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Objective Standard clinical characterization of patients with disorders of consciousness (DOC) relies on observation of motor output and may therefore lead to the misdiagnosis of vegetative state or minimally conscious state in patients with preserved cognition. We used conventional electroencephalographic (EEG) measures to assess a cohort of DOC patients with and without functional magnetic resonance imaging (fMRI)-based evidence of command-following, and correlated the findings with standard clinical behavioral evaluation and brain metabolic activity. Methods We enrolled 44 patients with severe brain injury. Behavioral diagnosis was established using standardized clinical assessments. Long-term EEG recordings were analyzed to determine wakeful background organization and presence of elements of sleep architecture. A subset of patients had fMRI testing of command-following using motor imagery paradigms (26 patients) and resting brain metabolism measurement using 18fluorodeoxyglucose positron emission tomography (31 patients). Results All 4 patients with fMRI evidence of covert command-following consistently demonstrated well-organized EEG background during wakefulness, spindling activity during sleep, and relative preservation of cortical metabolic activity. In the entire cohort, EEG organization and overall brain metabolism showed no significant association with bedside behavioral testing, except in a few cases when EEG was severely abnormal. Interpretation These findings suggest that conventional EEG is a simple strategy that complements behavioral and imaging characterization of DOC patients. Preservation of specific EEG features may be used to assess the likelihood of unrecognized cognitive abilities in severely brain-injured patients with very limited or no motor responses. Ann Neurol 2014;76:869–879

This study concerns the properties of neurons carrying signals for colour vision in primates. We investigated the variability of responses of individual parvocellular lateral geniculate neurons of dichromatic and trichromatic marmosets to drifting sinusoidal luminance and chromatic gratings. Response variability was quantified by the cycle-to-cycle variation in Fourier components of the response. Averaged across the population, the variability at low contrasts was greater than predicted by a Poisson process, and at high contrasts the responses were approximately 40% more variable than responses at low contrasts. The contrast-dependent increase in variability was nevertheless below that expected from the increase in firing rate. Variability falls below the Poisson prediction at high contrast, and intrinsic variability of the spike train decreases as contrast increases. Thus, while deeply modulated responses in parvocellular cells have a larger absolute variability than weakly modulated ones, they have a more favourable signal: noise ratio than predicted by a Poisson process. Similar results were obtained from a small sample of magnocellular and koniocellular ('blue-on') neurons. For parvocellular neurons with pronounced colour opponency, chromatic responses were, on average, less variable (10-15%, p

We described a novel approach to the study of how spike trains encode sensory information. This approach emphasizes the idea that spike trains are sequences of discrete events, rather than approximations to continuous signals. Aided by some simple heuristics, such as a caricature of neurons as coincidence detectors, we constructed candidate notions of "distances" between spike trains, considered as points in an abstract space. Each candidate distance was evaluated for relevance to biological encoding by determining whether it led to systematic, stimulus-dependent, clustering of the neural responses. We showed here that these distance can also be used to construct a "response space" for the neuron. The response space, which is typically not Euclidean, can represent two or three stimulus attributes. We also introduced the notion of a "consensus spike train," defined as the spike train with minimum average distance from a set of observed responses. For the distances we considered, the consensus spike train (for a particular stimulus) contained only those spikes that were present at consistent times across the observed responses to that stimulus, and thus contained fewer spikes than the typical observed responses. Nevertheless, these consensus spike trains provided an equivalent (or even superior) representation of the stimulus array.

Objective: Investigate and analyze the relationship between individual ossicular erosion and ABG among patients with cholesteatoma. Data from patients undergoing initial surgery for cholesteatoma were retrospectively reviewed to evaluate the relationships between preoperative PTA data, intraoperative assessment of individual ossicular destruction, and clinical characterization of cholesteatoma.Method: For each patient, the cholesteatoma was categorized as primary acquired, secondary acquired, congenital, or unable to discern. Ossicular destruction was graded, and ABG was calculated. For each ossicle, the relationship between degree of cholesteatoma involvement and ossicular erosion and the ABG were analyzed using univariate and multivariate linear regression.Results: A total of 158 primary cholesteatoma surgeries were performed by the senior author between 1992 and 2009 that met our inclusion criteria. The status of each ossicle was significantly associated with the ABG in a graded and independent manner;...

