The neural processes generating visual phenomenal consciousness: ERP and neuronavigated brain stimulation studies

One of the greatest conundrums to the contemporary science is the relation between consciousness and brain activity, and one of the specifi c questions is how neural activity can generate vivid subjective experiences. Studies focusing on visual consciousness have become essential in solving the empirical questions of consciousness. Th e main aim of this thesis is to clarify the relation between visual consciousness and the neural and electrophysiological processes of the brain. By applying electroencephalography and functional magnetic resonance image-guided transcranial magnetic stimulation (TMS), we investigated the links between conscious perception and attention, the temporal evolution of visual consciousness during stimulus processing, the causal roles of primary visual cortex (V1), visual area 2 (V2) and lateral occipital cortex (LO) in the generation of visual consciousness and also the methodological issues concerning the accuracy of targeting TMS to V1. Th e results showed that the fi rst eff ects of visual consciousness on electrophysiological responses (about 140 ms aft er the stimulus-onset) appeared earlier than the eff ects of selective attention, and also in the unattended condition, suggesting that visual consciousness and selective attention are two independent phenomena which have distinct underlying neural mechanisms. In addition, while it is well known that V1 is necessary for visual awareness, the results of the present thesis suggest that also the abutting visual area V2 is a prerequisite for conscious perception. In our studies, the activation in V2 was necessary for the conscious perception of change in contrast for a shorter period of time than in the case of more detailed conscious perception. We also found that TMS in LO suppressed the conscious perception of object shape when TMS was delivered in two distinct time windows, the latter corresponding with the timing of the ERPs related to the conscious perception of coherent object shape. Th e result supports the view that LO is crucial in conscious perception of object coherency and is likely to be directly involved in the generation of visual consciousness. Furthermore, we found that visual sensations, or phosphenes, elicited by the TMS of V1 were brighter than identically induced phosphenes arising from V2. Th ese fi ndings demonstrate that V1 contributes more to the generation of the sensation of brightness than does V2. Th e results also suggest that top-down activation from V2 to V1 is probably associated with phosphene generation. The results of the methodological study imply that when a commonly used landmark (2 cm above the inion) is used in targeting TMS to V1, the TMS-induced electric fi eld is likely to be highest in dorsal V2. When V1 was targeted according to the individual retinotopic data, the electric fi eld was highest in V1 only in half of the participants. Th is result suggests that if the objective is to study the role of V1 with TMS methodology, at least functional maps of V1 and V2 should be applied with computational model of the TMS-induced electric fi eld in V1 and V2. Finally, the results of this thesis imply that diff erent features of attention contribute diff erently to visual consciousness, and thus, the theoretical model which is built up of the relationship between visual consciousness and attention should acknowledge these diff erences. Future studies should also explore the possibility that visual consciousness consists of several processing stages, each of which have their distinct underlying neural mechanisms.

Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 µg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements. Within 40-50 min, the status epilepticus was established and lasted 8-12 h. These results are similar to those observed in the acute phase of the pilocarpine model of temporal lobe epilepsy and suggest that granulitoxin may be a useful tool not only to study the sodium channels, but also to develop a new experimental model of status epilepticus.

Uniform decrease of alpha-global field power induced by intermittent photic stimulation of healthy subjects

Nineteen-channel EEGs were recorded from the scalp surface of 30 healthy subjects (16 males and 14 females, mean age: 34 years, SD: 11.7 years) at rest and under trains of intermittent photic stimulation (IPS) at rates of 5, 10 and 20 Hz. Digitalized data were submitted to spectral analysis with fast fourier transformation providing the basis for the computation of global field power (GFP). For quantification, GFP values in the frequency ranges of 5, 10 and 20 Hz at rest were divided by the corresponding data obtained under IPS. All subjects showed a photic driving effect at each rate of stimulation. GFP data were normally distributed, whereas ratios from photic driving effect data showed no uniform behavior due to high interindividual variability. Suppression of alpha-power after IPS with 10 Hz was observed in about 70% of the volunteers. In contrast, ratios of alpha-power were unequivocal in all subjects: IPS at 20 Hz always led to a suppression of alpha-power. Dividing alpha-GFP with 20-Hz IPS by alpha-GFP at rest (R = alpha-GFP IPS/alpha-GFPrest) thus resulted in ratios lower than 1. We conclude that ratios from GFP data with 20-Hz IPS may provide a suitable paradigm for further investigations.

