Neurosciences

Multiple acyl-CoA dehydrogenase deficiency CoQ 10 deficiency Riboflavin Electron transfer flavoprotein ubiquinone oxidoreductase a b s t r a c t Multiple acyl-CoA dehydrogenase deficiency (MADD) is a metabolic disorder due to dysfunction of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO). Mutations in ETFDH, encoding ETF-QO have been associated with both riboflavin-responsive and non-responsive MADD as well as a myopathic form of CoQ 10 deficiency, although pathomechanisms responsible for these different phenotypes are not well-defined. We performed mutation analysis in four Taiwanese MADD patients. Three novel ETFDH mutations were identified in four patients and all harbored the p.A84T mutation. Muscle CoQ 10 levels and respiratory chain activities measured in two patients were normal. Three patients improved on riboflavin together with carnitine. Our results show that not all MADD patients have CoQ 10 deficiency. Based upon our data, riboflavin and carnitine may be the first-line treatment for MADD.

Autosomal-dominant Alzheimer disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studies from families with ADAD have been critical to support the amyloid cascade hypothesis of Alzheimer disease (AD), the basis for the current development of amyloid-based disease-modifying therapies in sporadic AD (SAD). However, whether the pathological changes in APP processing in the CNS in ADAD are similar to those observed in SAD remains unclear. In this study, we measured b-site APP-cleaving enzyme (BACE) protein levels and activity, APP and APP C-terminal fragments in brain samples from subjects with ADAD carrying APP or PSEN1 mutations (n = 18), patients with SAD (n = 27) and agematched controls (n = 22). We also measured sAPPb and BACE protein levels, as well as BACE activity, in CSF from individuals carrying PSEN1 mutations (10 mutation carriers and 7 non-carrier controls), patients with SAD (n = 32) and age-matched controls (n = 11). We found that in the brain, the pattern in ADAD was characterized by an increase in APP b-C-terminal fragment (b-CTF) levels despite no changes in BACE protein levels or activity. In contrast, the pattern in SAD in the brain was mainly characterized by an increase in BACE levels and activity, with less APP b-CTF accumulation than ADAD. In the CSF, no differences were found between groups in BACE activity or expression or sAPPb levels. Taken together, these data suggest that the physiopathological events underlying the chronic Ab production/clearance imbalance in SAD and ADAD are different. These differences should be considered in the design of intervention trials in AD.

We attempt to identify gene by childhood abuse interactions which predispose to the development of schizotypal traits in a familial bipolar disorder (BD) sample. Self-report measures of schizotypal personality traits (Schizotypal Personality Scale) and childhood maltreatment (Childhood Trauma Questionnaire) were administered to 222 participants from 44 families with BD. Variants of catechol-o-methyltransferase (COMT) and four other dopamine pathway-related genes: DRD4, DRD2,MAOA, and SLC6A3, were typed. BD type I (BD I) subjects scored significantly higher than their unaffected relatives on the Schizotypal Personality Scale. The val allele of the Val158 Met polymorphism of the COMT gene was associated with increased schizotypal personality trait scores in individuals exposed to higher levels of self-reported childhood trauma (p \ 0.05). There was no direct effect of the val158met polymorphism on schizotypal personality traits. Further, no passive correlation between COMT genotype and childhood trauma was found. We raise the possibility that genetically-driven variation in COMT may interact with childhood trauma to contribute to the risk of developing schizotypal personality traits.

Gender differences have been shown across many domains, and motor skills are no exception. One of the most robust findings is a significant sex difference in throwing accuracy, which reflects the advantage of men in targeting abilities. However, little is known about the basis of this difference. To try to dissect possible mechanisms involved in this difference, here we tested for gender variations in a prism adaptation throwing task. We tested 154 subjects in a visuomotor prism adaptation task that discriminates between motor performance, visuomotor adaptation and negative aftereffects. Our results corroborate men's significant better throwing accuracy, although there were no adaptation differences between genders. In contrast, women showed significant larger negative aftereffects, which could be explained by a larger contribution of spatial alignment. These results suggest that different learning mechanisms, like strategic calibration and spatial alignment, may have different contributions in men and women.

