Functional correlate and delineated connectivity pattern of human motion aftereffect responses substantiate a subjacent visual-vestibular interaction.

The visual motion aftereffect (MAE) is the most prominent aftereffect in the visual system. Regarding its function, psychophysical studies suggest its function to be a form of sensory error correction, possibly also triggered by incongruent visual-vestibular stimulation. Several observational imaging experiments have deducted an essential role for region MT+ in the perception of a visual MAE but not provided conclusive evidence. Potential confounders with the MAE such as ocular motor performance, attention, and vection sensations have also never been controlled for. Aim of this neuroimaging study was to delineate the neural correlates of MAE and its subjacent functional connectivity pattern. A rotational MAE (n = 22) was induced using differing visual stimuli whilst modulating ocular motor parameters in a 3T scanner. Data was analyzed with SPM12. Eye movements as a response to the same stimuli were studied by means of high-resolution videooculography. Analysis for all stimuli gave bilateral activations along the dorsal visual stream with an emphasis on area MT. The onset of a visual MAE revealed an additional response in the right medial superior temporal area (MST) and a concurrent deactivation of vestibular hub region OP2. There was no correlation for the BOLD effects during the MAE with either ocular motor or attention parameters. The functional correlate of a visual MAE in humans may be represented in the interaction between region MT and area MST. This MAE representation is independent of a potential afternystagmus, attention and the presence of egomotion sensations. Connectivity analyses showed that in the event of conflicting visual-vestibular motion information (here MAE) area MST and area OP2 may act as the relevant mediating network hubs.

Delineating function and connectivity of optokinetic hubs in the cerebellum and the brainstem.

Optokinetic eye movements are crucial for keeping a stable image on the retina during movements of the head. These eye movements can be differentiated into a cortically generated response (optokinetic look nystagmus) and the highly reflexive optokinetic stare nystagmus, which is controlled by circuits in the brainstem and cerebellum. The contributions of these infratentorial networks and their functional connectivity with the cortical eye fields are still poorly understood in humans. To map ocular motor centres in the cerebellum and brainstem, we studied stare nystagmus using small-field optokinetic stimuli in the horizontal and vertical directions in 22 healthy subjects. We were able to differentiate ocular motor areas of the pontine brainstem and midbrain in vivo for the first time. Direction and velocity-dependent activations were found in the pontine brainstem (nucleus reticularis, tegmenti pontis, and paramedian pontine reticular formation), the uvula, flocculus, and cerebellar tonsils. The ocular motor vermis, on the other hand, responded to constant and accelerating velocity stimulation. Moreover, deactivation patterns depict a governing role for the cerebellar tonsils in ocular motor control. Functional connectivity results of these hubs reveal the close integration of cortico-cerebellar ocular motor and vestibular networks in humans. Adding to the cortical concept of a right-hemispheric predominance for visual-spatial processing, we found a complementary left-sided cerebellar dominance for our ocular motor task. A deeper understanding of the role of the cerebellum and especially the cerebellar tonsils for eye movement control in a clinical context seems vitally important and is now feasible with functional neuroimaging.

Active pain coping is associated with the response in real-time fMRI neurofeedback during pain.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

Detection of central circuits implicated in the formation of novel pain memories.

Being able to remember physically and emotionally painful events in one's own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1) the central nervous system processes that underlie pain imagination, 2) the retrieval of pain memories, and 3) to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination), remembering one's own house (object memory), and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory). Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus - pain imagination > pain memory; midbrain - pain memory > pain imagination). Importantly, these findings were observed in the presence of consistent and reproducible psychophysical and behavioral measures that informed on the subjects' ability to imagine novel and familiar thoughts, as well as the subjects' pain perception.

The Mona Lisa effect: neural correlates of centered and off-centered gaze.

The Mona Lisa effect describes the phenomenon when the eyes of a portrait appear to look at the observer regardless of the observer's position. Recently, the metaphor of a cone of gaze has been proposed to describe the range of gaze directions within which a person feels looked at. The width of the gaze cone is about five degrees of visual angle to either side of a given gaze direction. We used functional magnetic resonance imaging to investigate how the brain regions involved in gaze direction discrimination would differ between centered and decentered presentation positions of a portrait exhibiting eye contact. Subjects observed a given portrait's eyes. By presenting portraits with varying gaze directions-eye contact (0°), gaze at the edge of the gaze cone (5°), and clearly averted gaze (10°), we revealed that brain response to gaze at the edge of the gaze cone was similar to that produced by eye contact and different from that produced by averted gaze. Right fusiform gyrus and right superior temporal sulcus showed stronger activation when the gaze was averted as compared to eye contact. Gaze sensitive areas, however, were not affected by the portrait's presentation location. In sum, although the brain clearly distinguishes averted from centered gaze, a substantial change of vantage point does not alter neural activity, thus providing a possible explanation why the feeling of eye contact is upheld even in decentered stimulus positions.

Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain perception.

fMRI-activation patterns in the detection of concealed information rely on memory-related effects.

Recent research on potential applications of fMRI in the detection of concealed knowledge primarily ascribed the reported differences in hemodynamic response patterns to deception. This interpretation is challenged by the results of the present study. Participants were required to memorize probe and target items (a banknote and a playing card, each). Subsequently, these items were repeatedly presented along with eight irrelevant items in a modified Guilty Knowledge Test design and participants were instructed to simply acknowledge item presentation by pressing one button after each stimulus. Despite the absence of response monitoring demands and thus overt response conflicts, the experiment revealed a differential physiological response pattern as a function of item type. First, probes elicited the largest skin conductance responses. Second, differential hemodynamic responses were observed in bilateral inferior frontal regions, the right supramarginal gyrus and the supplementary motor area as a function of item type. Probes and targets were accompanied by a larger signal increase than irrelevant items in these regions. Moreover, the responses to probes differed substantially from targets. The observed neural response pattern seems to rely on retrieval processes that depend on the depth of processing in the encoding situation.

Occurence and clinical predictors of spasticity after ischemic stroke.

BACKGROUND AND PURPOSE: There is currently no consensus on (1) the percentage of patients who develop spasticity after ischemic stroke, (2) the relation between spasticity and initial clinical findings after acute stroke, and (3) the impact of spasticity on activities of daily living and health-related quality of life. METHODS: In a prospective cohort study, 301 consecutive patients with clinical signs of central paresis due to a first-ever ischemic stroke were examined in the acute stage and 6 months later. At both times, the degree and pattern of paresis and muscle tone, the Barthel Index, and the EQ-5D score, a standardized instrument of health-related quality of life, were evaluated. Spasticity was assessed on the Modified Ashworth Scale and defined as Modified Ashworth Scale >1 in any of the examined joints. RESULTS: Two hundred eleven patients (70.1%) were reassessed after 6 months. Of these, 42.6% (n=90) had developed spasticity. A more severe degree of spasticity (Modified Ashworth Scale >or=3) was observed in 15.6% of all patients. The prevalence of spasticity did not differ between upper and lower limbs, but in the upper limb muscles, higher degrees of spasticity (Modified Ashworth Scale >or=3) were more frequently (18.9%) observed than in the lower limbs (5.5%). Regression analysis used to test the differences between upper and lower limbs showed that patients with more severe paresis in the proximal and distal limb muscles had a higher risk for developing spasticity (P

Illusion of pain: pre-existing knowledge determines brain activation of 'imagined allodynia'.

UNLABELLED: Allodynia means that innocuous tactile stimulation is felt as pain. Accordingly, cerebral activations during allodynia or touch should markedly differ. The aim of this study was to investigate whether the imagination of allodynia affects brain processing of touch in healthy subjects. Seventeen healthy subjects divided into 2 subgroups were investigated: The first group (n = 7) was familiar with allodynia, based on previous pain studies, whereas the second group (n = 10) had never knowingly experienced allodynia. Using functional magnetic resonance imaging, 2 experimental conditions were investigated. In one condition the subjects were simply touched at their left hand, whereas during the other condition they were asked to imagine pain (allodynia) during tactile stimulation of the right hand and to estimate the imagined pain on a numeric rating scale. Data processing and analysis were performed with the use of SPM5. The group analysis of all subjects revealed that tactile stimulation activated contralateral somatosensory cortices (S1 [primary] and S2 [secondary]), but the imagination of allodynia led to an additional activation of anterior cingulate cortex and bilateral activation of S2, insular cortex, and prefrontal cortices. Subgroup analysis using rating-weighted predictors revealed activation of the contralateral thalamus, anterior cingulate cortex, and amygdala and a bilateral activation of S1, S2, and insular cortex and prefrontal cortices in allodynia-experienced subjects. In contrast, allodynia-inexperienced subjects only activated contralateral S1 and bilateral S2. Just the imagination that touch is painful is able to partly activate the central pain system, but only when the subject has previous experience of this. According to our results, the medial pain system is involved in the encoding of imagined allodynia. PERSPECTIVE: This article reports that pain experience is able to alter central processing of sensory stimuli. Pain knowledge appears to be able to shift "normal" tactile processing to a different quality, resulting in modified brain activity. Therefore, our study may contribute to the current understanding of human pain and will promote future research on this field.

