Error blindness and motivational significance: Shifts in networks centering on anterior insula co-vary with error awareness and pupil dilation

This investigation aims to further our understanding of the brain mechanisms underlying the awareness of one's erroneous actions. While all errors are registered as such in the rostral cingulate zone, errors enter awareness only when the anterior insula cortex is activated. Aware but not unaware errors elicit autonomic nervous system reactivity. Our aim is to investigate the hypothesis that activation in the insula during error awareness is related to autonomic arousal and to inter-regional interactions with other areas of the brain. To examine the role of the anterior insula in error awareness, we assessed its functional connectivity to other brain regions along with autonomic nervous system reactivity in young healthy participants who underwent simultaneous pupil-diameter and functional magnetic resonance imaging measurements while performing a complex and error-prone task. Error blindness was associated with failures to engage sufficient autonomic reactivity. During aware errors increased pupil-diameter along with increased task-related activation within, and increased connectivity between anterior insula and task-related networks suggested an increased capacity for action-control information transfer. Increased pupil-diameter during aware errors was furthermore associated with decreased activation of the default-mode network along with decreased insular connectivity with regions of the default mode system, possibly reflecting decreased task-irrelevant information processing. This shifting mechanism may be relevant to a better understanding of how the brain and the autonomic nervous system interact to enable efficient adaptive behavior during cognitive challenge

Upper cervical cord atrophy is independent of cervical cord lesion volume in early multiple sclerosis: A two-year longitudinal study

Background: Upper cervical cord atrophy and lesions have been shown to be associated with disease and disability progression already in early relapsing-remitting multiple sclerosis (RRMS). However, their longitudinal relationship remains unclear. Objective: To investigate the cross-sectional and longitudinal relation between focal T2 cervical cord lesion volume (CCLV) and regional and global mean upper cervical cord area (UCCA), and their relations with disability. Methods: Over a two-year interval, subjects with RRMS (n = 36) and healthy controls (HC, n = 16) underwent annual clinical and MRI examinations. UCCA and CCLV were obtained from C1 through C4 level. Linear mixed model analysis was performed to investigate the relation between UCCA, CCLV, and disability over time. Results: UCCA at baseline was significantly lower in RRMS subjects compared to HCs (p = 0.003), but did not decrease faster over time (p ≥ 0.144). UCCA and CCLV were independent of each other at any of the time points or cervical levels, and over time. Lower baseline UCCA, but not CCLV, was related to worsening of both upper and lower extremities function over time. Conclusion: UCCA and CCLV are independent from each other, both cross-sectionally and longitudinally, in early MS. Lower UCCA, but not CCLV, was related to increasing disability over time

Benign mesenteric lymphangioma presenting as acute pancreatitis: a case report

Benign mesenteric lymphangiomas are rare intra-abdominal cysts which may be asymptomatic or present with a variety of abdominal symptoms including an acute abdomen. We are however not aware of any reports in the literature linking mesenteric lymphangioma to acute pancreatitis. We present the case of a 62-year-old man who was admitted with signs and symptoms of acute pancreatitis and a palpable abdominal mass. Computerised tomography (CT) of his abdomen confirmed the presence of a mesenteric cystic mass. He underwent a laparotomy at which a large thin walled mass filled with a chylous fluid was resected. Histological analysis of this cyst showed it to be a benign mesenteric lymphangioma

Risk factors for comorbid oppositional defiant disorder in attention-deficit/hyperactivity disorder

Oppositional defiant disorder (ODD) is highly prevalent in attention-deficit/hyperactivity disorder (ADHD). Individuals with both ADHD and ODD (ADHD + ODD) show a considerably worse prognosis compared with individuals with either ADHD or ODD. Therefore, identification of risk factors for ADHD + ODD is essential and may contribute to the development of (early) preventive interventions. Participants were matched for age, gender, and ADHD-subtype (diagnostic groups), and did not differ in IQ. Predictors included pre- and perinatal risk factors (pregnancy duration, birth weight, maternal smoking during pregnancy), transgenerational factors (parental ADHD; parental warmth and criticism in diagnostic groups), and postnatal risk factors (parental socioeconomic status [SES], adverse life events, deviant peer affiliation). Three models were assessed, investigating risk factors for ADHD-only versus controls (N = 86), ADHD + ODD versus controls (N = 86), and ADHD + ODD versus ADHD-only (N = 90). Adverse life events and parental ADHD were risk factors for both ADHD + ODD and ADHD-only, and more adverse life events were an even stronger risk factor for comorbid ODD compared with ADHD-only. For ADHD + ODD, but not ADHD-only, parental criticism, deviant peer affiliation, and parental SES acted as risk factors. Maternal smoking during pregnancy acted as minor risk factor for ADHD-only, while higher birth weight acted as minor risk factor for ADHD + ODD. No effects of age were present. Findings emphasise the importance of these factors in the development of comorbid ODD. The identified risk factors may prove to be essential in preventive interventions for comorbid ODD in ADHD, highlighting the need for parent-focused interventions to take these factors into account

Stimulant treatment profiles predicting co-occurring substance use disorders in individuals with attention-deficit/hyperactivity disorder

