Behavioural improvements with thalamic stimulation after severe traumatic brain injury.

Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.

Independent and redundant information in nearby cortical neurons.

In the primary visual cortex (V1), nearby neurons are tuned to similar stimulus features, and, depending on the manner and time scale over which neuronal signals are analyzed, the resulting redundancy may mitigate deleterious effects of response variability. We estimated information rates in the short-time scale responses of clusters of up to six simultaneously recorded nearby neurons in monkey V1. Responses were almost independent if we kept track of which neuron fired each spike but were redundant if we summed responses over the cluster. Redundancy was independent of cluster size. Summing neuronal responses to reduce variability discards potentially useful information, and the discarded information increases with cluster size.

Interspike intervals, receptive fields, and information encoding in primary visual cortex.

In the primate primary visual cortex (V1), the significance of individual action potentials has been difficult to determine, particularly in light of the considerable trial-to-trial variability of responses to visual stimuli. We show here that the information conveyed by an action potential depends on the duration of the immediately preceding interspike interval (ISI). The interspike intervals can be grouped into several different classes on the basis of reproducible features in the interspike interval histograms. Spikes in different classes bear different relationships to the visual stimulus, both qualitatively (in terms of the average stimulus preceding each spike) and quantitatively (in terms of the amount of information encoded per spike and per second). Spikes preceded by very short intervals (3 msec or less) convey information most efficiently and contribute disproportionately to the overall receptive-field properties of the neuron. Overall, V1 neurons can transmit between 5 and 30 bits of information per second in response to rapidly varying, pseudorandom stimuli, with an efficiency of approximately 25%. Although some (but not all) of our results would be expected from neurons that use a firing-rate code to transmit information, the evidence suggests that visual neurons are well equipped to decode stimulus-related information on the basis of relative spike timing and ISI duration.

Receptive field mechanisms of cat X and Y retinal ganglion cells.

We investigated receptive field properties of cat retinal ganglion cells with visual stimuli which were sinusoidal spatial gratings amplitude modulated in time by a sum of sinusoids. Neural responses were analyzed into the Fourier components at the input frequencies and the components at sum and difference frequencies. The first-order frequency response of X cells had a marked spatial phase and spatial frequency dependence which could be explained in terms of linear interactions between center and surround mechanisms in the receptive field. The second-order frequency response of X cells was much smaller than the first-order frequency response at all spatial frequencies. The spatial phase and spatial frequency dependence of the first-order frequency response in Y cells in some ways resembled that of X cells. However, the Y first-order response declined to zero at a much lower spatial frequency than in X cells. Furthermore, the second-order frequency response was larger in Y cells; the second-order frequency components became the dominant part of the response for patterns of high spatial frequency. This implies that the receptive field center and surround mechanisms are physiologically quite different in Y cells from those in X cells, and that the Y cells also receive excitatory drive from an additional nonlinear receptive field mechanism.

The nonlinear pathway of Y ganglion cells in the cat retina.

Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a "sandwich model" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells.

Intra-arterial cisplatin--associated optic and otic toxicity.

Over a 22-month period, we investigated optic and otic toxicity accompanying intra-arterial cisplatin therapy. Baseline and serial neurologic and ophthalmologic examinations, visual evoked potentials, and brain-stem auditory evoked potentials were performed in six patients, aged 37 to 53 years. Patients received infraophthalmic intra-arterial cisplatin (60 mg/m2) every month for three to 10 treatments (mean, six treatments). Five of the six patients had progressive optic toxicity. In two patients, the visual evoked potential prolongation preceded acuity loss by at least 4 months. Two patients had evidence of otic toxicity by either brain-stem auditory evoked potential or click threshold and brain-stem auditory evoked potential. Intra-arterial cisplatin neurotoxicity may be significant in patients with already limited survival. Visual evoked potential and brain-stem auditory evoked potential should be used to monitor patients receiving potentially neurotoxic therapy.

Common dynamics in temporal lobe seizures and absence seizures.