Evidence for cortical visual substitution of chronic bilateral vestibular failure (an fMRI study).

Bilateral vestibular failure (BVF) is a rare disorder of the labyrinth or the eighth cranial nerve which has various aetiologies. BVF patients suffer from unsteadiness of gait combined with blurred vision due to oscillopsia. Functional MRI (fMRI) in healthy subjects has shown that stimulation of the visual system induces an activation of the visual cortex and ocular motor areas bilaterally as well as simultaneous deactivations of multisensory vestibular cortex areas. Our question was whether the chronic absence of bilateral vestibular input (BVF) causes a plastic cortical reorganization of the above-described visual-vestibular interaction. We used fMRI to measure the differential effects of horizontal visual optokinetic stimulation (OKN) on activations and deactivations in 10 patients with BVF and compared their data directly to those of pairwise age- and sex-matched controls. We found that bilateral activation of the primary visual cortex (inferior and middle occipital gyri, Brodmann area BA 17, 18, 19), the motion-sensitive areas V5 in the middle and inferior temporal gyri (BA 37), and the frontal eye field (BA 8), the right paracentral and superior parietal lobule and the right fusiform and parahippocampal gyri was significantly stronger and the activation clusters were larger than that of the age-matched healthy controls. Small areas of BOLD signal decreases (deactivations), located primarily in the right posterior insula containing the parieto-insular vestibular cortex, were similar to those in the healthy controls. No other sensory brain areas showed unexpected activations or deactivations, e.g. the somatosensory or auditory cortex areas. Our finding of enhanced activations within the visual and ocular motor systems of BVF patients suggests that they might be correlated with an upregulation of visual sensitivity during tracking of visual motion patterns. Functionally, these enhanced activations are independent of optokinetic performance, since the mean slow-phase velocity of OKN in the BVF patients did not differ from that in normals. Although psychophysical and neurophysiological tests have provided various examples of how sensory loss in one modality leads to a substitutional increase of functional sensitivity in other modalities, this study presents the first evidence of visual substitution for vestibular loss by functional imaging.

Covariations among fMRI, skin conductance, and behavioral data during processing of concealed information.

Imaging techniques have been used to elucidate the neural correlates that underlie deception. The scientifically best understood paradigm for the detection of deception, however, the guilty knowledge test (GKT), was rarely used in imaging studies. By transferring a GKT-paradigm to a functional magnetic resonance imaging (fMRI) study, while additionally quantifying reaction times and skin conductance responses (SCRs), this study aimed at identifying the neural correlates of the behavioral and electrodermal response pattern typically found in GKT examinations. Prior to MR scanning, subjects viewed two specific items (probes) and were instructed to hide their knowledge of these. Two other specific items were designated as targets and required a different behavioral response during the experiment and eight items served as irrelevant stimuli. Reaction times and SCR amplitudes differed significantly between all three item types. The neuroimaging data revealed that right inferior frontal and mid-cingulate regions were more active for probe and target trials compared to irrelevants. Moreover, the differential activation in the right inferior frontal region was modulated by stimulus conflicts. These results were interpreted as an increased top-down influence on the stimulus-response-mapping for concealed and task-relevant items. Additionally, the influence of working memory and retrieval processes on this activation pattern is discussed. Using parametric analyses, reaction times and SCR amplitudes were found to be linearly related to activity in the cerebellum, the right inferior frontal cortex, and the supplementary motor area. This result provides a first link between behavioral measures, sympathetic arousal, and neural activation patterns during a GKT examination.

White matter fiber tracking computation based on diffusion tensor imaging for clinical applications.

Fiber tracking allows the in vivo reconstruction of human brain white matter fiber trajectories based on magnetic resonance diffusion tensor imaging (MR-DTI), but its application in the clinical routine is still in its infancy. In this study, we present a new software for fiber tracking, developed on top of a general-purpose DICOM (digital imaging and communications in medicine) framework, which can be easily integrated into existing picture archiving and communication system (PACS) of radiological institutions. Images combining anatomical information and the localization of different fiber tract trajectories can be encoded and exported in DICOM and Analyze formats, which are valuable resources in the clinical applications of this method. Fiber tracking was implemented based on existing line propagation algorithms, but it includes a heuristic for fiber crossings in the case of disk-shaped diffusion tensors. We successfully performed fiber tracking on MR-DTI data sets from 26 patients with different types of brain lesions affecting the corticospinal tracts. In all cases, the trajectories of the central spinal tract (pyramidal tract) were reconstructed and could be applied at the planning phase of the surgery as well as in intraoperative neuronavigation.

Brainstem and cerebellar fMRI-activation during horizontal and vertical optokinetic stimulation.

