40†Hz Steady-State Response in Human Auditory Cortex Is Shaped by Gabaergic Neuronal Inhibition.

The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, noninvasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in the human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography (MEG) recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants (13 males, 7 females). All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under a placebo. The GABAA receptor-agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA blocker memantine. Our findings indicate that the 40 Hz ASSR in the auditory cortex involves synaptic (and likely intracortical) inhibition via the GABAA receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.

Adaptive biasing of action-selective cortical build-up activity by stimulus history.

Decisions under uncertainty are often biased by the history of preceding sensory input, behavioral choices, or received outcomes. Behavioral studies of perceptual decisions suggest that such history-dependent biases affect the accumulation of evidence and can be adapted to the correlation structure of the sensory environment. Here, we systematically varied this correlation structure while human participants performed a canonical perceptual choice task. We tracked the trial-by-trial variations of history biases via behavioral modeling and of a neural signature of decision formation via magnetoencephalography (MEG). The history bias was flexibly adapted to the environment and exerted a selective effect on the build-up (not baseline level) of action-selective motor cortical activity during decision formation. This effect added to the impact of the current stimulus. We conclude that the build-up of action plans in human motor cortical circuits is shaped by dynamic prior expectations that result from an adaptive interaction with the environment.

Decision making: How the past guides the future in frontal cortex.

Our judgments of our environment are often shaped by heuristics and prior experience. New research shows that the resulting biases are encoded, and combined with new sensory input, by groups of neurons in the frontal cortex during decisions under uncertainty.

Adaptive History Biases Result from Confidence-Weighted Accumulation of past Choices.

Perceptual decision-making is biased by previous events, including the history of preceding choices: observers tend to repeat (or alternate) their judgments of the sensory environment more often than expected by chance. Computational models postulate that these so-called choice history biases result from the accumulation of internal decision signals across trials. Here, we provide psychophysical evidence for such a mechanism and its adaptive utility. Male and female human observers performed different variants of a challenging visual motion discrimination task near psychophysical threshold. In a first experiment, we decoupled categorical perceptual choices and motor responses on a trial-by-trial basis. Choice history bias was explained by previous perceptual choices, not motor responses, highlighting the importance of internal decision signals in action-independent formats. In a second experiment, observers performed the task in stimulus environments containing different levels of autocorrelation and providing no external feedback about choice correctness. Despite performing under overall high levels of uncertainty, observers adjusted both the strength and the sign of their choice history biases to these environments. When stimulus sequences were dominated by either repetitions or alternations, the individual degree of this adjustment of history bias was about as good a predictor of individual performance as individual perceptual sensitivity. The history bias adjustment scaled with two proxies for observers' confidence about their previous choices (accuracy and reaction time). Together, our results are consistent with the idea that action-independent, confidence-modulated decision variables are accumulated across choices in a flexible manner that depends on decision-makers' model of their environment.SIGNIFICANCE STATEMENT Decisions based on sensory input are often influenced by the history of one's preceding choices, manifesting as a bias to systematically repeat (or alternate) choices. We here provide support for the idea that such choice history biases arise from the context-dependent accumulation of a quantity referred to as the decision variable: the variable's sign dictates the choice and its magnitude the confidence about choice correctness. We show that choices are accumulated in an action-independent format and a context-dependent manner, weighted by the confidence about their correctness. This confidence-weighted accumulation of choices enables decision-makers to flexibly adjust their behavior to different sensory environments. The bias adjustment can be as important for optimizing performance as one's sensitivity to the momentary sensory input.

Pupil-linked arousal is driven by decision uncertainty and alters serial choice bias.

While judging their sensory environments, decision-makers seem to use the uncertainty about their choices to guide adjustments of their subsequent behaviour. One possible source of these behavioural adjustments is arousal: decision uncertainty might drive the brain's arousal systems, which control global brain state and might thereby shape subsequent decision-making. Here, we measure pupil diameter, a proxy for central arousal state, in human observers performing a perceptual choice task of varying difficulty. Pupil dilation, after choice but before external feedback, reflects three hallmark signatures of decision uncertainty derived from a computational model. This increase in pupil-linked arousal boosts observers' tendency to alternate their choice on the subsequent trial. We conclude that decision uncertainty drives rapid changes in pupil-linked arousal state, which shape the serial correlation structure of ongoing choice behaviour.

Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes study.

CONTEXT: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk. OBJECTIVE: We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes. DESIGN AND SETTING: We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study). INTERVENTION: We measured fasting morning plasma cortisol. MAIN OUTCOME MEASUREMENT: Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined. RESULTS: Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03). CONCLUSIONS: The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.