BACKGROUND CONTEXT: Low back pain (LBP) is associated with high health-care utilization and lost productivity. Numerous interventions are routinely used, although few are supported by strong evidence. Cost utility analyses (CUAs) may be helpful to inform decision makers. PURPOSE: To conduct a systematic review of CUAs of interventions for LBP. STUDY DESIGN: Systematic review. METHODS: A search strategy combining medical subject headings and free text related to LBP and health economic evaluations was executed in MEDLINE. Cost utility analyses combined with randomized controlled trials for LBP were included. Studies that were published before 1998, non-English, decision analyses, and duplicate reports were excluded. Search results were evaluated by two reviewers, who extracted data independently related to clinical study design, economic study design, direct cost components, utility results, cost results, and CUA results. RESULTS: The search produced 319 citations, and of these 15 met eligibility criteria. Most were from the United Kingdom (n58), published in the past 3 years (n512), studied chronic LBP or radiculopathy (n513), and had a follow-up O12 months (n513). Combined, there were 33 study groups who received a mean 2.1 interventions, most commonly education (n517), exercise therapy (n513), spinal manipulation therapy (n57), surgery (n57), and usual care from a general practitioner (n57). Mean baseline utility was 0.57, improving to 0.67 at follow-up; the mean difference in utility improvement between study groups was 0.04.

Background-From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. We sought to determine the specificity of previously demonstrated reversal learning impairments in youths with bipolar disorder (BD) by now comparing BD youths to those with severe mood dysregulation (SMD), major depressive disorder (MDD), anxiety (ANX), and healthy controls.

Two groups of 170 left and 173 right brain-damaged patients were given the Raven's Coloured Matrices, in order to study the influence of the hemispheric side of the lesion on this test of visual-spatial intelligence. A significant difference was found between the two hemispheric groups, the right brain-damaged patients scoring worse than the left hemisphere-damaged subjects. Furthermore, patients with right hemispheric lesions showed a striking tendency to neglect the responses lying on the left side of the page, whereas subjects with left hemispheric damage showed only a mild tendency to neglect the alternatives lying on the right half of the sheet. The worse performances obtained on the Coloured Matrices by right brain-damaged patients seemed due for the most part to unilateral spatial neglect. These findings suggest that the bad performances of patients affected by retro-rolandic right hemispheric lesions are not due to a general intellectual impairment, but rather to the detrimental effect of unilateral spatial neglect and of a general disorder in visual-spatial analysis.

The minimum frustration principle is a computational approach which states that, in the long timescales of evolution, proteins’ freeenergy decreases more than expected by thermodynamical contraints as their aminoacids assume conformations progressively closer to the lowest energetic state. Here we show that this general principle, borrowed from protein folding dynamics, can be fruitfully applied to nervous function too. Highligting the foremost role of energetic requirements, macromolecular dynamics, and, above all, intertwined timescales in brain activity, the minimum frustration principle elucidates a wide range of mental processes, from sensations to memory retrieval. Brain functions are compared to trajectories which, in long nervous timescales, are attracted towards the lowenergy bottom of funnel-like structures characterized both by robustness and plasticity. We discuss how the principle, as derived explicitly from evolution and selection of a funneling structure from microdyn...

Top-down controlled selective or divided attention to sounds and visual objects, as well as bottom-up triggered attention to auditory and visual distractors, has been widely investigated. However, no study has systematically compared brain activations related to all these types of attention. To this end, we used functional magnetic resonance imaging (fMRI) to measure brain activity in participants performing a tone pitch or a foveal grating orientation discrimination task, or both, distracted by novel sounds not sharing frequencies with the tones or by extrafoveal visual textures. To force focusing of attention to tones or gratings, or both, task difficulty was kept constantly high with an adaptive staircase method. A whole brain analysis of variance (ANOVA) revealed fronto-parietal attention networks for both selective auditory and visual attention. A subsequent conjunction analysis indicated partial overlaps of these networks. However, like some previous studies, the present results also suggest segregation of prefrontal areas involved in the control of auditory and visual attention. The ANOVA also suggested, and another conjunction analysis confirmed, an additional activity enhancement in the left middle frontal gyrus related to divided attention supporting the role of this area in top-down integration of dual task performance. Distractors expectedly disrupted task performance. However, contrary to our expectations, activations specifically related to the distractors were found only in the auditory and visual cortices. This suggests gating of the distractors from further processing perhaps due to strictly focused attention in the current demanding discrimination tasks.

