Potential evidence of parasite avoidance in an avian malarial vector

Epidemiological studies of malaria or other vector-transmitted diseases often consider vectors as passive actors in the complex life cycle of the parasites, assuming that vector populations are homogeneous and vertebrate hosts are equally susceptible to being infected during their lifetime. However, some studies based on both human and rodent malaria systems found that mosquito vectors preferentially selected infected vertebrate hosts. This subject has been scarcely investigated in avian malaria models and even less in wild animals using natural host-parasite associations. We investigated whether the malaria infection status of wild great tits, Parus major, played a role in host selection by the mosquito vector Culex pipiens. Pairs of infected and uninfected birds were tested in a dual-choice olfactometer to assess their attractiveness to the mosquitoes. Plasmodium-infected birds attracted significantly fewer mosquitoes than the uninfected ones, which suggest that avian malaria parasites alter hosts' odours involved in vector orientation. Reaction time of the mosquitoes, that is, the time taken to select a host, and activation of mosquitoes, defined as the proportion of individuals flying towards one of the hosts, were not affected by the bird's infection status. The importance of these behavioural responses for the vector is discussed in light of recent advances in related or similar model systems.

Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage.

Impact of cannabis inhalation on driving skills in occasional smokers

Objectives: Our aim was to study the brain regions involved in a divided attention tracking task related to driving in occasional cannabis smokers. In addition we assessed the relationship between THC levels in whole blood and changes in brain activity, behavioural and psychomotor performances. Methods: Twenty-one smokers participated to two independent cross-over fMRI experiments before and after smoking cannabis and a placebo. The paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. Half of the active tracking conditions included randomly presented traffic lights as distractors. Blood samples were taken at regular intervals to determine the time-profiles of the major cannabinoids. Their levels during the fMRI experiments were interpolated from concentrations measured by GCMS/ MS just before and after brain imaging. Results: Behavioural data, such as the discard between target and cursor, the time of correct tracking and the reaction time during traffic lights appearance showed a statistical significant impairment of subject s skills due to THC intoxication. Highest THC blood concentrations were measured soon after smoking and ranged between 28.8 and 167.9 ng/ml. These concentrations reached values of a few ng/ml during the fMRI. fMRI results pointed out that under the effect of THC, high order visual areas (V3d) and Intraparietal sulcus (IPS) showed an higher activation compared to the control condition. The opposite comparison showed a decrease of activation during the THC condition in the anterior cingulate gyrus and orbitofrontal areas. In these locations, the BOLD showed a negative correlation with the THC level. Conclusion: Acute cannabis smoking significantly impairs performances and brain activity during active tracking tasks, partly reorganizing the recruitment of brain areas of the attention network. Neural activity in the anterior cingulate might be responsible of the changes in the cognitive controls required in our divided attention task.

Selective integration of auditory-visual looming cues by humans.

An object's motion relative to an observer can confer ethologically meaningful information. Approaching or looming stimuli can signal threats/collisions to be avoided or prey to be confronted, whereas receding stimuli can signal successful escape or failed pursuit. Using movement detection and subjective ratings, we investigated the multisensory integration of looming and receding auditory and visual information by humans. While prior research has demonstrated a perceptual bias for unisensory and more recently multisensory looming stimuli, none has investigated whether there is integration of looming signals between modalities. Our findings reveal selective integration of multisensory looming stimuli. Performance was significantly enhanced for looming stimuli over all other multisensory conditions. Contrasts with static multisensory conditions indicate that only multisensory looming stimuli resulted in facilitation beyond that induced by the sheer presence of auditory-visual stimuli. Controlling for variation in physical energy replicated the advantage for multisensory looming stimuli. Finally, only looming stimuli exhibited a negative linear relationship between enhancement indices for detection speed and for subjective ratings. Maximal detection speed was attained when motion perception was already robust under unisensory conditions. The preferential integration of multisensory looming stimuli highlights that complex ethologically salient stimuli likely require synergistic cooperation between existing principles of multisensory integration. A new conceptualization of the neurophysiologic mechanisms mediating real-world multisensory perceptions and action is therefore supported.

