Vagus Nerve Stimulation as a Treatment for Catatonia: A Hypothesis

Background: Catatonia is a syndrome comprising psychomotor, behavioral, and autonomous symptoms which may occur in the context of severe schizophrenic, affective, and other mental disorders or medical conditions. Treatment options include high dose benzodiazepines (lorazepam) and electroconvulsive therapy (ECT) with some evidence for the effectiveness of glutamate antagonists. However, due to a lack of randomized controlled studies in this severely ill population, evidence base is weak.Methods: On occasion of the case of a patient with treatment resistant catatonia in schizoaffective disorder, we developed the hypothesis of vagus nerve stimulation (VNS) being a potential therapy for treatment resistant catatonia.Results: Based on a selective literature search, we found a remarkable overlap of the pathophysiology of catatonia on the one hand and the putative mechanisms of action of VNS on the other hand in several domains: functional brain imaging, involved neurotransmitter systems, clinical, and theoretical. We thus decided to use VNS as a single subject clinical trial. During the 1-year-follow-up, we observed a fluctuating, but ultimately marked improvement of both catatonic symptoms and general psychopathology.Conclusions: We assume there is a sufficient hypothetical corroboration for the potential effectiveness of VNS as a long-term treatment in predominantly catatonic syndromes. This hypothesis could be tested in proof-of-concept clinical trials

Code Generation Based Grading: Evaluating an Auto-grading Mechanism for "Explain-in-Plain-English" Questions

Comprehending and elucidating the purpose of code is often cited as being a key learning objective within introductory programming courses. To address this objective ``Explain-in-Plain-English'' questions, in which students are shown a segment of code and asked to provide an abstract description of the code's purpose, have been adopted. However, given EiPE questions require a natural language response, they often require manual grading which is time-consuming for course staff and delays feedback for students. With the advent of large language models (LLMs) capable of generating code, responses to EiPE questions can be used to generate code segments, the correctness of which can then be easily verified using test cases. We refer to this approach as "Code Generation Based Grading" (CGBG) and in this paper we explore its agreement with human graders using EiPE responses from past exams in an introductory programming course taught in Python. Overall, we find that CGBG achieves moderate agreement with human graders with the primary area of disagreement being its leniency with respect to low-level and line-by-line descriptions of code

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography

On the barrier-resilience of arrangements of ray-sensors

Given an arrangement A of n sensors and two points s and t in the plane, the barrier resilience of A with respect to s and t is the minimum number of sensors whose removal permits a path from s to t such that the path does not intersect the coverage region of any sensor in A. When the surveillance domain is the entire plane and sensor coverage regions are unit line segments, even with restricted orientations, the problem of determining the barrier resilience is known to be NP-hard. On the other hand, if sensor coverage regions are arbitrary lines, the problem has a trivial linear time solution. In this paper, we give an O(n2m) time algorithm for computing the barrier resilience when each sensor coverage region is an arbitrary ray, where m is the number of sensor intersections.Natural Sciences and Engineering Research Council of Canad

A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients

Label-free detection of DNA hybridization based on hydration-induced tension in nucleic acid films

The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.D.R. acknowledges the fellowship funded by the Autonomic Community of Madrid (CAM). J.T, M.C, J.M and D.R acknowledge financial support by Spanish Ministry of Science (MEC) under grant No. TEC2006-10316 and CAM under grant No. 200550M056. C.B. acknowledges funding provided by MEC under grant No. BIO2007-67523. Work at Centro de Astrobiología was supported by European Union (EU), Instituto Nacional de Técnica Aeroespacial (INTA), MEC and CAM. All the authors acknowledge A. Cebollada, J.M. García-Martín, J. García, J.L. Costa-Kramer, M. Arroyo-Hernández and J.V. Anguita for their assistance in the gold deposition on the cantilevers.Peer reviewe

Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia

Interoperable atlases of the human brain

International audienceThe last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different as-pects of the human brain including micro-and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topo-graphically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and represen-tation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored

Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping

A novel map of Broca's language region is proposed based on transmitter receptor distributions as functionally relevant molecular markers. It sheds new light on the relation between anatomy and functional segregation