In their Letter to the Editor, Bagnato et al. note the utility of standard EEG in diagnosis and prognostication of patients with disorders of consciousness (DOC) in early phases of recovery. These findings are consistent with our results that chronic DOC patients with imaging-based evidence of covert command following demonstrate preservation of EEG organization as a canonical finding 1. Thus, we agree that the use of EEG in assessments of DOC patients is likely to be useful particularly in identifying immediate evidence of dissociation of motor behavior and large-scale network activity potentially supporting cognition1,2. Because of the growing consensus we would like to take this opportunity to propose that short EEG recordings should be included as standard in routine clinical evaluation and in design of research studies involving patients with DOC in addition to quantitative behavioral assessments (such as the Coma Recovery Scale-Revised (CRS-R)3). The limitations are negligible as standard EEG is cheap, widely available, easily obtainable and has well-defined standards for interpretation. This is important as currently the accuracy of the clinical EEG categorization in separating behaviorally conscious from behaviorally unconscious patients is comparable1 to highly sophisticated quantitative analysis of high-density EEG recordings performed only in a few highly-specialized research laboratories4. Nevertheless, the question remains open whether a standard visual inspection of EEG recordings may actually be as useful in assessment of patients with DOC as more technically demanding analyses. In addition, there are clear theoretical advantages of using long-term EEG recordings including adequate sampling of wakeful and sleep stages: 1) significant fluctuations in clinical status are typical in this patient population and the ‘best’ behavioral state may be missed in a short recording, 2) certain sleep features (i.e. sleep spindles) are known markers of functional integrity of cortico-thalamic circuitry, which is also thought to be important in maintaining consciousness5. Additionally, presence of sleep spindles is clearly linked to prognosis of recovery after brain injury6. In our opinion, current efforts should further aim to include long-term EEG recordings in evaluation of patients who demonstrate evidence of preserved wakeful architecture if it is feasible. However, large-scale multi-center studies will be likely needed to answer the questions about the utility of visual analysis of EEG in diagnosis and prognostication of patients with DOC.

1. A model is proposed for the effect of contrast on the first-order frequency responses of cat retinal ganglion cells. The model consists of several cascaded low pass filters ('leaky integrators') followed by a single stage of negative feed-back. 2. Values of time constants and gain of the components in this model were chosen to approximate (with least-squared deviation) experimentally measured first-order frequency responses. In the experiments used for the analysis, the visual stimulus was a sine grating modulated by a sum of sinusoids. 3. For both X cells and Y cells, the over-all gain and the time constants of the cascade of low pass filters were insensitive to contrast. 4. In all cells, the gain-bandwidth product of the negative feed-back loop was markedly increased with increasing contrast. 5. The effect of stimulation in the periphery of the receptive fields on the first-order frequency response to a centrally placed spot was identical to the effect of increasing contrast in the grating experiments. In all cases, the gain-bandwidth product of the negative feed-back loop was the only model parameter affected by peripheral stimulation. 6. A similar effect of non-linear summation was investigated for two bars located in the receptive field periphery. 7. This analysis of the contrast gain control mechanism is compared with other models of retinal function.

1. The dynamics of the subunit mechanism of individual cat Y retinal ganglion cells are investigated. In order to isolate the response of the non-linear subunit mechanism, the visual stimuli were sine gratings of a spatial frequency sufficiently high so that contrast reversal of the grating elicited no fundamental response in any spatial phase. For study of the non-linear subunit mechanism, the contrast of the spatial spine grating was varied in time by a temporal modulation signal, consisting of either a square wave or a sum of sinusoids. 2. The responses of twenty-three Y ganglion cells (sixteen on-centre, seven off-centre) to these two stimulus types were measured at a range of contrasts. Responses to the sum-of-sinusoids signal were characterized by the second-order frequency kernel. The overall size of the second-order frequency kernel was approximately proportional to contrast. The deviation from proportionality suggested a power-law scaling, with a power in the range 0.8-0.9. 3. Square-wave responses, as characterized by the post-stimulus histogram, demonstrated identical responses at both reversals of the grating. A similar contrast dependence was observed in the overall size of the square-wave responses. 4. In order to attempt to predict the square-wave responses from the sum-of-sinusoids responses, the second-order frequency kernel measured at each contrast level was fitted with a lumped linear-static non-linear-linear model. In eighteen of twenty-three cells (eleven on-centre, seven off-centre), this model provided an adequate description of the response to the sum-of-sinusoids stimulus. In these cells, the linear-static non-linear-linear model accurately reproduced the square-wave response. 5. In the remaining five ganglion cells (all on-centre), the second-order frequency kernel could not be fitted by a linear-static non-linear-linear model. This diversity of dynamical properties among Y cells was not apparent from the responses of these Y cells to the square-wave temporal stimulus. 6. In the eighteen Y ganglion cells that were fitted well with the linear-static non-linear-linear model, substantial variation of the dynamical parameters was found. However, there were systematic differences between the dynamics of the typical on-centre and off-centre ganglion cells. These differences relate to both linear stages of the model, and are not merely consequences of the lower firing rate of the off-centre cells.(ABSTRACT TRUNCATED AT 400 WORDS)