Control of cortical excitability in epilepsy.
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Biomedical subjects
Publications and source records attributed to B Kotchoubey.
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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 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.
In two experiments, large letters H or Z composed of small letters (also H or Z) were presented. Subjects had to make a two-choice motor response (e.g. H--left key, Z--right key). A cue presented 500 ms before the letter indicated which level (global or local) was relevant. In Experiment I, a third letter (T) sometimes appeared either at the cued or the non-cued level; in the former case, subjects had to shift their attention and to respond to stimulus features located at the non-cued level. The interference effect (RT delay in response to incongruent stimuli as compared to congruent ones) was larger when the local, rather than global, level was cued. A slow anterior negativity preceding globally-cued stimuli and shorter N1 and P2 ERP component latencies to these stimuli indicated better preparation for processing of global, as compared to local, stimulus features. The shift from local to global focus yielded a larger increase of RT, error rate, and of the P600 latency than the global-to-local shift. The P600 latency changes were parallel to those of RT. In Experiment II, the attentional shift was provoked by stimulus color red-colored letters meant that the cue was invalid, and thus, subjects had to respond to the non-cued level. Neither the interference nor the attentional shift demonstrated any asymmetry between the global and local levels. ERPs also did not differ substantially after local and global cues. In the condition demanding a shift of focus (invalid cue, incongruent letter), a positive deflection of the lateralized readiness potential indicated the activation of the wrong response channel. The large RT increment in this condition was not accompanied by an increase of the P600 latency. Two possible mechanisms of attentional shift may be proposed, the first related to perceptual processes (e.g. an additional visual search), and the second, to the competition between two response intentions.
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.
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 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.
18 healthy subjects had to guess, which of two nonequiprobable events would occur next. Each trial was preceded by a cue which increased the probability of the corresponding event as compared to its global probability. Event-related potentials (ERPs) were recorded and then classified according to global probability of events, their relation to the preceeding cue (valid versus invalid cues) and to subject's prediction (predicted versus nonpredicted). Two late positive waves (P350 and P550) with parietal maxima were distinguished. Both waves had larger amplitudes in response to improbable events than to highly-probably events. Similarly, both had larger amplitudes following invalid cues than following valid cues, and this difference was larger in those subjects who tended to follow the cue than in those who tended to reject it. No difference in terms of ERP component amplitudes was found between predicted and unpredicted events; however, the latency of the P350 peak was longer following unpredicted events. Taken together with data of the literature, the present results indicate that ERP allow us to distinguish between two meanings of the word "expectancy": (1) the rule-related expectancy as cognitive estimation of the likelihood or "representativeness" of an event (based on grasping event contingencies), and (2) the goal-related expectancy manifested in the subject's overt behavior. Only the former "expectancy" affects the amplitude of the late positive wave ("P3"), while the latter does not.
Two experiments, an "active" and a "passive" oddball-paradigm (1. phase) with visual and auditive stimuli were performed. In both, two stimuli with a probability of 0.7/0.3 were presented. The oddball-sequence was replaced in the 2. phase without knowledge of the subjects by a sequence, in which only targets were presented. One group of the subjects has got an active task (counting the rare stimulus), the other group was told to view the stimuli passively. The rare stimulus in the oddball-sequence evoked a larger parietal P3, the auditive stimulation additionally a larger fronto-central N1 and the visual stimulation a larger central P2. The non-expected change into the 2. phase resulted in a reverse of the ERP-lateralization between 150-300 ms: Before the change of the probability the amplitudes were more negative left than right, thereafter more negative right than left. All components and effects in the active task maintained without task, but they decreased. The differences were larger with the visual stimuli. These results suggest, that the passive paradigm could be applied to patients with motoric deficits. From a theoretical point of view these results lead to certain difficulties in the interpretation of the functional importance of the P3. It can be explained better by the context-closure theory (Desmedt, 1980; Verleger, 1988) than by the context-updating theory (Donchin, 1981).
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.
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.
Brain evoked potentials (EPs) were recorded in human subjects participating in a free recall memory task involving retroactive interference. A learning list was presented five times. The fifth repetition was followed by an interference list. Both lists were composed of either words or abstract figures, and each subject experienced each of four possible combinations. Analysis of items recalled during the learning phase revealed larger N400 and P600 amplitudes for those items that were later forgotten vs remembered following the interference. This contradicts the usual finding that more positivity is associated with better memory. However, both the present as well as the extant findings can be explained in terms of cognitive resource allocation. Specifically, items receiving greater allocations are more likely to be immediately recalled. However, as the number of items in working memory increases, the allocation required to add new items also increases. Thus, items learned on later trials would receive larger allocations (i.e., larger positivities) than items learned earlier, yet would be more likely forgotten following the interference because their presence in memory would not be reinforced during later trials, as is the case with items learned earlier.
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.