Improving care for patients with dementia hospitalized for acute somatic illness in a specialized care unit: a feasibility study.

BACKGROUND: Persons with dementia hospitalized for an acute illness have a high risk of poor outcomes and add to the burden on acute care systems. We developed a segregated Special Care Unit (SCU) in a somatic hospital for patients with challenging behavior resulting from dementia and/or delirium. This pilot study evaluates the feasibility and patient outcomes. METHODS: The SCU was established with environmental features that allow for safe and unrestricted ambulation within the unit and create a home-like atmosphere. Daytime activities structure the day and assure additional professional presence. The staff received intensive specialized training. Feasibility criteria were: acceptance by the staff, avoidance of transfers to geriatric psychiatry, lack of serious falls and mortality. Patient outcome criteria were ADL (Barthel index), mobility scores and behavior scores (Wilcoxon's, McNemar tests, pre-post design). RESULTS: 332 consecutively admitted patients were enrolled. The SCU has been well received by the staff. Length of hospital stay did not differ from other hospital patients (15.3 +/- 8.3 vs. 15.0 +/- 10.3 days, p = 0.54). Six patients were transferred to geriatric psychiatry. Two patients suffered a fall-related hip fracture. The median Barthel Index improved significantly (admission 30, discharge 45, p < 0.001), with only 8.5% of patients suffering functional loss. Wandering, aggression and agitation were significantly reduced (p < 0.001). CONCLUSIONS: The SCU has improved the care of patients with challenging behavior. Decline in ADL function and institutionalization occurred to a lesser degree than would be expected in this group of patients. Despite the selection of patients with behavioral problems, transfer to psychiatry was rare.

SGS: a structured treatment and teaching programme for older patients with diabetes mellitus--a prospective randomised controlled multi-centre trial.

OBJECTIVES: evaluation of the effectiveness of a new structured diabetes teaching and treatment programme (DTTP) with specific didactical approaches and topics for geriatric patients with diabetes mellitus. DESIGN: a prospective randomised controlled multi-centre trial. SETTING AND PARTICIPANTS: a total of 155 geriatric patients were randomly admitted to either the new DTTP SGS (n = 83) or the standard DTTP (n = 72) for insulin-treated patients with type 2 diabetes mellitus (HbA1c 8.0 +/- 1.4%, age 76.2 +/- 6.3 years). MEASUREMENTS: biometrical data, metabolic control, acute complications, diabetes knowledge, self-management. RESULTS: SGS participants showed improved levels of HbA1c 6 months after the DTTP, and less acute complications than the standard group (P<0.009). Both groups demonstrated a good capacity for diabetes self-management and improvement in diabetes knowledge after the DTTP (P<0.01). CONCLUSION: the new SGS diabetes education programme, focusing on the learning capabilities and the particular needs of older persons, is effective in improving metabolic control and in maintaining auto-sufficiency in geriatric patients with diabetes mellitus.

Cognitive function is not associated with recurrent foot ulcers in patients with diabetes and neuropathy.

OBJECTIVE: To study whether there is an association between cognitive impairment and the relapse rate of foot ulcers in diabetic patients and those with previous foot ulcers. RESEARCH DESIGN AND METHODS: This single-center prospective study assessed the association of cognitive function and risk for ulcer relapse in 59 patients with diabetes (mean age 65.1 years, diabetes duration 16.5 years, and A1C 7.4%), peripheral neuropathy, and a history of foot ulceration. Premorbid and current cognitive functions were measured (multiple-choice vocabulary test [Lehrl], number-symbol test, mosaic test [HAWIE-R], and trail-making tests A and B [Reitan]). Prevalence of depression was evaluated retrospectively (diagnoses in patient files or use of antidepressive medication). Patients were re-examined after 1 year. RESULTS: Three patients (5%) died during follow-up (one of sepsis and two of heart problems). The remaining 56 patients (48%) developed 27 new foot ulcerations (78% superficial ulcerations [Wagner stage 1]). Characteristics of patients with and without ulcer relapse were not different. In a binary logistic regression analysis, cognitive function is not predictive of foot reulceration. CONCLUSIONS: Cognitive function is not an important determinant of foot reulceration.

Retinal vessel response to flicker light in children and adolescents with type 1 diabetes mellitus and overweight or obesity.