An observational study of variations in the appearance of the alar ligament on magnetic resonance imaging (MRI) and the normal range of lateral flexion and rotation of the atlas was performed to validate some of the premises underlying the use of MRI for the detection of injuries to the alar ligament. Fifteen healthy volunteers were included. Three sets of coronal proton-density images, and axial T2-weighted images of the craniovertebral junction, were obtained at 0.5 T with the neck in neutral position and laterally flexed (coronal proton density) or rotated (axial T2). Five of the subjects also underwent imaging at 1.5 T. The scans were independently examined twice by two radiologists. The presence of alar ligaments was recorded and a three-point scale used to grade the extent of hyperintensity exhibited by the structures: the ligament were graded as 2 and 3 if, respectively, less or more of its cross-section was hyperintense, whereas grade 1 represented a hypointense ligament. The effect of lateral flexion on image quality was assessed. Concordance analysis of the data were performed before and after dichotomising the data on grading. The atlanto-axial angle and rotation of the atlas were measured. The magnitude of movement to right was normalised to that to the left to give, respectively, the flexion index and the rotation index. The alar ligaments were most reliably seen on coronal proton-density scans, with a Maxwell's RE of 0.96 as compared with 0.46 for sagittal images. Flexion of the neck improved definition of the ligaments in only rare instances. Inter-observer disagreement was marked with respect to grading of the ligament on both coronal [composite proportion of agreement (p 0 )=0.44; 95% confidence intervals: 0.26, 0.64)] and sagittal scans [p 0 =0.40 (0.19, 0.63)]. Dichotomising the data did not appreciably improve reliability [Maxwell's RE: )0.11 (coronal scans), )0.20 (sagittal scans)]: for ligaments which demonstrated hypertensive areas (grades 2 and 3) there was complete lack of agreement for both coronal [p 2 =0 (0, 0.25)] and sagittal scans [p2=0 (0-0.30)]. A large response bias was found in the reports of both readers albeit in opposite directions. There was poor concordance between scans obtained at different field strengths [RE (coronal images)=0.25; RE (sagittal images)=0.14). Mean flexion index and mean rotation index were 1.00 (SD 0.03) and 1.01 (SD 0.06), respectively. The MR imaging may not be the investigation of choice for the investigation of subtle injuries to the alar ligament. Whether it can be substituted by kinematic assessment of the occipito-atlanto-axial complex with MRI warrants investigation.

Matrix coils are based on Gugliemi detachable coils (GDC) but are covered with polyglycolic/polylactic acid. We present our experience regarding the immediate posttreatment results of aneurysm embolization using the 2 coil systems. We embolized 219 aneurysms in 187 patients with the use of GDCs and 145 aneurysms in 120 patients with the use of Matrix coils. Age, sex distribution, unruptured aneurysm cases, and multiple aneurysm cases were similar in the 2 groups. The percentage of patients in severe clinical condition was significantly higher in the Matrix group. The mean aneurysm size was slightly larger in the GDC group but the mean neck size was larger in the Matrix group. Satisfactory occlusion (at least 90%) was achieved in 95.9% of GDC-treated aneurysms and in 98.6% of Matrix-treated aneurysms. Procedure-related complications occurred in 19.6% of GDC procedures and in 15.6% of the Matrix ones resulting in procedure-related mortality and morbidity of 3.7% and 2.7% for the GDC g...

In this fMRI study we investigated functional connectivity between components of the mentalising system during a social emotion task, using psychophysiological interaction (PPI) analysis. Ten adults (22–32 years) and 18 adolescents (11–18 years) were scanned while thinking about scenarios in which a social or a basic emotion would be experienced. Unlike basic emotions (such as disgust and fear), social emotions (such as embarrassment and guilt) require the representation of another’s mental states. In both adults and adolescents, an anterior rostral region of medial prefrontal cortex (arMPFC) involved in mentalising showed greater connectivity with the posterior superior temporal sulcus (pSTS) bordering on the temporo-parietal junction (TPJ) and with anterior temporal cortex (ATC) during social than during basic emotion. This result provides novel evidence that components of the mentalising system interact functionally during a social emotion task. Furthermore, functional connectivity differed between adolescence and adulthood. The adolescent group showed stronger connectivity between arMPFC and pSTS/TPJ during social relative to basic emotion than did the adult group, suggestive of developmental changes in functional integration within the mentalising system.

