Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Spoken words are processed during dexmedetomidine-induced unresponsiveness.

BACKGROUND: Studying the effects of anaesthetic drugs on the processing of semantic stimuli could yield insights into how brain functions change in the transition from wakefulness to unresponsiveness. Here, we explored the N400 event-related potential during dexmedetomidine- and propofol-induced unresponsiveness. METHODS: Forty-seven healthy subjects were randomised to receive either dexmedetomidine (n=23) or propofol (n=24) in this open-label parallel-group study. Loss of responsiveness was achieved by stepwise increments of pseudo-steady-state plasma concentrations, and presumed loss of consciousness was induced using 1.5 times the concentration required for loss of responsiveness. Pre-recorded spoken sentences ending either with an expected (congruous) or an unexpected (incongruous) word were presented during unresponsiveness. The resulting electroencephalogram data were analysed for the presence of the N400 component, and for the N400 effect defined as the difference between the N400 components elicited by congruous and incongruous stimuli, in the time window 300-600 ms post-stimulus. Recognition of the presented stimuli was tested after recovery of responsiveness. RESULTS: The N400 effect was not observed during dexmedetomidine- or propofol-induced unresponsiveness. The N400 component, however, persisted during dexmedetomidine administration. The N400 component elicited by congruous stimuli during unresponsiveness in the dexmedetomidine group resembled the large component evoked by incongruous stimuli at the awake baseline. After recovery, no recognition of the stimuli heard during unresponsiveness occurred. CONCLUSIONS: Dexmedetomidine and propofol disrupt the discrimination of congruous and incongruous spoken sentences, and recognition memory at loss of responsiveness. However, the processing of words is partially preserved during dexmedetomidine-induced unresponsiveness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study.

INTRODUCTION: The highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses. METHODS: One hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 µg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 µg ml-1; n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions. RESULTS: At the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRglu did not differ from placebo. CONCLUSIONS: At equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia. CLINICAL TRIAL REGISTRATION: NCT02624401.

Impairment of semantic knowledge in Parkinson disease.

BACKGROUND: Parkinson disease (PD) is commonly characterized by cognitive deterioration, but it is still unclear whether PD is associated with semantic impairments. OBJECTIVE: To evaluate semantic knowledge of concepts in patients with idiopathic PD, addressing concrete and abstract concepts, conceptual attributes, and conceptual relations. METHODS: Twelve patients with preserved cognitive status, 12 patients with mildly deteriorated cognitive status, and 12 control subjects were studied. The cognitive status of patients and controls was determined using detailed cognitive testing. Patients were participants in a university-based movement disorder program, and their PD diagnoses were clinically confirmed during long-term follow-up. The 2 patient groups were similar in age, level of education, disease duration, and parkinsonian disability. Patients were required to produce verbal descriptions of concrete and abstract concepts, to give ratings of the importance of concept attributes, and to assess and construct conceptual hierarchies. The description tasks included guiding questions, which were used if the spontaneous productions of the patients lacked any essentials expected in the answers. RESULTS: Patients with mild cognitive deterioration performed less well than the other groups in defining concrete and abstract concepts (P<.001 for both). External guidance did not help them markedly improve their performance. They also had difficulties in tasks calling for knowledge of the importance of given attributes to the concepts and in tasks demanding evaluation of hierarchical semantic relations between concepts (P<.001 for both). CONCLUSION: Semantic disruption is implied in idiopathic PD in association with incipient cognitive impairment.

Cognitive representations underlying the N400 priming effect.

The present study explored whether the N400 semantic priming effect is based on semantic similarity or lexical associations, or both. The event-related potentials showed N400 priming effects for both semantically similar and lexically associated word pairs in the 250-375 ms time-window. However, the effect lasted for a longer time for lexical associates, particularly in frontal and central electrode sites in the 375-500 ms time-window, suggesting that different types of processing may contribute to the N400 priming effects evoked by the two types of relationships.