Topographic abnormality of slow cortical potentials in schizophrenia

A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic) in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 ± 9.2 years; mean number of previous hospitalizations: 1.2 ± 1.9) and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative), whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P < 0.001). The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low) or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

Control of Robot by Means of Human Thought

Brain computer interface (BCI) is a kind of human machine interface, which provides a new interaction method between human and computer or other equipment. The most significant characteristic of BCI system is that its control input is brain electrical activities acquired from the brain instead of traditional input such as hands or eyes. BCI technique has rapidly developed during last two decades and it has mainly worked as an auxiliary technique to help the disable people improve their life qualities. With the appearance of low cost novel electrical devices such as EMOTIV, BCI technique has been applied to the general public through many useful applications including video gaming, virtual reality and virtual keyboard. The purpose of this research is to be familiar with EMOTIV EPOC system and make use of it to build an EEG based BCI system for controlling an industrial manipulator by means of human thought. To build a BCI system, an acquisition program based on EMOTIV EPOC system is designed and a MFC based dialog that works as an operation panel is presented. Furthermore, the inverse kinematics of RV-3SB industrial robot was solved. In the last part of this research, the designed BCI system with human thought input is examined and the results indicate that the system is running smoothly and displays clearly the motion type and the incremental displacement of the motion.

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

Statistical analysis of event-related potential elicited by verb-complement merge in Brazilian Portuguese

An interesting fact about language cognition is that stimulation involving incongruence in the merge operation between verb and complement has often been related to a negative event-related potential (ERP) of augmented amplitude and latency of ca. 400 ms - the N400. Using an automatic ERP latency and amplitude estimator to facilitate the recognition of waves with a low signal-to-noise ratio, the objective of the present study was to study the N400 statistically in 24 volunteers. Stimulation consisted of 80 experimental sentences (40 congruous and 40 incongruous), generated in Brazilian Portuguese, involving two distinct local verb-argument combinations (nominal object and pronominal object series). For each volunteer, the EEG was simultaneously acquired at 20 derivations, topographically localized according to the 10-20 International System. A computerized routine for automatic N400-peak marking (based on the ascendant zero-cross of the first waveform derivative) was applied to the estimated individual ERP waveform for congruous and incongruous sentences in both series for all ERP topographic derivations. Peak-to-peak N400 amplitude was significantly augmented (P < 0.05; one-sided Wilcoxon signed-rank test) due to incongruence in derivations F3, T3, C3, Cz, T5, P3, Pz, and P4 for nominal object series and in P3, Pz and P4 for pronominal object series. The results also indicated high inter-individual variability in ERP waveforms, suggesting that the usual procedure of grand averaging might not be considered a generally adequate approach. Hence, signal processing statistical techniques should be applied in neurolinguistic ERP studies allowing waveform analysis with low signal-to-noise ratio.

Use of magnitude-squared coherence to identify the maximum driving response band of the somatosensory evoked potential

The present study proposes to apply magnitude-squared coherence (MSC) to the somatosensory evoked potential for identifying the maximum driving response band. EEG signals, leads [Fpz'-Cz'] and [C3'-C4'], were collected from two groups of normal volunteers, stimulated at the rate of 4.91 (G1: 26 volunteers) and 5.13 Hz (G2: 18 volunteers). About 1400 stimuli were applied to the right tibial nerve at the motor threshold level. After applying the anti-aliasing filter, the signals were digitized and then further low-pass filtered (200 Hz, 6th order Butterworth and zero-phase). Based on the rejection of the null hypothesis of response absence (MSC(f) > 0.0060 with 500 epochs and the level of significance set at a = 0.05), the beta and gamma bands, 15-66 Hz, were identified as the maximum driving response band. Taking both leads together ("logical-OR detector", with a false-alarm rate of a = 0.05, and hence a = 0.0253 for each derivation), the detection exceeded 70% for all multiples of the stimulation frequency within this range. Similar performance was achieved for MSC of both leads but at 15, 25, 35, and 40 Hz. Moreover, the response was detected in [C3'-C4'] at 35.9 Hz and in [Fpz'-Cz'] at 46.2 Hz for all members of G2. Using the "logical-OR detector" procedure, the response was detected at the 7th multiple of the stimulation frequency for the series as a whole (considering both groups). Based on these findings, the MSC technique may be used for monitoring purposes.

