disease characteristics, and use of neurologists, other specialists, and disease-modifying agents (DMAs). We used chi(2) tests and logistic regressions to compare patients of neurologists and other providers and identify predictor variables and treatment factors associated with seeing neurologists. RESULTS: For their usual MS care, 72.2% of participants saw a neurologist. The probability of seeing a neurologist was significantly lower for people who lacked health insurance, were poor, lived in rural areas, or were African American; had been ill for more than 15 years; had difficulty walking but did not use an assistive device; or required a wheelchair/scooter or were confined to bed. People who reported one to two relapses in the preceding year and women were significantly more likely to see neurologists. Patients of neurologists were significantly more likely to take a DMA, attend an outpatient rehabilitation program, or see an occupational therapist, urologist, or physical therapist. CONCLUSIONS: People with multiple sclerosis who see neurologists are more likely than people who see other providers to receive treatment with disease-modifying agents and see rehabilitation specialists and urologists. While some people may choose other providers, economic, insurance, racial, and geographic factors appear to limit access to neurologists.

Access to health care for people with multiple sclerosis.

The Sonya Slifka Longitudinal Multiple Sclerosis (MS) Study follows a population-based cohort of approximately 2000 people with MS to study demographic and clinical characteristics, use and cost of health services, provider and treatment characteristics, neurological, economic, and psychosocial outcomes. We examined key indicators of access to health care and found that the majority of participants had health insurance, a usual source of care, and access to specialty care. Nevertheless, 3.8% did not have health insurance which, with application of sampling weights, corresponds to approximately 7000 people with MS in the US population. Even with insurance, population-based estimates indicated that substantial numbers of people with MS have plans that pay nothing toward prescription medication, limit their access to specialists, and restrict their choice of hospitals and providers. Some 9% of the sample, corresponding to 15,800 people with MS, did not have a usual source of MS care; 11.8% or 17,300 people did not have a usual source of general health care; and 31% or 57,400 people did not see the specialists that they or their physicians wanted them to see. Further, 10.5% or 19,400 people reported difficulty obtaining prescription medication, 4.1% or 7600 people encountered obstacles accessing medical care, and 2.4% or 4500 people could not obtain the mental health services they needed. Finally, out-of-pocket health care expenditures were twice those found for the general population. Two-thirds of study participants (representing almost 70,000 people) chose their MS care providers because they were neurologists or MS specialists, creating a demand that almost certainly exceeds current supply.

The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics.

The Sonya Slifka Longitudinal Multiple Sclerosis Study follows a population-based cohort of approximately 2000 people with multiple sclerosis (MS) to study demographic and clinical characteristics, course of illness, utilization and cost of health services, provider characteristics, use of MS specialists and disease modifying agents, and neurologic, economic and psychosocial outcomes. This report describes the study methodology, presents baseline demographic and clinical data, and evaluates the representativeness of the sample. A stratified random sample of persons with established and recently-diagnosed MS selected from the National Multiple Sclerosis Society (NMSS) mailing lists was supplemented with recently-diagnosed patients recruited through systematic nationwide outreach. Baseline data were collected by computer-assisted telephone interviews derived from standardized instruments; data collection continues at six-month intervals. The cohort was comparable to population-based and clinical samples with respect to demographics, course, relapse rate, symptoms, and severity of disability. Almost two-thirds of the cohort needed help with activities of daily living, three-quarters were limited in work or other activities, and half had emotional problems that compromised quality of life. The Slifka Study cohort is broadly representative of the MS population and the database can be used to address questions not answered by natural history studies, clinical databases, or population-based surveys.

Head circumference is an independent clinical finding associated with autism.

Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurable. As part of a study of genetic heterogeneity of autism, we scrutinized data from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) values of the autistic propositi (0.61+/-1.6) varied significantly from that of the normal population (0.0+/-1.0), (P<0.001). Comparison of the macrocephalic (OFCSD > 2.0, N = 32) with the normocephalic individuals (-2 SD < OFCSD < +2 SD, N = 95) showed no significant differences in sex ratio, morphological status, IQ, seizure prevalence, or recurrence risks. The macrocephalic individuals were slightly less apt than those with normocephaly to have a family history of Attention Deficit Hyperactivity Disorder (ADHD) (P<0.05). Each clinical subgroup of autism propositi, defined on the basis of phenotypic status, type of onset, seizure history, or IQ, had a higher than normal mean OFC indicating that macrocephaly is an independent clinical trait in autism. As in the non-autistic population, macrocephaly was highly familial with 45% of the macrocephalic and 37% of the normocephalic propositi having at least one macrocephalic parent. Microcephaly, however, was an independent significant variable that predicted the presence of other phenotypic or genetic traits and outcome. The microcephalic patients were more likely to have abnormal physical morphology, structural brain malformations, lower IQ, and seizures. Their sex ratio was closer to normal, and their relatives had a higher incidence of seizures.