Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice

Misfolded amyloid beta peptide (Abeta) is a pathological hallmark of Alzheimer's disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of Abeta over-production indicate that Abeta-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those Abeta-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets. Here, we report that the enzymatic activity of calcineurin, a key protein phosphatase involved in phosphorylation-dependent kinase activity crucial for synaptic plasticity and memory function, is upregulated in the CNS of the Tg2576 animal model for Abeta over-production. Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506 (10mg/kg i.p.) improves memory function. These results indicate that calcineurin may mediate some of the cognitive effects of excess Abeta such that inhibition of calcineurin shall be further explored as a potential treatment to reverse cognitive impairments in AD.     

Learning as a possible sign of non-reflective consciousness in persons with a diagnosis of vegetative state and pervasive motor impairment

A diagnosis of vegetative state represents a serious predicament, which basically precludes/minimizes rehabilitation perspectives. Reliability of the assessment approach in these situations is of paramount importance, but not easy to achieve. In recent studies, a learning assessment procedure has been suggested as a supplement in the diagnostic process and assessed with eight patients. The procedure involves an ABABCB sequence in which A represents baseline phases with no stimulation available, B intervention phases with stimuli delivered contingently on target responses, and C a control condition. This condition involves stimulation presented non-contingently. The patients’ ability to associate responding with environmental stimuli and thus increase such responding during the B phases, and reduce it during the A and C phases, may be considered a sign of learning. Learning might be viewed as representative of forms of concrete knowledge and presumably basic levels of consciousness. Preliminary results indicate that (a) signs of learning may appear in patients with a previous diagnosis of vegetative state and (b) the presence of those signs may require a revision of their diagnostic label and a reappraisal of their rehabilitation perspectives.     

Task instructions for persons with severe intellectual disability: reducing the number of instruction occasions after the acquisition phase

During the first part of the study, eight tasks were taught to four participants with severe intellectual disability. A portable computer‐aided system was used that presented one pictorial instruction per task step, individually. During the second part of the study, the same computer‐aided system was used but the number of instruction occasions available for the tasks was reduced. In one condition, the system presented all the step instructions but mostly in small clusters rather than individually. In another condition, the system presented only some of the instructions. Data for the first part of the study showed that the participants managed to perform 83–97% of the task steps correctly. Data for the second part of the study showed that the condition in which instructions were clustered was more effective in maintaining high percentages of correct performance. Implications of the findings are discussed. Copyright © 1999 John Wiley & Sons, Ltd.     

BRIEF REPORT: ENABLING BLIND PERSONS WITH SEVERE OR PROFOUND MENTAL RETARDATION TO OPERATE AN ACOUSTIC ORIENTATION SYSTEM INDEPENDENTLY

The aim of this study was to assess new technology for enabling two blind persons affected by severe or profound mental retardation to operate an acoustic orientation system independently. By operating this system, the subjects could move to different activity destinations within an occupational setting and carry out activities free from external assistance. The results showed that both subjects learned to operate the system on their own. The high level of independence they achieved is reviewed in relation to the new technology and the simplified responding it requires     

Is amenorrhea a clinically useful criterion for the diagnosis of anorexia nervosa?

Aim of the study was to evaluate the clinical characteristics and the treatment outcome of underweight patients with eating disorder (ED) not otherwise specified without amenorrhea (EDNOS-WA), compared with classical anorexia nervosa (AN) cases. Seventy-three consecutive female patients (57 AN, and 16 EDNOS-WA) were evaluated before and after a 20-week cognitive behaviour inpatient treatment (CBT-I). Assessment included anthropometry, the Eating Disorder Examination (EDE), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), and the Temperament and Character Inventory (TCI). At logistic regression analysis, amenorrhea was only predicted by baseline BMI and intense exercise, not by psychopathological variables. Response to CBT-I was good and similar between groups, without differences in the dropout rate or time-to-dropout. Our data lend support to the hypothesis that the criterion “amenorrhea” is of no clinical utility in the diagnosis and treatment of AN and could be removed in the forthcoming DSM-V proposal.     

Automatic prompting to reduce persistent tongue protrusion in a woman with severe to profound mental retardation

This study assessed whether an intervention approach relying on auditory prompting delivered automatically through a portable device was effective to reduce tongue protrusion in a woman with severe to profound mental retardation. The device involved (a) an optic sensor, i.e., a miniphotocell kept under the lower lip with medical tape, (b) a small signal transmission box, and (c) a Walkman for presenting the prompts. Initially, the automatic prompting condition was combined with occasional praise from a research assistant for having the tongue in the mouth. Analysis showed that the occurrence of tongue protrusion dropped from about 65% of the observation time during the initial baseline to less than 5% through the intervention. The study lasted 4.5 mo.     

Microswitch technology and contingent stimulation to promote adaptive engagement in persons with minimally conscious state: a case evaluation

This study assessed whether a post-coma woman functioning at the lower end of the minimally conscious state would (a) develop adaptive responding through the use of microswitch technology and contingent stimulation, (b) consolidate and maintain her responding over time, and (c) show evidence of response-consequences awareness (learning and discrimination). The study involved an ABABB¹CB¹ sequence in which the A represented baseline phases, the B and B¹ intervention phases, and the C a control phase with continuous stimulation. Results indicated that the woman developed adaptive responding and consolidated it over the intervention phases of the study. The woman also showed evidence of being aware of response-consequences links. Potential implications and limitations of these findings are discussed.     

Alarm Signals and Prompts to Eliminate Large Urinary Accidents in a Woman with Multiple Disabilities

Urine-triggered alarm signals and prompts were used to help a woman with multiple disabilities halt wetting episodes and walk to the toilet (thus avoiding large urinary accidents). Data indicated that the woman had a mean frequency of 1 large accident nearly every 2 days during the baseline phases and every 20 days during the intervention phases. During the latter phases, large accidents were replaced by small accidents (i.e. only a disposable tissue inside the underwear was wet), which did not cause environmental disruptions and did not require changes of clothes. Implications of the findings are discussed.     

Knowledge space theory, formal concept analysis, and computerized psychological assessment

In the present study, the use of knowledge space theory (KST), jointly with formal concept analysis (FCA), is proposed for developing a formal representation of the relations between the items of a questionnaire and a set of psychodiagnostic criteria. This formal representation can be used to develop an efficient adaptive tool for psychological assessment. Rusch and Wille (1996) have shown some interesting connections between KST and FCA; these connections are applied in the construction of knowledge structures, starting from a formal context representing the relations between items and criteria. The proposed general methodology was applied, as an example, to the Maudsley Obsessional-Compulsive Questionnaire. We used a data set provided by a sample of patients with a diagnosis of obsessive-compulsive disorder to validate the obtained structures. The parameters of the basic local independence model (BLIM) were estimated for the obtained knowledge structures. The fit of each model was tested by parametric bootstrap because of the sparseness of the derived data matrix. The results are discussed in light of both psychological and methodological relapses. In particular, we propose a reinterpretation of the BLIM parameters that seems suitable for testing reliability and construct validity; furthermore, it is pointed out how the obtained structures could represent the starting point for the development of a computerized assessment tool.     

Influence of assessment setting on the results of functional analyses of problem behavior

Analogue functional analyses are widely used to identify the operant function of problem behavior in individuals with developmental disabilities. Because problem behavior often occurs across multiple settings (e.g., homes, schools, outpatient clinics), it is important to determine whether the results of functional analyses vary across settings. This brief review covers 3 recent studies that examined the influence of different settings on the results of functional analyses and identifies directions for future research.