Semantic priming by pictures and words in the cerebral hemispheres.

In order to determine whether pictures would act as more effective semantic primes than words in the right cerebral hemisphere, automatic semantic activation in intact hemispheres was studied with primed GO-NOGO lexical decision tasks by presenting word-word and picture-word pairs to the left visual field (right hemisphere) or to the right visual field (left hemisphere). Response times in Experiment 1 showed that categorically related targets (e.g., TABLE-BED) were primed only in the right visual field after both word and picture primes. Experiment 2 found that picture primes activated the representations of the corresponding written names in both visual fields. These observations suggest that the range of automatic semantic activation is larger in the left than in the right hemisphere. The results implicate that semantic categories may be organized in a different fashion in the left than the right hemisphere.

Dissimilar age influences on two ERP waveforms (LPC and N400) reflecting semantic context effect.

Age-related changes in semantic context effects were examined using late event-related brain potentials (ERPs). Auditory ERPs to semantically congruous and incongruous final words in spoken sentences were recorded in 16 children (aged 5-11 years) and 16 adults. Previous findings concerning age-related effects on N400 were replicated: the N400 effect was significantly larger in children than in adults. The main new finding was that a late positive component (LPC) following N400 and modulated by semantic context in adults was not found in children. Thus, the common generalization that semantic context effects decline with age holds only for ERP components occurring in the N400 time window or earlier. The cognitive function reflected by the semantic LPC we observed is not clear, but it seems to have a role different from that of the N400, although in adults the components often co-exist as an N400-LPC complex.

Visual awareness of objects correlates with activity of right occipital cortex.

In the search for human neural correlates of visual awareness, cortical magnetic responses to coherent and meaningful objects were compared with responses to disorganized and meaningless non-objects when observers tried to detect the coherent objects. Three brief stimulus durations were included to vary the detection rate of the objects. Of the multiple brain regions activated, only the right lateral occipital cortex showed signals correlating with the proportion of correct object detections. The results suggest an important role for this area in visual awareness of objects.

The effects of electromagnetic field emitted by GSM phones on working memory.

The influence of pulsed radiofrequency (RF) electromagnetic fields of digital GSM mobile phones on working memory in healthy subjects were studied. Memory load was varied from 0 to 3 items in an n-back task. Each subject was tested twice within a single session, with and without the RF exposure (902MHz, 217Hz). The RF field speeded up response times when the memory load was three items but no effects of RF were observed with lower loads. The results suggest that RF fields have a measurable effect on human cognitive performance and encourage further studies on the interactions of RF fields with brain function.

The MMN amplitude increases in hypnosis: a case study.

The neural mechanisms associated with hypnosis were investigated in a single highly hypnotizable subject by measuring the mismatch negativity (MMN) component of auditory ERP, reflecting the preattentive discrimination of change in stimulus flow, in normal baseline state and under hypnosis. It has been proposed that the frontal inhibition associated with hypnosis can be measured as a decrease in MMN. ERPs were elicited using the passive oddball paradigm with standard and deviant sine tone stimuli of 500 and 553Hz, respectively. The measurement was repeated in five separate sessions. In hypnosis the MMN was significantly larger compared to baseline. The results indicate that hypnosis can give rise to altered information processing in the brain even at a relatively early, i.e. preattentive level and that the larger MMN measured under hypnosis does not support frontal inhibition theory.

The neural generation of a unified illusion in human vision.

The neural mechanisms of visual binding in humans were investigated by measuring the brain's high-frequency electric responses (36-44 Hz) to the subjective visual perception of a unified three-dimensional illusion. 40 Hz synchronization was found over occipital and right parieto-temporal areas 500-300 ms before visual awareness of the three-dimensional Gestalt was reported, but not during the viewing of the illusion. At lower frequency bands (8-13 Hz and 13-20 Hz) no corresponding synchronization was found. 40 Hz synchronization thus directly correlates with the construction and emergence of a unified visual percept and may reflect the rapid formation of transient functional connections between spatially separated cortical areas.