UNLABELLED: It was the goal of the trial to assess cardiovascular risk factors in children and adolescents with type 1 diabetes mellitus or overweight/obesity. All children and adolescents (n=77 [n=45 patients with diabetes mellitus, n=32 patients with overweight/obesity]) admitted to our hospital during the period from 01/07 to 31/08/2006 were included in the trial. Socio-demographic and laboratory data (age, sex, diabetes duration, BMI, BMI-SDS, HbA1c, fasting blood glucose, oGTT in patients with overweight/obesity, lipids, CRP, TSH, creatinine, and microalbuminuria) were assessed. The diameter of a retinal arterial and a venous segment was measured continuously on-line with a Dynamic Vessel Analyzer, carotid intima-media thickness (IMT) was measured, and 24-h-blood pressure monitoring was applied. RESULTS: Flicker light stimulation induces a comparable arterial dilatation in patients with type 1 diabetes and overweight/obesity. Univariate ANOVA in patients with type 1 diabetes shows an influence of diastolic blood pressure on arterial dilatation. Other factors such as BMI, age, diabetes duration, smoking, sex, HbA1c and insulin dose/kg had no effect. CONCLUSIONS: In children and adolescents with diabetes or overweight/obesity retinal vascular alterations seem to be more sensitive and already present before the occurrence of classic cardiovascular markers.

[Urinary incontinence]. / Inkontinenz.

Urinary incontinence is a common health problem of older adults and affects more than 50% of nursing home residents. Different types of urinary incontinence can be distinguished: urgency, stress, overflow (urinary retention) and extra-urethral incontinence. The pathogenesis of urinary incontinence in older patients is multifactorial. Age-related physiologic changes, urological or gynaecological ailments, neurological diseases, behavioural patterns and functional decline frequently contribute to incontinence to some extent. These pathogenetic factors may appear in close relation to frailty. As incontinence on the one hand may substantially contribute to decompensation of health reserves, and on the other hand is an indicator for frailty, early assessment and treatment are important. Clinical diagnostics focus on history, physical examination, bladder diary and measurement of postvoid residual volume. Diagnostic and therapeutic approaches to urinary incontinence should focus on finding and treating reversible causes. Behavioural interventions such as toileting procedures may reduce the level of incontinence even in severe cases. Frail older adults with functional decline and urgency incontinence often do not respond well to drug treatment. Paramount for the adequate care for incontinent seniors is the instruction of the affected person and--if necessary--of their caregiver in handling incontinence aids.

Effects of metabolic control, patient education and initiation of insulin therapy on the quality of life of patients with type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to evaluate the impact of initiation of insulin therapy, metabolic control and structured patient education on the diabetes-related quality of life (QoL) in insulin-treated patients with type 2 diabetes mellitus. METHODS: This prospective study was conducted with 71 consecutively recruited patients with insulin-treated diabetes at the University hospital. All patients participated an inpatient diabetes treatment and teaching program (DTTP) for conventional insulin therapy (mean age 68.9 years, HbA1c 10.1+/-1.4%, diabetes duration 11.2 years (range: 0-25.5 years), body-mass-index 28.7+/-5.7 kg/m(2). Diabetes-related quality of life was assessed before and 6 months after participation in the DTTP using the standardized questionnaire of Lohr analysing the subscales: social relations, physical complaints, worries about the future, dietary restrictions, fear of hypoglycaemia, and daily struggles. RESULTS: Only patients switched on insulin therapy showed significant improvement in diabetes-related quality of life 6 months after participation in the DTTP (p=0.03), fewer physical complaints (p=0.03), fewer worries about the future (p=0.02), fewer daily struggles (p=0.01) and less fear of hypoglycaemia (p<0.001), while patients, who were already on insulin therapy showed no improvements in diabetes-related quality of life. Though, residual analysis reveals that effects on patients' QoL are mainly caused by improvements in metabolic control. CONCLUSIONS: Improvements in metabolic control have a significant effect on different diabetes-related quality of life domains in patients with diabetes mellitus. PRACTICE IMPLICATIONS: Appropriate interventions resulting in better metabolic control, such as starting on insulin therapy within a structured patient education program seem to be an effective approach to improve patients' diabetes-related quality of life.

Cryoglobulinaemia type III with severe neuropathy and immune complex glomerulonephritis: remission after plasmapheresis and rituximab.

We describe the case of a 78-year-old woman with peripheral neuropathy, neurogenic muscular atrophy, skin ulcers, arthritis and immune complex glomerulonephritis. Detection of mixed cryoglobulins in combination with typical clinical symptoms, and the exclusion of hepatitis C and other underlying diseases, led to the rare diagnosis of essential cryoglobulinaemic vasculitis type III. Because initial interventions with prednisolone, plasmapheresis and cyclophosphamide pulse therapy failed to induce remission, therapy with rituximab, a chimeric monoclonal antibody that reacts specifically with the CD20 antigen, was initiated. Rituximab was administered intravenously at a dose of 375 mg/m(2) body surface. After five applications, the patient showed remission of clinical symptoms and complete normalisation of laboratory values. These results suggest that rituximab is an alternative therapeutical approach with strikingly good clinical outcome in patients with cryoglobulinaemic vasculitis type III.

