Task-free spectral EEG dynamics track and predict patient recovery from severe acquired brain injury.

For some patients, coma is followed by a state of unresponsiveness, while other patients develop signs of awareness. In practice, detecting signs of awareness may be hindered by possible impairments in the patient's motoric, sensory, or cognitive abilities, resulting in a substantial proportion of misdiagnosed disorders of consciousness. Task-free paradigms that are independent of the patient's sensorimotor and neurocognitive abilities may offer a solution to this challenge. A limitation of previous research is that the large majority of studies on the pathophysiological processes underlying disorders of consciousness have been conducted using cross-sectional designs. Here, we present a study in which we acquired a total of 74 longitudinal task-free EEG measurements from 16 patients (aged 6-22 years, 12 male) suffering from severe acquired brain injury, and an additional 16 age- and education-matched control participants. We examined changes in amplitude and connectivity metrics of oscillatory brain activity within patients across their recovery. Moreover, we applied multi-class linear discriminant analysis to assess the potential diagnostic and prognostic utility of amplitude and connectivity metrics at the individual-patient level. We found that over the course of their recovery, patients exhibited nonlinear frequency band-specific changes in spectral amplitude and connectivity metrics, changes that aligned well with the metrics' frequency band-specific diagnostic value. Strikingly, connectivity during a single task-free EEG measurement predicted the level of patient recovery approximately 3 months later with 75% accuracy. Our findings show that spectral amplitude and connectivity track patient recovery in a longitudinal fashion, and these metrics are robust pathophysiological markers that can be used for the automated diagnosis and prognosis of disorders of consciousness. These metrics can be acquired inexpensively at bedside, and are fully independent of the patient's neurocognitive abilities. Lastly, our findings tentatively suggest that the relative preservation of thalamo-cortico-thalamic interactions may predict the later reemergence of awareness, and could thus shed new light on the pathophysiological processes that underlie disorders of consciousness.

EEG theta and beta power spectra in adolescents with ADHD versus adolescents with ASD + ADHD.

Attention problems are common in youngsters with attention deficit hyperactivity disorder (ADHD) as well as in adolescents with combined autism spectrum disorder (ASD) and ADHD. However, it is unknown whether there is psychophysiological overlap and/or a difference in electroencephalogram (EEG) power spectra between ADHD and comorbid ASD and ADHD (ASD + ADHD), on and off stimulant medication. To explore potential differences and overlap, measures of theta and beta power in adolescents diagnosed with ADHD (n = 33) versus adolescents with combined ASD + ADHD (n = 20), categorized by stimulant medication use (57 % of the total sample), were compared. EEG measures were acquired in three conditions: (1) resting state, eyes closed (2) resting state, eyes open and (3) during an oddball task. In addition, performance on the d2 attention test was analyzed. Adolescents with ADHD displayed more absolute theta activity than adolescents with ASD + ADHD during the eyes open and task conditions, independent of stimulant medication use. In addition, only the adolescents with ADHD showed an association between diminished attention test performance and increased theta in the eyes open condition. Results of the current study suggest that although there is behavioral overlap between ADHD characteristics in adolescents with ADHD and adolescents with combined ASD + ADHD, the underlying psychophysiological mechanisms may be different. Adolescents with ASD + ADHD exhibited fewer of the EEG physiological signs usually associated with ADHD, although there was an overlap in attentional problems between the groups. This may indicate that treatments developed for ADHD work differently in some adolescents with ASD + ADHD and adolescents with ADHD only.

Cardiac reactivity and stimulant use in adolescents with autism spectrum disorders with comorbid ADHD versus ADHD.

A large number of youngsters with autism spectrum disorders (ASD) display comorbid attention deficit/hyperactivity disorder (ADHD) symptoms. However, previous studies are not conclusive whether psychophysiological correlates, like cardiac reactivity, are different for ASD with comorbid ADHD (ASD+) compared to ADHD. Therefore, the current study investigated (dis)similarities in cardiac reactivity and attention task performance. In a clinical sample, adolescents diagnosed with ASD+ (n = 20) versus ADHD (n = 36) and stimulant medication use (56 %) were compared during a baseline with eyes closed and task performance. Results for cardiac reactivity were similar for both diagnostic groups. Stimulant-medicated adolescents showed decreased adaptation of LF/HF ratio and faster reaction times than stimulant-free adolescents. The current study underlines the psychophysiological overlap of ADHD symptoms in adolescents with ASD+ and adolescents with ADHD.

Visual processing during recovery from vegetative state to consciousness: comparing behavioral indices to brain responses.

