Evgeniya Kirilina

The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy.

A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals. We used complementary fNIRS, fMRI, MR-angiography and peripheral physiological measurements (blood pressure, heart rate, skin conductance and skin blood flow) to study activation in the frontal lobe during a continuous performance task. The General Linear Model (GLM) was applied to analyse the fNIRS data, which included an additional predictor to account for systemic changes in the skin. We found that skin blood volume strongly depends on the cognitive state and that sources of task-evoked systemic signals in fNIRS are co-localized with veins draining the scalp. Task-evoked superficial artefacts were mainly observed in concentration changes of oxygenated haemoglobin and could be effectively separated from cerebral signals by GLM analysis. Based on temporal correlation of fNIRS and fMRI signals with peripheral physiological measurements we conclude that the physiological origin of the systemic artefact is a task-evoked sympathetic arterial vasoconstriction followed by a decrease in venous volume. Since changes in sympathetic outflow accompany almost any cognitive and emotional process, we expect scalp vessel artefacts to be present in a wide range of fNIRS settings used in neurocognitive research. Therefore a careful separation of fNIRS signals originating from activated brain and from scalp is a necessary precondition for unbiased fNIRS brain activation maps.

Identifying and quantifying main components of physiological noise in functional near infrared spectroscopy on the prefrontal cortex

Functional Near-Infrared Spectroscopy (fNIRS) is a promising method to study functional organization of the prefrontal cortex. However, in order to realize the high potential of fNIRS, effective discrimination between physiological noise originating from forehead skin haemodynamic and cerebral signals is required. Main sources of physiological noise are global and local blood flow regulation processes on multiple time scales. The goal of the present study was to identify the main physiological noise contributions in fNIRS forehead signals and to develop a method for physiological de-noising of fNIRS data. To achieve this goal we combined concurrent time-domain fNIRS and peripheral physiology recordings with wavelet coherence analysis (WCA). Depth selectivity was achieved by analyzing moments of photon time-of-flight distributions provided by time-domain fNIRS. Simultaneously, mean arterial blood pressure (MAP), heart rate (HR), and skin blood flow (SBF) on the forehead were recorded. WCA was employed to quantify the impact of physiological processes on fNIRS signals separately for different time scales. We identified three main processes contributing to physiological noise in fNIRS signals on the forehead. The first process with the period of about 3 s is induced by respiration. The second process is highly correlated with time lagged MAP and HR fluctuations with a period of about 10 s often referred as Mayer waves. The third process is local regulation of the facial SBF time locked to the task-evoked fNIRS signals. All processes affect oxygenated haemoglobin concentration more strongly than that of deoxygenated haemoglobin. Based on these results we developed a set of physiological regressors, which were used for physiological de-noising of fNIRS signals. Our results demonstrate that proposed de-noising method can significantly improve the sensitivity of fNIRS to cerebral signals.

Causal Influence of Articulatory Motor Cortex on Comprehending Single Spoken Words: TMS Evidence

Classic wisdom had been that motor and premotor cortex contribute to motor execution but not to higher cognition and language comprehension. In contrast, mounting evidence from neuroimaging, patient research, and transcranial magnetic stimulation (TMS) suggest sensorimotor interaction and, specifically, that the articulatory motor cortex is important for classifying meaningless speech sounds into phonemic categories. However, whether these findings speak to the comprehension issue is unclear, because language comprehension does not require explicit phonemic classification and previous results may therefore relate to factors alien to semantic understanding. We here used the standard psycholinguistic test of spoken word comprehension, the word-to-picture-matching task, and concordant TMS to articulatory motor cortex. TMS pulses were applied to primary motor cortex controlling either the lips or the tongue as subjects heard critical word stimuli starting with bilabial lip-related or alveolar tongue-related stop consonants (e.g., “pool” or “tool”). A significant cross-over interaction showed that articulatory motor cortex stimulation delayed comprehension responses for phonologically incongruent words relative to congruous ones (i.e., lip area TMS delayed “tool” relative to “pool” responses). As local TMS to articulatory motor areas differentially delays the comprehension of phonologically incongruous spoken words, we conclude that motor systems can take a causal role in semantic comprehension and, hence, higher cognition.

