Stimulus complexity enhances auditory discrimination in patients with extremely severe brain injuries.

There is controversy as to what extent the processing of spectrally rich sounds in the human auditory cortex is related to the processing of singular frequencies. An informative index of the function of the auditory cortex, particularly important in neurological patients, is the mismatch negativity (MMN), a component of auditory event-related potentials. In the present study the MMN was recorded in 79 patients with extremely severe diffuse brain injuries, most of them in persistent vegetative state or minimal consciousness state. Both sinusoidal ('pure') and complex musical tones were used. Different statistical approaches converged in that musical tones elicited an MMN significantly more frequently, and of a larger amplitude, than simple sine tones. This implies that using simple stimuli in clinical populations may lead to a severe underestimation of the functional state of a patient's auditory system. The findings are also in line with behavioral and physiological data indicating independent processing of complex sounds in the auditory cortex.

Brain-computer communication: self-regulation of slow cortical potentials for verbal communication.

OBJECTIVE: To test a training procedure designed to enable severely paralyzed patients to communicate by means of self-regulation of slow cortical potentials. DESIGN: Application of the Thought Translation Device to evaluate the procedure in patients with late-stage amyotrophic lateral sclerosis (ALS). SETTING: Training sessions in the patients' homes. PARTICIPANTS: Two male patients with late-stage ALS. INTERVENTIONS: Patients learned voluntary control of their slow cortical potentials by means of an interface between the brain and a computer. Training was based on visual feedback of slow cortical potentials shifts and operant learning principles. The learning process was divided into small steps of increasing difficulty. MAIN OUTCOME MEASURES: Accuracy of self-control of slow cortical potentials (percentage of correct responses). Learning progress calculated as a function of training session. RESULTS: Within 3 to 8 weeks, both patients learned to self-regulate their slow cortical potentials and to use this skill to select letters or words in the Language Support Program. CONCLUSIONS: This training schedule is the first to enable severely paralyzed patients to communicate without any voluntary muscle control by using self-regulation of an electroencephalogram potential only. The protocol could be a model for training patients in other brain-computer interface techniques.

Modification of slow cortical potentials in patients with refractory epilepsy: a controlled outcome study.

PURPOSE: To compare self-regulation of low-frequency EEG components (slow cortical potentials, SCPs) with other methods of seizure control for patients with drug-refractory partial epilepsy and to separate the real anticonvulsive effect from placebo effects. METHODS: Results of a treatment program of SCP self-regulation (experimental group) are compared with two groups of patients, one of which learned self-control of respiratory parameters (end-tidal CO2 and respiration rate: RES group); the other received medication with new anticonvulsive drugs (AEDs) in combination with psychosocial counseling (MED group). Clinical, cognitive, behavioral, and personality measures were assessed before and after treatment. In addition, to control for placebo responses, patients repeatedly estimated their beliefs in the efficiency of the respective treatment, their satisfaction and expectations, and the quality of the relationship with their therapists. RESULTS: SCP and MED groups showed a significant decrease of seizure frequency, but the RES group did not. Clear positive changes in the sociopsychological adjustment were obtained in all three groups, with the maximal improvement being attained in the RES group. CONCLUSIONS: All kinds of therapy result in considerable improvement of patients' emotional state, which may in part be due to potential placebo effects: however, this improvement is not related to the quality of the therapeutic effect proper (i.e., seizure reduction). Traditional double-blind control group designs are inappropriate for behavioral interventions or treatments with psychoactive pharmacologic drugs. Rather, specific tests can be developed to control the placebo effect and to separate it from the genuine therapeutic effects.

Self-initiation of EEG-based communication in paralyzed patients.