Intracellular recordings were obtained from pyramidal neurons in layer 5 of rat somatosensory and visual cortical slices maintained in vitro. When directly depolarized, one subclass of pyramidal neurons had the capacity to generate intrinsic burst discharges and another generated regular trains of single spikes. Burst responses were triggered in an all-or-none manner from depolarizing afterpotentials in most bursting neurons. Regular spiking cells responded to electrical stimulation of ascending afferents with a typical EPSP-IPSP sequence, whereas IPSPs were hard to detect in bursting cells. Orthodromic activation of the latter evoked a prominent voltage-dependent depolarization that could trigger a burst response. Intracellularly labelled bursting and regular spiking cells were located in layer 5b, but had distinctly different morphologies. Bursting neurons had a large pyramidal soma, a gradually emerging apical dendrite, and an extensive apical and basal dendritic tree. Their axonal collateral arborization was predominantly limited to layers 5/6. In contrast, regular spiking cells had a more rounded soma with abruptly emerging apical dendrite, a smaller dendritic arborization, and 2 to 8 ascending axonal collaterals that arborized widely in the supragranular layers. Both bursting and regular spiking cells had main axons that entered the subcortical white matter.

The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.

Progressive tumor growth depends on angiogenesis to sustain metabolic needs of tumor cells, thus providing a potential target for cancer therapy. Malignant gliomas have retained their dismal prognosis despite aggressive multimodal conventional therapeutic approaches, illustrating the need for novel therapeutic strategies. Gliomas are a suitable tumor type for probing angiogenesis inhibition as their proliferation is characterized by a prominent proliferative vascular component. In the present review, we discuss the current status and future directions of angiogenesis inhibition in gliomas. We focus on recently developed approaches inducing an antiangiogenic response such as targeted gene delivery, protein tyrosine kinase inhibitors and encapsulated producer cells. Although several of these modalities have shown promising results on their own, the true potential of these novel approaches lies in their combined use with radiotherapy or 'metronomically scheduled' chemotherapy. A combined approach potentially counteracts the selective pressure on hypoxia-resistant malignant tumor cells, circumvents endothelial resistance induced by local cytoprotective responses and enhances the delivery of cytotoxic agents by normalizing vascular physiology. Surrogate markers of angiogenesis currently under study may provide accurate assessment of response in individual patients. Future research on endothelial markers expressed on tumor-associated vasculature as well as endothelial responses to cytotoxic treatment will provide new avenues for molecularly targeted therapy in malignant gliomas. D

Degenerative scoliosis is a prevalent issue among the aging population. Controversy remains over the role of surgical intervention in patients with this disease. The authors discuss a suitable approach to help guide surgical treatment, including decompression, instrumented posterior spinal fusion, anterior spinal fusion, and osteotomy. These treatment options are based on clinical analysis, radiographic analysis of the mechanical stability of the deformity, given pain generators, and necessary sagittal balance. The high potential complication rates appear to be outweighed by the eventual successful clinical outcomes in patients suitable for operative intervention. This approach has had favorable outcomes and could help resolve the controversy.

Postprostatectomy incontinence remains a disabling condition. Sphincter injury, detrusor instability, and decreased bladder compliance have been previously reported as major factors. The aim of this study was to evaluate the urethral sphincter intrinsic component, which may provide passive continence. A urodynamic evaluation was performed in 20 patients undergoing a radical retropubic prostatectomy in the preoperative period and 3 months after surgery. Patients with disabled urinary incontinence underwent a new urodynamic evaluation 6 months later. The urethral pressure pro¢le was measured just before, then 10, 20, and 30 minutes after the injection of 0.5 mg/kg moxisylyte chlorhydrate, an alpha adrenergic blocker. Three di¡erent pressure components were de¢ned in urethral sphincter capacity: baseline, adrenergic, and voluntary. A postoperative intrinsic urethral sphincter pressure component was found in 17 patients and its value was under 6 cm H 2 O in ¢ve cases of severe incontinence. No signi¢cant di¡erence was observed for these patients on urethral pro¢le components 6 months later. In contrast, in cases of signi¢cant intrinsic component value, no incontinence was observed in most patients. Passive continence after radical prostatectomy should be a matter of concern and may also explain paradoxical incontinence, despite high voluntary urethral pressure obtained after reeducation. A follow-up evaluation of the intrinsic sphincter component is suggested, by using an alpha receptor blockage test during urodynamic studies in the management of patients with postprostatectomy incontinence.