Changes in Effective Connectivity Between Dorsal and Ventral Prefrontal Regions Moderate Emotion Regulation

Reappraisal, the cognitive reevaluation of a potentially emotionally arousing event, has been proposed to be based upon top-down appraisal systems within the prefrontal cortex (PFC). It still remains unclear, however, how different prefrontal regions interact to control and regulate emotional responses. We used fMRI and dynamic causal modeling (DCM) to characterize the functional interrelationships among dorsal and ventral PFC regions involved in reappraisal. Specifically, we examined the effective connectivity between the inferior frontal gyrus (IFG), dorsolateral PFC (DLPFC), and other reappraisal-related regions (supplementary motor area, supramarginal gyrus) during the up- and downregulation of emotions in response to highly arousing extreme sports film clips. We found DLPFC to be the central node of the prefrontal emotion regulation network, strongly interconnected with the IFG. The DCM analysis further revealed excitatory changes of connection strength from the DLPFC to the IFG and strong inhibitory changes of connection strength between the IFG and DLPFC during reappraisal. These bidirectional changes in connectivity strength indicate a feedback mechanism by which the IFG may select one out of several possible goal-appropriate reappraisals held active in working memory (represented in the DLPFC) and inhibits the DLPFC once the selection process is completed.

High-field EPR, ENDOR and ELDOR on bacterial photosynthetic reaction centers

We report on recent 95 and 360 GHz high-field electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR) and pulsed electron-electron double resonance (PELDOR) studies of wild-type and mutant reaction centers (RCs) from the photosynthetic bacteriumRhodobacter sphaeroides. Taking advantage of the excellent spectral and temporal resolution of EPR at 95 and 360 GHz, the electron-transfer (ET) cofactors radical ions and spin-correlated radical pairs were characterized by theirg- and hyperfine-tensor components, their anisotropicT2 relaxation as well as by the dipolar interaction between P865•+QA•− radical pairs. The goal of these studies is to better understand the dominant factors determining the specificity and directionality of transmembrane ET processes in photosynthetic RC proteins. In particular, our multifrequency experiments elucidate the subtle cofactor-protein interactions, which are essential for fine-tuning the ET characteristics, e.g., the unidirectionality of the light-induced ET pathways along the A branch of the RC protein. By our high-field techniques, frozen-solution RCs of novel site-specific single and double mutants ofR. sphaeroides were studied to modulate the ET characteristics, e.g., even to the extent that dominant B branch ET prevails. The presented multifrequency EPR work culminates in first 360 GHz ENDOR results from organic nitroxide radicals as well as in first 95 GHz high-field PELDOR results from orientationally selected spin-polarized radical pairs P865•+QA•−, which allow to determine the full geometrical structure of the pairs even in frozen-solution RCs.

The role of orbitofrontal cortex in processing empathy stories in 4- to 8-year-old children.

This study investigates the neuronal correlates of empathic processing in children aged 4–8 years, an age range discussed to be crucial for the development of empathy. Empathy, defined as the ability to understand and share another persons inner life, consists of two components: affective (emotion-sharing) and cognitive empathy (Theory of Mind). We examined the hemodynamic responses of preschool and school children (N = 48), while they processed verbal (auditory) and non-verbal (cartoons) empathy stories in a passive following paradigm, using functional Near-Infrared Spectroscopy. To control for the two types of empathy, children were presented blocks of stories eliciting either affective or cognitive empathy, or neutral scenes which relied on the understanding of physical causalities. By contrasting the activations of the younger and older children, we expected to observe developmental changes in brain activations when children process stories eliciting empathy in either stimulus modality toward a greater involvement of anterior frontal brain regions. Our results indicate that childrens processing of stories eliciting affective and cognitive empathy is associated with medial and bilateral orbitofrontal cortex (OFC) activation. In contrast to what is known from studies using adult participants, no additional recruitment of posterior brain regions was observed, often associated with the processing of stories eliciting empathy. Developmental changes were found only for stories eliciting affective empathy with increased activation, in older children, in medial OFC, left inferior frontal gyrus, and the left dorsolateral prefrontal cortex. Activations for the two modalities differ only little, with non-verbal presentation of the stimuli having a greater impact on empathy processing in children, showing more similarities to adult processing than the verbal one. This might be caused by the fact that non-verbal processing develops earlier in life and is more familiar.