BACKGROUND: Auditory stimulation is often used to evoke responses in unresponsive patients who have suffered severe brain injury. In order to investigate visual responses, we examined visual evoked potentials (VEPs) and behavioral responses to visual stimuli in vegetative patients during recovery to consciousness. METHODS: Behavioral responses to visual stimuli (visual localization, comprehension of written commands, and object manipulation) and flash VEPs were repeatedly examined in eleven vegetative patients every two weeks for an average period of 2.6months, and patients' VEPs were compared to a healthy control group. Long-term outcome of the patients was assessed 2-3years later. RESULTS: Visual response scores increased during recovery to consciousness for all scales: visual localization, comprehension of written commands, and object manipulation. VEP amplitudes were smaller, and latencies were longer in the patient group relative to the controls. VEPs characteristics at first measurement were related to long-term outcome up to three years after injury. CONCLUSIONS: Our findings show the improvement of visual responding with recovery from the vegetative state to consciousness. Elementary visual processing is present, yet according to VEP responses, poorer in vegetative and minimally conscious state than in healthy controls, and remains poorer when patients recovered to consciousness. However, initial VEPs are related to long-term outcome.

Mismatch negativity predicts recovery from the vegetative state.

OBJECTIVE: Mismatch negativity (MMN) is an automatic event related brain response, well investigated in the acute phase after severe brain injury: the presence of a MMN is often found to predict the emergence from coma, and the exclusion of shifting into a vegetative state (VS). In the present study MMN was examined during recovery from VS. METHODS: Ten vegetative patients were repeatedly examined every 2 weeks for an average period of 3.5 months. Amplitudes and latencies were related to the patients' recovery from VS to consciousness, and to a healthy norm group. In addition, MMN was examined on its prognostic value in VS patients, in predicting recovery to consciousness and long-term functional outcome. RESULTS: With recovery to consciousness MMN-amplitudes increased. A sudden increase was seen in MMN amplitude when patients started to show inconsistent behavioural responses to simple commands. At this level MMN resembled the MMN response as was seen in the norm group. In addition, the MMN-amplitude and latency during the first measurement predicted the patients' outcome on recovery to consciousness. CONCLUSIONS: With recovery from VS to consciousness the ability to process auditory stimulus deviance increases. A sudden enhancement in MMN-amplitude preceded overt communication with the environment. This might be indicative of the consolidation of neural networks underlying overt communication. Moreover, MMN can be helpful in identifying the ability to recover from VS. SIGNIFICANCE: MMN can be used to track recovery from the vegetative state in the post-acute phase after severe brain injury. In addition, MMN can be used to predict the ability to recover from the vegetative state.

Anticipatory attention to verbal and non-verbal stimuli is reflected in a modality-specific SPN.

The time estimation paradigm allows the recording of anticipatory attention for an upcoming stimulus unconfounded by any anticipatory motor activity. Three seconds after a warning signal (WS) subjects have to press a button. A button press within a time window from 2,850 ms to 3,150 ms after the WS is considered 'correct', a movement prior to 2,850 ms after the WS is labelled 'too early' and a movement after 3,150 ms is labelled 'too late'. Two seconds after the button press a Knowledge of Results (KR) stimulus is presented, informing the subject about the correctness of the response. Stimulus Preceding Negativity (SPN) is a slow wave which is recorded prior to the presentation of the KR stimulus. The SPN has a right hemisphere preponderance and is based upon activity in a network in which prefrontal cortex, the insula Reili and the parietal cortex are crucial. In the present study we asked two questions: (1) does the SPN show modality specificity and (2) does the use of verbal KR stimuli influence the right hemisphere preponderance? Auditory and visual stimuli were presented, in a verbal mode and in a non-verbal mode. SPN amplitudes prior to visual stimuli were larger over the visual cortex than prior to auditory stimuli. SPN amplitudes prior to auditory stimuli were larger over the frontal areas than prior to visual stimuli. The use of verbal stimuli did not influence the right hemisphere preponderance. We concluded that apart from the supramodal effect of KR stimuli in general, there is (first) a modality-specific activation of the relevant sensory cortical areas. The supramodal network underlying the attention for and the use of KR information is activated either from different sensory areas or from language processing cortical areas.

Wait and see.

Anticipatory behavior is aimed at goals that can be reached in the near future. Underlying this behavior are neurophysiological processes, which realize a setting of brain structures involved in the future perception, information processing and action. Anticipatory behavior is accompanied by slow brain potentials, which are generated in the cerebral cortex. They are known as the readiness potential (RP), the contingent negative variation (CNV) and the stimulus preceding negativity (SPN). The RP reflects the timing of a future voluntary movement. The CNV reflects the preparation of a signaled movement and the simultaneous anticipatory attention for the imperative stimulus. The SPN reflects partly the anticipatory attention for the upcoming stimulus. Although these slow potentials are generated in the cortex, the paper shows that a subcortical input from basal ganglia, and in the case of the RP also from the cerebellum, is a necessary condition for their emergence. Slow cortical potentials are the result of concerted activity in a number of cerebral networks, in which the thalamus forms a crucial node. It is suggested that the reticular nucleus of the thalamus plays a pivotal role in anticipatory attention.

