Watching the fetal brain at ‘rest’

Functional magnetic resonance imaging (fMRI) has allowed insights into the spatiotemporal distribution of human brain networks. According to the neurophysiological property of the fetal brain to generate spontaneous activity, we aimed to determine the feasibility of investigating the maturation of intrinsic networks, beginning at gestational week 20 in healthy human fetuses by combining resting-state fMRI and an analytical approach, independent component analysis (ICA).In this study, functional images of 16 fetuses with morphologically normal brain development, from 20 to 36 gestational weeks of age, were acquired on a 1.5 T unit (Philips Medical Systems, Best, The Netherlands) using single-shot, gradient-recalled echo-planar imaging. After preprocessing (motion correction, brain extraction), images were analyzed using single-subject ICA.We visualized a bilateral occipital network and medial and lateral prefrontal activity pattern that involved the future Brodmann areas 9-11. Furthermore, there was one either predominantly right (3/7 cases) or left (4/7 cases) hemispheric lateralized network that involved the superior temporal cortical regions (Brodmann areas 22 and 39). Frequency oscillations were in the range of 0.01-0.06 Hz for all networks.This study shows that resting-state networks (RSNs) are shaped and are detectable in utero. Further investigations of resting-state measurements in the fetus may therefore allow developmental brain activity monitoring and may provide insights into early brain function.     

The ‘glibenclamide-shift’ of centrally-acting antinociceptive agents in mice

Morphine-induced antinociception is antagonized by the K⁺-channel blocker glibenclamide (glyburide; Glib), implicating ATP-sensitive (K_ATP) K⁺ channels in the analgesic effect of opioids. The present study examined the generality of this conclusion by measuring the effect of Glib on supraspinal (intracerebroventricular; i.c.v.) antinociception produced by representative μ-opioids and the non-opioids pilocarpine and twoα₂-adrenoceptor agonists (clonidine and tizanidine) using the mouse tail-flick test. Concurrent administration of Glib (40 μg, i.c.v.) produced a significant rightward shift of the dose-response curve of morphine, levorphanol, methadone, pilocarpine, clonidine and tizanidine; a modest, but not statistically significant, rightward shift of the dose-response curves of the μ-selective peptides DAMGO ([d-Ala²,N-Me-Phe⁴, Gly-ol⁵]-enkephalin) and PL017 ([N-Me-Phe³,d-Pro⁴]-morphiceptin); and no shift of the dose-response curves of alfentanil, carfentanil, fentanyl, sufentanil, or β-endorphin. Glib produced aleftward shift of the dose-response curve of etorphine. These data support the involvement of K_ATP-type K⁺ channels in mediation of supraspinal antinociception, differentiate Glib-sensitive and Glib-insensitive opioid agonists, and reveal fundamental differences among antinociceptive agents in the extent of demonstrable utilization of this transduction pathway.     

Investigating the ‘placebo personality’ outside the pain paradigm

Aim

To identify personality traits related to placebo responding outside the context of pain.

Methods

Sixty three healthy volunteers completed the study. Personality traits were measured online one week prior to a laboratory session in which two psychosocial stress tests were administered. Prior to the second test, the placebo group received an intranasal spray of ‘serotonin’ (placebo) with the suggestion that it would enhance recovery. Subjective stress, heart rate and heart rate variability were measured. Self reported and physiological responses to the placebo suggestion were assessed against personality variables.

Results

Placebo effects were demonstrated in both self reported and physiological stress metrics. Lower optimism and less empathic concern predicted greater perceived benefits from the placebo treatment; and lower drive, fun, and sensation seeking were related to a greater physiological response to the manipulation. Multivariate analyses revealed lower optimism and behavioural drive to be predictive of responding to the placebo manipulation.

Conclusion

Findings are in contrast with prior work in pain paradigms which found higher levels of the same traits to be related to greater placebo analgesic responses. A cluster of traits characterised by behavioural drive, extraversion, optimism and novelty or fun seeking appears to be germane to placebo responsiveness, but contextual stimuli may generate different patterns of responding. A new conceptualisation of placebo responsiveness may be useful. Rather than a ‘placebo personality’ it may be that responsiveness is better typified by a two faceted transactional model, in which different personality facets respond to different contextual contingencies.     

High incidence of ‘synaesthesia for pain’ in amputees

Synaesthesia for pain is a phenomenon where a person experiences pain when observing or imagining another in pain. Anecdotal reports of this type of experience have most commonly occurred in individuals who have lost a limb. Distinct from phantom pain, synaesthesia for pain is triggered specifically in response to pain in another. Here, we provide the first preliminary investigation into synaesthesia for pain in amputees to determine the incidence and characteristics of this intriguing phenomenon. Self-referring amputees (n = 74) answered questions on synaesthesia for pain within a broader survey of phantom pain. Of the participants, 16.2% reported that observing or imagining pain in another person triggers their phantom pain. Further understanding of synaesthesia for pain may provide a greater insight to abnormal empathic function in clinical populations as well as therapeutic intervention for at risk groups.     

