Dundee ADHD continuing care proforma (revised)

These are two proforma (one for males the other for females) that facilitate the recording of clinical information about the ongoing clinical status of children and adolescents receiving treatment for ADHD. Whilst the Dundee ADHD care pathway has recorded similar clinical information in a standardised way for the last 10 years the previous clinical records required a new document for each clinic visit. This made it more difficult to assess the development of clinical response over time and increased the time required by clinicians to make evidence based treatment decisions. These revised proforma allow the clinician to view the information from up to 12 clinic visits at the same time and therefore simplify the clinical task and improving clinical care. The proforma were designed as a part of a collaboration between graphic and product designers and clinicians that was made possible through the wider ADHD Behavioural Clinical Data (ABCD) data visualisation collaboration funded through and award from the University of Dundee

A randomised double-blind placebo-controlled trial of minocycline and/or Omega-3 fatty acids added to treatment as usual for At Risk Mental States (NAYAB): study protocol

Background The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high, low and middle-income countries. Methods A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive are readily available in low/middle-income countries such as Pakistan, and if evidenced, may prove to be safe and effective for treating ARMS

Baseline characteristics, analysis plan and report on feasibility for the Prevention Of Decline in Cognition After Stroke Trial (PODCAST).

BACKGROUND: A common complication after stroke is development of cognitive impairment and dementia. However, effective strategies for reducing the risk of developing these problems remain undefined. Potential strategies include intensive lowering of blood pressure (BP) and/or lipids. This paper summarises the baseline characteristics, statistical analysis plan and feasibility of a randomised control trial of blood pressure and lipid lowering in patients post-stroke with the primary objective of reducing cognitive impairment and dementia. METHODS: The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) was a multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial internal pilot trial running in secondary and primary care. Participants without dementia were enrolled 3-7 months post ischaemic stroke or spontaneous intracerebral haemorrhage, and randomised to intensive versus guideline BP lowering (target systolic BP <125 mmHg versus <140 mmHg); patients with ischaemic stroke were also randomised to intensive or guideline lipid lowering (target LDL cholesterol <1.4 mmol/L versus <3 mmol/L). The primary outcome was the Addenbrooke's Cognitive Examination-Revised; a key secondary outcome was to assess feasibility of performing a large trial of one or both interventions. Data are number (%) or mean (standard deviation). The trial was planned to last for 8 years with follow-up between 1 and 8 years. The plan for reporting the main results is included as Additional file 2. RESULTS: 83 patients (of a planned 600) were recruited from 19 UK sites between 7 October 2010 and 31 January 2014. Delays, due to difficulties in the provision of excess treatment costs and to complexity of follow-up, led to few centres taking part and a much lower recruitment rate than planned. Patient characteristics at baseline were: age 74 (SD 7) years, male 64 (77 %), index stroke ischaemic 77 (93 %), stroke onset to randomisation 4.5 [SD 1.3] months, Addenbrooke's Cognitive Examination-Revised 86 (of 100, SD 8), Montreal Cognitive Assessment 24 (of 30, SD 3), BP 147/82 (SD 19/11) mmHg, total cholesterol 4.0 (SD 0.8) mmol/L and LDL cholesterol 2.0 (SD 0.7) mmol/L, modified Rankin Scale 1.1 (SD 0.8). CONCLUSION: Limited recruitment suggests that a large trial is not feasible using the current protocol. The effects of the interventions on BP, lipids, and cognition will be reported in the main publication. TRIAL REGISTRATION: ISRCTN85562386 registered on 23 September 2009

Erratum to: Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains.

