Assessment of a conceptually informed measure of emotion dysregulation: Evidence of construct validity vis a vis impulsivity and internalizing symptoms in adolescents with ADHD

ObjectivesDespite advances in understanding associations among attention‐deficit hyperactivity disorder (ADHD), emotion dysregulation (ED), and related outcomes, there is incongruity between ADHD‐relevant conceptualizations of ED and available measures of ED. To assess the psychometric properties of a parent‐report questionnaire of ED conceptualized as deficits in the ability to modulate the (a) speed/degree of emotion escalation; (b) expression intensity; and (c) speed/degree of de‐escalation.MethodsParticipants were 209 adolescents with ADHD (78% male; 13.5–17.8 years old [M = 15.2 SD = 0.91]). Questionnaire items were selected from parent‐report scales of ED and oppositional defiant disorder and subjected to exploratory factor analysis (EFA) and validity analyses.ResultsThe EFA revealed two factors, with speed/degree of escalation combined with intensity as factor one, and speed/degree of de‐escalation as factor two. Factor one scores were related to ADHD impulsivity symptoms but not to anxiety and depression symptoms and they remained predictors of impulsivity even in the presence of self‐report ED, evincing convergent, discriminant, and incremental validity. Factor two scores were related to anxiety and depression but not impulsivity, evincing convergent and discriminant validity.ConclusionThese results inform our understanding of ADHD‐relevant ED in adolescence and offer avenues for future research in measurement development, as well as for understanding ED and ADHD‐related impairment.     

Astrocytes enhance glioblastoma growth

Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies. Co-culture techniques were used to investigate the GBM growth enhancing potential of astrocytes. Cell sorting and RNA sequencing were used to generate a GBM-associated astrocyte signature and to investigate astrocyte-induced GBM genes. A NOD scid GBM mouse model was used for in vivo studies. A gene signature reflecting GBM-activated astrocytes was associated with poor prognosis in the TCGA GBM dataset. Two genes, periostin and serglycin, induced in GBM cells upon exposure to astrocytes were expressed at higher levels in cases with high “astrocyte signature score”. Astrocytes were shown to enhance glioblastoma cell growth in cell lines and in a patient-derived culture, in a manner dependent on cell–cell contact and involving increased cell proliferation. Furthermore, co-injection of astrocytes with glioblastoma cells reduced survival in an orthotopic GBM model in NOD scid mice. In conclusion, this study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies.     

Rapid recalibration of temporal order judgements: Response bias accounts for contradictory results

Recent history influences subsequent perception, decision‐making and motor behaviours. In this article, we address a discrepancy in the effects of recent sensory history on the perceived timing of auditory and visual stimuli. In the synchrony judgement (SJ) task, similar timing relationships in consecutive trials seem more synchronous (i.e. less like the repeated temporal order). This effect is known as rapid recalibration and is consistent with a negative perceptual aftereffect. Interestingly, the opposite is found in the temporal order judgement (TOJ) task (positive rapid recalibration). We aimed to determine whether a simple bias to repeat judgements on consecutive trials (choice‐repetition bias) could account for the discrepant results in these tasks. Preliminary simulations and analyses indicated that a choice‐repetition bias could produce apparently positive rapid recalibration in the TOJ and not the SJ task. Our first experiment revealed no evidence of rapid recalibration of TOJs, but negative rapid recalibration of associated confidence. This suggests that timing perception was rapidly recalibrated, but that the negative recalibration effect was obfuscated by a positive bias effect. In our second experiment, we experimentally mitigated the choice‐repetition bias effect and found negative rapid recalibration of TOJs. We therefore conclude that timing perception is negatively rapidly recalibrated, and this is observed consistently across timing tasks. These results contribute to a growing body of evidence that indicates multisensory perception is constantly undergoing recalibration, such that perceptual synchrony is maintained. This work also demonstrates that participants’ task responses reflect judgements that are contaminated by independent biases of perception and decision‐making.     

Complications from “Stem Cell Tourism” in Neurology

“Stem cell tourism,” the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the United States. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures. We also identified an urgent need for neurologist education and the creation of a national registry for reporting patient complications resulting from experimental stem cell interventions. ANN NEUROL 2020;88:661–668     

Do Optic Canal Dimensions Measured on CT Influence the Degree of Papilloedema and Visual Dysfunction in Idiopathic Intracranial Hypertension?

A recent study found that increased optic canal area on magnetic resonance imaging was associated with worse papilloedema in idiopathic intracranial hypertension (IIH). We repeated this study using more accurate computerized tomography derived measurements. Optic canal dimensions were measured from 42 IIH patients and 24 controls. These were compared with papilloedema grade. There was no correlation between any of the optic canal measurements and papilloedema grade and no significant difference in optic canal measurements between patients and controls. Our results cast doubt on the existing literature regarding the association between optic canal size and the degree of papilloedema in IIH.

CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH.     

Photoperiod-induced neurotransmitter plasticity declines with aging: An epigenetic regulation?

Neuroplasticity has classically been understood to arise through changes in synaptic strength or synaptic connectivity. A newly discovered form of neuroplasticity, neurotransmitter switching, involves changes in neurotransmitter identity. Chronic exposure to different photoperiods alters the number of dopamine (tyrosine hydroxylase, TH+) and somatostatin (SST+) neurons in the paraventricular nucleus (PaVN) of the hypothalamus of adult rats and results in discrete behavioral changes. Here, we investigate whether photoperiod-induced neurotransmitter switching persists during aging and whether epigenetic mechanisms of histone acetylation and DNA methylation may contribute to this neurotransmitter plasticity. We show that this plasticity in rats is robust at 1 and at 3 months but reduced in TH+ neurons at 12 months and completely abolished in both TH+ and SST+ neurons by 18 months. De novo expression of DNMT3a catalyzing DNA methylation and anti-AcetylH3 assessing histone 3 acetylation were observed following short-day photoperiod exposure in both TH+ and SST+ neurons at 1 and 3 months while an overall increase in DNMT3a in SST+ neurons paralleled neuroplasticity reduction at 12 and 18 months. Histone acetylation increased in TH+ neurons and decreased in SST+ neurons following short-day exposure at 3 months while the total number of anti-AcetylH3+ PaVN neurons remained constant. Reciprocal histone acetylation in TH+ and SST+ neurons indicates the importance of studying epigenetic regulation at the circuit level for identified cell phenotypes. The findings may be useful for developing approaches for noninvasive treatment of disorders characterized by neurotransmitter dysfunction.     

Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system

Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.     

Using amyloid PET imaging to diagnose Alzheimer’s disease in patients with multiple sclerosis

Journal of Neurology - Cognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits,...