Animal studies have shown that not only cortical, but also brainstem and cerebellar areas are involved in the initiation and generation of optokinetic nystagmus (OKN), e.g., cortico-(pretecto)pontine-olivo-cerebellar pathways. The aim of this fMRI study was to identify and differentiate brainstem and cerebellar areas involved in horizontal and vertical OKN (h/vOKN) in humans. In a group of nine healthy volunteers, hOKN and vOKN were statistically compared with a stationary control condition. There were common activated regions for hOKN and vOKN directions located in the transition zone between the posterior thalamus and the mesencephalon bilaterally covering the pretectal nucleus complex, which is known to be a major structure within the afferent branch of the optokinetic system. Furthermore, during hOKN, activation occurred bilaterally in the mediodorsal and dorsolateral ponto-medullary brainstem, which could be best attributed to the reticular formation, especially the paramedian pontine reticular formation (PPRF). For vOKN, additional activated areas in the dorsal mesencephalic brainstem could be best localized to the ocular motor nuclei and the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). For both OKN directions, the cerebellar activation was localized in the oculomotor vermis (declive VI, folium and tuber VIIA/B, in part pyramis VIIIA), and the flocculus bilaterally as well as widespread in the cerebellar hemispheres. In conclusion, fMRI allowed first attributions of neuronal substrates in the cerebellum and brainstem to hOKN and vOKN in humans. Consistent with the animal data, the dorsal ponto-medullary routes were involved bilaterally for hOKN, whereas the rostral mesencephalic routes were involved for vOKN.

Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study).

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion-sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction-dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compared with the control condition (stationary target) and with each other. Direction-dependent differences were not found in the cortical eye fields, but an asymmetry of activation occurred in paramedian visual cortex areas, and there were stronger activations in the hemisphere contralateral to the slow OKN phase (pursuit). This can be explained by a shift of the mean eye position of gaze (beating field) in the direction of the fast nystagmus phases of approximately 2.6 degrees, causing asymmetrical visual cortex stimulation. The absence of a significant difference in the activation pattern of the cortical eye fields supports the view that the processing of eye movements in both horizontal directions is mediated in the same cortical ocular motor areas. Furthermore, no hemispheric dominance for OKN processing was found in right-handed volunteers.

New partially parallel acquisition technique in cerebral imaging: preliminary findings.

In MRI applications where short acquisition time is necessary, the increase of acquisition speed is often at the expense of image resolution and SNR. In such cases, the newly developed parallel acquisition techniques could provide images without mentioned limitations and in reasonably shortened measurement time. A newly designed eight-channel head coil array (i-PAT coil) allowing for parallel acquisition of independently reconstructed images (GRAPPA mode) has been tested for its applicability in neuroradiology. Image homogeneity was tested in standard phantom and healthy volunteers. BOLD signal changes were studied in a group of six volunteers using finger tapping stimulation. Phantom studies revealed an important drop of signal even after the use of a normalization filter in the center of the image and an important increase of artifact power with reduction of measurement time strongly depending on the combination of acceleration parameters. The additional application of a parallel acquisition technique such as GRAPPA decreases measurement time in the range of about 30%, but further reduction is often possible only at the expense of SNR. This technique performs best in conditions in which imaging speed is important, such as CE MRA, but time resolution still does not allow the acquisition of angiograms separating the arterial and venous phase. Significantly larger areas of BOLD activation were found using the i-PAT coil compared to the standard head coil. Being an eight-channel surface coil array, peripheral cortical structures profit from high SNR as high-resolution imaging of small cortical dysplasias and functional activation of cortical areas imaged by BOLD contrast. In BOLD contrast imaging, susceptibility artifacts are reduced, but only if an appropriate combination of acceleration parameters is used.

Asymmetry in the human primary somatosensory cortex and handedness.

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness was documented using the Edinburgh Inventory and a dichotic listening test was performed as a measure for language dominance. Whereas thresholds, Erb potential, and P14 were symmetrical, amplitudes of the cortical N20 showed significant hemispheric asymmetry. In the left hemisphere, the N20 amplitude was higher, its generator was located further medial, and it had a stronger dipole moment. There was no difference in dipole orientation. As a possible morphological correlate, the size of the left postcentral gyrus exceeded that of the right. The cortical P22 component showed a lower amplitude and a trend toward weaker dipole strength in the left hemisphere. Across subjects, there were no significant correlations between laterality indices of N20, the size of the postcentral gyrus, handedness, or ear advantage. These data show that asymmetry of median nerve SEP occurs at the cortical level, only. However, both functional and morphological cortical asymmetry of somatosensory representation appears to vary independently of motor and language functions.