"Stopping for knowledge": The sense of beauty in the perception-action cycle.

According to a millennial-old philosophical debate, aesthetic emotions have been connected to knowledge acquisition. Recent scientific evidence, collected across different disciplinary domains, confirms this link, but also reveals that motor inhibition plays a crucial role in the process. In this review, we discuss multidisciplinary results and propose an original account of aesthetic appreciation (the stopping for knowledge hypothesis) framed within the predictive coding theory. We discuss evidence showing that aesthetic emotions emerge in correspondence with an inhibition of motor behavior (i.e., minimizing action), promoting a simultaneous perceptual processing enhancement, at the level of sensory cortices (i.e., optimizing learning). Accordingly, we suggest that aesthetic appreciation may represent a hedonic feedback over learning progresses, motivating the individual to inhibit motor routines to seek further knowledge acquisition. Furthermore, the neuroimaging and neuropsychological studies we review reveal the presence of a strong association between aesthetic appreciation and the activation of the dopaminergic reward-related circuits. Finally, we propose a number of possible applications of the stopping for knowledge hypothesis in the clinical and education domains.

Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis.

BACKGROUND: A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization. METHODS: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included. RESULTS: Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies. CONCLUSIONS: Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.

Cerebellar Clustering and Functional Connectivity During Pain Processing.

The cerebellum has been traditionally considered a sensory-motor structure, but more recently has been related to other cognitive and affective functions. Previous research and meta-analytic studies suggested that it could be involved in pain processing. Our aim was to distinguish the functional networks subserved by the cerebellum during pain processing. We used functional magnetic resonance imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting state acquisition. For the analysis of data, we used fuzzy c-mean to cluster cerebellar activity of each participant during nociception. The mean time courses of the clusters were used as regressors in a general linear model (GLM) analysis to explore brain functional connectivity (FC) of the cerebellar clusters. We compared our results with the resting state FC of the same cluster and explored with meta-analysis the behavior profile of the FC networks. We identified three significant clusters: cluster V, involving the culmen and quadrangular lobules (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus 2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus 2). Cluster V was more connected during pain with sensory-motor areas, cluster VI with cognitive areas, and cluster VII with emotional areas. Our results indicate that during the application of mechanical punctate stimuli, the cerebellum is not only involved in sensory functions but also with areas typically associated with cognitive and affective functions. Cerebellum seems to be involved in various aspects of nociception, reflecting the multidimensionality of pain perception.

The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients.

AIM: A growing number of neuropsychological studies reported that chemotherapy may impair brain functions, inducing persistent cognitive changes in a subset of cancer survivors. The aim of this paper was to investigate the neural basis of the chemotherapy induced neurobehavioral changes by means of metabolic imaging and neuropsychological testing. METHODS: We studied the resting brain [¹8F]FDG-PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients were studied prior and 32 after to chemotherapy. All patients underwent to a neuropsychological examination assessing cognitive impairment (tests for shifting attention, verbal memory, phonemic fluency), depression, anxiety and distress. RESULTS: Compared to no chemotherapy patients, the treated group showed significant bilateral lower rate of glucose metabolism in prefrontal cortices, cerebellum, medial cortices and limbic brain areas. The metabolism of these regions negatively correlated with number of cycles and positively with post-chemotherapy time. The treated group showed a poorer performance in many frontal functions, but similar level of depression, anxiety and distress. CONCLUSIONS: Chemotherapy induced significant long-term changes in metabolism of multiple regions with a prevailing involvement of the prefrontal cortex. The observed cognitive dysfunctions could be explained by these changes. The recovery from chemotherapy is probably affected by treatment duration and by the time elapsed after its end. We speculated that the mechanism could be an accelerating ageing / oxidative stress that, in some patients at risk, could result in an early and persistent cognitive impairment.

Virtual navigation for memory rehabilitation in a traumatic brain injured patient.

The use of 3D video games in memory rehabilitation has been explored very little. A virtual navigation task allows participants to encode the spatial layout of the virtual environment and activate areas involved in memory processing. We describe the rehabilitation of a 24-year-old man with traumatic brain injury presenting memory deficits, and evaluate the efficacy of a navigational training program measuring neuropsychological changes and fMRI modification cerebral activations. Memory improvement appears to be present both after navigational training and in follow-up testing. Furthermore, fMRI data suggest that this training may increase activation of the hippocampal and parahippocampal brain regions. The results suggest that intensive training in virtual navigational tasks may result in an enhancement of memory function in brain-damaged adults.