A psychophysiological analysis of inhibitory motor control in the stop-signal paradigm.

We examined two potential inhibitory mechanisms for stopping a motor response. Participants performed a standard visual two-choice task in which visual stop signals and no-go signals were presented on a small proportion of the trials. Psychophysiological measures were taken during task performance to examine the time course of response activation and inhibition. The results were consistent with a horse race model previously proposed to account for data obtained using a stop-signal paradigm. The pattern of psychophysiological responses was similar on stop-signal and no-go trials suggesting that the same mechanism may initiate inhibitory control in both situations. We found a distinct frontal brain wave suggesting that inhibitory motor control is instigated from the frontal cortex. The results are best explained in terms of a single, centrally located inhibition mechanism. Results are discussed in terms of current neurophysiological knowledge.

Inhibitory motor control in stop paradigms: review and reinterpretation of neural mechanisms.

What is the neurophysiological locus of inhibition when preparation for a manual response is countermanded? This paper evaluates data and models that pertain to inhibitory mechanisms operating in stop paradigms. In a model of De Jong, Coles and Logan (1995), (Strategies and mechanisms in nonselective and selective inhibitory motor control. Journal of Experimental Psychology: Human Perception and Performance, 21, 3, 498-511), a mechanism for nonselective inhibition operates peripheral to the motor cortex, while a selective mechanism operates at a central cortical level. We argue, however, that a peripheral mechanism of inhibition is incorrectly inferred from inhibition data available to date. Neurophysiological and psychophysiological data suggest that inhibitory processes always involve the cortex, and inhibitory effects are exerted upstream from the primary motor cortex. The prefrontal cortex and basal ganglia are candidate agents of response inhibition, whereas possible sites of inhibition are the thalamus and motor cortex.

Digital archival and exchange of events in a simple format for polygraphic recordings with application in event related potential studies.

This paper describes a simple method of event encoding as an extension to a previously defined standard format, the European Data Format (EDF). The specification ensures full backward compatibility with the existing definition. By using this extension, the format can be used to store both continuous recordings and selected epochs of recordings. The encoding is performed in a channel of event-codes or in a pseudo-channel for annotations. Standardisation of event encoding is discussed. Decoding of events or annotations from the extended format is implemented at the application level. Existing programs that do not support the new encoding scheme still operate correctly and can simply ignore the new channels in processing 'extended' data files. The event encoding is also compatible with EDF's capability to encode channels of different sampling frequency.

Motor and non-motor aspects of slow brain potentials.

In order to study motor and non-motor aspects of the contingent negative variation (CNV), fifteen right-handed subjects were asked to perform tightly controlled responses in a WS-S1-S2 paradigm. WS was a non-informative warning signal; S1 and S2 provided information about the response required at S2. This information was either delivered before a block of trials (Simple), at S1 (Precued), or at S2 (Choice). Negativity was larger prior to the informative than to the non-informative stimulus, suggesting the presence of a component called stimulus-preceding negativity (SPN). This finding supported the hypothesis that the late CNV consists of a readiness potential and an SPN. The scalp distribution of the SPN was different before S1 and before S2. The significance of these components is discussed in terms of motor preparation, stimulus anticipation and energetical processes.

Motor and non-motor components of the Contingent Negative Variation.

To study the contribution of the Stimulus-Preceding Negativity (SPN) to the late wave of the Contingent Negative Variation (CNV), negativity was recorded preceding an instruction stimulus (S1), an instruction stimulus to which a motor response was required (S2) and a stimulus that transmitted Knowledge of Results (KR). All recorded negativities showed a centro-parietal maximum. The pre-instruction negativities tended to be larger over the left hemisphere, while a right hemisphere preponderance was found for the pre-KR negativity. Unlike the pre-S1 negativity, the pre-KR negativity may depend on affective-motivational processes. The pre-S1 negativity was small and influenced by factors other than the instruction at S1. It is concluded that the SPN contributes to the late CNV, but that this contribution was relatively small.

Detection of EMG onset in ERP research.

Many researchers have used off-line techniques for the automatic detection of electromyogram (EMG) onset. However, very little is known about the accuracy of these methods. In the present study, five such methods are evaluated and their accuracy is reported. Five subjects were asked to produce fast (ballistic) and slow (ramp) contractions with thumb and index finger of the right hand in a simple reaction time task. EMG was recorded from the first dorsal interosseus muscle, and onsets were visually determined in the raw EMG. These onsets were compared with the onsets produced by the automated methods on the rectified and low-pass filtered EMG. Four of the automated methods produced very reliable estimates of the visually determined onsets, at least when additional constraints upon the initial estimates were made. Studies using automated methods for EMG onset detection should report findings about their accuracy.