Emergence and progression of ‘non-semantic’ deficits in semantic dementia

Although semantic dementia (SD) is defined as a selective disruption of conceptual knowledge, a number of group studies have now demonstrated that SD patients also show impaired performance on tasks not usually considered to have a high semantic load (e.g., reading words aloud and lexical or object decision). The aim of the current study was to document the relative deterioration, over time, of a number of semantic and so-called ‘non-semantic’ tasks in LF, a single case of SD for whom - by virtue of his work as a published cartoonist - we also have extensive data regarding his pre-morbid linguistic and drawing skills.In five testing rounds over a period of five years we administered semantic tests of object naming and object definition (on both of which LF was progressively impaired, as expected for a diagnosis of SD), plus verbal and non-verbal ‘non-semantic’ tasks of reading aloud, spelling, object and lexical decision, and delayed copy drawing.Initially, his only striking ‘non-semantic’ deficit was in the domain of spelling - a pronounced surface dysgraphia in an individual with demonstrably superior pre-morbid spelling skill. Over time, and in line with his declining semantic system, LF's performance gradually deteriorated on all of the ‘non-semantic’ tasks. The most vulnerable items on most tasks were those with low frequency and an atypical form.This report adds to the growing body of evidence that a number of cognitive processes not usually considered to be ‘semantic’ in their demands rely on the integrity of semantic knowledge for successful execution. Furthermore, it provides the first indication that these non-semantic deficits might emerge in an order predictable from the typicality structure of the relevant domain.     

Phenotype of spontaneous orofacial dyskinesia in neuregulin-1 ‘knockout’ mice

Studies in antipsychotic-naïve patients with schizophrenia indicate a baseline level of spontaneous involuntary movements, particularly orofacial dyskinesia. Neuregulin-1 is associated with risk for schizophrenia and its functional role can be studied in ‘knockout’ mice. We have shown previously that neuregulin-1 ‘knockouts’ evidence disruption in social behaviour. Neuregulin-1 ‘knockouts’ were assessed for four topographies of orofacial movement, both spontaneously and under challenge with the D₁-like dopamine receptor agonist SKF 83959. Neuregulin-1 ‘knockouts’ evidenced an increase in spontaneous incisor chattering, particularly among males. SKF 83959 induced incisor chattering, vertical jaw movements and tongue protrusions; the level of horizontal jaw movements was increased and that of tongue protrusions decreased in neuregulin-1 ‘knockouts’. These findings indicate that the schizophrenia risk gene neuregulin-1 is involved in the regulation of not only social behaviour but also orofacial dyskinesia. Orofacial dyskinesia in neuregulin-1 mutants may indicate some modest genetic relationship between risk for schizophrenia and vulnerability to spontaneous movement disorder.     

‘Normal’ semantic-phonemic fluency discrepancy in Alzheimer's disease? A meta-analytic study

In a meta-analysis of 135 studies involving 6000 patients with Alzheimer's disease (AD) and 6057 healthy controls, we examined the relative degree of semantic and phonemic fluency impairment in AD patients. The effect size for semantic fluency (d = 2.10: 95%CI 2.22-1.97) was significantly larger than for both phonemic fluency (d = 1.46: 95%CI 1.56-1.36) and picture naming (d = 1.54: 95%CI 1.66-1.40). In meta-regression analyses we found that studies with greater proportions of female patients and less severe dementia both led to better phonemic fluency; while perhaps surprisingly, increased patient education led to worse semantic fluency. Critically, in 50 studies measuring both semantic and phonemic fluency, the effect size for the semantic-phonemic discrepancy scores did not differ between AD patients and controls; and was unrelated to any of the moderator variables. The latter findings indicate that the semantic-phonemic fluency discrepancy measure often reported as an important distinguishing characteristic of AD patients may be an exaggerated normal tendency.     

Differential engagement of brain regions within a ‘core’ network during scene construction

Reliving past events and imagining potential future events engages a well-established “core” network of brain areas. How the brain constructs, or reconstructs, these experiences or scenes has been debated extensively in the literature, but remains poorly understood. Here we designed a novel task to investigate this (re)constructive process by directly exploring how naturalistic scenes are built up from their individual elements. We “slowed-down” the construction process through the use of auditorily presented phrases describing single scene elements in a serial manner. Participants were required to integrate these elements (ranging from three to six in number) together in their imagination to form a naturalistic scene. We identified three distinct sub-networks of brain areas, each with different fMRI BOLD response profiles, favouring specific points in the scene construction process. Areas including the hippocampus and retrosplenial cortex had a biphasic profile, activating when a single scene element was imagined and when 3 elements were combined together; regions including the intra-parietal sulcus and angular gyrus steadily increased activity from 1 to 3 elements; while activity in areas such as lateral prefrontal cortex was observed from the second element onwards. Activity in these sub-networks did not increase further when integrating more than three elements. Participants confirmed that three elements were sufficient to construct a coherent and vivid scene, and once this was achieved, the addition of further elements only involved maintenance or small changes to that established scene. This task offers a potentially useful tool for breaking down scene construction, a process that may be key to a range of cognitive functions such as episodic memory, future thinking and navigation.     

‘Listen to them’: Adolescents' views on helping young people who self-injure

Non-suicidal self-injury (NSSI) among adolescents is a significant problem, yet the majority do not seek professional help. Parents and teachers are arguably most in contact with young people, and are critical in identifying and referring adolescent self-injurers. This study explored what adolescents believe parents and teachers can do to help young people who self-injure. A school-based sample of 2637 students (aged 12–18 years) completed a self-report questionnaire. Adolescents believe having non-judgemental parents and teachers to talk to, improved parent–child relationships, referral to professionals, reduced school pressures, and student education, are pivotal to helping young self-injurers. However, many adolescents, particularly those exposed to NSSI, were unsure about whether parents and teachers could do anything to help. These finding have important implications for educational programs that prepare parents and teachers to address adolescent NSSI.