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Biomedical subjects

P Luu

Publications and source records attributed to P Luu.

16 recordsLinked to original sources

Scalp electrode impedance, infection risk, and EEG data quality.

OBJECTIVES: Breaking the skin when applying scalp electroencephalographic (EEG) electrodes creates the risk of infection from blood-born pathogens such as HIV, Hepatitis-C, and Creutzfeldt-Jacob Disease. Modern engineering principles suggest that excellent EEG signals can be collected with high scalp impedance ( approximately 40 kOmega) without scalp abrasion. The present study was designed to evaluate the effect of electrode-scalp impedance on EEG data quality. METHODS: The first section of the paper reviews electrophysiological recording with modern high input-impedance differential amplifiers and subject isolation, and explains how scalp-electrode impedance influences EEG signal amplitude and power line noise. The second section of the paper presents an experimental study of EEG data quality as a function of scalp-electrode impedance for the standard frequency bands in EEG and event-related potential (ERP) recordings and for 60 Hz noise. RESULTS: There was no significant amplitude change in any EEG frequency bands as scalp-electrode impedance increased from less than 10 kOmega (abraded skin) to 40 kOmega (intact skin). 60 Hz was nearly independent of impedance mismatch, suggesting that capacitively coupled noise appearing differentially across mismatched electrode impedances did not contribute substantially to the observed 60 Hz noise levels. CONCLUSIONS: With modern high input-impedance amplifiers and accurate digital filters for power line noise, high-quality EEG can be recorded without skin abrasion.

Artifacts↗

Regulating action: alternating activation of midline frontal and motor cortical networks.

OBJECTIVES: Focal electrical fields recorded over the midline prefrontal cortex have been found to index rapid evaluative decisions, including the recognition of having made an error in a speeded response task. The nature of these electrical fields and how they are related to cortical areas involved in response execution remains to be clarified. METHODS: As subjects performed a speeded response task the EEG was recorded with a 128-channel sensor array. By filtering out the large slow waves of the event-related potential, we found that the error-related negativity (Ne/ERN) arises from a midline frontal oscillation that alternates with oscillations over lateral sensorimotor cortex. Electrical source analyses were used to determine the brain sources involved in the generation of these oscillations. RESULTS: The results show that the midline and lateral oscillations have a period of about 200 ms (theta), and they are present for both correct and error responses. When an error is made, the midline error oscillation is recruited strongly, and it becomes correlated with the motor oscillation. Source analyses localized the midline error oscillation to centromedial frontal cortex and the lateral oscillation to sensorimotor cortices. CONCLUSIONS: Because of the similarity between the midline oscillation observed in the present study and frontal midline theta, the nature of the Ne/ERN may be clarified by the frontal midline theta literature. The correlation between the midline and sensorimotor oscillations suggests a possible mechanism for how midline frontal evaluative and monitoring networks contribute to action regulation.

Adolescent↗

Localizing acute stroke-related EEG changes: assessing the effects of spatial undersampling.

Because of its sensitivity to metabolic and ionic disturbances related to ischemia, the EEG can be a potentially useful tool for acute stroke detection and for monitoring affected tissue. However, the clinical use of the EEG in detecting stroke is determined in part by how accurately the spatial information is characterized. The purpose of the current study was to determine the effects of spatial undersampling on the distribution and interpretation of the stroke-related topographic EEG. Using a 128-channel sensor montage, EEG was recorded from six stroke patients acutely (between 8 and 36 hours) after symptom onset. The EEG was submitted to a spectral analysis and was compared with patient symptoms and MRI and computed tomographic findings. To determine loss of spatial and clinical information resulting from spatial undersampling, the average-referenced data from the original 128-channel recording montage were subsampled into 64-, 32-, and 19-channel arrays. Furthermore, the analytical findings were compared with a board-certified electroencephalographer's review of the raw EEG using a conventional clinical montage. As predicted, the results showed that accurate description of stroke-related topographic EEG changes is dependent on adequate spatial sampling density. Accurate description of the spatial distribution of the stroke-related EEG was achieved only with the 64- and 128-channel EEG. As the recording density decreases to 32 channels, the distribution of the scalp EEG spectra is distorted, potentially resulting in mislocalization of the affected region. Results of the clinical review by an expert electroencephalographer corroborated the quantitative analyses, and the results also demonstrated the shortcomings of the conventional 10-20 recording density for capturing focal EEG abnormalities in several cases. The EEG provides useful information about the localization of acute cerebral ischemia, but recording densities of 64 channels or higher are required for accurate spatial characterization of focal stroke-related EEG changes.