Topographic ERP analyses: a step-by-step tutorial review.

In this tutorial review, we detail both the rationale for as well as the implementation of a set of analyses of surface-recorded event-related potentials (ERPs) that uses the reference-free spatial (i.e. topographic) information available from high-density electrode montages to render statistical information concerning modulations in response strength, latency, and topography both between and within experimental conditions. In these and other ways these topographic analysis methods allow the experimenter to glean additional information and neurophysiologic interpretability beyond what is available from canonical waveform analyses. In this tutorial we present the example of somatosensory evoked potentials (SEPs) in response to stimulation of each hand to illustrate these points. For each step of these analyses, we provide the reader with both a conceptual and mathematical description of how the analysis is carried out, what it yields, and how to interpret its statistical outcome. We show that these topographic analysis methods are intuitive and easy-to-use approaches that can remove much of the guesswork often confronting ERP researchers and also assist in identifying the information contained within high-density ERP datasets.

Retest reliability of individual p3 topography assessed by high density electroencephalography.

BACKGROUND Some controversy remains about the potential applicability of cognitive potentials for evaluating the cerebral activity associated with cognitive capacity. A fundamental requirement is that these neurophysiological parameters show a high level of stability over time. Previous studies have shown that the reliability of diverse parameters of the P3 component (latency and amplitude) ranges between moderate and high. However, few studies have paid attention to the retest reliability of the P3 topography in groups or individuals. Considering that changes in P3 topography have been related to different pathologies and healthy aging, the main objective of this article was to evaluate in a longitudinal study (two sessions) the reliability of P3 topography in a group and at the individual level. RESULTS The correlation between sessions for P3 topography in the grand average of groups was high (r = 0.977, p<0.001). The within-subject correlation values ranged from 0.626 to 0.981 (mean: 0.888). In the between-subjects topography comparisons, the correlation was always lower for comparisons between different subjects than for within-subjects correlations in the first session but not in the second session. CONCLUSIONS The present study shows that P3 topography is highly reliable for group analysis (comprising the same subjects) in different sessions. The results also confirmed that retest reliability for individual P3 maps is suitable for follow-up studies for a particular subject. Moreover, P3 topography appears to be a specific marker considering that the between-subjects correlations were lower than the within-subject correlations. However, P3 topography appears more similar between subjects in the second session, demonstrating that is modulated by experience. Possible clinical applications of all these results are discussed.

Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients.

In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

Age-associated modulations of cerebral oscillatory patterns related to attention control.

Visual attention depends on bottom-up sensory activation and top-down attentional guidance. Although aging is known to affect sensory processing, its impact on the top-down control of attention remains a matter of debate. We investigated age-related modulations of brain oscillatory activity during visual attention using a variant of the attention network test (ANT) in 20 young and 28 elderly adults. We examined the EEG oscillatory responses to warning and target signals, and explored the correlates of temporal and spatial orienting as well as conflict resolution at target presentation. Time-frequency analysis was performed between 4 and 30Hz, and the relationship between behavioral and brain oscillatory responses was analyzed. Whereas temporal cueing and conflict had similar reaction time effects in both age groups, spatial cueing was more beneficial to older than younger subjects. In the absence of cue, posterior alpha activation was drastically reduced in older adults, pointing to an age-related decline in anticipatory attention. Following both cues and targets, older adults displayed pronounced motor-related activation in the low beta frequency range at the expense of attention-related posterior alpha activation prominent in younger adults. These findings support the recruitment of alternative motor-related circuits in the elderly, in line with the dedifferentiation hypothesis. Furthermore, older adults showed reduced midparietal alpha inhibition induced by temporal orienting as well as decreased posterior alpha activation associated with both spatial orienting and conflict resolution. Altogether, the results are consistent with an overall reduction of task-related alpha activity in the elderly, and provide functional evidence that younger and older adults engage distinct brain circuits at different oscillatory frequencies during attentional functions.

Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

Upregulation of vasopressin V1A receptor mRNA and protein in vascular smooth muscle cells following cyclosporin A treatment.

1. The major side effects of the immunosuppressive drug cyclosporin A (CsA) are hypertension and nephrotoxicity. It is likely that both are caused by local vasoconstriction. 2. We have shown previously that 20 h treatment of rat vascular smooth muscle cells (VSMC) with therapeutically relevant CsA concentrations increased the cellular response to [Arg8]vasopressin (AVP) by increasing about 2 fold the number of vasopressin receptors. 3. Displacement experiments using a specific antagonist of the vasopressin V1A receptor (V1AR) showed that the vasopressin binding sites present in VSMC were exclusively receptors of the V1A subtype. 4. Receptor internalization studies revealed that CsA (10(-6) M) did not significantly alter AVP receptor trafficking. 5. V1AR mRNA was increased by CsA, as measured by quantitative polymerase chain reaction. Time-course studies indicated that the increase in mRNA preceded cell surface expression of the receptor, as measured by hormone binding. 6. A direct effect of CsA on the V1AR promoter was investigated using VSMC transfected with a V1AR promoter-luciferase reporter construct. Surprisingly, CsA did not increase, but rather slightly reduced V1AR promoter activity. This effect was independent of the cyclophilin-calcineurin pathway. 7. Measurement of V1AR mRNA decay in the presence of the transcription inhibitor actinomycin D revealed that CsA increased the half-life of V1AR mRNA about 2 fold. 8. In conclusion, CsA increased the response of VSMC to AVP by upregulating V1AR expression through stabilization of its mRNA. This could be a key mechanism in enhanced vascular responsiveness induced by CsA, causing both hypertension and, via renal vasoconstriction, reduced glomerular filtration.

Computerunterstützte Rigiditätsmessung zur Differenzierung psychopathologischer Gruppen [Computer-assisted determination of rigidity in the differentiation of psychopathologic groups]

The measurement of rigidity and perseveration respectively gets increasing importance in clinical psychodiagnostics. Recently we have developed a computer-assisted technique which allows to get information about inadequate persisting in psychic processes and behaviour within shortest time and to differentiate between psychopathological groups. 257 patients of both sexes who came for elucidation of their disorders to the department of clinical psychodiagnostics were investigated. The most significant differences between the groups were found in redundance of second degree (the patient has to press 10 buttons indiscriminately according to the beat of a metronom--standard condition) and in personal speed (the patient has to press 10 buttons as fast as possible--speed condition). Furthermore the psychopathological groups were ranged in the particular variables of rigidity according to their mean values and their average ranges the schizophrenics and effective psychoses were characterized by a high tendency of perseveration while the neurotics, patients with organic brain syndrome and alcohol and drug dependents showed more flexibility.

Multisensory facilitation of behavior in monkeys: effects of stimulus intensity.

Multisensory stimuli can improve performance, facilitating RTs on sensorimotor tasks. This benefit is referred to as the redundant signals effect (RSE) and can exceed predictions on the basis of probability summation, indicative of integrative processes. Although an RSE exceeding probability summation has been repeatedly observed in humans and nonprimate animals, there are scant and inconsistent data from nonhuman primates performing similar protocols. Rather, existing paradigms have instead focused on saccadic eye movements. Moreover, the extant results in monkeys leave unresolved how stimulus synchronicity and intensity impact performance. Two trained monkeys performed a simple detection task involving arm movements to auditory, visual, or synchronous auditory-visual multisensory pairs. RSEs in excess of predictions on the basis of probability summation were observed and thus forcibly follow from neural response interactions. Parametric variation of auditory stimulus intensity revealed that in both animals, RT facilitation was limited to situations where the auditory stimulus intensity was below or up to 20 dB above perceptual threshold, despite the visual stimulus always being suprathreshold. No RT facilitation or even behavioral costs were obtained with auditory intensities 30-40 dB above threshold. The present study demonstrates the feasibility and the suitability of behaving monkeys for investigating links between psychophysical and neurophysiologic instantiations of multisensory interactions.

