A generalized theory for current-source density analysis in brain tissue

The current-source density (CSD) analysis is a widely used method in brain electrophysiology, but this method rests on a series of assumptions, namely that the surrounding extracellular medium is resistive and uniform, and in some versions of the theory, that the current sources are exclusively made by dipoles. Because of these assumptions, this standard model does not correctly describe the contributions of monopolar sources or of non-resistive aspects of the extracellular medium. We propose here a general framework to model electric fields and potentials resulting from current source densities, without relying on the above assumptions. We develop a mean-field formalism which is a generalization of the standard model, and which can directly incorporate non-resistive (non-ohmic) properties of the extracellular medium, such as ionic diffusion effects. This formalism recovers the classic results of the standard model such as the CSD analysis, but in addition, we provide expressions to generalize the CSD approach to situations with non-resistive media and arbitrarily complex multipolar configurations of current sources. We found that the power spectrum of the signal contains the signature of the nature of current sources and extracellular medium, which provides a direct way to estimate those properties from experimental data, and in particular, estimate the possible contribution of electric monopoles.Comment: Physical Review E, in press, 201

Estimating the contribution of assembly activity to cortical dynamics from spike and population measures

The hypothesis that cortical networks employ the coordinated activity of groups of neurons, termed assemblies, to process information is debated. Results from multiple single-unit recordings are not conclusive because of the dramatic undersampling of the system. However, the local field potential (LFP) is a mesoscopic signal reflecting synchronized network activity. This raises the question whether the LFP can be employed to overcome the problem of undersampling. In a recent study in the motor cortex of the awake behaving monkey based on the locking of coincidences to the LFP we determined a lower bound for the fraction of spike coincidences originating from assembly activation. This quantity together with the locking of single spikes leads to a lower bound for the fraction of spikes originating from any assembly activity. Here we derive a statistical method to estimate the fraction of spike synchrony caused by assemblies—not its lower bound—from the spike data alone. A joint spike and LFP surrogate data model demonstrates consistency of results and the sensitivity of the method. Combining spike and LFP signals, we obtain an estimate of the fraction of spikes resulting from assemblies in the experimental data

Free choice activates a decision circuit between frontal and parietal cortex

We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals

Network inference - with confidence - from multivariate time series

Networks - collections of interacting elements or nodes - abound in the natural and manmade worlds. For many networks, complex spatiotemporal dynamics stem from patterns of physical interactions unknown to us. To infer these interactions, it is common to include edges between those nodes whose time series exhibit sufficient functional connectivity, typically defined as a measure of coupling exceeding a pre-determined threshold. However, when uncertainty exists in the original network measurements, uncertainty in the inferred network is likely, and hence a statistical propagation-of-error is needed. In this manuscript, we describe a principled and systematic procedure for the inference of functional connectivity networks from multivariate time series data. Our procedure yields as output both the inferred network and a quantification of uncertainty of the most fundamental interest: uncertainty in the number of edges. To illustrate this approach, we apply our procedure to simulated data and electrocorticogram data recorded from a human subject during an epileptic seizure. We demonstrate that the procedure is accurate and robust in both the determination of edges and the reporting of uncertainty associated with that determination.Comment: 12 pages, 7 figures (low resolution), submitte

Neuronal Shot Noise and Brownian 1/f21/f^2 Behavior in the Local Field Potential

We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous $1/f^2$ scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this $1/f^2$ Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose extracellular fields slowly decay and 2) rapidly firing, temporally correlated cells that generate UP-DOWN states

Classical homeopathy in the treatment of cancer patients - a prospective observational study of two independent cohorts

BACKGROUND: Many cancer patients seek homeopathy as a complementary therapy. It has rarely been studied systematically, whether homeopathic care is of benefit for cancer patients. METHODS: We conducted a prospective observational study with cancer patients in two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n = 259), and one cohort with conventionally treated cancer patients (CG; n = 380). For a direct comparison, matched pairs with patients of the same tumour entity and comparable prognosis were to be formed. Main outcome parameter: change of quality of life (FACT-G, FACIT-Sp) after 3 months. Secondary outcome parameters: change of quality of life (FACT-G, FACIT-Sp) after a year, as well as impairment by fatigue (MFI) and by anxiety and depression (HADS). RESULTS: HG: FACT-G, or FACIT-Sp, respectively improved statistically significantly in the first three months, from 75.6 (SD 14.6) to 81.1 (SD 16.9), or from 32.1 (SD 8.2) to 34.9 (SD 8.32), respectively. After 12 months, a further increase to 84.1 (SD 15.5) or 35.2 (SD 8.6) was found. Fatigue (MFI) decreased; anxiety and depression (HADS) did not change. CG: FACT-G remained constant in the first three months: 75.3 (SD 17.3) at t0, and 76.6 (SD 16.6) at t1. After 12 months, there was a slight increase to 78.9 (SD 18.1). FACIT-Sp scores improved significantly from t0 (31.0 - SD 8.9) to t1 (32.1 - SD 8.9) and declined again after a year (31.6 - SD 9.4). For fatigue, anxiety, and depression, no relevant changes were found. 120 patients of HG and 206 patients of CG met our criteria for matched-pairs selection. Due to large differences between the two patient populations, however, only 11 matched pairs could be formed. This is not sufficient for a comparative study. CONCLUSION: In our prospective study, we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment. It would take considerably larger samples to find matched pairs suitable for comparison in order to establish a definite causal relation between these effects and homeopathic treatment

Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality. METHODS: As part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance. RESULTS: In their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals. CONCLUSION: Gender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored

Predicting Spike Occurrence and Neuronal Responsiveness from LFPs in Primary Somatosensory Cortex

Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neronal coding) and in the clinics (e.g. for improving invasive Brain-Machine Interface devices). However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I) cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise) and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role

Comparison of LFP-Based and Spike-Based Spectro-Temporal Receptive Fields and Cross-Correlation in Cat Primary Auditory Cortex

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2–40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4–8 Hz, 8–16 Hz and 16–40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16–40 Hz filtered LFP, compared to those based on the 4–8 Hz, 8–16 Hz and 2–40 Hz filtered LFP. This suggests greater frequency specificity for the 16–40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2–40 Hz filtered LFP (5.5 mm) and the 16–40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2–40 Hz (and 16–40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex