C. Weiller

Combining functional and anatomical connectivity reveals brain networks for auditory language comprehension

Cognitive functions are organized in distributed, overlapping, and interacting brain networks. Investigation of those large-scale brain networks is a major task in neuroimaging research. Here, we introduce a novel combination of functional and anatomical connectivity to study the network topology subserving a cognitive function of interest. (i) In a given network, direct interactions between network nodes are identified by analyzing functional MRI time series with the multivariate method of directed partial correlation (dPC). This method provides important improvements over shortcomings that are typical for ordinary (partial) correlation techniques. (ii) For directly interacting pairs of nodes, a region-to-region probabilistic fiber tracking on diffusion tensor imaging data is performed to identify the most probable anatomical white matter fiber tracts mediating the functional interactions. This combined approach is applied to the language domain to investigate the network topology of two levels of auditory comprehension: lower-level speech perception (i.e., phonological processing) and higher-level speech recognition (i.e., semantic processing). For both processing levels, dPC analyses revealed the functional network topology and identified central network nodes by the number of direct interactions with other nodes. Tractography showed that these interactions are mediated by distinct ventral (via the extreme capsule) and dorsal (via the arcuate/superior longitudinal fascicle fiber system) long- and short-distance association tracts as well as commissural fibers. Our findings demonstrate how both processing routines are segregated in the brain on a large-scale network level. Combining dPC with probabilistic tractography is a promising approach to unveil how cognitive functions emerge through interaction of functionally interacting and anatomically interconnected brain regions.

Implementation of visuospatial cues in response selection

We used functional magnetic resonance imaging to examine neuronal activity reflecting the dynamic interplay of external and internal guidance of action. Participants performed a choice reaction time task based on spatial visual cues with their right and left middle and index finger. In a given trial, the cue either fully determined the motor response (no-selection) or indicated the number and location of alternative responses (selection). Compared with fully determined responses, the selection among (two to four) alternative responses activated a widespread bilateral parieto-premotor-prefrontal cortical network along with the cerebellum. Within this network, task-related activity patterns allowed to delineate two sets of brain areas. In the anterior part of rostral dorsal premotor cortex (PMd), the rostral cingulate and supplementary motor area and the right dorsolateral prefrontal cortex, the increase in activity was independent of spatially defined restrictions. In contrast, there was an additional increase in activity in the posterior part of rostral PMd, superior parietal lobule and parieto-occipital sulcus bilaterally as well as in the right anterior intraparietal sulcus, when the visuospatial cue imposed specific constraints on response selection. We propose that the latter set of dorsal parieto-frontal areas subserves rapid implementation of spatial information during visually guided response selection.

Processing pathways in mental arithmetic--evidence from probabilistic fiber tracking.

Numerical cognition is a case of multi-modular and distributed cerebral processing. So far neither the anatomo-functional connections between the cortex areas involved nor their integration into established frameworks such as the differentiation between dorsal and ventral processing streams have been specified. The current study addressed this issue combining a re-analysis of previously published fMRI data with probabilistic fiber tracking data from an independent sample. We aimed at differentiating neural correlates and connectivity for relatively easy and more difficult addition problems in healthy adults and their association with either rather verbally mediated fact retrieval or magnitude manipulations, respectively. The present data suggest that magnitude- and fact retrieval-related processing seem to be subserved by two largely separate networks, both of them comprising dorsal and ventral connections. Importantly, these networks not only differ in localization of activation but also in the connections between the cortical areas involved. However, it has to be noted that even though seemingly distinct anatomically, these networks operate as a functionally integrated circuit for mental calculation as revealed by a parametric analysis of brain activation.

Extraction of prefronto-amygdalar pathways by combining probability maps

Many recent studies reported altered functional connectivity within the frontolimbic circuitry in a wide range of neuropsychiatric disorders. However, functional connectivity must rely on structural connections. In this study we applied a novel probabilistic fiber tracking method to assess the structural connectivity between the amygdala and different prefrontal brain regions in vivo. Twenty healthy subjects were investigated with diffusion tensor imaging. Probabilistic fiber tracking was started from the amygdala and different prefrontal brain regions. Resulting probability maps were combined using an extended multiplication of probabilistic maps to identify the most probable anatomical pathways connecting these structures. We found one ventral pathway through the uncinate fascicle, connecting the amygdala and the medial and lateral orbitofrontal cortices. In addition to this ventral pathway, we depicted distinct dorsal pathways (medial and lateral), which connect the amygdala with the anterior cingulate cortex and the dorsolateral prefrontal cortex. The dorso-medial pathway proceeds through the inferior thalamic peduncle, while the dorsolateral pathway travels through the external capsule. We believe that our approach provides a promising tool to assess the integrity of specific structural connections in patients with neuropsychiatric disorders.

Ventral and dorsal fiber systems for imagined and executed movement

Although motor imagery is an entirely cognitive process, it shows remarkable similarity to overt movement in behavioral and physiological studies. In concordance, brain imaging studies reported shared fronto-parietal sensorimotor networks commonly engaged by both tasks. However, differences in prefrontal and parietal regions point toward additional cognitive mechanisms in the context of imagery. Within the perspective of a general dichotomization into dorsal and ventral processing streams in the brain, the question arises whether motor imagery and overt movement could differentially involve the dorsal or ventral system. Therefore, we combined fMRI and DTI data of 20 healthy subjects to analyze the anatomical characteristics of connecting fronto-parietal association pathways of imagined and overt movements. We found a dichotomy of fiber pathways into dorsal and ventral systems: the superior longitudinal fascicle (SLF II-III) was found to connect frontal and parietal regions involved in both overt and imagined movements, whereas a ventral tract via the extreme/external capsule (EmC/EC) connects cortical regions specific for motor imagery that were situated more anteriorly and posteriorly. We suppose that motor imagery-related kinesthetic emulations are embedded into dorsal sensorimotor networks, and imagery-specific cognitive functions are implemented in the ventral system. These findings have implications for models of motor cognition.

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

BackgroundBy mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.ResultsAs patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearmans rho = 0.734; p = 0.01).ConclusionsThe hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.

The ventral fiber pathway for pantomime of object use.

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently. Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory-motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

Fiber pathways connecting cortical areas relevant for spatial orienting and exploration

By implementing a task that closely resembled a clinical test for diagnosing spatial neglect in stroke patients, Himmelbach et al. ( : Neuroimage 32:1747–1759) found significantly increased activation during active exploration in those cortical areas in healthy subjects that are known to induce spatial neglect in case of a lesion. The present study investigated whether direct intra‐hemispheric cortico‐cortical connections could be found between these activated clusters using a probabilistic fiber‐tracking approach in 52 healthy subjects. We found that parts of the extreme capsule (EmC) and the middle longitudinal fascicle (MdLF) connected the functional cluster in the prefrontal cortex with the superior temporal cortex and the temporo‐parietal junction (TPJ) area in both hemispheres. The activation peak in the TPJ was additionally connected to the inferior frontal cortex by parts of the arcuate fascicle and the superior longitudinal fascicle (SLF II) in the right hemisphere. Our study elucidates the connections constituting the perisylvian network for spatial orienting and attention. Hence, we complement the knowledge from patients suffering from spatial neglect by giving first empirical evidence for the complete postulated network in healthy subjects. Hum Brain Mapp 35:1031–1043, 2014.

Fronto-parietal dorsal and ventral pathways in the context of different linguistic manipulations.

This study investigates structural connectivity between left fronto-parietal brain regions that were identified in a previous fMRI study which used different linguistic manipulation tasks. Diffusion-weighted images were acquired from 20 volunteers. Structural connectivity between brain regions from the fMRI study was computed using probabilistic fiber tracking. For suprasegmental manipulation, left inferior parietal lobule (IPL) and left inferior frontal gyrus (IFG), pars opercularis, were connected by a dorsal pathway via the arcuate fascicle and superior longitudinal fascicle III. For segmental manipulation, left IPL and IFG, pars triangularis, were connected by a ventral pathway via the middle longitudinal fascicle and the extreme capsule. We conclude that the dorsal pathway provides a route for mapping from phonological memory in IPL to the inferior frontal articulatory network while the ventral pathway could facilitate the modulation of phonological units based on lexical-semantic aspects, mediate the complexity of auditory objects and the unification of actor-event schemata.

Polysomnographic Characteristics of Sleep in Stroke: A Systematic Review and Meta-Analysis

Background Research on sleep after stroke has focused mainly on sleep disordered breathing. However, the extend to which sleep physiology is altered in stroke survivors, how these alterations compare to healthy volunteers, and how sleep changes might affect recovery as well as physical and mental health has yet to be fully researched. Motivated by the view that a deeper understanding of sleep in stroke is needed to account for its role in health and well-being as well as its relevance for recovery and rehabilitation, we conducted a systematic review and meta-analysis of polysomnographic studies comparing stroke to control populations. Method Medline and PsycInfo databases were searched using stroke and words capturing polysomnographic parameters as search terms. This yielded 1692 abstracts for screening, with 15 meeting the criteria for systematic review and 9 for meta-analysis. Prisma best practice guidelines were followed for the systematic review; the Comprehensive Meta-Analysis software was used for random effects modelling. Results The meta-analysis revealed that patients with stroke have poorer sleep than controls. Patients had lower sleep efficiency (mean 75% vs 84%), shorter total-sleep-time (309.4 vs 340.3 min) and more wake-after-sleep-onset (97.2 vs 53.8 min). Patients also spend more time in stage 1 (13% vs 10%) and less time in stage 2 sleep (36% vs 45%) and slow-wave-sleep (10% vs 12%). No group differences were identified for REM sleep. The systematic review revealed a strong bias towards studies in the early recovery phase of stroke, with no study reporting specifically on patients in the chronic state. Moreover, participants in the control groups included community samples as well as other patients groups. Conclusions These results indicate poorer sleep in patients with stroke than controls. While strongly suggestive in nature, the evidence base is limited and methodologically diverse, and hands a clear mandate for further research. A particular need regards polysomnographic studies in chronic community-dwelling patients compared to age-matched individuals.