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence (ND). It remains unclear whether and how stimulant treatment may affect this risk. We aimed to investigate how stimulant use profiles influence the risk of SUDs and ND, using a novel data-driven community detection analysis to construct different stimulant use profiles. Comprehensive lifetime stimulant prescription data and data on SUDs and ND were available for 303 subjects with ADHD and 219 controls, with a mean age 16.3 years. Community detection was used to define subgroups based on multiple indicators of treatment history, start age, treatment duration, total dose, maximum dose, variability, stop age. In stimulant-treated participants, three subgroups with distinct medication trajectories were distinguished (late-and-moderately dosed, n = 91; early-and-moderately dosed, n = 51; early-and-intensely dosed, n = 103). Compared to stimulant-naïve participants (n = 58), the early-and-intense treatment group had a significantly lower risk of SUDs and ND (HR = 0.28, and HR = 0.29, respectively), while the early-and-moderate group had a significantly lower risk of ND only (HR = 0.30). The late-and-moderate group was at a significantly higher risk of ND compared to the other two treatment groups (HR = 2.66 for early-and-moderate, HR = 2.78 for early-and-intense). Our findings show that in stimulant-treated adolescents with ADHD, long-term outcomes are associated with treatment characteristics, something that is often ignored when treated individuals are compared to untreated individuals.</p

Laparoscopic resection of a lymphangiomatous cyst of the colon: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lymphangiomatous cysts are submucosal masses that are rarely found in the gastrointestinal tract and more often in the neck, oral cavity, and skin. These cysts are benign tumors and mostly clinically silent. Symptoms include abdominal pain, diarrhea, and rectal bleeding. Their pathogenesis remains unclear.</p> <p>Case presentation</p> <p>During a routine ultrasound examination of a Caucasian 25-year-old woman, a structure that raised our suspicions of an ovarian cyst was found. MRI showed a 4.5 cm cystic lesion in the cecal region. Laparoscopic exploration revealed unexpected contact with the ascending colon. The cyst, including its base and of portion of the colon, was resected laparoscopically. The histological examination revealed cystic lymphangioma.</p> <p>Conclusion</p> <p>Lymphangiomatous cysts of the colon are very rare lesions. Although their pathology is benign, the recommended treatment is resection, which can be performed with minimal invasiveness.</p

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

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Mislocalization of XPF-ERCC1 Nuclease Contributes to Reduced DNA Repair in XP-F Patients

Xeroderma pigmentosum (XP) is caused by defects in the nucleotide excision repair (NER) pathway. NER removes helix-distorting DNA lesions, such as UV–induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. The severity of XP varies tremendously depending upon which NER gene is mutated and how severely the mutation affects DNA repair capacity. XPF-ERCC1 is a structure-specific endonuclease essential for incising the damaged strand of DNA in NER. Missense mutations in XPF can result not only in XP, but also XPF-ERCC1 (XFE) progeroid syndrome, a disease of accelerated aging. In an attempt to determine how mutations in XPF can lead to such diverse symptoms, the effects of a progeria-causing mutation (XPFR153P) were compared to an XP–causing mutation (XPFR799W) in vitro and in vivo. Recombinant XPF harboring either mutation was purified in a complex with ERCC1 and tested for its ability to incise a stem-loop structure in vitro. Both mutant complexes nicked the substrate indicating that neither mutation obviates catalytic activity of the nuclease. Surprisingly, differential immunostaining and fractionation of cells from an XFE progeroid patient revealed that XPF-ERCC1 is abundant in the cytoplasm. This was confirmed by fluorescent detection of XPFR153P-YFP expressed in Xpf mutant cells. In addition, microinjection of XPFR153P-ERCC1 into the nucleus of XPF–deficient human cells restored nucleotide excision repair of UV–induced DNA damage. Intriguingly, in all XPF mutant cell lines examined, XPF-ERCC1 was detected in the cytoplasm of a fraction of cells. This demonstrates that at least part of the DNA repair defect and symptoms associated with mutations in XPF are due to mislocalization of XPF-ERCC1 into the cytoplasm of cells, likely due to protein misfolding. Analysis of these patient cells therefore reveals a novel mechanism to potentially regulate a cell's capacity for DNA repair: by manipulating nuclear localization of XPF-ERCC1

A Fast and Reliable Method for Simultaneous Waveform, Amplitude and Latency Estimation of Single-Trial EEG/MEG Data

The amplitude and latency of single-trial EEG/MEG signals may provide valuable information concerning human brain functioning. In this article we propose a new method to reliably estimate single-trial amplitude and latency of EEG/MEG signals. The advantages of the method are fourfold. First, no a-priori specified template function is required. Second, the method allows for multiple signals that may vary independently in amplitude and/or latency. Third, the method is less sensitive to noise as it models data with a parsimonious set of basis functions. Finally, the method is very fast since it is based on an iterative linear least squares algorithm. A simulation study shows that the method yields reliable estimates under different levels of latency variation and signal-to-noise ratioÕs. Furthermore, it shows that the existence of multiple signals can be correctly determined. An application to empirical data from a choice reaction time study indicates that the method describes these data accurately