Auditory motion affects visual biological motion processing.

The processing of biological motion is a critical, everyday task performed with remarkable efficiency by human sensory systems. Interest in this ability has focused to a large extent on biological motion processing in the visual modality (see, for example, Cutting, J. E., Moore, C., & Morrison, R. (1988). Masking the motions of human gait. Perception and Psychophysics, 44(4), 339-347). In naturalistic settings, however, it is often the case that biological motion is defined by input to more than one sensory modality. For this reason, here in a series of experiments we investigate behavioural correlates of multisensory, in particular audiovisual, integration in the processing of biological motion cues. More specifically, using a new psychophysical paradigm we investigate the effect of suprathreshold auditory motion on perceptions of visually defined biological motion. Unlike data from previous studies investigating audiovisual integration in linear motion processing [Meyer, G. F. & Wuerger, S. M. (2001). Cross-modal integration of auditory and visual motion signals. Neuroreport, 12(11), 2557-2560; Wuerger, S. M., Hofbauer, M., & Meyer, G. F. (2003). The integration of auditory and motion signals at threshold. Perception and Psychophysics, 65(8), 1188-1196; Alais, D. & Burr, D. (2004). No direction-specific bimodal facilitation for audiovisual motion detection. Cognitive Brain Research, 19, 185-194], we report the existence of direction-selective effects: relative to control (stationary) auditory conditions, auditory motion in the same direction as the visually defined biological motion target increased its detectability, whereas auditory motion in the opposite direction had the inverse effect. Our data suggest these effects do not arise through general shifts in visuo-spatial attention, but instead are a consequence of motion-sensitive, direction-tuned integration mechanisms that are, if not unique to biological visual motion, at least not common to all types of visual motion. Based on these data and evidence from neurophysiological and neuroimaging studies we discuss the neural mechanisms likely to underlie this effect.

Aging and the lateralization of oscillatory activities related to external and internal motor preparation

Selection of action may rely on external guidance or be motivated internally, engaging partially distinct cerebral networks. With age, there is an increased allocation of sensorimotor processing resources, accompanied by a reduced differentiation between the two networks of action selection. The present study examines the age effects on the motor-related oscillatory patterns related to the preparation of externally and internally guided movements. Thirty-two older and 30 younger adults underwent three delayed motor tasks with S1 as preparatory and S2 as imperative cue: Full, laterality instructed by S1 (external guidance); Free, laterality freely selected (internal guidance); None, laterality instructed by S2 (no preparation). Electroencephalogram (EEG) was recorded using 64 surface electrodes. Motor-Related Amplitude Asymmetries (MRAA), indexing the lateralization of oscillatory activities, were analyzed within the S1-S2 interval in the mu (9-12 Hz) and low beta (15-20 Hz) motor-related frequency bands. Reaction times to S2 were slower in older than younger subjects, and slower in the Free than in the Full condition in older subjects only. In the Full condition, there were significant mu MRAA in both age groups, and significant low beta MRAA only in older adults. The Free condition was associated with large mu MRAA in younger adults and limited low beta MRAA in older adults. In younger subjects, the lateralization of mu activity in both Full and Free conditions indicated effective external and internal motor preparation. In older subjects, external motor preparation was associated with lateralization of low beta in addition with mu activity, compatible with an increase of motor-related resources. In contrast, absence of mu and limited low beta lateralization in internal motor preparation was concomitant with reaction time slowing and suggested less efficient cerebral processes subtending free movement selection in older adults, indicating reduced capacity for internally driven action with age.

Perceptual and semantic contributions to repetition priming of environmental sounds.

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what" pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieved.