The role of theta and alpha oscillations for language comprehension in the human electroencephalogram.

The hypothesis is tested, whether increasing language processing demands draw on the capacity of working memory thereby leading to an increase in theta band power. Previous research has shown that theta reflects working memory whereas upper alpha semantic memory demands. Sentences were presented in four chunks in a reading and a semantic task. In the latter, subjects had to find a superordinate concept to a noun presented in the third chunk. The data show an increase in theta during sentence processing which was significantly smaller in the semantic task. In contrast, the upper alpha band exhibited a significantly larger change in band power during the semantic task and that time window in which subjects searched for the superordinate concept. Thus, we conclude that semantic processing does not draw selectively on the capacity of working memory and that different linguistic processes have no direct influence on theta oscillations.

Theta synchronization during episodic retrieval: neural correlates of conscious awareness.

The neural correlates of conscious awareness during successful memory retrieval were examined. In a recognition test, subjects indicated whether they consciously recalled the event in which a word was earlier presented (Remembering), or whether they recognized it on the basis that it was familiar in the absence of recollection (Knowing). An early EEG synchronization in the theta band predicted knowing, and a later remembering. Moreover, early and late event-related potentials were also found to predict knowing and remembering, respectively. The results indicate that the temporal dynamics of theta synchronization are related to the particular conscious experiences associated with memory retrieval.

Theta band power changes in normal and dyslexic children.

OBJECTIVE: Tonic and phasic (event-related) theta band power changes were analyzed in a sample of 8 dyslexic and 8 control children. Previous research with healthy subjects suggests that electroencephalograph (EEG) theta activity reflects the encoding of new information into working memory. The aim of the present study was to investigate whether the processing deficits of dyslexics are related to a reduced phasic theta response during reading. METHOD: The EEG was recorded while subjects were reading numbers, words and pseudowords and analyzed in a lower and upper theta band (4--8 Hz). A phasic response is measured in terms of an increase in event related band power during reading with respect to a reference interval. Tonic power is measured in terms of (log) band power during a reference interval. RESULTS: Large group differences in tonic and phasic lower theta were found for occipital sites where dyslexics show a complete lack of pseudoword processing. For words, only controls show a highly selective left hemispheric processing advantage. CONCLUSIONS: Dyslexics have a lack to encode pseudowords in visual working memory with a concomitant lack of frontal processing selectivity. The upper theta band shows a different pattern of results which can be best interpreted to reflect the effort during the encoding process.

Alpha and beta band power changes in normal and dyslexic children.

OBJECTIVE: Previous research with healthy subjects suggests that the lower alpha band reflects attentional whereas the upper alpha band semantic processes. The aim of the present study was to investigate whether dyslexics show deficits in attentional control and/or semantic encoding. METHOD: The EEG was recorded while subjects were reading numbers, words and pseudowords and analyzed in a lower and upper alpha and two beta bands (spanning a range of about 8--16 Hz). A phasic response is measured in terms of a decrease in event related band power during reading with respect to a reference interval. Tonic power is measured in terms of (log) band power during a reference interval. RESULTS: In the lower alpha band dyslexics show an increased phasic response to words and pseudowords at right hemispheric sites but a lack to respond to words at O1. The upper alpha band exhibits a highly selective phasic response to words at left frontal sites but for controls only, whereas dyslexics show a general increase in tonic upper alpha power. Whereas the low frequency beta band (beta-1a) exhibits a rather diffuse pattern, a highly selective finding was obtained for the beta-1b band. CONCLUSIONS: Dyslexics have a lack of attentional control during the encoding of words at left occipital sites and a lack of a selective topographic activation pattern during the semantic encoding of words. Because only in controls reading of words is associated with a strong beta-1b desynchronization at those recording sites which correspond to Broca's area (FC5) and the angular gyrus (CP5, P3), we may conclude that this frequency band reflects the graphemicphonetic encoding of words.

Episodic retrieval is reflected by a process specific increase in human electroencephalographic theta activity.

Is an increase in theta during retrieval due (primarily) to the access of a stored code or to more general processes? The electroencephalogram was recorded while subjects performed a recognition task with pictures. According to the event-related desynchronization/synchronization method, the percentage of band power changes was calculated during encoding and retrieval for a theta and three alpha bands. Significant results were obtained (with minor exceptions) only in the theta band. The increase in theta was significantly larger during retrieval than during encoding but did not differ significantly between new and successfully retrieved old pictures. Because a memory trace is lacking for new pictures, the increase in theta during retrieval reflects primarily general processing demands of a complex episodic memory system.

Simultaneous desynchronization and synchronization of different alpha responses in the human electroencephalograph: a neglected paradox?

This study aims to resolve a paradox. Experiments measuring alpha band power report an event related decrease (desynchronization) in alpha activity, whereas those measuring evoked alpha report synchronization. During a recognition memory task with human subjects, we measured the evoked (phase locked) and induced (not phase locked) alpha response. The findings reveal that evoked alpha is due to a transient phase locking (at about 100-200 ms poststimulus) of three alpha sub-bands which can be observed only at parieto-occipital sites. In contrast, induced alpha shows a widespread pattern of desynchronization at most recording sites. Thus, opposite alpha responses occur within similar time windows. Evoked alpha synchronization may reflect cortical inhibition which serves to increase the signal to noise ratio for activation processes following immediately later.

The time locked theta response reflects interindividual differences in human memory performance.

Recent research indicates that an increase in theta band power is related to episodic memory performance. In this study with human subjects, the evoked (time locked) and induced (not time locked) theta response is analyzed in a recognition task. The results show a strong evoked theta response during an early retrieval period of up to 400 ms. Only for good memory performers theta is strictly time locked, indicating that theta peaks appear in preferred time windows after a target is presented. This effect--which coincides with a large P3--suggests that good performance requires a strict timing of different processing stages that correspond to cycles of theta activity.

In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee.

A 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks after infusion. HBsAg and antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after the start of the infusion the HBsAg level was minimal with maximum loading of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could be dissociated by acid treatment. The HBsAg level was completely restored on day 7. Similar results were obtained for the preS1-containing particles that may represent the infectious viral particles in the chimpanzee serum. A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in artificial immune complexes with the pre-treatment HBsAg from the chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in the signal in the 30 min sample compared to non-competing anti-HBs conjugates. This indicates binding of HBsAg with 9H9 in the circulation of the chimpanzee. Immune-complexed 4-7B could not be detected by its corresponding 4-7B peptide conjugate, probably due to its low concentration in the complexes. It is concluded that human monoclonal anti-HBs can effectively reduce the level of HBsAg in serum from this chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to their different mechanisms of inactivation, probably with higher efficiency than that monitored by our HBsAg screening assays.

Pharmacokinetics, tolerability, and preliminary efficacy of human anti-Pseudomonas aeruginosa monoclonal antibodies in pneumonia and burn infection patients.

Human monoclonal antibody (hMAb) cocktail SM-17220 (also known as BT-570), a heterofunctional antibody mixture of 3 human IgM MAbs (HI-223, MH-4H7, and IN-2A8; ratio of 1:10:10) directed against Pseudomonas aeruginosa, were administered to patients with pneumonia or burn wounds (or both) to assess the pharmacokinetics, safety, antigenicity, and preliminary efficacy. Twenty mg of SM-17220 was IV infused over 60 min once daily on 3 consecutive days. Twenty patients (8 pneumonia, 4 burns, and 8 both) completed the study. SM-17220 was safe and well tolerated, and no subjects developed antibodies to SM-17220 and mouse J-chain during the follow-up of 8 weeks. Each MAb of SM-17220 had a half-life ranging from 49 to 91 h, similar to native human IgM. Both MH-4H7 and IN-2A8 administration resulted in a high serum level for about 4 days over an effective concentration, whereas HI-223 showed a lower serum level than expected. Some indications of a potential efficacy were observed and are discussed here.