Similarities among the clinical features of complex partial temporal lobe seizures and absence (petit mal) seizures suggest shared underlying mechanisms, but dissimilar electrographic features of the two seizure types have cast doubt on common neuronal substrates. However, visual inspection and traditional approaches to quantitative analysis of the electroencephalogram and electrocorticogram, such as Fourier analysis, may not be appropriate to identify and characterize the highly non-linear mechanisms likely to underlie ictal events. We previously introduced a technique, non-linear autoregressive analysis, that is designed to identify non-linear dynamics in the electroencephalogram [Schiff N. D. et al. (1991) Society of Neuroscience 21st Annual Meeting, 638.6; Schiff N. D. et al. (1995) Biol. Cybern. 72, 519-526, 527-533]. The non-linear autoregressive analysis technique is aimed at describing seizure discharges as a disturbance of synchrony at the level of neuronal circuits. In absence seizures, we showed that non-linear autoregressive analysis revealed a consistent "fingerprint" of these non-linearities in 3/s discharges within and across patients. Here, we investigate the possibility that non-linear autoregressive modeling of seizure records from patients with temporal lobe epilepsy might reveal common circuit mechanisms when compared with the non-linear autoregressive analysis fingerprint of absence seizures. Electrocorticographic records of seizure activity were obtained in four patients who had received subdural grids or strips implanted in preparation for epilepsy surgery. Decomposition of the multichannel data recorded from these patients by principal component analysis revealed that at least three to five independent "generators" were required to model the data from each patient. Non-linear autoregressive analysis of these extracted generators revealed non-linear dynamics in two patients. In both patients, the temporal aspects of these non-linearities were similar to the characteristic non-linearities identified in the non-linear autoregressive analysis fingerprint of absence seizures. In particular, both patients showed a non-linear interaction of signals 90 ms in the past with signals 150 ms in the past. This was the most prominent interaction seen in all patients with absence seizures (typical and atypical). These results suggest that seizures from some patients with temporal lobe epilepsy may share common underlying circuit mechanisms with those of absence seizures. Physiological interpretations of these results are considered and proposed mechanisms are placed into the context of the alterations of consciousness seen in both epilepsies.

Evaluation of poor performance and asymmetry in the Farnsworth-Munsell 100-hue test.

A statistical method for the analysis of errors on the Farnsworth-Munsell 100-hue test is introduced. The extent of asymmetry of errors are summarized by two indices, I1 and I2, derived from Fourier analysis of the error scores for the individual caps. The second index, I2, describes the (bipolar) color axis; the first index, I1, describes (monopolar) asymmetry of performance. The present analysis differs from previous approaches based on Fourier analysis of the errors in two ways: (1) a procedure is introduced which corrects the indices I1 and I2 for the biases that result from the segmentation of the test into four boxes; (2) statistics for the significance of I1 and I2 are derived by a Monte Carlo procedure, which properly handles the complex interdependence of individual error scores for each cap.

Sensory coding in cortical neurons. Recent results and speculations.

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.

How the brain uses time to represent and process visual information(1).

Information theory provides a theoretical framework for addressing fundamental questions concerning the nature of neural codes. Harnessing its power is not straightforward, because of the differences between mathematical abstractions and laboratory reality. We describe an approach to the analysis of neural codes that seeks to identify the informative features of neural responses, rather than to estimate the information content of neural responses per se. Our analysis, applied to neurons in primary visual cortex (V1), demonstrates that the informative precision of spike times varies with the stimulus modality being represented. Contrast is represented by spike times on the shortest time scale, and different kinds of pattern information are represented on longer time scales. The interspike interval distribution has a structure that is unanticipated from the firing rate. The significance of this structure is not that it contains additional information, but rather, that it may provide a means for simple synaptic mechanisms to decode the information that is multiplexed within a spike train. Extensions of this analysis to the simultaneous responses of pairs of neurons indicate that neighboring neurons convey largely independent information, if the decoding process is sensitive to the neuron of origin and not just the average firing rate. In summary, stimulus-related information is encoded into the precise times of spikes fired by V1 neurons. Much of this information would be obscured if individual spikes were merely taken to be estimators of the firing rate. Additional information would be lost by averaging across the responses of neurons in a local population. We propose that synaptic mechanisms sensitive to interspike intervals and dendritic processing beyond simple summation exist at least in part to enable the brain to take advantage of this extra information.