OBJECTIVES: Severely paralyzed patients could learn to voluntarily generate slow cortical potential (SCP) shifts in their electroencephalogram and to use these signals to operate a communication device. To enhance the patients' autonomy, the present study describes the development of a permanently available communication system that can be turned on and off by locked-in patients without external assistance. A skill necessary for turning the system on is the ability to regulate one's slow potentials in the absence of continuous feedback. METHODS: A stepwise learning approach was employed to train two paralyzed patients to regulate their SCPs without continuous feedback. Elements of the original communication system were gradually removed and elements of the new stand-by mode were introduced. RESULTS: At the end of the learning procedure, both patients achieved correct response rates of above 84% in training sessions without continuous feedback. This skill enabled them to turn the communication device on and off without assistance from others. CONCLUSIONS: These findings suggest that severely paralyzed individuals can learn to operate an EEG-based communication device autonomously.

The thought translation device (TTD) for completely paralyzed patients.

The thought translation device trains locked-in patients to self-regulate slow cortical potentials (SCP's) of their electroencephalogram (EEG). After operant learning of SCP self-control, patients select letters, words or pictograms in a computerized language support program. Results of five respirated, locked-in-patients are described, demonstrating the usefulness of the thought translation device as an alternative communication channel in motivated totally paralyzed patients with amyotrophic lateral sclerosis.

Learning and self-regulation of slow cortical potentials in older adults.

Two groups of subjects, aged 20-28 and 50-64, respectively, matched for health status and verbal abilities, learned to control their slow cortical potentials (SCP) in a feedback paradigm by producing, on command, SCP shifts in either positive or negative direction. Both groups were able to differentiate significantly between the positivity task and the negativity task, with the differentiation score being only slightly (and not significantly) lower in older than in younger subjects. In all conditions, however, significantly more negative brain responses were obtained in older than in younger subjects. This effect was larger in the positivity task versus negativity task, and larger in trials without continuous SCP feedback versus trials with feedback. Additionally four learning tasks were carried out with all subjects. The older group demonstrated substantial performance deficits in two tasks with explicit learning (verbal and visual). In contrast, implicit learning (perceptual learning and skill acquisition) was not impaired with age. The results are at odds with the idea of general age-related learning deficit and concur with the hypothesis that only explicit, but not implicit, learning processes are compromised in older subjects. The pattern of consistently more negative SCP shifts produced by elderly subjects may indicate their impaired cortical inhibition. Another interpretation, which does not exclude the inhibitory deficit hypothesis but seems to better agree with other psychophysiological data, may be that older subjects have disturbance in the system controlling arousal and effort.

Negative potential shifts and the prediction of the outcome of neurofeedback therapy in epilepsy.

About two-thirds of epilepsy patients who learn to control their slow cortical potential shifts (SCP) reduce their seizure rate, but the remaining third does not demonstrate clinical improvement. In the present study, this finding was replicated in a group of 27 patients with focal epilepsy. We found that patients who consistently produced larger negative SCP in all conditions during the first phase of treatment, showed no decrease in seizure frequency during the six-month follow-up, as compared with the three-month baseline phase. The large negative SCP explained about one-third of the variance of the clinical outcome. Age, medication, seizure history, or the localization of focus were found to be unrelated to clinical improvement.

The thought translation device: a neurophysiological approach to communication in total motor paralysis.

A thought translation device (TTD) for brain-computer communication is described. Three patients diagnosed with amyotrophic lateral sclerosis (ALS), with total motor paralysis, were trained for several months. In order to enable such patients to communicate without any motor activity, a technique was developed where subjects learn to control their slow cortical potentials (SCP) in a 2-s rhythm, producing either cortical negativity or positivity according to the task requirement. SCP differences between a baseline interval and an active control interval are transformed into vertical or horizontal cursor movements on a computer screen. Learning SCP self regulation followed an operant-conditioning paradigm with individualized shaping procedures. After prolonged training over more than 100 sessions, all patients achieved self-control, leading to a 70-80% accuracy for two patients. The learned cortical skill enabled the patients to select letters or words in a language-supporting program (LSP) developed for inter-personal communication. The results demonstrate that the fast and stable SCP self-control can be achieved with operant training and without mediation of any muscle activity. The acquired skill allows communication even in total locked-in states.

