Disconnections in personal neglect.

Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory).

Relationship between cardiac cycle and the timing of actions during action execution and observation.

Previous research suggests that there may be a relationship between the timing of motor events and phases of the cardiac cycle. This relationship has thus far only been researched using simple isolated movements such as key-presses in reaction-time tasks and only in a single subject acting alone. Other research has shown both movement and cardiac coordination among interacting individuals. Here, we investigated how the cardiac cycle relates to ongoing self-paced movements in both action execution and observation using a novel dyadic paradigm. We recorded electrocardiography (ECG) in 26 subjects who formed 19 dyads containing an action executioner and observer as they performed a self-paced sequence of movements. We demonstrated that heartbeats are timed to movements during both action execution and observation. Specifically, movements were less likely to culminate synchronously with the heartbeat around the time of the R-peak of the ECG. The same pattern was observed for action observation, with the observer's heartbeats occurring off-phase with movement culmination. These findings demonstrate that there is coordination between an action executioner's cardiac cycle and the timing of their movements, and that the same relationship is mirrored in an observer. This suggests that previous findings of interpersonal coordination may be caused by the mirroring of a phasic relationship between movement and the heart.

Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans.

Could nose-to-brain pathways mediate the effects of peptides such as oxytocin (OT) on brain physiology when delivered intranasally? We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing. We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration. Yet we also provide robust evidence confirming the validity of the intranasal route to target specific brain regions. Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

Dissociation in How Core Autism Features Relate to Interoceptive Dimensions: Evidence from Cardiac Awareness in Children.

Interoception in autism is receiving increasing research attention. Previously, differences were identified in autism on both objective and subjective measures of interoception, and an association with anxiety. Yet, it is currently unknown how interoception relates to core autism features. Here, in 49 autistic children, we consider how interoceptive accuracy (measured with heartbeat detection tasks) and sensibility (subjective judgements of awareness) relate to overall severity on the Autism Diagnostic Observation Schedule, and symptom domains of social-affective and repetitive, restricted behaviors. Socio-affective features were related to interoceptive sensibility, while repetitive restricted behaviors were related to interoceptive accuracy. This dissociation suggests disparate interoceptive mechanisms for the formation and/or maintenance of autistic features.

The link between interoceptive processing and anxiety in children diagnosed with autism spectrum disorder: Extending adult findings into a developmental sample.

Anxiety is a major associated feature of autism spectrum disorders. The incidence of anxiety symptoms in this population has been associated with altered interoceptive processing. Here, we investigated whether recent findings of impaired interoceptive accuracy (quantified using heartbeat detection tasks) and exaggerated interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires) in autistic adults, can be extended into a school-age sample of children and adolescents (n = 75). Half the sample had a verified diagnosis of an Autism Spectrum Disorder (ASD) and half were IQ- and age-matched children and adolescents without ASD. The discrepancy between an individual's score on these two facets of interoception (interoceptive accuracy and interoceptive sensibility), conceptualized as an interoceptive trait prediction error, was previously found to predict anxiety symptoms in autistic adults. We replicated the finding of reduced interoceptive accuracy in autistic participants, but did not find exaggerated interoceptive sensibility relative to non-autistic participants. Nonetheless, the positive association between anxiety and interoceptive trait prediction error was replicated. However, in this sample, the best predictor of anxiety symptoms was interoceptive sensibility. Finally, we observed lower metacognitive accuracy for interoception in autistic children and adolescents, relative to their non-autistic counterparts. Despite their reduced interoceptive accuracy on the heartbeat tracking task and comparable accuracy on the heartbeat discrimination task, the autistic group reported higher confidence than the typical group in the discrimination task. Findings are consistent with theories of ASD as a disorder of interoceptive processing, but highlight the importance of validating cognitive models of developmental conditions within developmental populations.

Altering movement parameters disrupts metacognitive accuracy.

Correctly estimating the confidence we should have in our decisions has traditionally been viewed as a perceptual judgement based solely on the strength or quality of sensory information. However, accumulating evidence has demonstrated that the motor system contributes to judgements of perceptual confidence. Here, we manipulated the speed at which participants' moved using a behavioural priming task and showed that increasing movement speed above participants' baseline measures disrupts their ability to form accurate confidence judgements about their performance. Specifically, after being primed to move faster than they would naturally, participants reported higher confidence in their incorrect decisions than when they moved at their natural pace. We refer to this finding as the adamantly wrong effect. The results are consistent with the hypothesis that veridical feedback from the effector used to indicate a decision is employed to form accurate metacognitive judgements of performance.

