Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators

Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models. Burak and Fiete (2009, PLoS Comput Biol) recently examined noise in two continuous attractor models, but did not consider oscillatory interference models in detail. Here we analyze an oscillatory interference model to examine the effects of noise on its stability and spatial firing properties. We show analytically that the square of the drift in encoded position due to noise is proportional to time and inversely proportional to the number of oscillators. We also show there is a relatively fixed breakdown point, independent of many parameters of the model, past which noise overwhelms the spatial signal. Based on this result, we show that a pair of oscillators are expected to maintain a stable grid for approximately t = 5µ3/(4πσ)2 seconds where µ is the mean period of an oscillator in seconds and σ2 its variance in seconds2. We apply this criterion to recordings of individual persistent spiking neurons in postsubiculum (dorsal presubiculum) and layers III and V of entorhinal cortex, to subthreshold membrane potential oscillation recordings in layer II stellate cells of medial entorhinal cortex and to values from the literature regarding medial septum theta bursting cells. All oscillators examined have expected stability times far below those seen in experimental recordings of grid cells, suggesting the examined biological oscillators are unfit as a substrate for current implementations of oscillatory interference models. However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed

Asenapine in the Treatment od Acute Mania : a Real-World Observational Study with 6 Months Follow-up

Asenapine is a second-generation antipsychotic with a unique pharmacological profile that was recently approved for the treatment of moderate/severe manic episodes. Real-world data on rapidity of action in inpatient settings are lacking. The aims of the current real-world observational study were to evaluate: (i) short-term efficacy of asenapine after 7 days (T0-T1) in patients hospitalized for a manic episode in the course of bipolar I disorder or schizoaffective disorder (group A), (ii) differences in length of stay (LoS), and (iii) rehospitalization compared to a control population (group B) with a 6-month follow-up. Twenty patients were included in each group. The mean total Young Mania Rating Scale score decreased by 12.6 (SD \ub110.3; t(17) = 5.2, P < 0.005), implying a mean 37.8% improvement. A statistically significant reduction was observed for all Young Mania Rating Scale items, except for \u201csexual interest.\u201d The mean total BPRS score decreased by 17.2 (SD \ub114.9; t(17) = 4.9, P < 0.005). A statistically significant reduction was observed for several items, including \u201cconceptual disorganization,\u201d \u201cgrandiosity,\u201d \u201cunusual thought content,\u201d and \u201cexcitement\u201d. Length of stay was 17.9 (SD \ub19.0) days for group A and 14.7 (SD \ub112.7) days for group B; the result of the Kruskal-Wallis test showed no significant differences (\u3c72 = 2.199, P = 0.138). Despite a high discontinuation rate, only 17.7% of patients in group Awere rehospitalized in the following 6 months compared to 41.2% of those in group B (relative risk = 0.43, 95% confidence interval, 0.13\u20131.39). Findings from this small, preliminary study at least partially support the results of previous trials, confirming effectiveness and tolerability in the context of comorbidity and polypsychopharmacology

Grid alignment in entorhinal cortex

The spatial responses of many of the cells recorded in all layers of rodent medial entorhinal cortex (mEC) show mutually aligned grid patterns. Recent experimental findings have shown that grids can often be better described as elliptical rather than purely circular and that, beyond the mutual alignment of their grid axes, ellipses tend to also orient their long axis along preferred directions. Are grid alignment and ellipse orientation aspects of the same phenomenon? Does the grid alignment result from single-unit mechanisms or does it require network interactions? We address these issues by refining a single-unit adaptation model of grid formation, to describe specifically the spontaneous emergence of conjunctive grid-by-head-direction cells in layers III, V, and VI of mEC. We find that tight alignment can be produced by recurrent collateral interactions, but this requires head-direction (HD) modulation. Through a competitive learning process driven by spatial inputs, grid fields then form already aligned, and with randomly distributed spatial phases. In addition, we find that the self-organization process is influenced by any anisotropy in the behavior of the simulated rat. The common grid alignment often orients along preferred running directions (RDs), as induced in a square environment. When speed anisotropy is present in exploration behavior, the shape of individual grids is distorted toward an ellipsoid arrangement. Speed anisotropy orients the long ellipse axis along the fast direction. Speed anisotropy on its own also tends to align grids, even without collaterals, but the alignment is seen to be loose. Finally, the alignment of spatial grid fields in multiple environments shows that the network expresses the same set of grid fields across environments, modulo a coherent rotation and translation. Thus, an efficient metric encoding of space may emerge through spontaneous pattern formation at the single-unit level, but it is coherent, hence context-invariant, if aided by collateral interactions