Changes in EEG power spectra during biofeedback of slow cortical potentials in epilepsy.

The goal of the study was to explore parallel changes in EEG spectral frequencies during biofeedback of slow cortical potentials (SCPs) in epilepsy patients. Thirty-four patients with intractable focal epilepsy participated in 35 sessions of SCP self-regulation training. The spectral analysis was carried out for the EEG recorded at the same electrode site (Cz) that was used for SCP feedback. The most prominent effect was the increase in the theta 2 power (6.0-7.9 Hz) and the relative power decrement in all other frequency bands (particularly delta 1, alpha 2 and beta 2) in transfer trials (i.e., where patients controlled their SCPs without continuous feedback) compared with feedback trials. In the second half of the training course (i.e., sessions 21-35) larger power values in the delta, theta, and alpha bands were found when patients were required to produce positive versus negative SCP shifts. Both across-subject and across-session (within-subject) correlations between spectral EEG parameters, on the one hand, and SCP data, on the other hand, were low and inconsistent, contrary to high and stable correlations between different spectral variables. This fact, as well as the lack of considerable task-dependent effects during the first part of training, indicates that learned SCP shifts did not directly lead to the specific dynamics of the EEG power spectra. Rather, these dynamics were related to nonspecific changes in patients' brain state.

Self-regulation of slow cortical potentials in completely paralyzed human patients.

The study was intended to answer the question whether self-regulation of brain activity can be operantly learnt when the brain is disconnected from motor periphery. Two neurological patients with nearly complete motor paralysis learned bi-directional control of their slow cortical potentials (SCP) at vertex. After 4-6 weeks training both patients could reliably differentiate between SCP shifts in a negative versus positive direction. With one patient, training has been continued for a subsequent 4 months, which resulted in precise self-control, i.e. the patient was able to produce positive SCP shifts on command with an accuracy of about 95%. This indicates that self-regulation of cortical excitability (as manifested in the SCP) does not require feedback loops from the periphery. Although we cannot rule out that healthy subjects may employ behavioral strategies such as muscle contractions or changes in breathing, obviously humans can also control their SCP without using these strategies.

Behavioral psychophysiological intervention in a mentally retarded epileptic patient with brain lesion.

Behavioral psychophysiological treatment entailing Slow Cortical Potential (SCP) biofeedback training and behavioral self-control training was conducted with a 27-year-old male epileptic patient (seizures for 23 years) with Wechsler IQ 64 who underwent callosotomy. The patient had 12/week secondary generalized tonic-clonic seizures. The treatment, consisting of 43 SCP training sessions and 22 behavioral control sessions, yielded a highly significant reduction of seizure frequency to about 7.5/week; such a decrease had never been observed after administration of new anticonvulsant drugs, nor after the callosotomy. During SCP feedback training, the patient was able to produce highly-significant cortical differentiation of SCPs of about 4 microV. In addition, he developed several new behaviors indicating growing ability of self-perception and self-regulation. These findings suggest that a combination of SCP biofeedback with behavioral treatment of epilepsy can be used even in mentally retarded patients with organic brain disorders.

Beyond habituation: long-term repetition effects on visual event-related potentials in epileptic patients.

Sixteen patients with partial epilepsy learned to produce positive or negative slow cortical potential shifts in a biofeedback condition during 20 consecutive training sessions. Visual ERPs to the presentation of the feedback and the discriminative stimulus were recorded at vertex. Regardless of the subjects' task (positivity versus negativity), amplitudes of the P2 (mean peak latency about 225 ms) and P3a (322 ms) components decreased across sessions, resulting in appearance and subsequent enhancement of a negative wave N2 (298 ms) between P2 and P3a. As N2 grew the P2 latency decreased and the P3a latency increased. Additionally, the P3b (472 ms) decreased with repetition, however, it did so slower than P2 and P3a. A comparison between the present data, on the one hand, and those obtained in the ERP habituation paradigm within one session, on the other hand, indicates that some repetition effects cannot be explained by habituation.

