Mary M. Conte

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.

Visual evoked potentials in dyslexics and normals: failure to find a difference in transient or steady-state responses.

We measured transient and steady-state checkerboard contrast-reversal visual evoked potentials (VEPs) in ten dyslexics, five patient controls, and 11 normals over a range of contrasts and luminances. Latency, amplitude, and phase measurements failed to distinguish the responses of dyslexics from those of normals or patient controls. Decreases in luminance or contrast resulted in an increased latency of the transient VEP in all groups, but these changes also did not distinguish the responses of dyslexics from those of the controls. Response variability was similar in dyslexics and normals, but was increased in subjects with attention deficit-hyperactivity disorder (ADHD). Performance on standardized psychometric testing did differentiate the dyslexics from controls, but did not correlate with VEP responses.

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.

Nonlinear preprocessing in short-range motion.

The phenomenon of non-Fourier motion (visually perceived motion that cannot be explained simply on the basis of the autocorrelation structure of the visual stimulus) is well recognized, and is generally considered to be due to nonlinear preprocessing of the visual stimulus prior to a stage of standard motion analysis. We devised a sequence of novel visual stimuli in which the availability of a motion stimulus depends on the nature of the nonlinear preprocessing: an nth order stimulus Pn will generate a perception of motion if it is preprocessed by a nonlinearity of polynomial order n or greater, but not if preprocessed by a nonlinearity of polynomial order less than n. We found that unambiguous motion direction was perceived for P2, P3, and P4, but not for higher-order stimuli, and we measured the contrast thresholds for direction discrimination with superimposed noise. We found that an asymmetric compressive nonlinearity can, in a unified fashion, account for these results, while a purely quadratic nonlinearity or a rectification of the form T(p) = magnitude of p cannot. We compared velocity discrimination judgements for second-order non-Fourier stimuli (P2) with standard drifting gratings. Although velocity comparisons were veridical, uncertainties were greater for the non-Fourier stimuli. This could be reproduced by substituting a Fourier grating with superimposed noise for the non-Fourier grating. These findings are consistent with a single pathway which processes both Fourier and non-Fourier short-range motion, and are discussed in the context of other investigations which have been interpreted as demonstrating separate pathways.

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.

Preservation of electroencephalographic organization in patients with impaired consciousness and imaging‐based evidence of command‐following

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.

Cortical interactions in texture processing: scale and dynamics.

We investigate the neural computations underlying pattern processing with stimuli based on textures balanced for spatial frequency content (and second-order correlations) but not for higher-order correlations (Julesz et al. 1978). Interchange between two such isodipole textures produces a robust human visual evoked potential (VEP). The difference in population activity driven by two isodipole textures is quantified by the antisymmetric component of the VEP. Statistical properties of the textures eliminate contributions from linear mechanisms to the antisymmetric VEP. The dependence of the antisymmetric VEP on check size and fourth-order correlation statistics is used to test nonlinear models for the underlying neural computations. Linear summation, followed by a simple nonlinearity (such as rectification, saturation, or threshold), is inconsistent with the data. More elaborate models, in which a second nonlinear stage combines the output of local nonlinear mechanisms, are consistent with the data, provided that an appropriate spatial scale is chosen for the second stage of processing. For checks 4 min or smaller, the deduced interaction length is 10-15 min. For checks larger than 4 min, the interaction length is proportional to check size.

Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. DOI: http://dx.doi.org/10.7554/eLife.01157.001

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.

Coherence and transparency of moving plaids composed of Fourier and non-Fourier gratings.

We examined the perceptual coherence of two-component moving plaids. The gratings that constituted the plaids were either standard Fourier gratings (F), in which luminance was determined by a drifting sinusoid, or non-Fourier gratings (NF), in which the contrast of a random background was modulated by a drifting sinusoid. These NF gratings are examples of stimuli that generate a compelling percept of motion, even though they fail to elicit a motion signal from motion analyzers based on standard cross-correlation (Chubb & Sperling, 1988). Naive observers viewed three types of stimuli consisting of superpositions of these two components: (1) two standard drifting gratings (F/F), (2) two non-Fourier drifting gratings (NF/NF), and (3) one standard and one non-Fourier drifting grating (F/NF). As expected, the F/F stimulus yielded a compelling percept of coherent motion. The dominant percept of all the observers for the NF/NF stimulus was one of coherent motion, provided that both gratings were visible and of approximately equal contrast. None of the observers reported a dominant percept of coherent motion for the F/NF condition, over a wide range of contrasts for the two grating components and across two varieties of NF gratings. In view of the results of Albright (1992) and Albright and Chaudhuri (1989), that show that single cells in macaque V1 and MT respond to both F and NF motion, one cannot interpret our findings as evidence that F and NF motion are processed independently. Alternative, “higher level” interpretations based on the intrinsically ambiguous nature of the stimuli and physical laws governing the appearance of transparent objects are discussed.