Young adolescents with autism show abnormal joint attention network: A gaze contingent fMRI study.

Behavioral research has revealed deficits in the development of joint attention (JA) as one of the earliest signs of autism. While the neural basis of JA has been studied predominantly in adults, we recently demonstrated a protracted development of the brain networks supporting JA in typically developing children and adolescents. The present eye-tracking/fMRI study now extends these findings to adolescents with autism. Our results show that in adolescents with autism JA is subserved by abnormal activation patterns in brain areas related to social cognition abnormalities which are at the core of ASD including the STS and TPJ, despite behavioral maturation with no behavioral differences. Furthermore, in the autism group we observed increased neural activity in a network of social and emotional processing areas during interactions with their mother. Moreover, data indicated that less severely affected individuals with autism showed higher frontal activation associated with self-initiated interactions. Taken together, this study provides first-time data of JA in children/adolescents with autism incorporating the interactive character of JA, its reciprocity and motivational aspects. The observed functional differences in adolescents ASD suggest that persistent developmental differences in the neural processes underlying JA contribute to social interaction difficulties in ASD.

Look into my eyes: Investigating joint attention using interactive eye-tracking and fMRI in a developmental sample.

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects.

The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis.

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others' (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.

Pattern classification of valence in depression.

Neuroimaging biomarkers of depression have potential to aid diagnosis, identify individuals at risk and predict treatment response or course of illness. Nevertheless none have been identified so far, potentially because no single brain parameter captures the complexity of the pathophysiology of depression. Multi-voxel pattern analysis (MVPA) may overcome this issue as it can identify patterns of voxels that are spatially distributed across the brain. Here we present the results of an MVPA to investigate the neuronal patterns underlying passive viewing of positive, negative and neutral pictures in depressed patients. A linear support vector machine (SVM) was trained to discriminate different valence conditions based on the functional magnetic resonance imaging (fMRI) data of nine unipolar depressed patients. A similar dataset obtained in nine healthy individuals was included to conduct a group classification analysis via linear discriminant analysis (LDA). Accuracy scores of 86% or higher were obtained for each valence contrast via patterns that included limbic areas such as the amygdala and frontal areas such as the ventrolateral prefrontal cortex. The LDA identified two areas (the dorsomedial prefrontal cortex and caudate nucleus) that allowed group classification with 72.2% accuracy. Our preliminary findings suggest that MVPA can identify stable valence patterns, with more sensitivity than univariate analysis, in depressed participants and that it may be possible to discriminate between healthy and depressed individuals based on differences in the brain's response to emotional cues.

Products for Alzheimer's self-stimulatory wanderers.

The objective of this study was to develop a variety of sensory stimulation products for the behavioral intervention of patients with Alzheimer's type dementia. Many caregivers have relied on physical and chemical restraints as the primary method of patient intervention due to the lack of appropriate dementia management products. This significantly lowers the sufferer's quality of care and life. As the age group most susceptible to Alzheimer's disease (65 and older) is the fastest growing segment of our society, an appropriate care solution must be sought. The specific aim of this study was to develop products that are sensory satisfying for the Alzheimer's patient that exhibits self-stimulatory wandering behavior. Sensory satisfying objects for product development would be determined through structured observations of self-stimulatory wanderers in an institutionalized setting. Variations of product design and mounting would be pursued in order to develop products that are not only safe and effective for patient use, but are easy for the caregiver to implement and maintain. Such products would have widespread commercial application in both the institutional and private care settings such as nursing homes, adult day care facilities, Alzheimer's care facilities, convalescent homes, mental health institutions, and assisted-living facilities.

Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin.

The syntrophins are a family of structurally related proteins that contain multiple protein interaction motifs. Syntrophins associate directly with dystrophin, the product of the Duchenne muscular dystrophy locus, and its homologues. We have generated alpha-syntrophin null mice by targeted gene disruption to test the function of this association. The alpha-Syn(-/)- mice show no evidence of myopathy, despite reduced levels of alpha-dystrobrevin-2. Neuronal nitric oxide synthase, a component of the dystrophin protein complex, is absent from the sarcolemma of the alpha-Syn(-/)- mice, even where other syntrophin isoforms are present. alpha-Syn(-/)- neuromuscular junctions have undetectable levels of postsynaptic utrophin and reduced levels of acetylcholine receptor and acetylcholinesterase. The mutant junctions have shallow nerve gutters, abnormal distributions of acetylcholine receptors, and postjunctional folds that are generally less organized and have fewer openings to the synaptic cleft than controls. Thus, alpha-syntrophin has an important role in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse.

Success in using non-invasive mechanical ventilation is predicted by patient pathophysiology. A retrospective review of 199 patients.

