Information processing in severe disorders of consciousness: vegetative state and minimally conscious state.

OBJECTIVE: To study the presence of electrophysiological indicators of remaining cortical functions in patients with persistent vegetative state (PVS) and minimally conscious state (MCS). Previous electrophysiological and PET data indicated that some PVS patients have partially intact cortical processing functions. However, it remains unclear whether the reported patients were representative for PVS population or just some exceptional cases. Methods: Event-related brain responses to stimuli of different complexity levels, recorded in 98 patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four main indicators of cortical functions were: (i) N1-P2 complex as an index of simple, undifferentiated cortical processing; (ii) mismatch negativity as an index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave as an index of deep cortical analysis of physical stimuli, and (iv) brain responses to semantic stimuli. RESULTS: Cortical responses were found in all PVS patients with a background EEG activity > 4 Hz. All responses investigated, including those to semantic stimuli that indicated comprehension of meaning, occurred significantly above chance, though less frequently than in patients with severe brain injuries who were conscious. CONCLUSIONS: Cortical responses were lacking in most patients with severe EEG slowing (< 4 Hz). Follow-up data revealed that the presence of a mismatch negativity, a short disease duration, and the traumatic etiology were related to a better outcome. SIGNIFICANCE: The data show that in a subpopulation of PVS patients with preserved thalamocortical feedback connections, remaining cortical information processing is a consistent finding and may even involve semantic levels of processing.     

Effect of an ACTH 4–9 analog on human cortical evoked potentials in a constant foreperiod reaction time paradigm

Thirty male volunteers, receiving either 40 mg ACTH 4–9 analog (Org 2766) or 40 mg placebo in a double-blind setting, participated in an experiment which investigated cortical evoked potentials, slow cortical potentials, EEG power spectrum, heart rate and response speed within a constant foreperiod reaction time paradigm. EEG was recorded frontally, precentrally and parietally. Subjects receiving Org 2766 responded significantly faster than placebo controls. Larger or advanced evoked potential components, a smaller late slow wave component, a tendency for more activity in lower alpha range and more pronounced decrease in mean heart rate across trials were found in peptide subjects as compared to placebo controls. These results suggest an effect of Org 2766 on cortical processes associated with early stimulus selection and processing.     

Attentional modulation of cortical neuromagnetic gamma response to biological movement

Processing of biological motion represented solely by a set of lights on the joints of a human body is traditionally viewed as largely independent of attention. Here, by manipulating attention-related task demands, we assess changes in the neuromagnetic cortical response to a point-light walker. Irrespective of task demands, biological motion evokes an increase in oscillatory gamma activity over the left parieto-occipital region at 80 ms post-stimulus. Only an attended walker, however, yielded further peaks over the right parietal (120 ms) and temporal (155 ms) cortices. By contrast, the magnetoencephalographic (MEG) response to an ignored walker is restricted to the left parieto-occipital region. In addition, peaks in oscillatory activity occur in response to both attended (canonical and scrambled) configurations at 180-200 ms from stimulus onset over the right fronto-temporal regions, most likely reflecting maintenance of the target configuration in working memory. For the first time, we demonstrate that the time course and topographic dynamics of oscillatory gamma activity in response to biological movement undergoes top-down influences and can be profoundly modulated by the withdrawal of attention.     

Electromagnetic evidence of altered visual processing in autism

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli and enhanced activity of early visual areas. Ten autistic and ten matched control participants underwent 151-channel whole-head magnetoencephalography. Participants were presented with 400 embedded or isolated letters (‘S’ or ‘H’) and asked to indicate which of the two letters was shown. Performance was equal in both groups, but event-related magnetic fields differed between groups in an early (100–150 ms) and a later (350–400 ms) time window. In the early time window, autistic individuals differed from control participants in the embedded, but not in the isolated condition, reflecting reduced processing of the irrelevant context in autistic individuals. In the later time window, amplitude differences between the embedded and isolated conditions were measured in control participants only, suggesting that “disembedding” processes were not required in autistic individuals. Source localisation indicated that activity in individuals with ASD peaked in the primary visual cortex in both conditions and time windows indicating an effortless (automatic, bottom-up) local process, whereas activity in controls peaked outside the visual cortex.     