Mitochondria play a key role in common neurodegenerative diseases and contain their own genome: mtDNA. Common inherited polymorphic variants of mtDNA have been associated with several neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions. However, there are conflicting reports describing the role of rare inherited variants and somatic point mutations in neurodegenerative disorders, and recent evidence also implicates mtDNA levels. To address these issues we studied 1363 post mortem human brains with a histopathological diagnosis of Parkinson's disease (PD), Alzheimer's disease (AD), Frontotemporal dementia - Amyotrophic Lateral Sclerosis (FTD-ALS), Creutzfeldt Jacob disease (CJD), and healthy controls. We obtained high-depth whole mitochondrial genome sequences using off target reads from whole exome sequencing to determine the association of mtDNA variation with the development and progression of disease, and to better understand the development of mtDNA mutations and copy number in the aging brain. With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects. However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease. In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD. Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation

VR_Stab: Perceptual Stability in VR

Data and analysis code (for R) supporting paper submitted to Perception in early 2022: “Investigating distortions in perceptual stability during different self-movements using Virtual Reality” by Paul A. Warren, Graham Bell and Yu L

Direct speech quotations promote low relative-clause attachment in silent reading of English

The implicit prosody hypothesis (Fodor, 1998, 2002) proposes that silent reading coincides with a default, implicit form of prosody to facilitate sentence processing. Recent research demonstrated that a more vivid form of implicit prosody is mentally simulated during silent reading of direct speech quotations (e.g., Mary said, “This dress is beautiful”), with neural and behavioural consequences (e.g., Yao, Belin, & Scheepers, 2011; Yao & Scheepers, 2011). In this study, we explored the relation between ‘default’ and ‘simulated’ implicit prosody in the context of relative-clause (RC) attachment in English. English RC-attachment structures were embedded in direct speech, indirect speech or narrative sentences. Participants either completed sentence fragments ending in incomplete RCs (Experiment 1) or rated the felicity of unambiguous low vs. high RC-attachments in silent reading (Experiment 2) and in oral reading (Experiment 3), respectively. In this data collection, you will find task instructions, data and R scripts for each of the three experiment

Human neuronal extracellular vesicles contain a transcriptional network and tetraspanin-defined subpopulations

Healthy brain function is mediated by several complementary signalling pathways, many of which are driven by extracellular vesicles (EVs). EVs are heterogeneous in both size and cargo and are constitutively released from cells into the extracellular milieu. They are subsequently trafficked to recipient cells, whereupon their entry can modify the cellular phenotype. Here, in order to further understand the functional role of EVs in neurons, we isolated EVs by size exclusion chromatography from human induced pluripotent stem cell (iPSC)-derived neurons. Electron microscopy and dynamic light scattering revealed that the isolated EVs had a diameter of 30-100 nm. Transcriptomic and proteomics analyses of the EVs and neurons identified key molecules enriched in the EVs involved in cell surface interaction (integrins and collagens), internalisation pathways (clathrin- and caveolin-dependent), downstream signalling pathways (phospholipases, integrin-linked kinase and MAPKs), and long-term impacts on cellular development and maintenance. Overall, we show that key signalling networks and mechanisms are enriched in EVs isolated from human iPSC-derived neurons, and identify subpopulations of EVs defined by differential tetraspanin expression