On the possible manifestation of harmonic-anharmonic dynamical transition in glassy media in electron paramagnetic resonance of nitroxide spin probes

Continuous wave (cw) electron paramagnetic resonance (EPR) and echo-detected (ED) EPR were applied to study molecular motions of nitroxide spin probes in glassy glycerol and o-terphenyl. A linear decrease with increasing temperature of the total splitting in the cw EPR line shape was observed at low temperatures in both solvents. Above some temperature points the temperature dependencies become sharper. Within the model of molecular librations, this behavior is in qualitative and quantitative agreement with the numerical data on neutron scattering and Mossbauer absorption for molecular glasses and biomolecules, where temperature dependence of the mean-squared amplitude of the vibrational motion was obtained. In analogy with these data the departure from linear temperature dependence in cw EPR may be ascribed to the transition from harmonic to anharmonic motion (this transition is called dynamical transition). ED EPR spectra were found to change drastically above 195 K in glycerol and above 245 K in o-terphenyl, indicating the appearance of anisotropic transverse spin relaxation. This appearance may also be attributed to the dynamical transition as an estimation shows the anisotropic relaxation rates for harmonic and anharmonic librational motions and because these temperature points correspond well to those known from neutron scattering for these solvents. The low sensitivity of ED EPR to harmonic motion and its high sensitivity to the anharmonic one suggests that ED EPR may serve as a sensitive tool to detect dynamical transition in glasses and biomolecules.

Restricted orientational motion of nitroxides in molecular glasses: direct estimation of the motional time scale basing on the comparative study of primary and stimulated electron spin echo decays.

A comparative study of anisotropic relaxation in two-pulse primary and three-pulse stimulated electron spin echo decays provides a direct way to distinguish fast (correlation time tau(c)<10(-6) s) and slow (tau(c)>10(-6) s) motions. Anisotropic relaxation is detected as a difference of the decay rates for different resonance field positions in anisotropic electron paramagnetic resonance spectra. For fast motion anisotropic relaxation influences the primary echo decay and does not influence the stimulated echo decay. For slow motion it is seen in both two-pulse echo and three-pulse stimulated echo decays. For nitroxide spin probes dissolved in glassy glycerol only fast motion was found below 200 K. Increase of temperature above 200 K results in the appearance of slow motion. Its amplitude increases rapidly with temperature increase. While in glycerol glass slow motion appears above glass transition temperature T(g), in ethanol glass it is observable below T(g). The scenario of motional dynamics in glasses is proposed which involves the broadening of the correlation time distribution with increasing temperature.

Orientational motion of nitroxides in molecular glasses: Dependence on the chemical structure, on the molecular size of the probe, and on the type of the matrix

Echo detected electron paramagnetic resonance (EPR) study of orientational molecular motion of nitroxide spin probes in glassy solvents was performed by evaluating the anisotropic transverse relaxation rate 1/T(2) at different positions of the EPR spectrum. Experiments were done on nitroxides of different sizes and shapes, in different solvent glasses, with different deuteration degree, and at different temperatures. We found that the properties of the solvent glass have a much stronger impact on the relaxation rate than the size and shape of the nitroxide have. We concluded that the anisotropic relaxation is induced by reordering of the solvent cage and not by small angle fluctuations of the nitroxide in the cage or intramolecular motion of nitroxide.

Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions.

Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information.