Micturition, or urination, occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. The neural circuitry that controls this process is complex and highly distributed: it involves pathways at many levels of the brain, the spinal cord and the peripheral nervous system and is mediated by multiple neurotransmitters. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary or reflex micturition, leading to urinary incontinence. This is a major health problem, especially in those with neurological impairment. Here we review the neural control of micturition and how disruption of this control leads to abnormal storage and release of urine.

Situations in which rewards are unexpectedly obtained or withheld represent opportunities for new learning. Often, this learning includes identifying cues that predict reward availability. Unexpected rewards strongly activate midbrain dopamine neurons. This phasic signal is proposed to support learning about antecedent cues by signaling discrepancies between actual and expected outcomes, termed a reward prediction error. However, it is unknown whether dopamine neuron prediction error signaling and cue-reward learning are causally linked. To test this hypothesis, we manipulated dopamine neuron activity in rats in two behavioral procedures, associative blocking and extinction, that illustrate the essential function of prediction errors in learning. We observed that optogenetic activation of dopamine neurons concurrent with reward delivery, mimicking a prediction error, was sufficient to cause long-lasting increases in cue-elicited reward-seeking behavior. Our findings establish a causal role for temporally precise dopamine neuron signaling in cue-reward learning, bridging a critical gap between experimental evidence and influential theoretical frameworks. npg

Background and purpose: Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis. Methods: A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20-year period. Patients' characteristics and outcomes were compared between two 10-year periods: (i) 1991-2001 and (ii) 2002-2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4-6 (severe disability or death) 90 days after admission. Results: A total of 279 patients were studied. Causes of encephalitis were infections (n = 149, 53%), immune-mediated causes (n = 41, 15%) and undetermined causes (n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immunemediated causes. At day 90, 208 (75%) patients had an mRS = 0-3 and 71 (25%) had an mRS = 4-6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06-17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47-11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53-0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17-2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01-1.07). Conclusions: Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.

With regard to THC (Δ 9 -tetrahydrocannabinol), the main psychoactive constituent identified in the plant Cannabis sativa L, several facts are indisputable. Cannabis remains the most commonly used drug in the UK among those who reported driving under the influence of illegal drugs in the previous 12 months. There is a significant dose-related decrement in driving performance following cannabis use; raised blood THC concentrations are significantly associated with increased traffic crash and death risk. When cannabis and alcohol are detected together, there is a greater risk to road safety than when either drug is used alone. Patterns of use are important when interpreting blood concentration data: Smoking infrequently a single cannabis cigarette leads to peak plasma THC concentrations (21-267 μg/L) causing acute intoxication. In habitual, daily users, plasma THC concentrations range from 1.0 to 11.0 μg/L and are maintained by sequestration of the drug from the tissues. These facts undoubtedly make setting thresholds for drug-driving legislation difficult but there is clearly a case for cannabis. Determining minimum blood THC concentrations at which a driver becomes sufficiently impaired to be unable to safely drive a vehicle is of particular concern given the increasing medicinal use of the drug. Internationally legislation for driving under the influence of drugs (DUID) is based on either a proof of impairment or a per se approach. For the latter this can be either zerotolerance or based on concentration limits such as those used for alcohol. The different approaches are considered against current scientific evidence.

results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is required for amnestic and/or nonamnestic domains.

