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PubMed2004

Distribution of fallout radionuclides (7Be, 137Cs, 210Pb and 239,240Pu) in soils of Taiwan.

Depth profiles and cumulative deposition of four fallout radionuclides (7Be, 137Cs, 210Pb and 239,240Pu) were determined in presumably undisturbed soils in Taiwan. Inventories of these radionuclides in different areas correlate significantly with each other (except 7Be) and with mean annual rainfall, providing a necessary condition for the development of soil erosion studies in Taiwan. However, the data show very large spatial variability between and within landscape units, reflecting the steep topographic and meteorological gradients in the island. Thus, the application of fallout radionuclides to study soil conservation in Taiwan is expected to be a demanding task; it will call for dense sampling even at undisturbed reference sites.

Environmental Monitoring↗

PubMed2005

A novel sandwich ELISA for alpha1 domain based detection of soluble HLA-G heavy chains.

The detection of soluble human leukocyte antigen G (HLA-G) has been a technically demanding task for several years now and various enzyme linked immunosorbent assay (ELISA) formats have been designed. However, no ELISA test has been described so far which is able to detect all possible kinds of soluble HLA-G (sHLA-G) molecules that might occur in bio fluids. Here we describe a new ELISA approach able to recognize soluble alpha1 domain containing heavy chains of all HLA-G isoforms. The detection limit is shown to be at about 150 pg soluble recombinant HLA-G1 heavy chain per milliliters. Detectable HLA-G fragments are shown to occur in the supernatants of different HLA-G transfected cell lines and appear to be particularly abundant in supernatant of trophoblast derived choriocarcinoma cell lines. The novel ELISA employs the well characterized HLA-G mAbs 4H84 and MEM-G1 which ensure high HLA-G specificity. A negative control ELISA format, designed against non-existing analytes, has been established to reveal non-specific signal interference.

Antibodies, Monoclonal↗

PubMed2004

A new strategy for analysis of phenotype marker antigens in hollow neurospheres.

Changes in expression of phenotypic markers characterizing the cells comprising intact neurospheres are difficult to determine easily and accurately. The problem is compounded by the diversity of cell populations and phenotypes involved, and consequent non-uniform protein expression across the neurosphere wall, or around the circumference. Therefore, interpreting the effects of phenotype modifying conditions has been a complex and demanding task. Here, we report a novel direct method for measuring protein expression in immunofluoerescently labeled intact neurospheres by densitometric image analysis of optical cross-sections, obtained by scanning laser confocal microscopy. To demonstrate our methodology, hollow human neurospheres were exposed to basic fibroblast growth factor (FGF2), which reportedly induces neuronal commitment in monolayer cultures of neuroprogenitor cells derived from neurospheres. We determined that this treatment downregulated nestin and vimentin, protein markers accepted to indicate an immature, uncommitted phenotype. Neuron specific enolase was only marginally affected. Our strategy allows quantitation of changes in expression of marker proteins that is comparable to Western blot analysis. In addition to discriminating heterogeneity in protein expression, suitable optics may allow the resolution down to single cell level. We propose that this novel strategy, with or without confocal microscopy, may be applied to other biological systems. Analysis of protein expression by the cells comprising tubular or cylindrical cellular structures, or approximately spherical cell aggregates, can be performed efficiently using a small sample size.

Antigens↗

PubMed2006

Measurement of phase gradients in the EEG.

Previous research has shown that spatio-temporal waves in the EEG are generally of long spatial wavelength and form smooth patterns of phase gradients at particular time-samples. This paper describes a method to measure smooth phase gradients of long spatial wavelength in the EEG. The method depends on the global pattern of phase at a given frequency and time and is therefore robust to variations, over time, in phase-lag between particular sites. Phases were estimated in the EEG signal using wavelet or short time-series Fourier methods. During an auditory oddball task, phases across the scalp tend to fall within a limited circular range, a range that is not indicative of phase-synchrony nor waves with multiple periods. At times the phases tended to maintain a spatially and temporally ordered relationship. The relative phases were analysed using three phase gradient basis functions, providing a measure of the amount of variance explained, across the electrodes, by smooth changes in relative phase from a single minimum or single maximum. The data from 586 adult subjects were analysed and it was found that the probability of phase gradient events varies with time and frequency in the stimulus-locked average, and with task demands. The temporal extent of spatio-temporal waves was measured by detecting smoothly changing patterns of phase latencies across the scalp. The specific spatial pattern and timing of phase gradients correspond closely to the latency distributions of certain ERPs.