The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: a magnetoencephalographic study

Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to (i) assess cerebrocortical insulin effects in humans, (ii) compare these effects between 10 lean and 15 obese subjects, and (iii) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity (P = 0.046) and the beta and theta band of spontaneous cortical activity (P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < -0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent (P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.     

A new (semantic) reflexive brain-computer interface: in search for a suitable classifier

The goal of the current study is to find a suitable classifier for electroencephalogram (EEG) data derived from a new learning paradigm which aims at communication in paralysis. A reflexive semantic classical (Pavlovian) conditioning paradigm is explored as an alternative to the operant learning paradigms, currently used in most brain-computer interfaces (BCIs). Comparable with a lie-detection experiment, subjects are presented with true and false statements. The EEG activity following true and false statements was classified with the aim to separate covert ‘yes’ from covert ‘no’ responses.Four classification algorithms are compared for classifying off-line data collected from a group of 14 healthy participants: (i) stepwise linear discriminant analysis (SWLDA), (ii) shrinkage linear discriminant analysis (SLDA), (iii) linear support vector machine (LIN-SVM) and (iv) radial basis function kernel support vector machine (RBF-SVM).The results indicate that all classifiers perform at chance level when separating conditioned ‘yes’ from conditioned ‘no’ responses. However, single conditioned reactions could be successfully classified on a single-trial basis (single conditioned reaction against a baseline interval). All of the four investigated classification methods achieve comparable performance, however results with RBF-SVM show the highest single-trial classification accuracy of 68.8%. The results suggest that the proposed paradigm may allow affirmative and negative (disapproving negative) communication in a BCI experiment.     

Toward a brain-computer interface for Alzheimer's disease patients by combining classical conditioning and brain state classification

Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.     

Task-specific plasticity of somatosensory cortex in patients with writer's cramp

Focal dystonias such as writer's cramp are characterized by muscular cramps that accompany the execution of specific motor tasks. Until now, the pathophysiology of focal dystonia remains incompletely understood. Recent studies suggest that the development of writer's cramp is related to abnormal organization of primary somatosensory cortex (SI), which in turn leads to impaired motor function. To explore contributions of SI on mechanisms of task specificity in focal dystonia, we investigated dynamic alterations in the functional organization of SI as well as sensory-motor gating for rest, left- and right-handed writing and brushing in writer's cramp patients and healthy controls. The functional organization of somatosensory cortex was assessed by neuromagnetic source imaging (151 channel whole-head MEG). In accordance with previous reports, distances between cortical representations of thumb and little finger of the affected hand were smaller in patients compared to healthy subjects. However, similar to healthy controls, patients showed normal modulation of the functional organization of SI as induced by the execution of different motor tasks. Both in the control subjects and patients, cortical distances between representations of thumb and little finger increased when writing and brushing compared to the resting condition. Although, cramps only occured during writing, no differences in the organization of SI were seen among motor tasks. Our data suggest that despite alterations in the organization of primary somatosensory cortex in writer's cramp, the capability of SI to adapt dynamically to different tasks is not impaired.     

Complexity of electrocortical dynamics in children: developmental aspects

Dimensional complexity (DCx) is an EEG measure derived from nonlinear systems theory that can be indicative of the global dynamical complexity of electrocortical activity. This study examined developmental changes in DCx, as well as the effects of cognitive tasks, gender, and brain topography, and compared DCx with traditional spectral power measures. EEG was recorded in three groups of children at mean age of 7.5 (n = 37), 13.8 (n = 42), and 16.4 (n = 56) years at rest and during the performance of verbal and spatial cognitive tasks. DCx measured both at rest and during tasks increased with age. Specific effects of brain topography, condition, and gender became stronger with age, suggesting an increase in structural and functional differentiation of the cortex. Hemispheric asymmetry of DCx recorded during tasks also increased with age, with the task-induced DCx reduction being stronger in the left hemisphere. Gender differences in DCx suggested faster cerebral maturation in girls over late adolescence. Relationships between DCx and spectral power varied as a function of tasks and scalp locations, suggesting that these EEG measures can reflect different aspects of cortical functioning.