This research aimed to develop a Fetal Alcohol Behavior Scale (FABS) that describes the behavioral essence of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), regardless of age, race, sex, and 10. Using a reference sample of 472 diagnosed patients with FAS or FAE, ages 2 to 51, five studies are described. The FABS demonstrates high item-to-scale reliability (Cronbach's (Y = 0.91) and good test-retest reliability (r = 0.69) over an average interval of 5 years. It identifies many of the subjects with known or presumed prenatal alcohol exposure in detection studies using both prison and general samples. FABS scores also predict dependent living among adult patients with FASIFAE. The FABS is uncorrelated with 10, sex, age, race, and diagnosis (FAS versus FAE). We outline areas of further work to define the specificity and utility of this FABS.

Much research in the last two decades has demonstrated that human responses deviate from the performance deemed normative according to various models of decision making and rational judgment (e.g., the basic axioms of utility theory). This gap between the normative and the descriptive can be interpreted as indicating systematic irrationalities in human cognition. However, four alternative interpretations preserve the assumption that human behavior and cognition is largely rational. These posit that the gap is due to (1) performance errors, (2) computational limitations, (3) the wrong norm being applied by the experimenter, and (4) a different construal of the task by the subject. In the debates about the viability of these alternative explanations, attention has been focused too narrowly on the modal response. In a series of experiments involving most of the classic tasks in the heuristics and biases literature, we have examined the implications of individual differences in performa...

What is an emotion?'' William James's seminal paper in Mind (1884) proposed the idea that physiological and behavioral responses precede subjective experience in emotions that are marked by ''distinct bodily expression.'' This notion has broadly inspired the investigation of emotion-specific autonomic nervous system activity, a research topic with great longevity. The trajectory of this literature is traced through its major theoretical challenges from the Cannon-Bard, activation, and Schachter-Singer theories, through its rich empirical history in the field of psychophysiology. Although these studies are marked by various findings, the overall trend of the research supports the notion of autonomic specificity for basic emotions. The construct of autonomic specificity continues to influence a number of core theoretical issues in affective science, such as the existence of basic or 'natural kinds' of emotion, the structure of affective space, the cognition-emotion relationship, and the function of emotion. Moreover, James's classic paper, which stimulated the emergence of psychology from philosophy and physiology in the latter nineteenth century, remains a dynamic force in contemporary emotion research.

A controversial entity, Eagle's syndrome, is reviewed. After an anatomical description of the maxillo-vertebro-pharyngeal region we summarize the causative, diagnostic and therapeutic aspects of the syndrome. Two different conditions are often reported as Eagle's syndrome: one characterized by dysphagia and unilateral pharyngeal pain radiating to the ear and worsened by swallowing; the other characterized by pain in the head and neck region due to compression of the neurovascular structure by an elongated styloid process. The latter also includes typical cranial neuralgias (such as glossopharyngeal neuralgia) and carotidynia. We believe that the term "Eagle's syndrome" is legitimate only in the first case and in those "atypical" painful head and neck conditions related to an elongated styloid process and relieved by styloidectomy. We believe Eagle's syndrome deserves consideration in the International Headache Classification. € Eagle's syndrome, elongated styloid process, stylalgia, stylohyoid syndrome L Montalbetti,

This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.

The two contrasting theoretical approaches to visual perception, the constructivist and the ecological, are briefly presented and illustrated through their analyses of space and size perception. Earlier calls for their reconciliation and unification are reviewed. Neurophysiological, neuropsychological, and psychophysical evidence for the existence of two quite distinct visual systems, the ventral and the dorsal, is presented. These two perceptual systems differ in their functions; the ventral system's central function is that of identification, while the dorsal system is mainly engaged in the visual control of motor behavior. The strong parallels between the ecological approach and the functioning of the dorsal system, and between the constructivist approach and the functioning of the ventral system are noted. It is also shown that the experimental paradigms used by the proponents of these two approaches match the functions of the respective visual systems. A dual-process approa...

This study was performed with the aim of determining the diagnostic profile of newborns with hypotonia and of analyzing the usefulness of different procedures in the diagnostic process. One hundred thirty-eight hypotonic newborns were identified through the search of hospital records in a 10-year period: 121 (88%) had central hypotonia and 13 (9%) had peripheral hypotonia, whereas 4 (3%) remained unclassified. Analysis of the contribution of clinical data and results of investigations led to the construction of an algorithm, by which all cases in the group were diagnosed. Step 1, which included clinical data and results of examinations, solved 50% of all diagnosed cases. Neuroimaging techniques made up step 2 and contributed to the diagnosis in 13%. Step 3 was accomplished by a search through Oxford Medical Databases, which yielded the final diagnosis in 9%, whereas karyotyping and fluorescent in situ hybridization for Prader-Willi syndrome comprised step 4 and contributed to the di...