Acoustic Stimulation↗

PubMed2006

A novel electrode-pipette design for simultaneous recording of extracellular spikes and iontophoretic drug application in awake behaving monkeys.

We developed a novel design of an electrode-pipette combination (EPC) which allows access to brain structures in awake behaving primates without the need for guide tubes or to mechanically open the dura prior to electrode insertion. The EPC consists of an etched tungsten in glass electrode flanked by two pipettes which allow for local and highly controlled iontophoretic administration of neuroactive substances. These EPCs have excellent single cell isolation properties and are sturdy enough to penetrate the primate dura for up to 8 weeks following either a craniotomy or a dura scrape (i.e. even after substantial built up of fibrous scar tissue). We show that the EPCs can be used to selectively manipulate the cholinergic system in primate V1 during passive fixation and while animals perform an attentionally demanding task.

Acetylcholine↗

PubMed2005

Predicting rRNA-, RNA-, and DNA-binding proteins from primary structure with support vector machines.

In the post-genome era, the prediction of protein function is one of the most demanding tasks in the study of bioinformatics. Machine learning methods, such as the support vector machines (SVMs), greatly help to improve the classification of protein function. In this work, we integrated SVMs, protein sequence amino acid composition, and associated physicochemical properties into the study of nucleic-acid-binding proteins prediction. We developed the binary classifications for rRNA-, RNA-, DNA-binding proteins that play an important role in the control of many cell processes. Each SVM predicts whether a protein belongs to rRNA-, RNA-, or DNA-binding protein class. Self-consistency and jackknife tests were performed on the protein data sets in which the sequences identity was < 25%. Test results show that the accuracies of rRNA-, RNA-, DNA-binding SVMs predictions are approximately 84%, approximately 78%, approximately 72%, respectively. The predictions were also performed on the ambiguous and negative data set. The results demonstrate that the predicted scores of proteins in the ambiguous data set by RNA- and DNA-binding SVM models were distributed around zero, while most proteins in the negative data set were predicted as negative scores by all three SVMs. The score distributions agree well with the prior knowledge of those proteins and show the effectiveness of sequence associated physicochemical properties in the protein function prediction. The software is available from the author upon request.

Amino Acid Sequence↗

PubMed2005

Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease.

It is well recognised that patients with Parkinson's disease exhibit cognitive deficits, even in the earliest disease stages. Whereas, L-DOPA therapy in early Parkinson's disease is accepted to improve the motor symptoms, the effects on cognitive performance are more complex: both positive and negative effects have been observed. The purpose of the present article is to review the effects of L-DOPA medication in Parkinson's disease on cognitive functions in the broad domains of cognitive flexibility and working memory. The review places the effects in Parkinson's disease within a framework of evidence from studies with healthy human volunteers, rodents and non-human primates as well as computational modeling work. It is suggested that beneficial or detrimental effects of L-DOPA are observed depending on task demands and basal dopamine levels in distinct parts of the striatum. The study of the beneficial and detrimental cognitive effects of L-DOPA in Parkinson's disease has substantial implications for the understanding and treatment development of cognitive abnormalities in Parkinson's disease as well as normal health.

Animals↗

PubMed2005

Neurocognitive correlates of incidental verbal memory encoding: a magnetoencephalographic (MEG) study.