Effects of 902 MHz electromagnetic field emitted by cellular telephones on response times in humans.

The present study examined possible influences of a 902 MHz electromagnetic field emitted by cellular telephones on cognitive functioning in 48 healthy humans. A battery of 12 reaction time tasks was performed twice by each participant in a counterbalanced order: once with and once without the exposure to the field. The results showed that the exposure to the electromagnetic field speeded up response times in simple reaction time and vigilance tasks and that the cognitive time needed in a mental arithmetics task was decreased. The results suggest that exposure to the electromagnetic field emitted by cellular telephones may have a facilitatory effect on brain functioning, especially in tasks requiring attention and manipulation of information in working memory.

Effects of electromagnetic field emitted by cellular phones on the EEG during a memory task.

The effects of electromagnetic fields (EMF) emitted by cellular phones on the ERD/ERS of the 4-6 Hz, 6-8 Hz, 8-10 Hz and 10-12 Hz EEG frequency bands were studied in 16 normal subjects performing an auditory memory task. All subjects performed the memory task both with and without exposure to a digital 902 MHz EMF in counterbalanced order. The exposure to EMF significantly increased EEG power in the 8-10 Hz frequency band only. Nonetheless, the presence of EMF altered the ERD/ERS responses in all studied frequency bands as a function of time and memory task (encoding vs retrieval). Our results suggest that the exposure to EMF does not alter the resting EEG per se but modifies the brain responses significantly during a memory task.

Visual object recognition in multiple sclerosis.

Deficits in tasks measuring visual processing have been earlier reported in studies of MS. Yet, the nature and severity of visual-processing deficits in MS remains unclear. We used a new method in order to measure the different stages of visual processing in object recognition: shape recognition, familiarity recognition, semantic categorization, and identification with naming. Six two-choice reaction-time tasks were presented to 30 MS patients and 15 healthy controls. The patients were divided into cognitively preserved and cognitively deteriorated study groups according to their cognitive status. The purpose was to find out whether deficits at specific stages of visual processing can be found in cognitively deteriorated MS patients. Cognitively deteriorated MS patients did not perform as well as cognitively preserved MS patients or healthy controls. They were slower already at the early stage of visual processing where discrimination of whole objects from scrambled ones was required. They also had higher error rates in tasks requiring object familiarity detection and object identification with naming. Thus, cognitively deteriorated MS patients had difficulties in visual shape recognition and semantic-lexical processing. However, variation of performances was large within both of the patient groups indicating that even patients without a generalized cognitive decline may have deficits in some stages of the visual processing. We suggest that because of the heterogeneity of the patients, every single case needs to be examined separately in order to identify the possible deficits in visual processing.

Sematic memory deficit in multiple sclerosis; impaired understanding of conceptual meanings.

The aim of the present study was to determine whether a cognitive decline, related to multiple sclerosis (MS), also involves deficits in semantic memory. Semantic memory function was evaluated by studying the conscious understanding of conceptual meanings. A group of MS patients with cognitive decline was presented with four tasks concerning concepts, their attributes and relationships to other concepts. The tasks were designed to measure spontaneous, cued and recognition performance separately. The patients had difficulties in understanding conceptual meanings. Easing the retrieval demands of the tasks did not help them to improve their performance which was poorer than the control group's on every task used. The results indicate a retrieval deficit combined with an underlying storage deficit in the semantic memory of MS patients with cognitive decline.

Words interact with colors in a globally aphasic patient: evidence from a Stroop-like task.