The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials.

Oxytocin is a neuropeptide regulating social-affiliative and reproductive behaviour in mammals. Despite robust preclinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin, human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception. In the present study, we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double-blind, placebo-controlled, cross-over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ- and C-fibre nerve endings in the epidermis, at the same time as recording the ensuing laser-evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, the present study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin-induced modulation of cortical activity after noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C-fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing.

Error-based training and emergent awareness in anosognosia for hemiplegia.

Residual forms of awareness have recently been demonstrated in subjects affected by anosognosia for hemiplegia, but their potential effects in recovery of awareness remain to date unexplored. Emergent awareness refers to a specific facet of motor unawareness in which anosognosic subjects recognise their motor deficits only when they have been requested to perform an action and they realise their errors. Four participants in the chronic phase after a stroke with anosognosia for hemiplegia were recruited. They took part in an "error-full" or "analysis of error-based" rehabilitative training programme. They were asked to attempt to execute specific actions, analyse their own strategies and errors and discuss the reasons for their failures. Pre- and post-training and follow-up assessments showed that motor unawareness improved in all four patients. These results indicate that unsuccessful action attempts with concomitant error analysis may facilitate the recovery of emergent awareness and, sometimes, of more general aspects of awareness.

Gemcitabine as palliative treatment in patients with unresectable pancreatic cancer previously treated with placement of a covered metal stent. A randomized controlled trial.

PURPOSE: To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL). PATIENTS AND METHODS: Forty-nine patients with unresectable PC and obstructive jaundice, previously treated with the placement of a covered metal biliary endoprosthesis, were randomized to receive gemcitabine (group A: 9 males, 7 females) or to be followed without any anticancer intervention (group B: 18 males, 15 females). Gemcitabine was administered weekly as intravenous (i.v.) 30 min infusion of 1000 mg/m2 for 3 consecutive weeks followed by 1-week rest (28-day cycle). QoL was evaluated with the QLQ-C30 questionnaire. RESULTS: 229 gemcitabine doses were administered (median doses per patient 14.3, range 7-22). No statistically significant differences were observed regarding survival (group A: median 21 weeks, range 13-33; group B: median 22 weeks, range 13-29; p=0.809). According to the average QLQ-C30 score, group B patients showed statistically significant higher values (p=0.0001). Leukopenia, neutropenia, thrombocytopenia and anemia were the most common side effects in group A (81.25, 68.75, 62.50 and 31.25%, respectively). CONCLUSION: Gemcitabine didn't show to improve survival and QoL in patients with advanced PC previously treated with a covered metallic biliary endoprosthesis due to obstructive jaundice.

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial.

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5 mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30 mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49+/-6 wk) as compared to the control group (28+/-1 wk) and to the SSTR negative group (28+/-2 wk), LR=20.39, df=2, P<0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group, respectively. CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

Palliative treatment of advanced esophageal cancer with metal-covered expandable stents. A cost-effectiveness and quality of life study.

PURPOSE: The aim of this retrospective study was to evaluate the efficacy and safety of endoscopic therapy with self-expanding metallic endoprostheses in the management of inoperable primary malignant esophageal obstruction or stenosis and the cost-effectiveness of the method. PATIENTS AND METHODS: Between 5/1997-12/2002, obstruction of the esophagus was diagnosed in 78 patients (52 males, 26 females, age range 53-102, mean 72.3 years). The etiology was squamous cell carcinoma (n=42) and adenocarcinoma of the oesophagus (n=36). In total, 89 ultraflex metal stents were introduced endoscopically. In 46 patients dilation with Savary dilators prior to stent placement was required. A cost-effective analysis was performed, comparing oesophageal stenting with laser therapy. RESULTS: Stents were placed successfully in all patients. After 48 h, all patients were able to tolerate solid or semi-solid food. During the follow-up period 8 patients developed dysphagia due to food impaction (treated successfully endoscopically). Eleven patients developed recurrent dysphagia 4-16 weeks after stenting due to tumor overgrowth and were treated with placement of a second stent. The median survival time was 18 weeks. There was no survival difference between squamous cell and adenocarcinoma of the esophagus. A similar cost was calculated for both procedures. A significant improvement in quality of life was noted in patients undergoing stenting (96% and 75% vs. 71% and 57% for the first two months). CONCLUSION: Placement of self-expanding metal stents is a safe and cost-effective treatment modality that improves the quality of life, compared with laser therapy, for patients with inoperable malignant esophageal obstruction.