Protein tyrosine kinase inhibitors modify kainic acid-induced epileptiform activity and mossy fiber sprouting but do not protect against limbic cell death

Intrahippocampal administration of kainic acid (KA) induces synaptic release of neurotrophins, mainly brain-derived neurotrophic factor, which contributes to the acute neuronal excitation produced by the toxin. Two protein tyrosine kinase inhibitors, herbimycin A and K252a, were administered intracerebroventricularly, in a single dose, to attenuate neurotrophin signaling during the acute effects of KA, and their role in epileptogenesis was evaluated in adult, male Wistar rats weighing 250-300 g. The latency for the first Racine stage V seizure was 90 ± 8 min in saline controls (N = 4) which increased to 369 ± 71 and 322 ± 63 min in animals receiving herbimycin A (1.74 nmol, N = 4) and K252a (10 pmol, N = 4), respectively. Behavioral alterations were accompanied by diminished duration of EEG paroxysms in herbimycin A- and K252a-treated animals. Notwithstanding the reduction in seizure severity, cell death (60-90% of cell loss in KA-treated animals) in limbic regions was unchanged by herbimycin A and K252a. However, aberrant mossy fiber sprouting was significantly reduced in the ipsilateral dorsal hippocampus of K252a-treated animals. In this model of temporal lobe epilepsy, both protein kinase inhibitors diminished the acute epileptic activity triggered by KA and the ensuing morphological alterations in the dentate gyrus without diminishing cell loss. Our current data indicating that K252a, but not herbimycin, has an influence over KA-induced mossy fiber sprouting further suggest that protein tyrosine kinase receptors are not the only factors which control this plasticity. Further experiments are necessary to elucidate the exact signaling systems associated with this K252a effect.

Delta sleep instability in children with chronic arthritis

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 ± 6.7 vs 95.8 ± 4.0), sleep stage in minutes: stage 1 (16.8 ± 8.5 vs 17.8 ± 4.0), stage 2 (251.9 ± 41 vs 262.8 ± 38.1), stage 3 (17.0 ± 6.0 vs 15.1 ± 5.7), stage 4 (61.0 ± 21.7 vs 77.1 ± 20.4), and rapid eye movement sleep (82.0 ± 27.6 vs 99.0 ± 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Meningoencephalitis caused by a zygomycete fungus (Basidiobolus) associated with septic shock in an immunocompetent patient: 1-year follow-up after treatment

Zygomycosis is an infection caused by opportunistic fungi of the Zygomycetes class, specifically those from the Mucorales and Entomophthorales orders. It is an uncommon disease, mainly restricted to immunocompromised patients. We report a case of a 73-year-old male patient with a history of fever (39°C) lasting for 1 day, accompanied by shivering, trembling, and intense asthenia. The patient was admitted to the intensive care unit with complex partial seizures, and submitted to orotracheal intubation and mechanical ventilation under sedation with midazolam. The electroencephalogram showed evidence of non-convulsive status epilepticus. There is no fast specific laboratory test that permits confirmation of invasive fungal disease. Unless the physician suspects this condition, the disease may progress rapidly while the patient is treated with broad-spectrum antibiotics. Differential diagnosis between fungal and bacterial infection is often difficult. The clinical presentation is sometimes atypical, and etiological investigation is not always successful. In the present case, the histopathological examination of the biopsy obtained from the right temporal lobe indicated the presence of irregular, round, thick-walled fungi forming papillae and elongated structures of irregular diameter, with no septa, indicative of zygomycete (Basidiobolus). Treatment with liposomal amphotericin B and fluconazole was initiated after diagnosis of meningoencephalitis by zygomycete, with a successful outcome.

A comparison of electrophysiological changes during the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and normal sleepers

The EEG of the sleep onset period of psychophysiological insomniacs, psychiatric insomniacs and controls was compared using power spectral analysis (FFT). Eighteen drug-free subjects were equally divided into three groups according to their responses in the Brock Sleep and Insomnia Questionnaire, the Minnesota Multiphasic Personality Inventory and the Sleep Disorders Questionnaire. Group 1 consisted of psychophysiological insomniacs, group 2 included insomniacs with an indication of psychiatric disturbances, and group 3 was a control group. EEG, EOG and EMG were recorded for two consecutive nights. Power spectral analysis (FFT) of EEG at C4 from the sleep onset period (defined as lights out to the first five minutes of stage 2) was performed on all standard frequency bands, delta: .5-4 Hz; theta: 4-8 Hz; alpha: 8-12 Hz; sigma: 12-15 Hz beta: 15-25 Hz. Psychophysiological insomniacs had less alpha during wakefulness than the other two groups and did not show the dramatic drop in alpha across the sleep onset period, which characterizes normal sleep. They also had less delta, especially during stage 2 on night 2. They also showed less delta in the last quartile of the chronological analysis of the sleep onset period. Psychiatric insomniacs showed lower relative beta power values overall while psychophysiological insomniacs showed higher relative beta power values during wakefulness. This microanalysis 11 confirms that the sleep onset period is generally similar for psychiatric insomniacs and normal sleepers. This may be due to the sample of psychiatric insomniacs being heterogeneous or may reflect a sleep onset system that is essentially intact. Psychophysiological insomniacs have higher cortical arousal during the sleep onset period than do the psychiatric insomniacs and the controls. Clear differences in the sleep onset period of psychophysiological insomniacs exist. The dramatic changes in power values in these two groups are not seen in the psychophysiological insomniacs, which may make the discrimination between wakefulness and sleep more difficult.