Adult↗

Medial frontal cortex in action monitoring.

Effective behavior requires continuous action monitoring. Electrophysiological studies in both monkeys and humans have shown activity in the medial frontal cortex that reflects dynamic control and monitoring of behavioral acts. In humans, the centromedial frontal cortex shows an electrical response within 100 msec of an error, the error-related negativity (ERN). The ERN occurs only when subjects are aware of making an error, suggesting that a critical factor may be self-monitoring of the action process. In the present study, we examined late responses in a deadline reaction time task, in which the subject becomes increasingly aware of making an error as the response becomes increasingly late. We found evidence of response conflict before errors defined by late responses but not before errors defined by incorrect responses. The results also show a linear increase in the amplitude of the ERN with increasingly late responses. These data suggest that frontal networks provide dynamic representations that monitor and evaluate the unfolding action plan.

Adolescent↗

Cognitive and emotional influences in anterior cingulate cortex.

Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.

Journal Article↗

Tracking the time course of object categorization using event-related potentials.

Object categorization processes were investigated by measuring event-related potentials while subjects categorized objects at the superordinate (e.g. animal), basic (e.g. dog) and subordinate (e.g. beagle) levels of abstraction. An enhanced negative deflection (N1) was found at posterior recording sites for subordinate level categorizations compared with basic level categorizations and was interpreted as a marker of increased visual analysis. In contrast, superordinate level categorizations produced a larger frontal negativity relative to basic level categorizations and were interpreted as an indicator of increased semantic processing. These results suggest a neurophysiological basis for the separate cognitive processes responsible for subordinate and superordinate object categorizations.

Adult↗

Mood and spatial memory: emotion and right hemisphere contribution to spatial cognition.

Depressed persons show an impairment of spatial cognition that may reflect the influence of affective arousal on right hemisphere cognition. We examined normal university students to determine whether individual differences in mood and arousal levels would be related to performance on a spatial memory task. Right-hemisphere specialization for this spatial memory task was confirmed by a left field advantage for the targets and this field asymmetry was enhanced as task difficulty was increased. Event-related brain potentials (ERPs), assessed with a 64-channel sensor array, showed a processing negativity contralateral to the target in the P300 interval (300-500 ms after the target appeared). This effect increased as task difficulty was increased. A stronger posterior negativity for good (rather than bad) targets may suggest that attention was allocated toward the good locations. A suggestion of right hemisphere sensitivity to mood in this normal sample was a tendency for the subjects high in Negative Arousal not to show the normal right hemisphere (left field) superiority for the spatial memory task. Interestingly, a medial frontal lobe negativity was elicited in the ERPs by the bad targets, perhaps paralleling the error-related negativity observed in other paradigms. This medial frontal negativity was also seen in response to the feedback stimulus for the bad targets. Motivation may be important to this frontal effect: It was enhanced for subjects describing themselves as high in either positive or negative affective arousal during the task.

Adolescent↗

P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro.

To identify novel inhibitors of transcriptional activation by the HIV Tat protein, we used a combination of in vitro and in vivo Tat-dependent transcription assays to screen >100,000 compounds. All compounds identified blocked Tat-dependent stimulation of transcriptional elongation. Analysis of a panel of structurally diverse inhibitors indicated that their target is the human homolog of Drosophila positive transcription elongation factor b (P-TEFb). Loss of Tat transactivation in extracts depleted of the kinase subunit of human P-TEFb, PITALRE, was reversed by addition of partially purified human P-TEFb. Transfection experiments with wild-type or kinase knockout PITALRE demonstrated that P-TEFb is required for Tat function. Our results suggest that P-TEFb represents an attractive target for the development of novel HIV therapeutics.

Animals↗

Binding of SP1 to the immediate-early protein-responsive element of the human cytomegalovirus DNA polymerase promoter.

