Altered network properties of the fronto-parietal network and the thalamus in impaired consciousness.

Recovery of consciousness has been associated with connectivity in the frontal cortex and parietal regions modulated by the thalamus. To examine this model and to relate alterations to deficits in cognitive functioning and conscious processing, we investigated topological network properties in patients with chronic disorders of consciousness recovered from coma. Resting state fMRI data of 34 patients with unresponsive wakefulness syndrome and 25 in minimally conscious state were compared to 28 healthy controls. We investigated global and local network characteristics. Additionally, behavioral measures were correlated with the local metrics of 28 regions within the fronto-parietal network and the thalamus. In chronic disorders of consciousness, modularity at the global level was reduced suggesting a disturbance in the optimal balance between segregation and integration. Moreover, network properties were altered in several regions which are associated with conscious processing (particularly, in medial parietal, and frontal regions, as well as in the thalamus). Between minimally conscious and unconscious patients the local efficiency of medial parietal regions differed. Alterations in the thalamus were particularly evident in non-conscious patients. Most of the regions affected in patients with impaired consciousness belong to the so-called 'rich club' of highly interconnected central nodes. Disturbances in their topological characteristics have severe impact on information integration and are reflected in deficits in cognitive functioning probably leading to a total breakdown of consciousness.

EEG-response consistency across subjects in an active oddball task.

The active oddball paradigm is a candidate task for voluntary brain activation. Previous research has focused on group effects, and has largely overlooked the potential problem of interindividual differences. Interindividual variance causes problems with the interpretation of group-level results. In this study we want to demonstrate the degree of consistency in the active oddball task across subjects, in order to answer the question of whether this task is able to reliably detect conscious target processing in unresponsive patients. We asked 18 subjects to count rare targets and to ignore frequent standards and rare distractors in an auditory active oddball task. Event-related-potentials (ERPs) and time-frequency data were analyzed with permutation-t-tests on a single subject level. We plotted the group-average ERPs and time-frequency data, and evaluated the numbers of subjects showing significant differences between targets and distractors in certain time-ranges. The distinction between targets/distractors and standards was found to be significant in the time-range of the P300 in all participants. In contrast, significant differences between targets and distractors in the time-range of the P3a/b were found in 8 subjects, only. By including effects in the N1 and in a late negative component there remained 2 subjects who did not show a distinction between targets and distractors in the ERP. While time-frequency data showed prominent effects for target/distractor vs. standard, significant differences between targets and distractors were found in 2 subjects, only. The results suggest that time-frequency- and ERP-analysis of the active oddball task may not be sensitive enough to detect voluntary brain activation in unresponsive patients. In addition, we found that time-frequency analysis was even less informative than ERPs about the subject's task performance. Despite suggesting the use of more sensitive paradigms and/or analysis techniques, the present results give further evidence that electroencephalographic research should rely more strongly on single-subject analysis because interpretations of group-effects may be misleading.

Real movement vs. motor imagery in healthy subjects.

Motor imagery tasks are well established procedures in brain computer interfaces, but are also used in the assessment of patients with disorders of consciousness. For testing awareness in unresponsive patients it is necessary to know the natural variance of brain responses to motor imagery in healthy subjects. We examined 22 healthy subjects using EEG in three conditions: movement of both hands, imagery of the same movement, and an instruction to hold both hands still. Single-subject non-parametric statistics were applied to the fast-Fourier transformed data. Most effects were found in the α- and ß-frequency ranges over central electrodes, that is, in the µ-rhythm. We found significant power changes in 18 subjects during movement and in 11 subjects during motor imagery. In 8 subjects these changes were consistent over both conditions. The significant power changes during movement were a decrease of µ-rhythm. There were 2 subjects with an increase and 9 subjects with a decrease of µ-rhythm during imagery. α and ß are the most responsive frequency ranges, but there is a minor number of subjects who show a synchronization instead of the more common desynchronization during motor imagery. A (de)synchronization of µ-rhythm can be considered to be a normal response.

Inter-individual variability of oscillatory responses to subject's own name. A single-subject analysis.

In previous studies event-related potentials and oscillations in response to subject's own name have been analyzed extensively on group-level in healthy subjects and in patients with a disorder of consciousness. Subject's own name as a deviant produces a P3. With equiprobable stimuli, non-phase-locked alpha oscillations are smaller in response to subject's own name compared to other names or subject's own name backwards. However, little is known about replicability on a single-subject level. Seventeen healthy subjects were assessed in an own-name paradigm with equiprobable stimuli of subject's own name, another name, and subject's own name backwards. Event-related potentials and non-phase locked oscillations were analyzed with single-subject, non-parametric statistics. No consistent results were found either for ERPs or for the non-phase locked changes of oscillatory activities. Only 4 subjects showed a robust effect as expected, that is, a lower activity in the alpha-beta range to subject's own name compared to other conditions. Four subjects elicited a higher activity for subject's own name. Thus, analyzing the EEG reactivity in the own-name paradigm with equiprobable stimuli on a single-subject level yields a high variance between subjects. In future research, single-subject statistics should be applied for examining the validity of physiologic measurements in other paradigms and for examining the pattern of reactivity in patients.

EEG frequency analysis of responses to the own-name stimulus.

OBJECTIVE: The neuronal response to hearing a subject's own (SON) compared with other names has been examined in healthy subjects as well as in patients with disorders of consciousness. So far, on electroencephalographic data, only event-related potentials (ERPs) were considered. In this study, we examined the frequency properties of SON. METHODS: Data of 17 healthy subjects were processed for equiprobable stimuli of SON, other- and own-name backwards by calculating ERPs, evoked and induced activity for a period of 2000 ms from stimulus onset in the delta, theta, lower and upper alpha bands and averaging for four consequent temporal segments of 500 ms each. RESULTS: For SON, the N1 component's amplitude was larger, while induced activity in the alpha band decreased in the second temporal segment (of 500-1000 ms). No differences between other- and own-name backwards were found. CONCLUSIONS: The late reactivity may indicate responses to a stimulus after having recognised it. Alpha is known to play a role in attention and alertness. The results may reflect the fact that the SON stimulus enhances alertness. SIGNIFICANCE: The findings correlate previous work about alertness and alpha activity with those about attention capturing of the SON stimulus. We suggest using frequency analysis in research on disorders of consciousness.

Functional involvement of the cerebral cortex following paramedian bithalamic infarction.

To investigate further the functional mechanisms underlying the so-called 'loss of psychic self-activation' following paramedian bithalamic lesions, we used transcranial magnetic stimulation (TMS) in a patient who presented with this clinical picture after paramedian bithalamic infarction due to arterial occlusion. The patient showed higher motor thresholds than the controls; the cortical silent period and intracortical inhibition to paired-pulse stimulation, two different forms of inhibition that are believed to reflect GABAergic mechanisms, were significantly increased; short latency afferent inhibition (SAI), a technique that may give direct information about the function of some cholinergic circuits in the human brain, was significantly reduced. This study first demonstrates that there are changes in the intracortical excitatory and inhibitory circuits in this neurobehavioral syndrome, that lead to cortical hypoexcitability. The modulation in GABAergic activity may result in excitability changes in those cholinergic cortical networks that are involved in SAI. TMS may provide important information on connections between the thalamus and cortex and may help in better understanding the role of the thalamo-cortical relationship in behavioural changes associated with thalamic stroke.