A new method for self-regulation of slow cortical potentials in a timed paradigm.

A new method of slow cortical potential (SCP) biofeedback is described, in which subjects were presented with a sequence of two alternating tones. Subjects learned to adjust their SCPs with the 4-s rhythm of presented tones by producing directed SCP changes only in certain inter-tone intervals. Specifically, they learned to simultaneously produce two EEG signals: 1) positive or negative SCP shift at vertex, and 2) SCP asymmetry between the right and the left central area. After one training session, 13 healthy participants were able to differentiate significantly between the negativity and the positivity conditions; this differentiation was achieved within less than 300 ms after the discriminative signal, i.e. much faster than in previous studies employing traditional SCP biofeedback technique. However, these participants did not produce a significant hemispheric asymmetry in the first session. In the second experiment, five subjects participated in prolonged training (6 to 17 sessions). Highly significant control of SCP asymmetry over the precentral cortex was attained in four out of five participants. Advantages and disadvantages of the new method as compared with the "classical" SCP biofeedback technique are discussed.

Stability of cortical self-regulation in epilepsy patients.

Biofeedback-supported self-regulation of slow cortical potentials (SCP) is increasingly being used for treatment of intractable epilepsy. However, it is unknown whether the acquired ability to regulate one's own cortical potentials remains stable over time. In this study, 18 patients with drug-resistant partial epilepsy performed 35 training sessions in which they learned to generate slow cortical potential shifts in either positive or negative direction. At the end of training, they differentiated significantly between required cortical positivity and required cortical negativity. Six months after this point, they still demonstrated an unchanged between-condition differentiation. The performance in the booster session was particularly good in trials without continuous SCP feedback. The ability to generate positive SCP shifts was related to decrease of seizure frequency during the 6 months follow-up period compared with the 3 month baseline period. This data indicate that the acquired ability of humans to regulate their cortical potentials did not decrease over a 6 month period but rather, tended to consolidate.

Self-regulation of slow cortical potentials in epilepsy: a retrial with analysis of influencing factors.

Twenty sessions of biofeedback training were carried out with 12 drug-resistant patients with focal epilepsy who learned to produce either negative or positive shifts of their slow cortical potentials (SCPs) at vertex. Feedback trials were interspersed with transfer trials in which only a discriminative stimulus (signalizing whether positivity or negativity was required) was presented, without feedback signal. Patients were able to differentiate significantly between the conditions of cortical positivity and cortical negativity, with larger differentiation scores being obtained in feedback trials than in transfer trials. The amplitude of positivity generated in the positivity condition increased linearly across sessions both in feedback and in transfer trials. The largest negativity was produced in the 5th session; after this, more transient negativities were generated, whose amplitude decreased towards the end of trial. The mean severity of seizures, estimated as the frequency of seizures weighted by their subjective 'strength', decreased significantly after training as compared to the pre-training phase. The data suggest that (1) patients could learn to achieve a state of cortical disfacilitation and (2) with progressed learning, they became less motivated for (or afraid of) producing considerable negative shifts, since extensive negativity may reflect cortical over-excitation and therefore be associated with early signs of seizures. The inability of producing cortical negativity is however not necessarily a bad predictor.

Self-regulation of interhemispheric asymmetry in humans.

Five healthy right-handed subjects learned to control hemispheric asymmetry with biofeedback of the amplitude difference of slow cortical potentials between the left and the right precentral areas. Six training sessions were conducted with subject I, 12 sessions with subjects II and III, and 14 sessions, with subjects IV and V. Performance of four out of five subjects improved continuously as a function of sessions. Towards the end of training, these subjects demonstrated highly significant differentiation between conditions where right versus left precentral negativity was required. In subject V, no improvement was observed after 14 training sessions. The data indicate that most subjects can learn to self-generate fast electroencephalograph (EEG) differences between the left and the right sensorimotor cortical regions.