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.

Response variability of marmoset parvocellular neurons.

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<0.01) than luminance responses of equal magnitude. Conversely, non-opponent parvocellular neurons showed the opposite tendency. This is consistent with a supra-additive noise source prior to combination of cone signals. In summary, though variability of parvocellular neurons is largely independent of the way in which they combine cone signals, the noise characteristics of retinal circuitry may augment specialization of parvocellular neurons to signal luminance or chromatic contrast.

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.

Computational modeling of non-Fourier motion: further evidence for a single luminance-based mechanism.

It is generally assumed that the perception of non-Fourier motion requires the operation of some nonlinearity before motion analysis. We apply a computational model of biological motion processing to a class of non-Fourier motion stimuli designed to investigate nonlinearity in human visual processing. The model correctly detects direction of motion in these non-Fourier stimuli without recourse to any preprocessing nonlinearity. This demonstrates that the non-Fourier motion in some non-Fourier stimuli is directly available to luminance-based motion mechanisms operating on measurements of local spatial and temporal gradients.

Temporal coding of contrast in primary visual cortex: when, what, and why.

How do neurons in the primary visual cortex (V1) encode the contrast of a visual stimulus? In this paper, the information that V1 responses convey about the contrast of static visual stimuli is explicitly calculated. These responses often contain several easily distinguished temporal components, which will be called latency, transient, tonic, and off. Calculating the information about contrast conveyed in each component and in groups of components makes it possible to delineate aspects of the temporal structure that may be relevant for contrast encoding. The results indicate that as much or more contrast-related information is encoded into the temporal structure of spike train responses as into the firing rate and that the temporally coded information is manifested most strongly in the latency to response onset. Transient, tonic, and off responses contribute relatively little. The results also reveal that temporal coding is important for distinguishing subtle contrast differences, whereas firing rates are useful for gross discrimination. This suggests that the temporal structure of neurons' responses may extend the dynamic range for contrast encoding in the primate visual system.

Formal and attribute-specific information in primary visual cortex.

We estimate the rates at which neurons in the primary visual cortex (V1) of anesthetized macaque monkeys transmit stimulus-related information in response to three types of visual stimulus. The stimuli-randomly modulated checkerboard patterns, stationary sinusoidal gratings, and drifting sinusoidal gratings-have very different spatiotemporal structures. We obtain the overall rate of information transmission, which we call formal information, by a direct method. We find the highest information rates in the responses of simple cells to drifting gratings (median: 10.3 bits/s, 0.92 bits/spike); responses to randomly modulated stimuli and stationary gratings transmit information at significantly lower rates. In general, simple cells transmit information at higher rates, and over a larger range, than do complex cells. Thus in the responses of V1 neurons, stimuli that are rapidly modulated do not necessarily evoke higher information rates, as might be the case with motion-sensitive neurons in area MT. By an extension of the direct method, we parse the formal information into attribute-specific components, which provide estimates of the information transmitted about contrast and spatiotemporal pattern. We find that contrast-specific information rates vary across neurons-about 0.3 to 2.1 bits/s or 0.05 to 0.22 bits/spike-but depend little on stimulus type. Spatiotemporal pattern-specific information rates, however, depend strongly on the type of stimulus and neuron (simple or complex). The remaining information rate, typically between 10 and 32% of the formal information rate for each neuron, cannot be unambiguously assigned to either contrast or spatiotemporal pattern. This indicates that some information concerning these two stimulus attributes is confounded in the responses of single neurons in V1. A model that considers a simple cell to consist of a linear spatiotemporal filter followed by a static rectifier predicts higher information rates than are found in real neurons and completely fails to replicate the performance of real cells in generating the confounded information.

General strategy for hierarchical decomposition of multivariate time series: implications for temporal lobe seizures.

We describe a novel method for the analysis of multivariate time series that exploits the dynamic relationships among the multiple signals. The approach resolves the multivariate time series into hierarchically dependent underlying sources, each driven by noise input and influencing subordinate sources in the hierarchy. Implementation of this hierarchical decomposition (HD) combines principal components analysis (PCA), autoregressive modeling, and a novel search strategy among orthogonal rotations. For model systems conforming to this hierarchical structure, HD accurately extracts the underlying sources, whereas PCA or independent components analysis does not. The interdependencies of cortical, subcortical, and brainstem networks suggest application of HD to multivariate measures of brain activity. We show first that HD indeed resolves temporal lobe ictal electrocorticographic data into nearly hierarchical form. A previous analysis of these data identified characteristic nonlinearities in the PCA-derived temporal components that resembled those seen in absence (petit mal) seizure electroencephalographic traces. However, the components containing these characteristic nonlinearities accounted for only a small fraction of the power. Analysis of these data with HD reveals furthermore that components containing characteristic nonlinearities, though small, can be at the origin of the hierarchy. This finding supports the link between temporal lobe and absence epilepsy.

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.

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.

Asymptotic bias in information estimates and the exponential (Bell) polynomials.

We present a new derivation of the asymptotic correction for bias in the estimate of information from a finite sample. The new derivation reveals a relationship between information estimates and a sequence of polynomials with combinatorial significance, the exponential (Bell) polynomials, and helps to provide an understanding of the form and behavior of the asymptotic correction for bias.

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.

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.

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.

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.

Visual function and brain organization in non-decussating retinal-fugal fibre syndrome.

