The link between visual exploration and neuronal activity: A multi-modal study combining eye tracking, functional magnetic resonance imaging and transcranial magnetic stimulation

In the present multi-modal study we aimed to investigate the role of visual exploration in relation to the neuronal activity and performance during visuospatial processing. To this end, event related functional magnetic resonance imaging er-fMRI was combined with simultaneous eye tracking recording and transcranial magnetic stimulation (TMS). Two groups of twenty healthy subjects each performed an angle discrimination task with different levels of difficulty during er-fMRI. The number of fixations as a measure of visual exploration effort was chosen to predict blood oxygen level-dependent (BOLD) signal changes using the general linear model (GLM). Without TMS, a positive linear relationship between the visual exploration effort and the BOLD signal was found in a bilateral fronto-parietal cortical network, indicating that these regions reflect the increased number of fixations and the higher brain activity due to higher task demands. Furthermore, the relationship found between the number of fixations and the performance demonstrates the relevance of visual exploration for visuospatial task solving. In the TMS group, offline theta bursts TMS (TBS) was applied over the right posterior parietal cortex (PPC) before the fMRI experiment started. Compared to controls, TBS led to a reduced correlation between visual exploration and BOLD signal change in regions of the fronto-parietal network of the right hemisphere, indicating a disruption of the network. In contrast, an increased correlation was found in regions of the left hemisphere, suggesting an intent to compensate functionality of the disturbed areas. TBS led to fewer fixations and faster response time while keeping accuracy at the same level, indicating that subjects explored more than actually needed.

Evaluation and quantification of spectral information in tissue by confocal microscopy

A confocal imaging and image processing scheme is introduced to visualize and evaluate the spatial distribution of spectral information in tissue. The image data are recorded using a confocal laser-scanning microscope equipped with a detection unit that provides high spectral resolution. The processing scheme is based on spectral data, is less error-prone than intensity-based visualization and evaluation methods, and provides quantitative information on the composition of the sample. The method is tested and validated in the context of the development of dermal drug delivery systems, introducing a quantitative uptake indicator to compare the performances of different delivery systems is introduced. A drug penetration study was performed in vitro. The results show that the method is able to detect, visualize and measure spectral information in tissue. In the penetration study, uptake efficiencies of different experiment setups could be discriminated and quantitatively described. The developed uptake indicator is a step towards a quantitative assessment and, in a more general view apart from pharmaceutical research, provides valuable information on tissue composition. It can potentially be used for clinical in vitro and in vivo applications.

Affective and linguistic processing of speech prosody: DC potential studies

Speech melody or prosody subserves linguistic, emotional, and pragmatic functions in speech communication. Prosodic perception is based on the decoding of acoustic cues with a predominant function of frequency-related information perceived as speaker's pitch. Evaluation of prosodic meaning is a cognitive function implemented in cortical and subcortical networks that generate continuously updated affective or linguistic speaker impressions. Various brain-imaging methods allow delineation of neural structures involved in prosody processing. In contrast to functional magnetic resonance imaging techniques, DC (direct current, slow) components of the EEG directly measure cortical activation without temporal delay. Activation patterns obtained with this method are highly task specific and intraindividually reproducible. Studies presented here investigated the topography of prosodic stimulus processing in dependence on acoustic stimulus structure and linguistic or affective task demands, respectively. Data obtained from measuring DC potentials demonstrated that the right hemisphere has a predominant role in processing emotions from the tone of voice, irrespective of emotional valence. However, right hemisphere involvement is modulated by diverse speech and language-related conditions that are associated with a left hemisphere participation in prosody processing. The degree of left hemisphere involvement depends on several factors such as (i) articulatory demands on the perceiver of prosody (possibly, also the poser), (ii) a relative left hemisphere specialization in processing temporal cues mediating prosodic meaning, and (iii) the propensity of prosody to act on the segment level in order to modulate word or sentence meaning. The specific role of top-down effects in terms of either linguistically or affectively oriented attention on lateralization of stimulus processing is not clear and requires further investigations.

Functional imaging of visuospatial processing in Alzheimer's disease

Alzheimer's disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.

Modulation of anticipatory emotion and perception processing by cognitive control.

Strategies of cognitive control are helpful in reducing anxiety experienced during anticipation of unpleasant or potentially unpleasant events. We investigated the associated cerebral information processing underlying the use of a specific cognitive control strategy during the anticipation of affect-laden events. Using functional magnetic resonance imaging, we examined differential brain activity during anticipation of events of unknown and negative emotional valence in a group of eighteen healthy subjects that used a cognitive control strategy, similar to "reality checking" as used in psychotherapy, compared with a group of sixteen subjects that did not exert cognitive control. While expecting unpleasant stimuli, the "cognitive control" group showed higher activity in left medial and dorsolateral prefrontal cortex areas but reduced activity in the left extended amygdala, pulvinar/lateral geniculate nucleus and fusiform gyrus. Cognitive control during the "unknown" expectation was associated with reduced amygdalar activity as well and further with reduced insular and thalamic activity. The amygdala activations associated with cognitive control correlated negatively with the reappraisal scores of an emotion regulation questionnaire. The results indicate that cognitive control of particularly unpleasant emotions is associated with elevated prefrontal cortex activity that may serve to attenuate emotion processing in for instance amygdala, and, notably, in perception related brain areas.