Naming in Frontotemporal Dementia and its neural correlates

The study sought to understand the basis for naming problems in the behavioural form of frontotemporal dementia (bvFTD) through direct comparison with semantic dementia (SD) and examination of neural correlates. The data addresses the question whether naming problems in bvFTD arise secondary to patients' frontal executive disorder or occur independently as additional linguistic deficits. The data show test scores for 71 patients with bvFTD and 32 with SD on the Graded Naming test (a published challenging test of naming), the Manchester naming test (a less demanding test of picture naming) and a word-picture matching test that uses the same stimuli as the Manchester naming test (10 pictures of animals, 10 of fruits/vegetables, 10 articles of clothing and 10 household objects). The nature of naming errors is indicated for each test item and are summarised as separate variables. Naming errors are classified in terms of the following types: semantic (e.g. "dog" for rabbit), superordinate category (e.g. "animal" for rabbit), associative (this includes descriptions of an object's function, gestural demonstrations of its use and associated information e.g. "in Australia" for kangaroo), visually related misidentifications, omissions (which includes generic responses that convey insufficient information to convey recognition) and viable alternative responses (e.g. "coat" for jacket). The data also shows independent (blind) visual ratings of magnitude of atrophy based on coronal magnetic resonance scan images. Different regions of the frontal and temporal lobes are rated in accordance with the scheme defined by Davies et al Neuroradiology, 2009, 51, 491-503. Background clinical data includes scores on standard executive tests: verbal fluency, Weigls block sorting and Brixton spatial anticipation test. BvFTD patients, as expected, perform better than the SD group on the language test, but deficits are identified in about half of patients. There are strong inverse correlations between naming scores in both groups and atrophy in temporal lobe structures, particularly the temporal pole and fusiform gyrus, whereas comprehension in SD, measured by word picture matching, correlates more strongly with posterior than anterior temporal lobe atrophy. Error analysis shows a significant relationship in both groups between associative-type responses and temporal pole atrophy, whereas 'don't know' responses, suggestive of a loss of conceptual knowledge, correlates with more posterior temporal regions. There is some correlation in bvFTD between naming and executive performance but not frontal lobe atrophy. The data support the view that naming problems in bvFTD can arise independently of 'frontal' executive deficits and highlight clinical overlap with bvFTD. The findings have implications for the hub-and-spoke model of semantic memory and argue against the notion of the temporal pole as a semantic hub

Brixton test data in bvFTD and SD

The Brixton Spatial Anticipation Test is a widely used test of executive function. There has hitherto been surprisingly little systematic examination of the usefulness of the test in behavioural variant frontotemporal dementia (bvFTD), the prototypical degenerative disorder of the frontal lobes. The dataset relates to a study that explored the sensitivity and specificity of the Brixton test through a direct comparison of 76 patients with bvFTD and 34 with semantic dementia (SD), characterised by degeneration of the temporal lobes. All patients had been referred to a specialist cognitive clinic within a neuroscience centre and the Brixton test had been administered as part of their clinical diagnostic work-up. The study of patients' Brixton performance investigated both quantitative (error scores, sets achieved) and qualitative (error types) aspects of performance. bvFTD patients, as predicted, performed significantly more poorly than SD patients and achieved fewer sets (i.e. identified fewer rule shifts). bvFTD patients were distinguished too by more frequent perseverative and random errors. Perseverations could be subdivided into those representing repetition of an immediately preceding response, an immediately preceding rule, or an earlier rule that is not the immediately preceding one. A distinction could also be drawn between perseverations of the immediately preceding rule that take note of the position of the blue circle (stimulus-related) and those that do not (stimulus unrelated). bvFTD patients could be distinguished from SD by the presence of the latter. The data confirm the value of the Brixton test in the clinical assessment of bvFTD and point to the clinical and theoretical value of analysis of errors

Mental simulations of phonological representations are causally linked to silent reading of direct versus indirect speech

In three experiments, this project explored the phonological aspect and the causal role of speech simulations in silent reading of tongue twisters in direct speech, indirect speech and non-speech sentences. Embodied theories propose that language is understood via mental simulations of sensory states related to perception and action. Given that direct speech (e.g., She says, “It’s a lovely day!”) is perceived to be more vivid than indirect speech (e.g., She says (that) it’s a lovely day) in perception, recent research shows in silent reading that more vivid speech representations are mentally simulated for direct speech than for indirect speech. This ‘simulated’ speech is found to contain suprasegmental prosodic representations (e.g., speech prosody) but its phonological detail and its causal role in silent reading of direct speech remain unclear. The results demonstrated greater visual tongue-twister effects (phonemic interference) during silent reading (Experiment 1) but not oral reading (Experiment 2) of direct speech as compared to indirect speech and non-speech. The tongue-twister effects in silent reading of direct speech were selectively disrupted by phonological interference (concurrent articulation) as compared to manual interference (finger tapping) (Experiment 3). The results replicated more vivid speech simulations in silent reading of direct speech, and additionally extended them to the phonological dimension. Crucially, they demonstrated a causal role of phonological simulations in silent reading of direct speech, at least in tongue-twister reading. The findings are discussed in relation to multidimensionality and task dependence of mental simulation and its mechanisms