Why ��Willusionism�� Leads to ��Bad Results��: Comments on Baumeister, Crescioni, and Alquist

Drawing on results discussed in the target article by Baumeister et al. (1), I argue that the claim that the modern mind sciences are discovering that free will is an illusion (“willusionism”) is ambiguous and depends on how ordinary people understand free will. When interpreted in ways that the evidence does not justify, the willusionist claim can lead to ‘bad results.’ That is, telling people that free will is an illusion leads people to cheat more, help less, and behave more aggressively, but these responses may be based on people’s interpreting willusionist claims to mean that they lack the powers of rational choice and self-control.     

B��cher, kongresse/Veranstaltungen, personalia, News

Mitteilungen der gesellschaft

Bücher, kongresse/Veranstaltungen, personalia, News     

Rehabilitation��Emerging Technologies, Innovative Therapies, and Future Objectives

Stroke is the leading cause of long-term disability. The goal of stroke rehabilitation is to improve recovery in the years after a stroke and to decrease long-term disability. This article, titled “Rehabilitation—Emerging Technologies, Innovative Therapies, and Future Objectives” gives evidence-based information on the type of rehabilitation approaches that are effective to improve functional mobility and to address cognitive impairments. We review the importance of taking a translational approach to neurorehabilitation, considering the interaction of motor and cognitive systems, skilled learned purposeful limb movement, and spatial navigation ability. Known biologic mechanisms of neurorecovery are targeted in relation to technology implemented by members of the multidisciplinary team. Results from proof-of-concept, within subjects, and randomized controlled trials are presented, and the implications for optimal stroke rehabilitation strategies are discussed. Developing clinical practices are highlighted and future research directions are proposed with goals to provide insight on what the next steps are for this burgeoning discipline.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-011-0057-x) contains supplementary material, which is available to authorized users.     

What makes community psychiatric nurses label non-psychotic chronic patients as ��difficult��: patient, professional, treatment and social variables

Purpose

To determine which patient, professional, treatment and/or social variables make community psychiatric nurses (CPNs) label non-psychotic chronic patients as ??difficult??.

Methods

A questionnaire was designed and administered to 1,946 CPNs in the Netherlands. Logistic regression was used to design models that most accurately described the variables that contributed to perceived difficulty.

Results

Six variables were retained in the final logistic model. Perception-related variables (feeling powerless, feeling that the patient is able but unwilling to change, and pessimism about the patient??s change potential) dominated treatment-related variables (number of contacts per week and admission to a locked ward in the last year) and social variables (number of psychosocial problems).

Conclusion

This research shows that perceived difficulty is related to complex treatment situations, not so much to individual patient characteristics. If the constructed model has good predictive qualities, which remains to be tested in longitudinal research, it may be possible to accurately predict perceived patient difficulty. When used as a screening tool, such a model could improve treatment outcomes.     

Revisiting Arieti's ��Listening Attitude�� and Hallucinated Voices

Silvano Arieti proposed that auditory/verbal hallucinations (AVHs) are triggered by momentary states of heightened auditory attention that he identified as a “listening attitude.” Studies and clinical observations by our group support this view. Patients enrolled in our repetitive transcranial magnetic stimulation trials, if experiencing a significant curtailment of these hallucinations, often report an episodic sense that their voices are still occurring even if they no longer can be heard, suggesting episodic states of heightened auditory expectancy. Moreover, a functional magnetic resonance study reported by our group detected activation in the left insula prior to hallucination events. This finding is suggestive of activation in the same region detected in healthy subjects during “auditory search” in response to ambiguous sounds when anticipating meaningful speech. AVHs often are experienced with a deep emotional salience and may occur in the context of dramatic social isolation that together could reinforce heightened auditory expectancy. These findings and clinical observations suggest that Arieti''s original formulation deserves further study.     

