How does performance of the Friedreich Ataxia Functional Composite compare to rating scales?

Progression of Friedreich ataxia (FRDA) is often measured using neurological rating scales such as the Friedreich Ataxia Rating Scale (FARS). Performance scales comprising functional measures have been used in other conditions due to their increased sensitivity and reproducibility and may replace examination-based measures. The aims of this study were to examine the relationship between the Friedreich Ataxia Functional Composite (FAFC) measures and characteristics of FRDA to determine if the FAFC is more sensitive to clinical change over time compared to its components. One hundred and twenty-two individuals completed the timed 25-foot walk (T25FW), 9-Hole Peg Test (9HPT) and the low-contrast letter acuity (LCLA) test at baseline, 63 at year 1, 34 at year 2 and 25 at year 3. Composite scores, Z2 (T25FW and 9HPT) and Z3 (T25FW, 9HPT and LCLA) were created. Correlation analyses were conducted. Change in FAFC components were examined over 1, 2, and 3 years. The FARS, Z2, Z3 and 9HPT showed significant change over all time points compared to baseline. The T25FW only demonstrated significant change over 3 years. The LCLA demonstrated no significant change over any of the time points. The FAFC shows significant change over time and indicates disease progression, however, this may result from individual components driving the differences. The LCLA showed no change over time, rendering Z3 redundant. The FAFC is of limited value in cohorts with non-ambulant individuals as it leads to skewing of the dataset and is better suited to less affected populations.     

Is a computational model useful to understand the effect of deep brain stimulation in Parkinson's disease?

A growing number of computational models have been proposed over the last few years to help explain the therapeutic effect of deep brain stimulation (DBS) on motor disorders in Parkinson's disease (PD). However, none of these has been able to explain in a convincing manner the physiological mechanisms underlying DBS. Can these models really contribute to improving our understanding? The model by Rubin and Terman [31] represents one of the most comprehensive and biologically plausible models of DBS published recently. We examined the validity of the model, replicated its simulations and tested its robustness. While our simulations partially reproduced the results presented by Rubin and Terman [31], several issues were raised including the high complexity of the model in its non simplified form, the lack of robustness of the model with respect to small perturbations, the nonrealistic representation of the thalamus and the absence of time delays. Computational models are indeed necessary, but they may not be sufficient in their current forms to explain the effect of chronic electrical stimulation on the activity of the basal ganglia (BG) network in PD.     

How to manage conflicts of interest with industry?

The use of medications has risen steadily in psychiatry. Perhaps in response, during the past few years there has been increasing scrutiny of alleged unethical behaviours by medical researchers, educators, and practitioners secondary to influence by the pharmaceutical industry. Research is quite consistent that gifts and generous financial arrangements can dampen skepticism, sometimes unconsciously, and thereby persuade recipients to advocate for or prescribe medications that are more expensive, but no more effective, than alternatives. Interestingly, this research-backed premise that physicians can be lured by gifts remains often disbelieved by recipients. Adding to such inducements to prescribe new, expensive medications are pressures from patients due to the increasing ubiquity of direct-to-consumer advertising. Criticism from patient advocate groups, government agencies, and the press has sparked debate within the profession. Many medical journals, academic medical centre research and educational endeavours, and medical organizations are reviewing policies to eliminate, or better manage, their conflicts of interest with industry. The basic ethical standard is that although pharmaceutical companies' primary concern is for its shareholders, physicians' primary concern must be for their patients.     

How specific is the association of two disorders with respect to the association with a third disorder?

A common problem in psychiatric epidemiology is that of finding appropriate statistical methods to determine the specificity of an association of two disorders (A and B), when disorder A is also associated with a third disorder C. This paper discusses this problem, which is particularly frequent in mental disorders due to substantial comorbidity between disorders. It is suggested that a measure of specificity of association (MSA) can be applied to address this problem. By building on mutually exclusive categories, classes, this measure indicates a high specificity of association A–B whenever two conditions are fulfilled: (a) there is a considerable difference in strength of association of A with pure B (not C) on the one hand and A with pure C (not B) on the other hand, and (b) the association of A with comorbid cases (cases that have both disorders B and C) is at least not stronger than the association of A with pure B cases. The measure is based on a logistic regression model with the probability of having disorder A as the outcome and mutually exclusive categories of B and C as explanatories as well as possibly other confounding variables. Statistical inference in MSA is based on a bias-corrected bootstrap confidence interval. This paper exemplifies the use of this measure with an example from a longitudinal prospective study on the relationship of nicotine dependence with ‘affective’ and ‘anxiety’ disorders. Copyright © 1999 Whurr Publishers Ltd.     