Human cytomegalovirus (HCMV), a member of the herpesvirus family of DNA viruses, encodes two major immediate-early (IE) transcription factors, IE72 and IE86, that are important for regulated expression of the viral genome. The purpose of this study was to identify the host cellular components required for regulation of the HCMV DNA polymerase promoter (UL54) by HCMV IE proteins. Extensive mutagenesis defined a DNA element located between -54 and -43 relative to the transcription start site that was required for both basal transcriptional activity and transactivation by viral IE proteins. A single copy of the UL54 -54/-43 sequence enhanced the responsiveness of a heterologous minimal promoter to HCMV IE proteins. Fractionation of extracts prepared from uninfected cells led to the isolation of two cellular proteins with apparent molecular masses of 95 and 105 kDa that bound specifically to the UL54 -54/-43 element. Biochemical and immunochemical analyses identified this protein as the transcription factor SP1. Although initial inspection of the UL54 -54/-43 sequence did not predict an SP1 binding site, subsequent analyses indicated that it is indeed a nonconsensus GC box. We propose that SP1 is required to direct basal levels of promoter activity and that SP1-regulated transcription complexes allow the entry of HCMV IE proteins into the transcription cycle.

Cell Extracts↗

Inhibition of the association of RNA polymerase II with the preinitiation complex by a viral transcriptional repressor.

Transcriptional repression is an important component of regulatory networks that govern gene expression. In this report, we have characterized the mechanisms by which the immediate early protein 2 (IE2 or IE86), a master transcriptional regulator of human cytomegalovirus, down-regulates its own expression. In vitro transcription and DNA binding experiments demonstrate that IE2 blocks specifically the association of RNA polymerase II with the preinitiation complex. Although, to our knowledge, this is the first report to describe a eukaryotic transcriptional repressor that selectively impedes RNA polymerase II recruitment, we present data that suggest that this type of repression might be widely used in the control of transcription by RNA polymerase II.

Base Sequence↗

Emotional expectancy: brain electrical activity associated with an emotional bias in interpreting life events.

University students in either an optimistic or pessimistic mood state read brief stories of daily life events as event-related brain potentials were collected during the final word of each story. For subjects in a pessimistic mood, a bias to expect negative outcomes was seen as an N400/P300 effect over posterior scalp regions. For subjects in an optimistic mood, a differentiation between good and bad outcomes was also observed, but it was specific to medial frontal areas. Analysis of single-trial P300 latencies suggested that semantically incongruent and mood-incongruent outcome words resulted in increased median latency of the late positive complex (LPC) and resulted in increased variability of LPC latency across trials.

Adolescent↗

Social and emotional self-regulation.

In humans, frontal lesions result in deficits of social and emotional behavior that are often surprising in the presence of intact language and other cognitive skills. The connections between the motivation and memory functions of limbic cortex and the motor planning functions of frontal neocortex must be fundamental to meeting the daily challenges of self-regulation. The connectional architecture of limbic and neocortical networks suggests a model of function. The densely interconnected paralimbic cortices may serve to maintain a global motivational context within which specific actions are articulated and sequenced within frontal neocortical networks. The paralimbic networks represent the visceral and kinesthetic information that is integral to the representation of the bodily self. In a general sense, the implicit self-representation within paralimbic networks may shape the significance of perceptions and the motivational context for developing actions. The network architecture of the frontal lobe reflects the dual limbic origins of frontal cortex, in the dorsal archicortical and ventral paleocortical structures. In this paper, we speculated that these two limbic-cortical pathways apply different motivational biases to direct the frontal lobe representation of working memory. The dorsal limbic mechanisms projecting through the cingulate gyrus may be influenced by hedonic evaluations, social attachments, and they may initiate a mode of motor control that is holistic and impulsive. In contrast, the ventral limbic pathway from the amygdala to orbital frontal cortex may implement a tight, restricted mode of motor control that reflects adaptive constraints of self-preservation. In the human brain, hemispheric specialization appears to have led to asymmetric elaborations of the dorsal and ventral pathways. Understanding the inherent asymmetries of corticolimbic architecture may be important in interpreting the increasing evidence that the left and right frontal lobes contribute differently to normal and pathological forms of self-regulation.