In our current study, we applied whole head magnetoencephalography (MEG) in a subsequent memory paradigm. Magnetic fields were recorded while 20 healthy subjects (10 females, 10 males) incidentally encoded words during semantic and structural verbal processing tasks. Physiological data were then sorted according to the performance in subsequent memory tests and according to levels of processing, respectively, and analyzed for gender effects. Behavioral results show a clear advantage of semantic processing over structural processing with respect to retrieval success for both females and males. Despite alikeness of behavioral data, MEG results show considerable differences between males and females concerning both subsequent memory effects and levels of processing effects. For male subjects, we identified more distinct magnetic fields in anterior regions for subsequently remembered than for subsequently forgotten words (latency range from 300-650 ms after word onset) and for semantic processing than for structural processing, respectively. For female subjects, corresponding magnetic field differences pointed to posterior regions (subsequent memory effects from 450 ms to 750 ms after word onset). No qualitative differences were observed between subsequent memory effects during semantic processing compared to subsequent memory effects during structural processing. We try to reconcile results from male data with previous findings concerning subsequent memory effects by proposing the concept of width of processing, which holds that incidental memory formation is mediated by frontal activity on a physiological level and brought forward on a cognitive level by enhanced associating imposed by the task demands of semantic processing. Female data cannot be fully incorporated in this framework, but all the more prompt further gender-specific analyses of subsequent memory effects.

Adult↗

PubMed2005

Frontal midline EEG dynamics during working memory.

We show that during visual working memory, the electroencephalographic (EEG) process producing 5-7 Hz frontal midline theta (fmtheta) activity exhibits multiple spectral modes involving at least three frequency bands and a wide range of amplitudes. The process accounting for the fmtheta increase during working memory was separated from 71-channel data by clustering on time/frequency transforms of components returned by independent component analysis (ICA). Dipole models of fmtheta component scalp maps were consistent with their generation in or near dorsal anterior cingulate cortex. From trial to trial, theta power of fmtheta components varied widely but correlated moderately with theta power in other frontal and left temporal processes. The weak mean increase in frontal midline theta power with increasing memory load, produced entirely by the fmtheta components, largely reflected progressively stronger theta activity in a relatively small proportion of trials. During presentations of letter series to be memorized or ignored, fmtheta components also exhibited 12-15 Hz low-beta activity that was stronger during memorized than during ignored letter trials, independent of letter duration. The same components produced a brief 3-Hz burst 500 ms after onset of the Probe letter following each letter sequence. A new decomposition method, log spectral ICA, applied to normalized log time/frequency transforms of fmtheta component Memorize-letter trials, showed that their low-beta activity reflected harmonic energy in continuous, sharp-peaked theta wave trains as well as independent low-beta bursts. Possibly, the observed fmtheta process variability may index dynamic adjustments in medial frontal cortex to trial-specific behavioral context and task demands.

Adult↗

PubMed2005

Emotion and attention interactions in social cognition: brain regions involved in processing anger prosody.

Multiple levels of processing are thought to be involved in the appraisal of emotionally relevant events, with some processes being engaged relatively independently of attention, whereas other processes may depend on attention and current task goals or context. We conducted an event-related fMRI experiment to examine how processing angry voice prosody, an affectively and socially salient signal, is modulated by voluntary attention. To manipulate attention orthogonally to emotional prosody, we used a dichotic listening paradigm in which meaningless utterances, pronounced with either angry or neutral prosody, were presented simultaneously to both ears on each trial. In two successive blocks, participants selectively attended to either the left or right ear and performed a gender-decision on the voice heard on the target side. Our results revealed a functional dissociation between different brain areas. Whereas the right amygdala and bilateral superior temporal sulcus responded to anger prosody irrespective of whether it was heard from a to-be-attended or to-be-ignored voice, the orbitofrontal cortex and the cuneus in medial occipital cortex showed greater activation to the same emotional stimuli when the angry voice was to-be-attended rather than to-be-ignored. Furthermore, regression analyses revealed a strong correlation between orbitofrontal regions and sensitivity on a behavioral inhibition scale measuring proneness to anxiety reactions. Our results underscore the importance of emotion and attention interactions in social cognition by demonstrating that multiple levels of processing are involved in the appraisal of emotionally relevant cues in voices, and by showing a modulation of some emotional responses by both the current task-demands and individual differences.

Acoustic Stimulation↗

PubMed2005

A special role for numbers in working memory? An fMRI study.

Although numbers carry averbal semantics (i.e., magnitude), they are often utilized in verbal Working Memory (vWM) tasks. However, vWM is thought to rely on a purely phonological code. Here, we tested the influence of (a) averbal semantics and (b) different tasks on performance in a vWM context by examining stimulus and task-specific variation of activity in the horizontal parts of the intraparietal sulcus (hIPS). The hIPS has previously been shown to subserve magnitude processing modulated by (a) specific stimuli and (b) specific tasks. Two variants of an n-back paradigm (comparison and identity match tasks) utilizing letters and numbers as stimulus material at different levels of vWM load were administered in 16 participants. Behavioral and functional imaging data reveal stimulus-specific modulation of activity in the hIPS suggesting a semantic influence of numbers. In the identity match task, numbers induced additional hIPS activation compared to letters while letters never induced additional hIPS activation when compared to numbers. Letters as compared to numbers only induced additional hIPS activation in the comparison task. These results question the assumption of a purely phonological code in vWM because hIPS activation subserving magnitude processing is modulated by stimulus semantics and task demands.

Adult↗

PubMed2006

The effect of gender on planning: An fMRI study using the Tower of London task.

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.

Adult↗

PubMed2006

Semantic ambiguity processing in sentence context: Evidence from event-related fMRI.

Lexical semantic ambiguity is the phenomenon when a word has multiple meanings (e.g. 'bank'). The aim of this event-related functional MRI study was to identify those brain areas, which are involved in contextually driven ambiguity resolution. Ambiguous words were selected which have a most frequent, dominant, and less frequent, subordinate meaning. These words were presented in two types of sentences: (1) a sentence congruent with the dominant interpretation and (2) a sentence congruent with the subordinate interpretation. Sentences without ambiguous words served as a control condition. The ambiguous words always occurred early in the sentences and were biased towards one particular meaning by the final word(s) of the sentence; the event at the end of the sentences was modeled. The results indicate that a bilaterally distributed network supports semantic ambiguity comprehension: left (BA 45/44) and right (BA 47) inferior frontal gyri and left (BA 20/37) and right inferior/middle temporal gyri (BA 20). The pattern of activation is most consistent with a scenario in which initially a frequency-based probabilistic choice is made between the alternative meanings, and the meaning is updated when this interpretation does not fit into the final disambiguating context. The neural pattern is consistent with the results of other neuroimaging experiments which manipulated various aspects of integrative and context processing task demands. The presence of a bilateral network is also in line with the lesion and divided visual field literature, but contrary to earlier claims, the two hemispheres appear to play similar roles during semantic ambiguity resolution.

Adult↗

PubMed2004

Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate.

Memory decline in aging results from multiple factors that influence both executive function and the medial temporal lobe memory system. In advanced aging, frontal-striatal systems are preferentially vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion. Frontal-striatal change may underlie mild memory difficulties in aging that are most apparent on tasks demanding high levels of attention and controlled processing. Through separate mechanisms, Alzheimer's disease preferentially affects the medial temporal lobe and cortical networks, including posterior cingulate and retrosplenial cortex early in its progression, often before clinical symptoms are recognized. Disruption of the medial temporal lobe memory system leads directly to memory impairment. Recent findings further suggest that age-associated change is not received passively. Reliance on reserve is emerging as an important factor that determines who ages gracefully and who declines rapidly. Functional imaging studies, in particular, suggest increased recruitment of brain areas in older adults that may reflect a form of compensation.

Aging↗

PubMed2006

Task and content modulate amygdala-hippocampal connectivity in emotional retrieval.