Endometrial seedlings. A survival instinct? Immunomodulation and its role in the pathophysiology of endometriosis.

Endometriosis occurs when ectopic cells from the endometrium implant within the peritoneum. It is considered as a disease of multifactorial aetiology and affects 7-10% of women of reproductive age worldwide. In endometriosis, the immune system is thought to be dysfunctional and various studies have shown cytokine imbalance. Commonly upregulated cytokines include Tumour necrosis factor-alpha, interferon gamma and interleukin-10. Through analysis of the molecular makeup of the peritoneal fluid, a change is shown to occur, conferring resistance from macrophages and lymphocytes to endometrial cells. This is possibly due to a reduced Inter-cellular adhesion molecule-1 synthesis. Survival of ectopic endometrial cells also arises through the expression of human leukocyte antigens. Apart from the survival of ectopic/eutopic cells in endometriosis, there is marked cellular proliferation, which has also been attributed to a change in the expression of proteins such as Bcl-2-Associated X protein, B-cell lymphoma-2 protein, transforming growth factor-beta and the enzyme aromatase. Danazol and aromatase inhibitors modulate the immune system, thus allowing partial restoration of cytokine levels. Pharmacogenomics may be the way forward in developing novel treatment modalities for endometriosis.

Altered resting state attentional networks in diabetic neuropathic pain.

BACKGROUND: Chronic pain can be considered as a highly salient stimulus that continuously taxes the attentional and salience processing networks, thus interfering with cognitive abilities and, more specifically, consuming attentional resources. The aim of the paper was to explore whether and how diabetic neuropathic pain (NP) affects attentional networks. METHODS: The authors sought to achieve this by investigating resting state functional connectivity (rsFC) in diabetic NP patients and comparing it with that of matched healthy controls. RESULTS: NP patients showed a widespread reduction in connectivity in both the dorsal and ventral attentional networks, as well as in the dorsal anterior cingulated cortex (ACC), typically implicated in salience processing. The authors also found a generalised reduction in the length of functional connections in the NP group: in all the examined networks, the Euclidean distance between connected voxels was significantly shorter in patients than in controls. CONCLUSION: In diabetic NP, a parieto-fronto-cingulate network controlling attention to external stimuli is impaired. In line with previous studies, chronic pain can disrupt the synchrony of a common pool of brain areas, involved in self-monitoring, pain processing and salience detection.

Disrupted intrinsic functional connectivity in the vegetative state.

It is debatable as to whether the spontaneous blood-oxygen-level dependent fluctuations that are observed in the resting brain in turn reflect consciously directed mental activity or, alternatively, constitute an intrinsic property of functional brain organisation persisting in the absence of consciousness. This report shows for the first time, in three patients, that the persistent vegetative state (PVS) is marked by a dysfunctional default mode network, with decreased connectivity in several brain regions, including the dorsolateral prefrontal cortex and anterior cingulated cortex, especially in the right hemisphere. This finding supports the view that the resting state is involved in self-consciousness, and that the right-hemisphere default state may play a major role in conscious processes. It is speculated that the default state may act as a surrogate marker of PVS with awareness contents and, therefore, could replace a more complex activation paradigm.

Communicative impairment in traumatic brain injury: a complete pragmatic assessment.

The aim of the present study was to examine the communicative abilities of traumatic brain injury patients (TBI). We wish to provide a complete assessment of their communicative ability/disability using a new experimental protocol, the Assessment Battery of Communication, (ABaCo) comprising five scales--linguistic, extralinguistic, paralinguistic, context and conversational--which investigate all the main pragmatic elements involved in a communicative exchange. The ABaCo was administered to 21 TBI subjects and to a control group. The results showed that performance by TBI patients was worse than that of controls on all scales; moreover they showed a trend of increasing difficulty in understanding and producing different pragmatic phenomena, i.e., standard communication acts, deceits and ironies, whether such phenomena are expressed through the linguistic or extralinguistic modality.

Motor imagery of walking following training in locomotor attention. The effect of "the tango lesson".

The hypothesis of this study is that focusing attention on walking motor schemes could modify sensorimotor activation of the brain. Indeed, gait is a learned automated process, mostly regulated by subcortical and spinal structures. We examined the functional changes in the activity of the cerebral areas involved in locomotor imagery tasks, before and after one week of training consisting of physical and mental practice. The aim of the training was to focus the subject's conscious attention on the movements involved in walking. In our training, subjects were asked to perform basic tango steps, which require specific ways of walking; each tango lesson ended with motor imagery training of the performed steps. The results show that training determines an expansion of active bilateral motor areas during locomotor imagery. This finding, together with a reduction of visuospatial activation in the posterior right brain, suggests a decreased role of visual imagery processes in the post-training period in favor of motor-kinesthetic ones.

Online measures of basic language skills in children with early focal brain lesions.

Twenty children with early focal lesions were compared with 150 age-matched control subjects on 11 online measures of the basic skills underlying language processing, a digit span task, and 6 standardized measures. Although most of the children with brain injury scored within the normal range on the majority of the tasks, they also had a disproportionately high number of outlier scores on the reaction time tests. This evidence for a moderate impairment of the basic skills underlying language processing contrasts with other evidence suggesting that these children acquire normal control of the functional use of language. Furthermore, these children scored within the normal range on a measure of general cognitive ability, suggesting that there is no particular sparing of linguistic functions at the expense of general cognitive functions. Using the MPD procedure (Valdés-Pérez & Pericliev, 1997), we found that the controls and the five clinical groups could be best distinguished with two measures of online processing (word repetition and visual number naming) and one standardized test subcomponent (the CELF Oral Directions subtest). The 12 children with left hemisphere lesions scored significantly lower than the 8 other children on the CELF-RS measure. Within the group of children with cerebral infarct, the nature of the processing disability could be linked fairly well to site of lesion. Otherwise, there was little relation between site or size of lesion and the pattern of deficit. These results support a model in which damage to the complex functional circuits subserving language leads to only minor deficits in process efficiency, because of the plasticity of developmental processes.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.

Affective disorders in hospitalized children and adolescents with mental retardation: a retrospective study.

We contrasted a sample of children and adolescents with affective disorders and mental retardation with a comparison group on behavioral symptoms, associated diagnoses, and psychopharmacologic treatment. Fifty consecutive patients with both impaired intellectual functioning and at least one affective disorder admitted to a psychiatric inpatient unit for children and adolescents with developmental disabilities and psychiatric disorders were matched to a group of 50 inpatients without depression. Behavioral symptoms such as suicidal ideation or gestures, crying, irritability, sleep problems, agitation, mood lability, and social withdrawal/isolation occurred significantly more often in the affective group than in the comparison group. Aggression, however, was the most frequent behavior concern for both groups, whereas disruption/destruction was identified significantly more often in the comparison group. Regarding Axis I diagnoses, the comparison group was more often identified with externalizing disorders (ADHD, ODD), though there was a high rate of comorbidity in the affective disorder group. The behavioral symptoms used to diagnosis normally developing children and adolescents appear to be applied in making affective disorders diagnoses in this sample of children and adolescents with mental retardation.

Psychiatric and behavioral disorders in hospitalized preschoolers with developmental disabilities.

Describes the types of psychiatric and behavioral disturbance present in 169 preschoolers with developmental disabilities admitted to a specialized psychiatric inpatient unit. Differences in the proportion of some diagnoses and behavior problems across cognitive functioning level and across age were found. Seventy-two percent of the sample had one or more medical diagnosis. Similarities and differences with earlier reports in the literature are discussed.

Efficacy of methylphenidate and behavioral intervention on classroom behavior in children with ADHD and mental retardation.

Using a combination of an alternating treatment and double-blind placebo-controlled drug design, the independent and combined effects of two behavioral interventions and two doses of methylphenidate (MPH) in 3 children with Attention Deficit Hyperactivity Disorder (ADHD) and mental retardation (MR) were assessed. In this single subject design, 2 of the 3 subjects responded positively to medication as measured by increased on-task behavior. The first behavioral intervention, a token economy for on-task behavior, was ineffective for increasing either on-task behavior or work accuracy when combined with placebo. However, improvement in work accuracy was realized with implementation of a second behavioral intervention that specifically targeted accuracy independent of drug conditions. The current findings highlight both the positive effects and limitations of the two commonly used treatment modalities for ADHD. Future studies should continue to extend this area of investigative efforts to produce more data-based knowledge as to the appropriate doses of treatment, both pharmacological and behavioral, with children with both ADHD and mental retardation.