Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG)

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories

Assessment of Plasma Antioxidants, Oxidative Stress and Polyunsaturated Fatty Acids in Paediatric Cancer Patients: A Prospective Cohort Pilot Study

Background: Paediatric cancer patients may have a limited dietary intake, particularly nutrients high in antioxidants, docosahexanoic acid (DHA) and eicosapentanoic acid (EPA). Objective: To investigate the antioxidant status (TAS), antioxidant capacity (TAC), oxidative stress, DHA and EPA of paediatric cancer patients during treatment. Methods: A prospective cohort study of Scottish children aged <18 years, diagnosed with and treated for cancer between April-2013 to Jan-2014 was performed. Clinical data and blood samples were collected at baseline and 6 months. Data were stratified by treatment risk (low, medium and high) and nutritional support. We used Oxygen Radical Absorbance Capacity (ORAC) Antioxidant Assay to measure TAC, thiobarbituric acid reactive substances (TBARS) for lipid peroxidation and high performance liquid chromatography and Inductively Coupled Plasma Mass Spectrometry for TAS. The analyses of DHA and EPA were performed by analysing fatty acidmethyl esters (FAME) using gas-liquid chromatography. The reference ranges used were: Yagi 1998 (1.86-3.94) _mol for lipid peroxidation and Damsgaard.,et al. 2014 for EPA (0.45-0.77) % and DHA (2.22-3.76) %. Results: 20 patients (median (IQR) age 4.2 (1.5-8.5) years; 50% males) were recruited. There were no significant changes in plasma TAS, TAC and EPA, but lipid peroxidation significantly decreased from 7.4 (6.2-9.0) at baseline to 5.3 (4.5-6.4) _mol/MDA at 6 months(p = 0.003). The median (IQR) blood percentage of DHA significantly increased from 1.3 (0.9-1.9) to 1.8 (1.3-2.1) (p = 0.001). Lipid peroxidation was high in 95% (19/20) of patients at baseline and 94% (15/16) at 6 months; whilst DHA and EPA were low in 95%(19/20) and 70% (14/20) at baseline and 87.5% (14/16) and 60% (12/16) at 6 months. Children on high-treatment risk exhibited the highest oxidative stress levels. No statitically significant differences were found between non-supplemented and supplemented children in any of the following parameters (TAS, TAC, oxidative stress, EPA and DHA). Conclusion: There was a high prevalence of oxidative stress, especially in children treated with high-risk protocols and during the initial phases of treatment. Nutritional support does not appear to provide enough TAS, EPA and DHA in this cohort; however, larger high-quality population based studies are warranted to confirm these findings. Keywords: Paediatric cancer; Antioxidants; Oxidative stress; Docosahexanoic acid; Eicosapentanoic acidsch_dieThe Determinants of Nutritional Risk in Paediatric Cancer2pub4313pub

Low Plasma Vitamin D (25-Hydroxycholecalciferol) in Children and Adolescents Diagnosed with Cancer: A Case-Control Study

Introduction: Children and young people with cancer are less likely to spend time outdoors and they may also have a limited dietary intake. In addition, some cancer treatments can increase vitamin D catabolism. Objectives: This study aimed to investigate if there was an increased risk of poor vitamin D status in newly diagnosed childhood cancer patients compared to healthy controls in Scotland. Methods: Plasma 25 (OH) D was measured in children and adolescents during initial cancer treatment and compared to 33 healthy controls. Vitamin D deficiency was classified as plasma 25 (OH) D <25 nmol/l, with a plasma 25 (OH) D of 25-49 nmol/l classified as insufficient. Results: Forty-one patients (median age 3.8 years, IQR 1.9-8.0) were diagnosed with cancer, 63% were male. Twenty-three (56 %) had solid tumours, 18 (44%) had haematological cancers. Median (IQR) plasma 25 (OH) D at recruitment was 37.0 nmol/l (23.7-58.2). Ten patients (24%) had vitamin D deficiency and 17 (41%) patients were classified as insufficient. The median (IQR) plasma 25 (OH) D in the control group (n = 33) was 37.5 nmol/l (29.0-58.0). Six controls (18%) had vitamin D deficiency and 14 (42%) were classified as having insufficient results. Plasma 25 (OH) D did not differ (p > 0.05) between the patients and the controls. Conclusions: Almost three in four Scottish children treated for cancer had vitamin D deficiency or insufficiency; there was no increased risk of poor vitamin D status compared to healthy controls. Assessment of vitamin D status at diagnosis and in response to the course of treatment appears necessary to optimise nutritional management.sch_dieThe determinants of nutritional risk in children and young people with cancer3pub4423pub

Recognizing recurrent neural networks (rRNN): Bayesian inference for recurrent neural networks

Recurrent neural networks (RNNs) are widely used in computational neuroscience and machine learning applications. In an RNN, each neuron computes its output as a nonlinear function of its integrated input. While the importance of RNNs, especially as models of brain processing, is undisputed, it is also widely acknowledged that the computations in standard RNN models may be an over-simplification of what real neuronal networks compute. Here, we suggest that the RNN approach may be made both neurobiologically more plausible and computationally more powerful by its fusion with Bayesian inference techniques for nonlinear dynamical systems. In this scheme, we use an RNN as a generative model of dynamic input caused by the environment, e.g. of speech or kinematics. Given this generative RNN model, we derive Bayesian update equations that can decode its output. Critically, these updates define a 'recognizing RNN' (rRNN), in which neurons compute and exchange prediction and prediction error messages. The rRNN has several desirable features that a conventional RNN does not have, for example, fast decoding of dynamic stimuli and robustness to initial conditions and noise. Furthermore, it implements a predictive coding scheme for dynamic inputs. We suggest that the Bayesian inversion of recurrent neural networks may be useful both as a model of brain function and as a machine learning tool. We illustrate the use of the rRNN by an application to the online decoding (i.e. recognition) of human kinematics

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed

The motor theory of speech perception holds that we perceive the speech of another in terms of a motor representation of that speech. However, when we have learned to recognize a foreign accent, it seems plausible that recognition of a word rarely involves reconstruction of the speech gestures of the speaker rather than the listener. To better assess the motor theory and this observation, we proceed in three stages. Part 1 places the motor theory of speech perception in a larger framework based on our earlier models of the adaptive formation of mirror neurons for grasping, and for viewing extensions of that mirror system as part of a larger system for neuro-linguistic processing, augmented by the present consideration of recognizing speech in a novel accent. Part 2 then offers a novel computational model of how a listener comes to understand the speech of someone speaking the listener's native language with a foreign accent. The core tenet of the model is that the listener uses hypotheses about the word the speaker is currently uttering to update probabilities linking the sound produced by the speaker to phonemes in the native language repertoire of the listener. This, on average, improves the recognition of later words. This model is neutral regarding the nature of the representations it uses (motor vs. auditory). It serve as a reference point for the discussion in Part 3, which proposes a dual-stream neuro-linguistic architecture to revisits claims for and against the motor theory of speech perception and the relevance of mirror neurons, and extracts some implications for the reframing of the motor theory

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases