Jonathan D. Victor

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.

The effect of contrast on the transfer properties of cat retinal ganglion cells.

1. Variation in stimulus contrast produces a marked effect on the dynamics of the cat retina. This contrast effect was investigated by measurement of the responses of X and Y ganglion cells. The stimuli were sine gratings or rectangular spots modulated by a temporal signal which was a sum of sinusoids. Fourier analysis of the neural response to such a stimulus allowed us to calculate first order and second order frequency kernels. 2. The first order frequency kernel of both X and Y ganglion cells became more sharply tuned at higher contrasts. The peak amplitude also shifted to higher temporal frequency at higher contrasts. Responses to low frequencies of modulation (less than 1 Hz) grew less than proportionally with contrast. However, response amplitudes at higher modulation frequencies (greater than 4 Hz) scaled approximately proportionally with contrast. Also, there was a marked phase advance in these latter components as contrast increased. 3. The contrast effect was significantly larger for Y cells than for X cells. 4. The first order frequency kernel was measured with single sine waves as well as with the sum of sinusoids as a modulation signal. The transfer function measured in this way was much less affected by increases in contrast. This implied that stimulus energy at one temporal frequency could affect the response amplitude and phase shift at another temporal frequency. 5. Direct proof was found that modulation at one frequency modifies the response at other frequencies. This was demonstrated by perturbation experiments in which the modulation stimulus was the sum of one strong perturbing sinusoid and seven weak test sinusoids. 6. The shape of the graph of the amplitude of the first order frequency kernel vs. temporal frequency did not depend on the amplitudes of the first order components, but rather on local retinal contrast. This was shown in an experiment with a sine grating placed at different positions in the visual field. The shape of the first order kernel did not vary with spatial phase, while the magnitudes of the first order responses varied greatly with spatial phase. 7. Models for the contrast gain control mechanism are considered in the Discussion.

An Integrated Functional Magnetic Resonance Imaging Procedure for Preoperative Mapping of Cortical Areas Associated with Tactile, Motor, Language, and Visual Functions

OBJECTIVETo 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. METHODSSensitivity 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). RESULTSFor 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. CONCLUSIONThis 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.

A new statistic for steady-state evoked potentials ☆

Steady-state evoked potentials are often characterized by the amplitude and phase of the Fourier component at one or more frequencies of interest. We introduce a new statistic for the evaluation of these Fourier components. This statistic, denoted T2circ, is based on the same physiologic assumptions concerning the sources of variability of a Fourier component that are made in the use of the Rayleigh phase-coherence statistic as well as the standard T2 statistic (Hotelling 1931) for multivariate data. However, the T2circ statistic also exploits the relationship between the real and imaginary components of Fourier estimates, which is not exploited by T2, and utilizes amplitude information, which is ignored by the Rayleigh criterion. For these reasons, the T2circ statistic is more efficient than previously used criteria for detection and quantitation of steady-state responses, both in principle and in practice.

Visual discrimination of textures with identical third-order statistics

We found a new class of two-dimensional random textures with identical third-order statistics that can be effortlessly discriminated. Discrimination is based on local “granularity” differences between these iso-trigon texture pairs. This is the more surprising since it is commonly assumed that texture granularity (grain) is determined by the power spectrum which, in turn, can be obtained from the second-order statistics. Because textures with identical third-order statistics must have identical second-order statistics (i.e., identical power spectra), visible texture granularity is not controlled by power spectra, and not even by third-order statistics.

The use of m-sequences in the analysis of visual neurons: Linear receptive field properties

We have used Sutters (1987) spatiotemporal m-sequence method to map the receptive fields of neurons in the visual system of the cat. The stimulus consisted of a grid of 16 x 16 square regions, each of which was modulated in time by a pseudorandom binary signal, known as an m-sequence. Several strategies for displaying the m-sequence stimulus are presented. The results of the method are illustrated with two examples. For both geniculate neurons and cortical simple cells, the measurement of first-order response properties with the m-sequence method provided a detailed characterization of classical receptive-field structures. First, we measured a spatiotemporal map of both the center and surround of a Y-cell in the lateral geniculate nucleus (LGN). The time courses of the center responses was biphasic: OFF at short latencies, ON at longer latencies. The surround was also biphasic--ON then OFF--but somewhat slower. Second, we mapped the response properties of an area 17 directional simple cell. The response dynamics of the ON and OFF subregions varied considerably; the time to peak ranged over more than a factor of two. This spatiotemporal inseparability is related to the cells directional selectivity (Reid et al., 1987, 1991; McLean & Palmer, 1989; McLean et al., 1994). The detail with which the time course of response can be measured at many different positions is one of the strengths of the m-sequence method.

Sparse coding and high-order correlations in fine-scale cortical networks

Connectivity in the cortex is organized at multiple scales, suggesting that scale-dependent correlated activity is particularly important for understanding the behaviour of sensory cortices and their function in stimulus encoding. We analysed the scale-dependent structure of cortical interactions by using maximum entropy models to characterize multiple-tetrode recordings from primary visual cortex of anaesthetized macaque monkeys (Macaca mulatta). We compared the properties of firing patterns among local clusters of neurons (<300 μm apart) with those of neurons separated by larger distances (600–2,500 μm). Here we report that local firing patterns are distinctive: whereas multi-neuronal firing patterns at larger distances can be predicted by pairwise interactions, patterns within local clusters often show evidence of high-order correlations. Surprisingly, these local correlations are flexible and rapidly reorganized by visual input. Although they modestly reduce the amount of information that a cluster conveys, they also modify the format of this information, creating sparser codes by increasing the periods of total quiescence, and concentrating information into briefer periods of common activity. These results imply a hierarchical organization of neuronal correlations: simple pairwise correlations link neurons over scales of tens to hundreds of minicolumns, but on the scale of a few minicolumns, ensembles of neurons form complex subnetworks whose moment-to-moment effective connectivity is dynamically reorganized by the stimulus.

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 ∼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.

Determination of awareness in patients with severe brain injury using EEG power spectral analysis

OBJECTIVE To determine whether EEG spectral analysis could be used to demonstrate awareness in patients with severe brain injury. METHODS We recorded EEG from healthy controls and three patients with severe brain injury, ranging from minimally conscious state (MCS) to locked-in-state (LIS), while they were asked to imagine motor and spatial navigation tasks. We assessed EEG spectral differences from 4 to 24 Hz with univariate comparisons (individual frequencies) and multivariate comparisons (patterns across the frequency range). RESULTS In controls, EEG spectral power differed at multiple frequency bands and channels during performance of both tasks compared to a resting baseline. As patterns of signal change were inconsistent between controls, we defined a positive response in patient subjects as consistent spectral changes across task performances. One patient in MCS and one in LIS showed evidence of motor imagery task performance, though with patterns of spectral change different from the controls. CONCLUSIONS EEG power spectral analysis demonstrates evidence for performance of mental imagery tasks in healthy controls and patients with severe brain injury. SIGNIFICANCE EEG power spectral analysis can be used as a flexible bedside tool to demonstrate awareness in brain-injured patients who are otherwise unable to communicate.

A method of nonlinear analysis in the frequency domain.

A method is developed for the analysis of nonlinear biological systems based on an input temporal signal that consists of a sum of a large number of sinusoids. Nonlinear properties of the system are manifest by responses at harmonics and intermodulation frequencies of the input frequencies. The frequency kernels derived from these nonlinear responses are similar to the Fourier transforms of the Wiener kernels. Guidelines for the choice of useful input frequency sets, and examples satisfying these guidelines, are given. A practical algorithm for varying the relative phases of the input sinusoids to separate high-order interactions is presented. The utility of this technique is demonstrated with data obtained from a cat retinal ganglion cell of the Y type. For a high spatial frequency grafting, the entire response is contained in the even-order nonlinear components. Even at low contrast, fourth-order components are detectable. This suggests the presence of an essential nonlinearity in the functional pathway of the Y cell, with its singularity at zero contrast.