To figure out whether the main empirical question "Is our brain hardwired to believe in and produce God, or is our brain hardwired to perceive and experience God?" is answered, this paper presents systematic critical review of the positions, arguments and controversies of each side of the neuroscientific-theological debate and puts forward an integral view where the human is seen as a psychosomatic entity consisting of the multiple levels and dimensions of human existence (physical, biological, psychological, and spiritual reality), allowing consciousness/mind/spirit and brain/body/matter to be seen as different sides of the same phenomenon, neither reducible to each other. The emergence of a form of causation distinctive from physics where mental/conscious agency (a) is neither identical with nor reducible to brain processes and (b) does exert "downward" causal influence on brain plasticity and the various levels of brain functioning is discussed. This manuscript also discusses the role of cognitive processes in religious experience and outlines what can neuroscience offer for study of religious experience and what is the significance of this study for neuroscience, clinicians, theology and philosophy. A methodological shift from "explanation" to "description" of religious experience is suggested. This paper contributes to the ongoing discussion between theologians, cognitive psychologists and neuroscientists.

Cerebellar afferent Raphe interpositus Biotinylated dextran amine Single axon reconstruction a b s t r a c t Integration of cortical Purkinje cell inputs and brain stem inputs is essential in generating cerebellar outputs to the cerebellar nuclei (CN). Currently, collaterals of climbing and mossy fiber axons, noradrenergic, serotoninergic and cholinergic axons, and collaterals of rubrospinal axons are known to innervate the CN from the brain stem. We investigated whether other afferents to the CN from the medulla exist in the rat. Retrograde labeling revealed the presence of neurons that project to the CN but not to the cerebellar cortex in the median reticular formation in the rostrodorsal medulla (tentatively named 'caudal raphe interpositus area', CRI). Anterograde tracer injection into the CRI labeled abundant axonal terminals in the CN, mainly in the ventral parvocellular part of the posterior interposed and lateral nucleus. Axonal reconstruction showed that a single CRI axon projected to the CN with 170-1086 varicosities, more broadly and densely than collaterals of a mossy or climbing fiber axon. CRI axons had no or a few collaterals that projected to the granular and Purkinje cell layers of the cerebellar cortex with some small terminals, indicating that these axons are different from mossy fiber axons. CRI axons also had http://dx.Abbreviations: 4V, forth ventricle; 5-HT, 5-hydroxytriptamine; V, trigeminal nucleus; VI, abducens nucleus; VII, facial nucleus; AIN, anterior interposed nucleus; BDA, biotinylated dextran amine; C, caudal; CN, cerebellar nuclei; CRI, caudal raphe interpositus area; D, dorsal; DAB, 3,3 0 -diaminobenzidine; DLH, dorsolateral hump of the anterior interposed nucleus; DLP, dorsolateral protuberance; DMC, dorsomedial crest of the anterior interposed nucleus; gVII, genu of the facial nerve; GL, granular layer; GRN, gigantocellular reticular nucleus; HRP, horseradish peroxidase; icp, inferior cerebellar peduncle; IO, inferior olive; IN, interposed nucleus; L, lateral; L.II-VI, lobules II-VI; LN, lateral nucleus; LN-parvo, ventral parvocellular subdivision of the lateral nucleus; Lt, left; LVN, lateral vestibular nucleus; M, medial; ML, molecular layer; MN, medial nucleus; MN-CM, caudomedial subdivision of the medial nucleus; MN-M, middle subdivision of the medial nucleus; mlf, medial longitudinal fasciculus; MVN, medial vestibular nucleus; nVII, tract of the facial nerve; NRTP, nucleus reticularis tegmenti pontis; PC, Purkinje cell; PCG, pontine central gray; PCL, Purkinje cell layer; PHA-L, Phaseolus vulgaris leucoagglutinin; PIN, posterior interposed nucleus; PIN-parvo, ventral parvocellular subdivision of the posterior interposed nucleus; PrH, prepositus hypoglossi (I. Sugihara).