The ability to remember emotional events is crucial for adapting to biologically and socially significant situations. Little is known, however, about the nature of the neural interactions supporting the integration of mnemonic and emotional information. Using fMRI and dynamic models of effective connectivity, we examined regional neural activity and specific interactions between brain regions during a contextual memory retrieval task. We independently manipulated emotional context and relevance of retrieved emotional information to task demands. We show that retrieval of emotionally valenced contextual information is associated with enhanced connectivity from hippocampus to amygdala, structures crucially involved with encoding of emotional events. When retrieval of emotional information is relevant to current behavior, amygdala-hippocampal connectivity increases bidirectionally, under modulatory influences from orbitofrontal cortex, a region implicated in representation of affective value and behavioral guidance. Our findings demonstrate that both memory content and behavioral context impact upon large scale neuronal dynamics underlying emotional retrieval.

Amygdala↗

PubMed2007

From thought to action: the parietal cortex as a bridge between perception, action, and cognition.

The lateral intraparietal area (LIP) is a subdivision of the inferior parietal lobe that has been implicated in the guidance of spatial attention. In a variety of tasks, LIP provides a "salience representation" of the external world-a topographic visual representation that encodes the locations of salient or behaviorally relevant objects. Recent neurophysiological experiments show that this salience representation incorporates information about multiple behavioral variables-such as a specific motor response, reward, or category membership-associated with the task-relevant object. This integration occurs in a wide variety of tasks, including those requiring eye or limb movements or goal-directed or nontargeting operant responses. Thus, LIP acts as a multifaceted behavioral integrator that binds visuospatial, motor, and cognitive information into a topographically organized signal of behavioral salience. By specifying attentional priority as a synthesis of multiple task demands, LIP operates at the interface of perception, action, and cognition.

Animals↗

PubMed2004

Time course and hemispheric lateralization effects of complex pitch processing: evoked magnetic fields in response to rippled noise stimuli.

To delineate the time course and processing stages of pitch encoding at the level of the supratemporal plane, the present study recorded evoked magnetic fields in response to rippled noise (RN) stimuli. RN largely masks simple tonotopic representations and addresses pitch processing within the temporal domain (periodicity encoding). Four dichotic stimulus types (111 or 133 Hz RN at one ear, white noise to the other one) were applied in randomized order during either visual distraction or selective auditory attention. Strictly periodic signals, noise-like events, and mixtures of both signals served as control conditions. (1) Attention-dependent ear x hemisphere interactions were observed within the time domain of the M50 field, indicating early streaming of auditory information. (2) M100 responses to strictly periodic stimuli were found lateralized to the right hemisphere. Furthermore, the higher-pitched stimuli yielded enhanced activation as compared to the lower-pitch signals (pitch scaling), conceivably reflecting sensory memory operations. (3) Besides right-hemisphere pitch scaling, the relatively late M100 component in association with the RN condition (latency = 136 ms) showed significantly stronger field strengths over the left hemisphere. Control experiments revealed this lateralization effect to be related to noise rather than pitch processing. Furthermore, subtle noise variations interacted with signal periodicity. Obviously, thus, complex task demands such as RN encoding give rise to functional segregation of auditory processing across the two hemispheres (left hemisphere: noise, right hemisphere: periodicity representation). The observed noise/periodicity interactions, furthermore, might reflect pitch-synchronous spectral evaluation at the level of the left supratemporal plane, triggered by right-hemisphere representation of signal periodicity.

Acoustic Stimulation↗

PubMed2005

Electrophysiological indices of strategic episodic retrieval processing.

Event-related potentials (ERPs) were acquired during test phases of a recognition memory exclusion task, in order to contribute to current understanding of the processes responsible for the ways in which memory retrieval can be controlled strategically. Participants were asked to endorse old words from one study task (targets) and to reject new test words as well as those from a second study task (non-targets). The study task designated as the target category varied across test phases. The left-parietal ERP old/new effect--the electrophysiological signature of recollection--was reliable for targets only in all test phases, consistent with the view that participants control recollection strategically in service of task demands. The contrast between the ERPs evoked by new test words separated according to target designation revealed reliable differences at midline, anterior and right-hemisphere locations. These differences likely reflect processes that form part of a retrieval attempt and are interpreted here as indices of processes that are important for the strategic regulation of episodic retrieval.

Adolescent↗