Functional neuroimaging, psychophysical and electrophysiological investigations were performed in a patient with non-decussating retinal-fugal fibre syndrome, an inborn achiasmatic state in which the retinal projections of each eye map entirely to the ipsilateral primary visual cortex. Functional magnetic resonance imaging (fMRI) studies showed that for monocularly presented simple visual stimuli, only the ipsilateral striate cortex was activated. Within each hemisphere's striate cortex, the representation of the two hemifields overlapped extensively. Despite this gross miswiring, visual functions that require precise geometrical information (such as vernier acuity) were normal, and there was no evidence for the confounding of visual information between the overlapping ipsi-lateral and contralateral representations. Contrast sensitivity and velocity judgments were abnormal, but their dependence on the orientation and velocity of the targets suggests that this deficit was due to ocular instabilities, rather than the miswiring per se. There were no asymmetries in performance observed in visual search, visual naming or illusory contour perception. fMRI analysis of the latter two tasks under monocular viewing conditions indicated extensive bilateral activation of striate and prestriate areas. Thus, the remarkably normal visual behavior achieved by this patient is a result of both the plasticity of visual pathways, and efficient transfer of information between the hemispheres.

Two-frequency analysis of interactions elicited by Vernier stimuli.

In five subjects, we measured visual evoked potentials (VEPs) elicited by Vernier targets in which the contrast of the two components of the stimuli were modulated by sinusoids at distinct frequencies fl and f2. This approach allows for the extraction of VEP signatures of spatial interactions, namely, responses at intermodulation frequencies n1f1 + n2f2, without the need to introduce motion into the stimulus. The most prominent interactions were at the sum frequency f1 + f2, and, for frequency pairs that were sufficiently separated, the difference frequency f1- f2. These responses had a systematic dependence on the temporal parameters of the stimulus, corresponding to an effective latency of 145 to 165 ms. Fourth-order interactions were also detected, particularly at the frequencies 2f1 +/- 2f2. These VEP signatures of interaction were similar to interactions seen for colinear line segments separated by a gap. Thus, for Vernier stimuli devoid of motion, VEP signatures of interaction are readily detected but are not specific to hyperacuity displacements. The distribution of interactions across harmonic orders is consistent with local rectification preceding the spatial interactions. Their effective latencies and dependence on spatial parameters are consistent with interactions within V1 receptive fields or mediated by horizontal connections between cells with a similar orientation tuning within V1.

Gating of local network signals appears as stimulus-dependent activity envelopes in striate cortex.

Neuronal activity often is treated as a composition of a stimulus-driven component and a second component that corrupts the signal, adding or deleting spikes at random. Standard quantitative methods such as peristimulus histograms and Fourier analysis use stimulus-locked averaging to enhance detection of the driven component of neuronal responses and de-emphasize the "noise." However, neural activity also includes bursts, oscillations, and other episodic events that standard averaging methods overlook. If this activity is stimulus independent, it can be characterized by standard power spectral analysis (or autocorrelation). But activity that is excited by (but not temporally locked to) the visual stimulus cannot be characterized by averaging or standard spectral analysis. Phase-locked spectral analysis (PLSA) is a new method that examines this "residual" activity-the difference between the individual responses to each cycle of a periodic stimulus and their average. With PLSA, residual activity is characterized in terms of temporal envelopes and their carriers. Previously, PLSA demonstrated broadband interactions between periodic visual stimuli and fluctuations in the local field potential of macaque V1. In the present study, single-unit responses (SUA) from parafoveal V1 in anesthetized macaque monkey are examined with this technique. Recordings were made from 21 neurons, 6 of which were recorded in pairs along with multiunit activity (MUA) from separate electrodes and 8 of which were recorded along with MUA from the same electrode. PLSA was applied to responses to preferred (orientation, direction, and spatial frequency) and nonpreferred drifting gratings. For preferred stimuli, all cells demonstrated broadband (1-10 Hz and higher) residual activity that waxed and waned with the stimulus cycle, suggesting that changes in the residual activity are introduced routinely by visual stimulation. Moreover, some reconstructed envelopes indicate that the residual activity was sharply gated by the stimulus cycle. Oscillations occasionally were seen in the power spectrum of single units. Phase-locked cross-spectra were determined for 3 SUA/SUA pairs and 11 SUA/MUA pairs. Residual activity in the cross-spectra was generally much less than the residual activity determined separately from each neuron. The reduction in the residual activity in the cross-spectra suggests that nearby neurons may gate inputs from distinct and relatively independent neuronal subpopulations that together generate the background rhythms of striate cortex.

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.

Topical papaverine and facial nerve dysfunction in cerebellopontine angle surgery.

HYPOTHESIS: Topical application of 3% papaverine hydrochloride in the cerebellopontine angle (CPA) produces reversible conduction block of the facial nerve. BACKGROUND: A case of loss of spontaneous and evoked facial muscle activity, and transient postoperative facial paralysis, after topical application of papaverine in the CPA during surgery for an acoustic neuroma using intraoperative cranial nerve monitoring is reported. Other cases of transient neurologic dysfunction after use of this drug have been reported. METHODS: A rabbit model of CPA surgery via suboccipital craniectomy, with intraoperative monitoring of the facial nerve, was used in this experiment. RESULTS: No significant difference in facial muscle stimulation thresholds was identified after application of varying concentrations of papaverine to the facial nerve in the CPA. CONCLUSION: Although the intraoperative event described in the report is suggestive of an effect of papaverine on facial nerve function, this effect could not be reproduced in an established animal model of CPA surgery.