Metrics of the normal anterior sclera: imaging with optical coherence tomography

BACKGROUND To investigate anterior scleral thickness in a cohort of healthy subjects using enhanced depth imaging anterior segment optical coherence tomography. METHODS Observational case series. The mean scleral thickness in the inferonasal, inferotemporal, superotemporal, and superonasal quadrant was measured 2 mm from the scleral spur on optical coherence tomography in healthy volunteers. RESULTS Fifty-three eyes of 53 Caucasian patients (25 male and 28 female) with an average age of 48.6 years (range: 18 to 92 years) were analysed. The mean scleral thickness was 571 μm (SD 84 μm) in the inferonasal quadrant, 511 μm (SD 80 μm) in the inferotemporal quadrant, 475 (SD 81 μm) in the superotemporal, and 463 (SD 64 μm) in the superonasal quadrant. The mean scleral thickness was significantly different between quadrants (p < 0.0001, repeated measures one-way ANOVA). The association between average scleral thickness and age was statistically significant (p < 0.0001, Pearson r = 0.704). CONCLUSIONS Enhanced depth imaging optical coherence tomography revealed the detailed anatomy of the anterior sclera and enabled non-invasive measurements of scleral thickness in a non-contact approach. The anterior scleral thickness varies significantly between quadrants, resembling the spiral of Tillaux. An association of increasing scleral thickness with age was found.

Differential recruitment of brain networks during visuospatial and color processing: Evidence from ERP microstates

Recent functional magnetic resonance imaging (fMRI) studies consistently revealed contributions of fronto-parietal and related networks to the execution of a visuospatial judgment task, the so-called "Clock Task". However, due to the low temporal resolution of fMRI, the exact cortical dynamics and timing of processing during task performance could not be resolved until now. In order to clarify the detailed cortical activity and temporal dynamics, 14 healthy subjects performed an established version of the "Clock Task", which comprises a visuospatial task (angle discrimination) and a control task (color discrimination) with the same stimulus material, in an electroencephalography (EEG) experiment. Based on the time-resolved analysis of network activations (microstate analysis), differences in timing between the angle compared to the color discrimination task were found after sensory processing in a time window starting around 200ms. Significant differences between the two tasks were observed in an analysis window from 192ms to 776ms. We divided this window in two parts: an early phase - from 192ms to ∼440ms, and a late phase - from ∼440ms to 776ms. For both tasks, the order of network activations and the types of networks were the same, but, in each phase, activations for the two conditions were dominated by differing network states with divergent temporal dynamics. Our results provide an important basis for the assessment of deviations in processing dynamics during visuospatial tasks in clinical populations.

Very Late Scaffold Thrombosis: Intracoronary Imaging and Histopathological and Spectroscopic Findings.

BACKGROUND Bioresorbable scaffolds provide transient lumen support followed by complete resorption. OBJECTIVES This study examined whether very late scaffold thrombosis (VLScT) occurs when resorption is presumed to be nearly complete. METHODS Patients with VLScT at 3 tertiary care centers underwent thrombus aspiration followed by optical coherence tomography (OCT). Thrombus aspirates were analyzed by histopathological and spectroscopic examination. RESULTS Between March 2014 and February 2015, 4 patients presented with VLScT at 44 (case 1), 19 (cases 2 and 4), and 21 (case 3) months, respectively, after implantation of an Absorb Bioresorbable Vascular Scaffold 1.1 (Abbott Laboratories, Abbott Park, Illinois). At the time of VLScT, all patients were taking low-dose aspirin, and 2 patients were also taking prasugrel. OCT showed malapposed scaffold struts surrounded by thrombus in 7.1%, 9.0%, and 8.9% of struts in cases 1, 2, and 4, respectively. Scaffold discontinuity with struts in the lumen center was the cause of malapposition in cases 2 and 4. Uncovered scaffold struts with superimposed thrombus were the predominant findings in case 3. OCT percent area stenosis at the time of VLScT was high in case 1 (74.8%) and case 2 (70.9%) without evidence of excessive neointimal hyperplasia. Spectroscopic thrombus aspirate analysis showed persistence of intracoronary polymer fragments in case 1. CONCLUSIONS VLScT may occur at advanced stages of scaffold resorption. Potential mechanisms specific for VLScT include scaffold discontinuity and restenosis during the resorption process, which appear delayed in humans; these findings suggest an extended period of vulnerability for thrombotic events.

Short-term changes in magnetic resonance imaging and disease activity in response to infliximab

To characterise and quantify short-term changes in local inflammation using magnetic resonance imaging (MRI), and to correlate the findings with clinical disease activity in response to infliximab in patients with spondyloarthritis.

Deposition, imaging, and clearance: what remains to be done?

Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.