Brain Diseases↗

Efficient induction of fibrosarcomas by v-jun requires mutations in the DNA binding region and the transactivation domain.

v-jun is the transforming gene of ASV 17, a retrovirus isolated from a spontaneous chicken fibrosarcoma. There are three mutations in the viral Jun protein (v-Jun) as compared to its cellular progenitor c-Jun: a deletion in the transactivation domain (called delta) and two amino acid substitutions in and near the DNA binding region. The effect of each of these mutations on fibrosarcoma development is described. All three mutations contribute towards tumor formation, and their cumulative effect makes v-Jun more tumorigenic compared to Jun proteins that carry only one or two of the mutations. Viruses rescued from tumors induced by c-Jun carrying the two amino acid substitutions in the DNA binding region have increased transforming and tumorigenic potential. These increases are probably due to further mutations that result in the expression of a rearranged Jun protein. Taken together the results show that the evolution of the c-Jun oncoprotein to an efficient carcinogen requires mutations in the transactivation and DNA binding regions.

Animals↗

Formation of gluconeogenic precursors in rat skeletal muscle during fasted-refed transition.

During the fasted-refed transition, hepatic glycogen repletion from glucose can occur by the direct and indirect pathway. In the indirect pathway, glucose is first metabolized to 3-carbon intermediates that then are converted in the liver to glucose 6-phosphate via the gluconeogenic pathway before conversion to glycogen. The present study evaluated whether skeletal muscle is a major source of 3-carbon intermediates (i.e., lactate, pyruvate, and alanine) during refeeding of 1-day fasted rats. Arteriovenous differences for lactate, pyruvate, and alanine across the anesthetized rat hindlimbs were used to evaluate muscle metabolism in the fed, fasted, and refed state. In the fasted state, liver glycogen was depleted, and muscle released 3-carbon intermediates. One hour after refeeding, hepatic glycogen was 30% repleted, and blood lactate, pyruvate, and alanine increased. Despite this, the release of alanine by muscle diminished at this time and lactate was removed. At 4 h after refeeding, 3-carbon intermediates were all released by hindlimb tissue but in an amount not greater than in the fasted state. Overall, these results suggest that skeletal muscle in the rat is not a major source of 3-carbon precursors for early postprandial hepatic glycogen repletion via the indirect pathway, nor is the rise in 3-carbon intermediates in blood during refeeding caused by their increased output by muscle.

Alanine↗

Differential effects of sodium butyrate, dimethyl sulfoxide, and retinoic acid on membrane-associated antigen, enzymes, and glycoproteins of human rectal adenocarcinoma cells.

The effects of sodium butyrate, dimethyl sulfoxide (DMSO), and retinoic acid on the growth, morphology, carcinoembryonic antigen content, cell surface membrane-associated enzyme activities, and glycoprotein profiles of a human rectal adenocarcinoma cell line (HRT-18) in culture were compared. All three agents reversibly caused a marked increase in doubling times, a decrease in saturation densities, and a markedly reduced colony-forming efficiency in soft agar. Only butyrate caused gross morphological changes including cell enlargement, flattening, and increased membranous process formation. Carcinoembryonic antigen content was increased during culture in butyrate, while it was reduced by DMSO and unchanged by retinoic acid. The activities of membrane-associated enzymes were altered significantly in the butyrate-treated cells. For example, an increase in the activities of alkaline phosphatase (10-fold), gamma-glutamyl transpeptidase activity (3-fold) and sucrase activity (2-fold) was observed, while those of aminooligopeptidase and K+-stimulated phosphatase actually showed slight decreases. DMSO- or retinoic acid-treated cells showed a marked decrease in alkaline phosphatase activity, but other enzyme activities remained unchanged. Surface protein-labeling patterns of lactoperoxidase-catalyzed iodinated HRT-18 cells showed no significant change from the control cells following treatment with DMSO or retinoic acid. The most prominent change caused by butyrate treatment was the appearance of a major glycoprotein band with an apparent molecular weight of 60,000. These data indicate that the use of butyrate, DMSO, and retinoic acid may provide useful information concerning the identification of differentiation-associated markers of human rectal cancer cells. Furthermore, these agents, although having similar effects on the growth properties, have different effects on the morphology and on the biochemical properties of human rectal cancer cells.

Adenocarcinoma↗