BACKGROUND: To determine the effect of patient pathophysiology on the success or failure of noninvasive mechanical ventilation as determined by the need for subsequent endotracheal intubation. METHODS: Center-based, retrospective case analysis of all patients placed on non-invasive mechanical ventilation for acute respiratory distress. MEASUREMENTS AND RESULTS: Retrospective chart review was performed on patients who were treated with non-invasive mechanical ventilation from 1/94-6/97. Patients were divided into those with rapidly reversible disease processes (RRDP), and those with non rapidly reversible disease processes (NRRP). The proportion of patients requiring subsequent intubation in each group was compared. There were 116 patients with RRDP and 83 patients with NRRD. In the RRDP group, 85.8 percent (95 percent confidence interval 80.9-90.7 percent) of patients did not require intubation. In the NRRP group, 35.7 percent (95 percent C.I. 29.0-42.4 percent) did not require intubation (X2 analysis, p < .001). Multivariate analysis identified patient pathophysiology as the only variable associated with subsequent intubation. CONCLUSIONS: Patient pathophysiology based upon their expected clinical course can be used to predict the success of non-invasive mechanical ventilation (NIMV). Patients with NRRD, such as pneumonia, myocardial infarct and sepsis, are much more likely to fail non-invasive mechanical ventilation and require subsequent endotracheal intubation.

Early probable Alzheimer's disease and awareness context theory.

The purpose of this research was to explore the explanatory value of Awareness Context Theory for social interactional issues in early probable Alzheimer's Disease (AD). Glaser and Strauss's Awareness Context Theory [Glaser and Strauss (1965) Awareness of Dying, Aldine, New York] served as the framework for the analysis of interview data from 14 early probable AD clients and 14 family caregivers, a written autobiographical account, a fictionalized account, observations of a family care-giver focus group, and excerpts that focused on early AD from field notes recorded during two years of participant observation at a specialized AD daycare center and a family caregiver support group. Initial open-ended study questions focused on the experience of early AD from the diverse perspectives represented in the data. After preliminary analysis of data suggesting emergent fit with Awareness Context Theory, questions were refocused to address awareness contexts. Data were coded and analyzed for fit with the theory. Awareness Context Theory provided a useful heuristic for thinking about the nuances and complexities of social interaction in early AD. Attention to awareness contexts should enable health care providers to suggest interventions to improve caregiver-client interactions.

Toileting: a biobehavioral challenge in Alzheimer's dementia care.

As the trajectory of Alzheimer's disease (AD) progresses, problems with toileting become evident. This research addresses the range and variation of toileting problems, management strategies used by family and employed caregivers, and interactive and contextual conditions associated with toileting. Qualitative ethology was used to analyze data from over 120 hours of participant observation at an Alzheimer's Day Care Center, in clients' homes, and support groups; and interviews with families (n = 16) and staff members (n = 13). Toileting emerged as a complex event with many stages, as unaesthetic and unpleasant for caregivers and clients, and as occasionally resulting in catastrophic reactions. Caregivers read cues and interpret toileting behaviors. They provide physical and cognitive assistance while attempting to avoid accidents and catastrophic events. Client, staff member, and contextual variables affect toileting events. Recommendations for practice and research are proposed.

Reducing the rate of paramedic needlesticks in emergency medical services: the role of self-capping intravenous catheters.

OBJECTIVE: To determine whether the frequency of unintentional needlesticks can be reduced by replacing conventional i.v. catheters with self-capping ones. METHODS: Retrospective cohort, historically controlled study, conducted in an emergency medical services advanced life support (ALS) service. The ALS service annually transports 12,000 patients, for whom i.v. therapy is attempted in about 65% of cases. The needlestick rate per 1,000 patients receiving attempts at i.v. access was examined during the 2 10-month periods, before and after introduction of a self-capping i.v. catheter. RESULTS: For the 2 periods, the percentage of patients for whom i.v. access was attempted remained constant at 65%. The success rate for i.v. access was statistically unchanged from 88% to 90% (p > 0.5, power = 0.995). During the period prior to use of the new catheter, 44 injuries were reported overall. Of these, 15 were due to unintentional needlesticks, 11 associated with contaminated needles. Following the system-wide introduction of the new catheter, only 1 of 31 reported injuries was due to needlestick (uncontaminated). The extrapolated annual incidence of contaminated needlesticks decreased from 169 (95% CI; 85, 253) to 0 (95% CI; 0, 46) per 100,000 i.v.attempts. The extrapolated incidence for all needlesticks decreased from 231 (95% CI; 132, 330) to 15 (95% CI; 0, 40) per 100,000 i.v. attempts. The absolute number of needlesticks and the proportion of injuries due to needlesticks decreased significantly (p < 0.005). CONCLUSION: The use of i.v. catheters with self-capping needles was associated with a significant reduction in the absolute number of inadvertent needlesticks as well as the proportion of injuries due to needlesticks among ALS providers. The use of self-capping i.v. catheters was feasible and did not appear to be a deterrent to initiating i.v. therapy in the out-of-hospital environment.