Patientenverf��gungsgesetz

Current legal regulations concerning the right of self-determination of subjects who are not competent to give consent have been in force since 2009. According to the new regulations, such subjects can exercise their right of self-determination through a legal guardian who will assess and impose their will. If there is an operative advance directive covering the specific case, the guardian is bound by the provisions laid down in it. Although primarily intended for end-of-life decisions, the law applies in all cases of a subject's inability to give consent, including the context of mental illness. It allows the persons concerned to define certain aspects of medical treatment in advance. On the one hand, the right of self-determination of mentally ill people is thus strengthened. On the other hand, the new regulations can also cause significant ethical conflict involving patients and their representatives as well as family members and practitioners. The present contribution presents the consequences of the amendment for the treatment of mentally ill people. Case studies are described in order to illustrate the new regulations in clinical situations.     

Spontaneous pain, pain threshold, and pain tolerance in Parkinson��s disease

The mechanisms underlying pain in Parkinson's disease (PD) are unclear. Although a few studies have reported that PD patients may have low pain threshold and tolerance, none could accurately assess whether there was a correlation between sensory thresholds and demographic/clinical features of PD patients. Thus, tactile threshold, pain threshold, and pain tolerance to electrical stimuli in the hands and feet were assessed in 106 parkinsonian patients (of whom 66 reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear regression models determined relationships between psychophysical parameters and demographic/clinical features. Female gender, severity of disease, medical disease associated with painful symptoms, and dyskinesia were more frequently observed in PD patients experiencing pain, even though dyskinesia did not reach significance. Pain threshold and pain tolerance were significantly lower in PD patients than in control subjects, whereas the tactile threshold yielded comparable values in both groups. Multivariable linear regression analyses yielded significant inverse correlations of pain threshold and pain tolerance with motor symptom severity and Beck depression inventory. Pain threshold and pain tolerance did not differ between PD patients with and without pain. In the former group, there was no relationship between pain threshold and the intensity/type of pain, and number of painful body parts. These findings suggest that pain threshold and pain tolerance tend to decrease as PD progresses, which can predispose to pain development. Female gender, dyskinesia, medical conditions associated with painful symptoms, and postural abnormalities secondary to rigidity/bradikinesia may contribute to the appearance of spontaneous pain in predisposed subjects.     

Neuronal estrogen receptor-�� mediates neuroprotection by 17��-estradiol

17β-Estradiol (E₂) was shown to exert neuroprotective effects both in in vitro and in vivo models of stroke. Although these effects of E₂ are known to require estrogen receptor-α (ERα), the cellular target of estrogen-mediated neuroprotection remains unknown. Using cell type-specific ER mutant mice in an in vivo model of stroke, we specifically investigated the role of ERα in neuronal cells versus its role in the microglia in the mediation of neuroprotection by estrogens. We generated and analyzed two different tissue-specific knockout mouse lines lacking ERα either in cells of myeloid lineage, including microglia, or in the neurons of the forebrain. Both E₂-treated and E₂-untreated mutant and control mice were subjected to a permanent middle cerebral artery occlusion for 48 h, and the infarct volume was quantified. Although the infarct volume of E₂-treated female myeloid-specific ERα knockout mice was similar to that of E₂-treated control mice, both male and female neuron-specific ERα mutant mice had larger infarcts than did control mice after E₂ treatment. We conclude that neuronal ERα in female and male mice mediates neuroprotective estrogen effects in an in vivo mouse model of stroke, whereas microglial ERα is dispensable.     

��Willpower�� over the life span: decomposing self-regulation

In the 1960s, Mischel and colleagues developed a simple ‘marshmallow test’ to measure preschoolers’ ability to delay gratification. In numerous follow-up studies over 40 years, this ‘test’ proved to have surprisingly significant predictive validity for consequential social, cognitive and mental health outcomes over the life course. In this article, we review key findings from the longitudinal work and from earlier delay-of-gratification experiments examining the cognitive appraisal and attention control strategies that underlie this ability. Further, we outline a set of hypotheses that emerge from the intersection of these findings with research on ‘cognitive control’ mechanisms and their neural bases. We discuss implications of these hypotheses for decomposing the phenomena of ‘willpower’ and the lifelong individual differences in self-regulatory ability that were identified in the earlier research and that are currently being pursued.     