Conventional or threshold-hunting TMS? A tale of two SICIs

Background

In human primary motor cortex (M1), the paired-pulse transcranial magnetic stimulation (TMS) paradigm of short-interval intracortical inhibition (SICI) can be expressed conventionally as a percent change in the relative amplitude of a conditioned motor evoked potential to non-conditioned; or adaptive threshold-hunting a target motor evoked potential amplitude in the absence or presence of a conditioning stimulus, and noting the relative change in stimulation intensity. The suitability of each approach may depend on the induced current direction, which probe separate M1 interneuronal populations.

Is precise discrimination of low level motion needed for heading discrimination?

Normal observers judge heading well both when moving in a straight line and when moving along a curved path. Judgments of curved path motion require depth variations in the scene while judgments of straight line heading (pure translation) do not. Here we show that a stroke patient who is impaired in low level 2D motion discrimination tasks and cannot accurately judge 3D structure from motion can accurately judge heading for straight line self-motion. This patient is impaired in judgments of curved path self-motion. This suggests that accurate heading judgments for observer translation do not require accurate 2D motion perception or 3D reconstruction of the scene. Judgments of curved path motion appear more dependent on accurate 2D motion perception.     

How much of reinforcement learning is working memory, not reinforcement learning? A behavioral, computational, and neurogenetic analysis

Instrumental learning involves corticostriatal circuitry and the dopaminergic system. This system is typically modeled in the reinforcement learning (RL) framework by incrementally accumulating reward values of states and actions. However, human learning also implicates prefrontal cortical mechanisms involved in higher level cognitive functions. The interaction of these systems remains poorly understood, and models of human behavior often ignore working memory (WM) and therefore incorrectly assign behavioral variance to the RL system. Here we designed a task that highlights the profound entanglement of these two processes, even in simple learning problems. By systematically varying the size of the learning problem and delay between stimulus repetitions, we separately extracted WM-specific effects of load and delay on learning. We propose a new computational model that accounts for the dynamic integration of RL and WM processes observed in subjects' behavior. Incorporating capacity-limited WM into the model allowed us to capture behavioral variance that could not be captured in a pure RL framework even if we (implausibly) allowed separate RL systems for each set size. The WM component also allowed for a more reasonable estimation of a single RL process. Finally, we report effects of two genetic polymorphisms having relative specificity for prefrontal and basal ganglia functions. Whereas the COMT gene coding for catechol-O-methyl transferase selectively influenced model estimates of WM capacity, the GPR6 gene coding for G-protein-coupled receptor 6 influenced the RL learning rate. Thus, this study allowed us to specify distinct influences of the high-level and low-level cognitive functions on instrumental learning, beyond the possibilities offered by simple RL models.     

How do memory clinics compare with traditional old age psychiatry services?

METHODS: 100 consecutive referrals to the Northern Memory Clinic (NMC) were compared with 100 referrals to a traditional Old Age Psychiatry (OAPsych) service in the same city in terms of demographic variables, cognitive function (assessed by the Mini-Mental State Examination), and diagnosis. The study also examined the ability of psychometric assessments (CAMCOG, MMSE, Trail-Making Tests A & B, Word Fluency) and CT scans included in the NMC assessment to differentiate between those with and without DSM-IV dementia. RESULTS: NMC patients were significantly younger than OAPsych patients, had lower levels of cognitive impairment, and had a wider range of diagnoses. The NMC patients who were diagnosed as having dementia were found to be at least 2 years earlier in the course of the disease than those seen by the OAPsych team. The CAMCOG and MMSE were proved to be effective at distinguishing between patients diagnosed as dementing versus non-dementing with cut-offs of 82/83 and 23/24 respectively, confirming previous findings. The Memory subscale of the CAMCOG, though much shorter, was equally as effective using a cut-off of 20/21. Trail-Making Tests, Word Fluency (FAS), and measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans were poor indicators of dementia in this sample. CONCLUSIONS: This study confirms that the memory clinic is targeting a distinct patient group compared to traditional old age psychiatry services, is identifying cases of dementia much earlier, and as such has potential to make valuable contributions to patient care.     

Is Alzheimer's disease preventable? A review of two decades of epidemiological research

This paper reviews the epidemiological literature on Alzheimer's disease. Increasing age emerges as one of the most powerful risk factors for the development of dementia/Alzheimer's disease across all populations studied. Examination of age-independent risk factors suggests that there are few environmental or clinical factors that seem to be related consistently to increased risk of dementia/Alzheimer's disease. In contrast, familial/genetic risk factors do seem to influence the incidence of dementia/Alzheimer's disease. Age, ethnicity and gender all have been found to moderate the effects of both genetic and environmental risk factors.The overall weight of evidence suggests that the primary influence of both risk and protective factors is to modify rather than determine the expression of dementia during the course of the adult lifespan.