Power spectra and coherence in the EEG of a vegetative patient with severe asymmetric brain damage.

OBJECTIVES: To examine differences in power spectra and intra-hemispheric coherence between the left and right hemispheres in the presence of severe asymmetric brain damage. METHODS: Power spectra and coherence functions were computed for a patient with severe damage to subcortical gray matter structures on the right side but relative preservation on the left. RESULTS: Power spectra differed modestly over the hemispheres, with greater low frequency power and less high frequency power over the more damaged right hemisphere. Coherence differed dramatically, with marked reduced coherence over the right hemisphere, particularly frontally where the damage was most extensive. CONCLUSIONS: Damage to subcortical structures of one hemisphere may result in a marked reduction in coherence in the ipsilateral EEG with only a modest change in the power spectrum. We speculate that the physiologic basis of this selective change is damage to structures mediating communication between cortical areas.

An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.

OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Complex visual textures as a tool for studying the VEP.

A method of separating components of the visual evoked potential by using complex visual textures is described. Interchange of visual textures with identical power specta and third-order autocorrelations elicits a response which may be analyzed into symmetric and asymmetric components. It is shown that the asymmetric component depends on complex attributes of form. Mechanisms that generate this component must possess nonlinear interactions among multiple areas of the visual pattern. These interactions are likely to be more complex than rectification following spatial summation. It is concluded that the asymmetric component reflects intracortical, rather than precortical, processing.

Motion mechanisms have only limited access to form information.

We investigate the roles of spatial frequency content, flicker and higher-order elements of form ("features") in the generation of motion percepts. These cues are separated through the use of dynamic visual stimuli based on stochastic textures. Flicker alone and spatial frequency content alone suffice to generate a strong motion percept, but higher-order elements of form alone generate a much weaker motion percept. Thus, even for achromatic stimuli, all pattern information is not equally available for motion processing. Furthermore, higher-order form information, which by itself does not provide a strong cue to motion, is shown to interact with other visual information to facilitate determination of direction of motion.

Illusory contour strength does not depend on the dynamics or relative phase of the inducers.

We use a new objective measure of illusory contour strength, threshold reduction for aspect ratio discrimination, to examine the effect of dynamics and relative phase on the Kanizsa illusion. We found no dependence of illusory contour strength on the relative phase of flickering inducers (in phase, antiphase, or in quadrature phase) either for the standard Kanizsa square, or for modifications that facilitated or interfered with amodal completion. Comparison with a vernier acuity task indicates that the distance between the inducers, rather than the nature of the task, accounts for the insensitivity to relative phase.

Spatial organization of nonlinear interactions in form perception.

We examined the perception of structure in a family of visual textures whose second-order correlation structure is flat. These textures were generated by two-dimensional recursion rules, in a manner which extends the construction of Julesz, Gilbert and Victor (1978; Biological Cybernetics, 31, 137-140). Textures generated by some recursion rules elicited a visually salient percept of structure, while textures generated by other recursion rules did not. Textures whose statistical structure was visually salient produced evoked responses which differed from the response evoked by completely random textures. The size of this VEP difference correlated well with psychophysical measures. Since the textures were constructed to have identical global spatial frequency spectra, models for the extraction of visual structure must be essentially nonlinear. Models based on symmetry, information content, or simple spatial extent (but not pattern) of correlation fail to explain the observed results. Models based on the cooperative interaction of pairs of nonlinear subunits provide a reasonable qualitative account of the findings. The critical model features are (i) the presence of multiple nonlinear subunits, and (ii) a second nonlinearity, such as a threshold, at the stage of combination of subunit signals.

Neither occlusion constraint nor binocular disparity accounts for the perceived depth in the 'sieve effect'.