Effect of continuous quality improvement methods on reducing triage to thrombolytic interval for acute myocardial infarction.

OBJECTIVES: To assess the timeliness of thrombolytic therapy in the ED for selected patients with acute myocardial infarction (AMI) following continuous quality improvement (CQI) interventions. METHODS: A retrospective, historical comparison study was performed of triage-to-thrombolytic time intervals for AMI patients using chart review for data collection. Patients treated after implementation of the CQI process vs a historical control group were compared. The patients with AMI who had received thrombolytics during the one-year period prior to the CQI interventions and who had documentation of time intervals served as the control group. The patients treated during a four-month period, beginning about one and a half years following introduction of the CQI interventions, served as the intervention group. Interventions included: a triage protocol, CQI review, and staff feedback. RESULTS: The mean triage-to-thrombolytic interval was longer for the control group (72 +/- 25 vs 40.0 +/- 22 min; p < 0.0001). The mean triage-to-ECG interval also was longer for the control group (16.5 +/- 8.9 vs 8.5 +/- 7.5 min; p < 0.0001). Most (79%) of the study group received thrombolytic therapy within 60 minutes, and 39% within 30 minutes, whereas 39% of the control group received thrombolytic therapy within 60 minutes, and 3% within 30 minutes. CONCLUSION: The implementation of CQI techniques, including 100% chart review, intensive systems analysis, and staff feedback, had a positive effect on the timeliness of thrombolytic therapy for the ED patients who had AMI. As a result, most (79%) of the patients received therapy within the 60-minute time window recommended currently by the American Heart Association.

Desert locusts in Africa: a disaster?

Migrating locusts, especially the desert locust (Schistocerca gregaria), have been feared in Africa for thousands of years as famine-inducing pests. Instead of simply waiting for outbreaks to occur, attempts are being made to take preventive action against these pests. Since the breeding areas of the desert locust are distributed across the entire Sahel region, the Arabian peninsula, Pakistan and India, a gigantic logistical and organizational effort is required. Every year, millions of dollars are spent on these preventive control measures, which are still unable to prevent locust plagues completely. The outbreaks in 1987/88 and 1993/94 are the most recent examples. Exactly how large potential disasters caused by gigantic locust swarms may be and whether the effort and expense involved in preventing them pays off economically has never been systematically investigated. The Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ) project, 'Integrated Biological Control of Grasshoppers and Locusts', has attempted to assess, on the basis of the available data, what the costs and potential benefits are and to identify the difficulties involved in developing an effective strategy.

Wandering in Alzheimer's dementia patients.

The purpose of this research was to describe wandering behaviors of institutionalized patients with Alzheimer's disease in their natural environment. Such descriptive information is necessary before successful product and/or nursing intervention programs can be developed. Videotaped behavioral observations yielded detailed data descriptive of patients with middle and late dementia. These patients have the physical ability to perform various functions, activities, or actions; the individual's mental ability is less supportive of physical ability. The degree of task simplicity required to enable the patient to complete unsupervised tasks depends on the level of dementia. The need for interventions is greatest during unstructured periods of the day.

Heterogeneous distribution and upregulation of mu, delta and kappa opioid receptors in the amygdala.

Levels of mu, delta and kappa opioid receptors in 4 subnuclei of the rat amygdala were determined by quantitative autoradiography following chronic treatment with naloxone or saline. A different distribution of each receptor subtype was observed, with mu binding greatest in the lateral nucleus (La), delta greatest in the basolateral (Bl), and kappa greatest in the medial (Me). Levels of all 3 receptors were very low in the central nucleus. Receptor upregulation following chronic naloxone treatment was also anatomically heterogeneous. Increases in mu receptors were statistically significant in the Me, Bl and La, while increases in delta and kappa receptors were significant only in the Bl.

Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas.

Recent evidence suggests that kappa opiate receptors may play a key role in the regulation of appetite. Such evidence implies that kappa receptors might be localized within specific brain areas known to regulate ingestive behaviors. On the basis of this implication we employed an in vitro film autoradiographic technique using 3H-ethylketocyclazozine as ligand to identify putative kappa receptors within CNS "taste" nuclei and surrounding areas. Coronal cryostat sections of rat brain were incubated with ligand in the presence of D-Ala2, D-Leu5-enkephalin (DADLE) and morphine, apposed to LKB Ultrofilm for 60 days, processed and kappa receptor densities evaluated with the aid of a hand held photometer and video image analyzer. Highest kappa receptor densities were found within various gustatory and feeding sites including the rostral pole of the nucleus of the solitary tract, parabrachial nuclei, ventral posterior and medial portions of the thalamus, medial hypothalamus, medial nuclei of the amygdala and bed nucleus of the stria terminalis. Various other midline and medial limbic areas also showed significant kappa densities.