Stroop-like manual reaction time tasks were administered to 16 controls and one globally aphasic patient who was unable to match written color words with the corresponding color. Although the patient could not explicitly access the meaning of written color words, he showed a similar pattern of performance in the reaction time tasks as the controls: written words were processed automatically and they interacted with the processing of the color of the letters. Thus, the results of this study suggested that it is possible to process unrecognized words implicitly to a cross-domain semantic level where the processing of words interacts with the processing of colors. The results from this and other studies on implicit language processing indicate that linguistic stimuli can be analysed to relatively high levels without any awareness.

Semantic processing without conscious understanding in a global aphasic: evidence from auditory event-related brain potentials.

We report a global aphasic who showed evidence of implicit semantic processing of spoken words. Auditory event-related brain potentials (ERPs) to semantically congruous and incongruous final words in spoken sentences were recorded. 17 elderly adults served as control subjects. Their ERPs were more negative to incongruous than to congruous final words between 300 and 800 ms after stimulus onset (N400), and more positive between 800 and 1500 ms (Late Positivity). The aphasic showed an exactly similar pattern of ERP components as the controls did, but his performance in a task demanding explicit differentiation between semantically congruous and incongruous sentences was at the chance level. During follow-up, his explicit understanding recovered over the chance level but the ERPs remained fairly similar. We conclude that implicit semantic activation at the conceptual level can take place even in the absence of conscious (explicit) comprehension of the meaningfulness of linguistic stimuli.

Knowledge of concept meanings in Alzheimer's disease.

The present study focuses on semantic deficits in Alzheimer's disease (AD). We distinguish three different levels of semantic knowledge: (1) lexical, (2) semantic-conceptual, (3) conscious understanding. We devised methods that tap levels (2) and (3). Our aim was to determine how much guidance AD patients need to consciously access a given semantic-conceptual field and how well they can understand the meanings of concepts and semantic relations. Four different tasks were used to tap different kinds of concepts, the relationships between concepts and their attributes, and the hierarchical structure among different concepts. The retrieval demands of the tasks were eased by presenting guiding questions. The results revealed that AD patients have deficient voluntary access to semantic-conceptual representations. The deficits persist even in passive recognition and forced-choice tasks. We conclude that AD patients have a generalized access deficit, although some aspects of the results are suggestive of storage deficit.

Effects of electromagnetic fields emitted by cellular phones on the electroencephalogram during a visual working memory task.

PURPOSE: To examine the effects of electromagnetic fields (EMF) emitted by cellular phones on the event-related desynchronization/synchronization (ERD/ERS) responses of the 4-6, 6-8, 8-10 and 10-12Hz EEG frequency bands during cognitive processing. MATERIALS AND METHODS: Twenty-four subjects performed a visual sequential letter task (n-back task) with three different working memory load conditions: zero, one and two items. All subjects performed the memory task both with and without exposure to a digital 902 MHz EMF in counterbalanced order. RESULTS: The presence of EMF altered the ERD/ERS responses in the 6-8 and 8-10 Hz frequency bands but only when examined as a function of memory load and depending also on whether the presented stimulus was a target or not. CONCLUSIONS: The results suggest that the exposure to EMF modulates the responses of EEG oscillatory activity approximately 8 Hz specifically during cognitive processes.

Anterior brain functions and hypnosis: a test of the frontal hypothesis.

Neuropsychological frontal lobe tests were used to compare individuals with high (n = 8) and low (n = 9) hypnotizability during both baseline and hypnosis conditions. Subjects were assessed on two hypnotic susceptibility scales and a test battery that included the Stroop test, word fluency to letter- and semantic-designated categories, tests of simple reaction time and choice reaction time, a vigilance task, and a questionnaire of 40 self-descriptive statements of focused attention. Effects for hypnotic susceptibility and hypnosis/control conditions were scant across the dependent variables. High hypnotizables scored higher on the questionnaire at baseline, and their performance on the word-fluency task during hypnosis was reduced to a greater extent than lows. Findings indicate that although the frontal area may play an important role regarding hypnotic response, the mechanisms seem to be much more complex than mere general inhibition.