TDP-43 pathological changes in early onset familial and sporadic Alzheimer��s disease, late onset Alzheimer��s disease and Down��s Syndrome: association with age, hippocampal sclerosis and clinical phenotype

TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer's disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down's Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present.     

A test of the role of two prefrontal/ subcortical networks in the ��sequencing�� of non-motor, visuo-spatial information

There are a number of prefrontal/sub-cortical networks in the brain (e.g., cerebellar-thalamic-prefrontal or basal ganglia/supplementary motor cortex circuits) that despite having a clear role in motor function have been shown to be involved in non-motor tasks. In this project we test for the involvement of these networks in a dimensional judgment task that utilizes visual perceptual, visual spatial processing and requires the ordering of dimensional (height) information. Unlike previous studies examining non-motor sequencing, we directly compare both non-motor and motor versions of our dimensional judgment task. In addition, we examine activation uniquely associated with correct task responses. The findings provide evidence for the role of cortical not subcortical structures in the sequencing of visuo-spatial material apart from any motor output requirements. Our results suggest that the inferior parietal cortex (BA 7, 40) and medial frontal regions (BA 6, 8, 9 including the SMA) are instrumental to the task. Based on these results, we propose a prefrontal/parietal network plays a role in the implementation of a comparator mechanism that makes accurate comparisons along the dimension of interest, holds the information in working memory, and then (regardless of whether the information is correct or incorrect) generates a tag or abstract code that assigns the information a place in an ordered sequence. Most important, the information involved can be visual/symbolic and non-motor (not just motor) in nature.     

Trafficking of glucose, lactate, and amyloid-�� from the inferior colliculus through perivascular routes

Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-¹⁴C]glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-¹⁴C]glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss. Brief infusion of [1-¹⁴C]glucose and -[¹⁴C]lactate into the inferior colliculus of conscious rats during acoustic stimulation labeled the meninges, consistent with perivascular clearance of [¹⁴C]metabolites from interstitial fluid. Microinfusion of Evans blue albumin and amyloid-β₁₋₄₀ (Aβ) caused perivascular labeling in the inferior colliculus, labeled the surrounding meninges, and Aβ-labeled-specific blood vessels in the caudate and olfactory bulb and was deposited in cervical lymph nodes. Efflux of extracellular glucose, lactate, and Aβ into perivascular fluid pathways is a normal route for clearance of material from the inferior colliculus that contributes to underestimates of brain energetics. Convergence of ‘watershed'' drainage to common pathways may facilitate perivascular amyloid plaque formation and pathway obstruction in Alzheimer''s disease.     

Reciprocal Induction Between ��-Synuclein and ��-Amyloid in Adult Rat Neurons

In spite of definite roles for ??-amyloid (A??) in familial Alzheimer??s disease (AD), the cause of sporadic AD remains unknown. Amyloid senile plaques and Lewy body pathology frequently coexist in neocortical and hippocampal regions of AD and Parkinson??s diseases. However, the relationship between A?? and ??-synuclein (??-Syn), the principle components in the pathological structures, in neuronal toxicity and the mechanisms of their interaction are not well studied. As A?? and ??-Syn accumulate in aging patients, the biological functions and toxicity of these polypeptides in the aging brain may be different from those in young brain. We examined the neurotoxicity influences of A??1-42 or ??-Syn on mature neurons and the effects of A??1-42 or ??-Syn on the production of endogenous ??-Syn or A??1-40 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats. Treatment of neurons with high concentrations of A??1-42 or ??-Syn caused significant apoptosis of neurons. Following A??1-42 treatment at sub apoptotic concentrations, both intra- and extra-cellular ??-Syn levels were significantly increased. Reciprocally, the non-toxic levels of ??-Syn treatment also increased intra- and extra-cellular A??1-40 levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed ??-Syn-induced A??1-40 elevation, as well as A??1-42-induced ??-Syn elevation. Thus, high concentrations of A??1-42 and ??-Syn exert toxic effects on mature neurons; however, non-toxic concentration treatment of these polypeptides induced the production of each other reciprocally with possible involvement of PI3K pathway.     