The role of daytime napping in sleepiness and cognitive function in 24-70 year olds /

Daytime napping improves well-being and performance for young adults. The benefits of napping in older adults should be investigated because they have fragmented nocturnal sleep, cognitive declines, and more opportunity to nap. In addition, experience with napping might influence the benefits of napping. Study 1 examined the role of experience with napping in young adults. Habitual (n = 23) and non-habitual nappers (n = 16) were randomly assigned to a 20-minute nap or a 20- minute reading condition. Both groups slept the same according to macro architecture. However, microarchitecture showed greater theta, alpha, and beta power during Stage 1, and greater delta, alpha, and sigma power during Stage 2 for habitual nappers, for the most part indicating better sleep. Both groups felt less sleepy after the nap. P2 latency, reflecting information processing, decreased after the nap for habitual nappers, and after the control condition for non-habitual nappers. In sum, both groups who slept felt better, but only the habitual nappers who napped gained a benefit in terms of information processing. Based on this outcome, experience with napping was investigated in Study 2. Study 2 examined the extent to which daytime napping enhanced cognition in older adults, especially frontal lobe function. Cognitive deficits in older adults may be due to sleep loss and age-related decline in brain functioning. Longer naps were expected to provide greater improvement, particularly for older adults, by reducing sleep pressure. Thirty-two adults, aged 24-70 years, participated in a repeated measures dose-response manipulation of sleep pressure. Twenty- and sixty-minute naps were compared to a no-nap condition in three age groups. Mood, subjective sleepiness, reaction time, working memory, 11 novelty detection, and waking electro physiological measures were taken before and after each condition. EEG was also recorded during each nap or rest condition. Napping reduced subjective sleepiness, improved working memory (serial addition / subtraction task), and improved attention (reduced P2 amplitude). Physiological sleepiness (i.e., waking theta power) increased following the control condition, and decreased after the longer nap. Increased beta power after the short nap, and seen with older adults overall, may have reflected increased mental effort. Older adults had longer latencies and smaller amplitudes for several event-related potential components, and higher beta and gamma power. Following the longer nap, gamma power decreased for older adults, but increased for young adults. Beta and gamma power may represent enhanced alertness or mental effort. In addition, Nl amplitude showed that benefits depend on the preceding nap length as well as age. Since the middle group had smaller Nl amplitudes following the short nap and rest condition, it is possible that they needed a longer nap to maintain alertness. Older adults did not show improvements to Nl amplitude following any condition; they may have needed a nap longer than 60 minutes to gain benefits to attention or early information processing. Sleep characteristics were not related to benefits of napping. Experience with napping was also investigated. Subjective data confirmed habitual nappers were happier to nap, while non-habitual nappers were happier to stay awake, reflecting self-identified napping habits. Non-habitual nappers were sleepier after a nap, and had faster brain activity (i.e., heightened vigilance) at sleep onset. These reasons may explain why non-habitual nappers choose not to nap.

Subjective, behavioural and electrophysiological measurements of the time-course and intensity of sleep inertia after a full night of sleep /

Several recent studies have described the period of impaired alertness and performance known as sleep inertia that occurs upon awakening from a full night of sleep. They report that sleep inertia dissipates in a saturating exponential manner, the exact time course being task dependent, but generally persisting for one to two hours. A number of factors, including sleep architecture, sleep depth and circadian variables are also thought to affect the duration and intensity. The present study sought to replicate their findings for subjective alertness and reaction time and also to examine electrophysiological changes through the use of event-related potentials (ERPs). Secondly, several sleep parameters were examined for potential effects on the initial intensity of sleep inertia. Ten participants spent two consecutive nights and subsequent mornings in the sleep lab. Sleep architecture was recorded for a fiiU nocturnal episode of sleep based on participants' habitual sleep patterns. Subjective alertness and performance was measured for a 90-minute period after awakening. Alertness was measured every five minutes using the Stanford Sleepiness Scale (SSS) and a visual analogue scale (VAS) of sleepiness. An auditory tone also served as the target stimulus for an oddball task designed to examine the NlOO and P300 components ofthe ERP waveform. The five-minute oddball task was presented at 15-minute intervals over the initial 90-minutes after awakening to obtain six measures of average RT and amplitude and latency for NlOO and P300. Standard polysomnographic recording were used to obtain digital EEG and describe the night of sleep. Power spectral analyses (FFT) were used to calculate slow wave activity (SWA) as a measure of sleep depth for the whole night, 90-minutes before awakening and five minutes before awakening.