Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example

Molecular characterization is increasingly changing clinical practice, in both diagnosis and treatment. BRAF is a proto-oncogene that is mutated in ~2%-4% of lung cancers, but the incidence rises to 40%-45% among papillary thyroid cancers. Furthermore, BRAF is a promising target in lung cancer treatment. The present case study covers both the challenges of molecular differential diagnosis and the perspectives opened by targeted therapy by discussing the history of a 78-year-old female affected by a papillary histotype carcinoma with BRAF mutation associated with both thyroid and lung localizations. A differential diagnosis was possible as a consequence of a multidisciplinary approach including an in-depth molecular characterization. Based on this molecular feature, the patient was successfully treated with the BRAF inhibitor dabrafenib after the failure of treatment with standard regimen. To the best of our knowledge, this is the first published case of non-small-cell lung cancer with metastasis to thyroid and with BRAF V600E mutation

Investigation of a new bis(carboxylate)triazole-based anchoring ligand for dye-sensitised solar cell chromophore complexes

A novel anchoring ligand for dye-sensitised solar cell chromophoric complexes, 1-(2,2’-bipyrid-4-yl)-1,2,3-triazole-4,5-dicarboxylic acid (dctzbpy), is described. The new dye complexes [Ru(bpy)2(dctzbpy)][PF6]2 (AS16), [Ir(ppy)2(dctzbpy)][PF6] (AS17) and [Re(dctzbpy)(CO)3Cl] (AS18) were prepared in a two stage procedure with intermediate isolation of their diester analogues, AS16-Et2, AS17-Et2 and AS18-Et2 respectively. Electrochemical analysis of AS16-Et2, AS17-Et2 and AS18-Et2 reveal reduction potentials in the range -1.50 to -1.59 V (vs Fc+/Fc) which is cathodically shifted with respect to that of the model complex [Ru(bpy)2(dcbH2)]2+ (1) (Ered = -1.34 V, dcbH2 = 2,2’-bipyridyl-4,4’dicarboxylic acid). This therefore demonstrates that the LUMO of the complex is correctly positioned for favourable electron transfer into the TiO2 conduction band upon photoexcitation. The higher energy LUMOs for AS16 to AS18 and a larger HOMO-LUMO gap result in blue-shifted absorption spectra and hence reduced light harvesting efficiency relative to their dcbH2 analogues. Preliminary tests on TiO2 n-type and NiO p-type DSSCs have been carried out. In the cases of the Ir(III) and Re(I) based dyes AS17 and AS18 these show inferior performance to their dcbH2 analogues. However, the Ru(II) dye AS16 (η = 0.61 %) exhibits significantly greater efficiency than 1 (η = 0.1 %). In a p-type cell AS16 shows the highest photovoltaic efficiency (η = 0.028 %), almost three times that of cells incorporating the benchmark dye coumarin C343

Using the Oxford Cognitive Screen to detect cognitive impairment in stroke patients: a comparison with the Mini-Mental State Examination

Background: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. Objective: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. Methods: 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. Results: About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. Conclusion: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Functional mapping of left parietal areas involved in simple addition and multiplication. A single-case study of qualitative analysis of errors

All electrostimulation studies on arithmetic have so far solely reported general errors. Nonetheless, a classification of the errors during stimulation can inform us about underlying arithmetic processes. The present electrostimulation study was performed in a case of left parietal glioma. The patient\u2019s erroneous responses suggested that calculation was mainly applied for addition and a combination of retrieval and calculation was mainly applied for multiplication. The findings of the present single-case study encourage follow up with further data collection with the same paradigm

Rule perseveration during task-switching in brain tumor: a severe form of task-setting impairment

It has been proposed that at least two distinct processes are engaged during task switching: reconfiguration of the currently relevant task-set and interference resolution arising from the competing task-set. While in healthy individuals the two are difficult to disentangle, their disruption is thought to cause different impairments in brain-damaged patients. Yet, the observed deficits are inconsistent across studies and do not allow drawing conclusions regarding their independence. Forty-one brain tumor patients were tested on a task-switching paradigm. We compared their performance between switch and repeat trials (switch cost) to assess rule reconfiguration, and between trials requiring the same response (congruent) and a different response for the two tasks (incongruent) to assess interference control. In line with previous studies, we found the greatest proportion of errors on incongruent trials, suggesting an interference control impairment. However, a closer look at the distribution of errors between two task rules revealed a rule perseveration impairment: patients with high error rate on incongruent trials often applied only one task rule throughout the task, and less frequently switched to the alternative one. Multivariate lesion-symptom mapping analysis unveiled the relationship between lesions localized in left orbitofrontal and posterior subcortical regions and perseveration scores, measured as absolute difference in accuracy between two task rules. This finding points to a more severe task-setting impairment, not reflected as a mere switching deficit, but instead as a difficulty in creating stable task representations, in line with recent accounts of orbitofrontal cortex functions suggesting its critical role in representing task states

Subcortical mapping of calculation processing in the right parietal lobe

Preservation of calculation processing in brain surgery is crucial for patients' quality of life. Over the last decade, surgical electrostimulation was used to identify and preserve the cortical areas involved in such processing. Conversely, subcortical connectivity among different areas implicated in this function remains unclear, and the role of surgery in this domain has not been explored so far. The authors present the first 2 cases in which the subcortical functional sites involved in calculation were identified during right parietal lobe surgery. Two patients affected by a glioma located in the right parietal lobe underwent surgery with the aid of MRI neuronavigation. No calculation deficits were detected during preoperative assessment. Cortical and subcortical mapping were performed using a bipolar stimulator. The current intensity was determined by progressively increasing the amplitude by 0.5-mA increments (from a baseline of 1 mA) until a sensorimotor response was elicited. Then, addition and multiplication calculation tasks were administered. Corticectomy was performed according to both the MRI neuronavigation data and the functional findings obtained through cortical mapping. Direct subcortical electrostimulation was repeatedly performed during tumor resection. Subcortical functional sites for multiplication and addition were detected in both patients. Electrostimulation interfered with calculation processing during cortical mapping as well. Functional sites were spared during tumor removal. The postoperative course was uneventful, and calculation processing was preserved. Postoperative MRI showed complete resection of the tumor. The present preliminary study shows for the first time how functional mapping can be a promising method to intraoperatively identify the subcortical functional sites involved in calculation processing. This report therefore supports direct electrical stimulation as a promising tool to improve the current knowledge on calculation processing connectivity