The Relation Between Sox9, TGF-��1, and Proteoglycan in Human Intervertebral Disc Cells

Objective

The aim of this study is to elucidate the effects of transforming growth factor-β (TGF-β)1 and L-ascorbic acid on proteoglycan synthesis, and the relationship between Sox9, proteoglycan, and TGF-β1 in intervertebral disc cells.

Methods

Human intervertebral disc tissue was sequentially digested to 0.2% pronase and 0.025% collagenase in DMEM/F-12 media and extracted cells were cultured in 37℃, 5% CO₂ incubator. When intervertebral disc cells were cultured with TGF-β1 or L-ascorbic acid, the production level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay. The changes of Sox9 mRNA and protein levels via TGF-β1 were detected by RT-PCR and Western blot analysis in each.

Results

The amount of sGAG was increased with the lapse of time during incubation, and sGAG content of pellet cultured cells was much larger than monolayer culture. When primary cultured intervertebral disc cells in monolayer and pellet cultures were treated by TGF-β1 20 ng, sGAG content of experimental group was increased significantly compared to control group in both cultures. L-Ascorbic acid of serial concentrations (50-300 ug/ml) increased sGAG content of mono layer cultured intervertebral disc cells significantly in statistics. The co-treatment of TGF-β1 and L-ascorbic acid increased more sGAG production than respective treatment. After treating with TGF-β1, Sox9 mRNA and protein expression rates were significantly increased in disc cells compared with the control group.

Conclusion

This study suggests that TGF-β1 would increase sulfated glycosaminoglycan (sGAG) and other proteoglycans such as versican by elevating Sox9 mRNA and protein expressions in order.     

Lateralisierte ?Out-of-body experience��

The authors report 2 patients with an out-of-body experience (OBE) as an epileptic phenomenon. The autoscopic illusion was constantly lateralized. One patient had a contralateral lesion, while in the other patient a contralateral lesion was suspected. Patients with autoscopic phenomena should be asked for a lateralization as this might be an indication of a contralateral brain pathology. Generally, patients should explicitly be asked for autoscopic perceptions, as these are probably only rarely mentioned spontaneously. Limitations of the hypothesis of a cerebral lesion which is located contralaterally to the autoscopic illusion are the retrospective nature of data collection and the small number of published reports in the literature on lateralization of autoscopic phenomena.     

Oxidative stress increases phosphorylation of I��B kinase-�� by enhancing NF-��B-inducing kinase after transient focal cerebral ischemia

The IκB kinase (IKK) complex is a central component in the classic activation of the nuclear factor-κB (NF-κB) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKKα (pIKKα) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-κB-inducing kinase (NIK) (an upstream kinase of IKKα), pIKKα, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKKα in mouse brain endothelial cells after tFCI. Nuclear factor-κB-inducing kinase was increased, and it enhanced pH3 by inducing pIKKα after oxygen–glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKKα were confirmed by coimmunoprecipitation. Treatment with IKKα small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKKα, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke).     

��berlegungen zur Wirksamkeit von Psychopharmaka

Current systematic reviews yielded relatively small efficacy effect sizes of different psychopharmacological agents compared to placebo. It seems that these effect sizes have decreased compared to earlier meta-analyses. We speculate about factors explaining the decrease of effect size such as lower methodological requirements for earlier randomised controlled trials, but in particular enormous methodological problems of current trials such as chronic patient populations, exclusion of severely ill patients by the protocols, sponsoring by the pharmaceutical industry and so-called professional patients. A few examples from general medicine are used to illustrate that the effect sizes of other medications are often also surprisingly small. Psychotropic drugs are efficacious, but they need to be prudently applied according to evidence-based criteria.