A special care unit for acutely ill patients with dementia and challenging behaviour as a model of geriatric care.

This paper describes the development and management of a new model of care for hospitalized patients with challenging behaviour evoked by dementia and/or delirium. To ameliorate care for patients with dementia in a geriatric acute care hospital a segregated Special Care Unit for patients with challenging behaviour was created. Environmental features allow for safe and unrestricted ambulation within the unit and create a home-like atmosphere. Day-time activities structure the day and assure additional professional presence in the unit. An intensive training program for the staff was provided. The SCU has been well accepted by the staff and is considered to be an improvement in care. Psychological burden of the nurses did not increase over a time period of one year in caring for these difficult patients.

[A structured treatment and educational program for patients with type 2 diabetes mellitus, insulin therapy and impaired cognitive function (DikoL)]. / Ein strukturiertes Behandlung- und Schulungsprogramm für Patienten mit Typ-2-Diabetes mellitus, Insulintherapie und verminderter kognitiver Leistunsfähigkeit (DikoL).

BACKGROUND AND PURPOSE: More than 50% of patients with type-2 diabetes mellitus and impaired cognitive function are overtaxed with some topics of established structured treatment and teaching programs for patients with insulin therapy. This leads to substantial deficits in respect of the patients' ability of diabetes self-management (insulin injections, self-monitoring) and the need for help by relatives and social workers. The consequences are an impaired quality of life and a great deal of expense in the welfare system. Since 1996, a specialized structured treatment and teaching program for patients with type-2 diabetes mellitus, insulin therapy, and impaired cognitive function (DikoL) has been developed. Main differences in comparison to established programs were less theoretical topics (no pathophysiology, no insulin action, no complicated calculation of carbohydrate pounds) and more time for practical exercise. In a randomized prospective study, the effectiveness of the DikoL program was evaluated. PATIENTS AND METHODS: All patients with type-2 diabetes mellitus (n = 106, age 68.6 +/- 8.7 years, median diabetes duration 10.3 [0.03-35.4] years, HbAlC 10.3+ 1.7% [HPLC, Diamat, normal range 4.5-6.3%], cognitive function 87.7 +12.3 IQ points), admitted to hospital to participate in a structured treatment and teaching program between April 1999 and June 2000, were studied. Patients with impaired cognitive function (< 91 IQ points) were randomized: they participated either in an established structured treatment and teaching program according to Berger et al. (standard group: n = 35) or in the DikoL program(DikoL group: n = 33). Immediately after participation and 0.5 years later, the quality of diabetes control, patients' knowledge of diabetes, their ability for diabetes self-management, and their satisfaction with the program were evaluated. RESULTS: Patients of the DikoL group had a comparable quality of diabetes control (HbAlc: DikoL vs. standard group: 8.5 + 1.3 vs. 8.3 +/- 1.4%; p = 0.62)and diabetes-related knowledge (DikoL vs. standard group: 9.6 +/- 4.4 vs.10.3 + 3.8 points; p = 0.52), but significantly better results in respect of their ability for diabetes self-management (DikoL vs. standard group: 15.9 +/- 3.1 vs. 12.5 +/- 4.1 points; p = 0.001) than patients of the standard group. Moreover, in the DikoL group there was a tendency to a lower number of patients needing third-party assistance (n = 1 patient of the DikoL group vs. n = 5 patients of the standard group; p = 0.13). There were no acute complications (hypoglycemia, comata, and foot ulcers) in neither group. Following participation in the DikoL program, patients reached a better score in the questionnaire evaluating satisfaction with the treatment and teaching program (DikoL vs. standard group:52.5 + 4.5 vs. 44.7 + 76 points; p < 0,001). CONCLUSION: Following the wishes of the majority of diabetes educators as well as diabetologists but also patients' wishes, a specially designed structured treatment and teaching program for patients with type-2 diabetes mellitus, insulin therapy, and impaired cognitive function was designed. DikoL is the first program evaluated in a randomized, prospective trial. It clearly demonstrated a bet-ter outcome for patients with impaired cognitive function in respect of diabetes self-management and satisfaction. With its implementation, patients' quality of diabetes care can be improved in a substantial manner.