Current notions of binocular depth perception include (1) neural computations that solve the correspondence problem and calculate retinal positional disparity, and (2) recovery of ecologically valid occlusion relationships. The former framework works well for stimuli with unambiguous interocular correspondence, but less so for stimuli without well-defined disparity cues. The latter framework has been proposed to account for the phenomenon of perceived depth in stimuli without interocular correspondence, but its mechanism remains unclear. In order to obtain more insight into the mechanism, we studied the depth percept elicited by a family of stereograms - 'sieve' stimuli, adapted from Howard (1995) [Perception, 24, 67-74] - with interocular differences but no well-defined positional disparity cue. The perceived depth was measured by comparison to references at various depths established by standard retinal disparity and was consistently found to lie behind the fixation plane. Moreover, the magnitude of the depth percept depended on both the horizontal and vertical spatial characteristics of the stimulus in ways that were at odds with constraints of occlusion geometry. In comparison to the depth percept elicited by stimuli with well-defined disparity cues, the precision of the percept from the sieve stimuli was 10-20 times worse, suggesting that a different underlying computation was involved. Thus, neither of the above frameworks accounts for the depth percept arising from these stimuli. We discuss implications of our results for physiologically based computations underlying binocular depth perception.

Investigation of a patient with severely impaired direction discrimination: evidence against the intersection-of-constraints model.

A man with presumed posterior cortical atrophy had a markedly elevated threshold for orientation discrimination (approx. 25 deg) and selective impairment of "pop-out" tasks based on orientation. Direction discrimination for moving plaids was superior to direction discrimination for their component gratings. The superior performance for plaids disappeared when the spatial frequencies of the component gratings were altered to eliminate coherence. This finding implies that extraction of plaid motion is not dependent on pre-processing within narrow spatial frequency bands. It is inconsistent with simulations based on the "intersection of constraints" model, which predict that the error rate for plaids would be larger than the error rate for gratings, particularly for the plaids composed of gratings moving at nearly opposing angles. It is consistent with models such as the Heeger [(1987) Journal of the Optical Society of America A, 4, 1455-1471] model, which extract direction from the pattern of activity across broadly-tuned spatiotemporal filters.

Comparison of thresholds for high-speed drifting vernier and a matched temporal phase-discrimination task.

For rapidly translating targets, vernier thresholds correspond to millisecond asynchronies between targets. The 'temporal hypothesis' is that these thresholds reflect the limiting sensitivity of asynchrony detectors. Previous studies showed that temporal thresholds are generally higher than vernier thresholds, but failed to reject the 'temporal hypothesis' because stimuli had differing spatiotemporal characteristics, and temporal thresholds depend strongly on stimulus and task. Here we use matched grating stimuli to test - and reject - the temporal hypothesis. Expressed as asynchrony, temporal phase discrimination was typically 10-fold poorer than vernier thresholds, and differed in dependence on spatial frequency, temporal frequency, contrast, and susceptibility to stroboscopic masks.

The role of high-order phase correlations in texture processing.

Isodipole textures are pairs of texture ensembles whose autocorrelations, and hence power spectra, are equal. Examples of readily discriminable isodipole textures are well known. Such discriminations appear to require feature extraction, since the isodipole condition eliminates ensemble differences in spatial frequency content. We studied the effects of phase decorrelation on VEP indices of discrimination of isodipole texture pairs. Phase decorrelation, which ranged from 0.125 pi radians (slight randomization) to pi radians (complete randomization), was introduced in two ways: by independent jittering of each spatial Fourier component, and by a product method, which preserved correlations among certain quadruples of spatial Fourier components, despite pairwise decorrelation. For the even/random isodipole texture pair, independent phase decorrelation greater than 0.5 pi radians markedly reduced VEP indices of texture discrimination for all check sizes, and eliminated them entirely for check sizes of 8 min or greater. However, the product method preserved texture discrimination signals even with complete pairwise randomization of spatial phases. For the triangle/random isodipole texture pair, both kinds of phase decorrelation eliminated VEP indices of texture discrimination. These results imply that isodipole texture discrimination is based on fundamentally local processing, and not on global Fourier amplitudes-since the phase manipulations which eliminate texture discrimination preserve the Fourier amplitudes. The dependence of the antisymmetric response component (the odd harmonics) on phase decorrelation and texture type is consistent with a previously proposed model for feature extraction, and leads to constraints on how texture processing is modulated by contrast. The limited contribution of global spectral characteristics for small checks is consistent with a previously identified breakdown in scale-invariant processing.