Search

IntroductionPost-stroke depressive symptoms (PSDS) are common and relevant for patient outcome, but their complex pathophysiology is ill understood. It likely involves social, psychological and biological factors. Lesion location is a readily available information in stroke patients, but it is unclear if the neurobiological substrates of PSDS are spatially localized. Building on previous analyses, we sought to determine if PSDS are associated with specific lesion locations, structural disconnection and/or localized functional diaschisis.MethodsIn a prospective observational study, we examined 270 patients with first-ever stroke with the Hospital Anxiety and Depression Scale (HADS) around 6 months post-stroke. Based on individual lesion locations and the depression subscale of the HADS we performed support vector regression lesion-symptom mapping, structural-disconnection-symptom mapping and functional lesion network-symptom-mapping, in a reanalysis of this previously published cohort to infer structure–function relationships.ResultsWe found that depressive symptoms were associated with (i) lesions in the right insula, right putamen, inferior frontal gyrus and right amygdala and (ii) structural disconnection in the right temporal lobe. In contrast, we found no association with localized functional diaschisis. In addition, we were unable to confirm a previously described association between depressive symptom load and a network damage score derived from functional disconnection maps.DiscussionBased on our results, and other recent lesion studies, we see growing evidence for a prominent role of right frontostriatal brain circuits in PSDS.

Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site.We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis.Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect.We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients.

Voxelwise disconnection mapping is a novel approach to disclose lesion-symptom relationships for symptoms caused by white matter disconnection. It uses MRI-based fiber tracking in healthy subjects seeded from patient’s focal brain lesions. Resulting individual disconnection maps can then be statistically associated with symptoms. Despite increasing use in the recent years, the validity of this approach remains to be investigated. In this study, we validated both, our own implementation and the implementation provided within BCBtoolkit. For technical validation, we used simulated symptoms based on overlap of 70 real stroke lesions with tracts from a white matter atlas. For clinical validation, paresis scores and lesions from 316 patients with stroke were used. We found that voxelwise disconnection mapping is technically valid and outperforms the standard voxel-based lesion-symptom mapping approach for symptoms caused by white matter disconnection. Supporting its clinical validity and utility, we were able to reproduce the known association between corticospinal tract damage and contralateral hemiparesis. In addition, we demonstrate that the validity can be substantially diminished by relatively minor methodological changes. Based on these results, we derive methodological recommendations for the future use of voxelwise disconnection mapping. Our study highlights the importance of validating novel methodological approaches in the rapidly evolving field of neuroimaging.

Several mechanisms have been attributed to post-stroke loss and recovery of language functions. However, the significance and timing of domain-general and homotopic right-hemispheric activation is controversial. We aimed to examine the effect of left-hemispheric lesion location and time post-stroke on right-hemispheric activation. Voxel-based lesion analyses were informed by auditory language-related fMRI activation of 71 patients with left middle cerebral artery stroke examined longitudinally in the acute, subacute and early chronic phase. Language activation was determined in several right-hemispheric regions of interest and served as regressor of interest for voxel-based lesion analyses. We found that an acute to chronic increase of language activation in the right supplementary motor area was associated with lesions to the left extreme capsule as part of the ventral language pathway. Importantly, this activation increase correlated significantly with improvement of out-of-scanner comprehension abilities. We interpret our findings in terms of successful domain-general compensation in patients with critical left frontotemporal disconnection due to damage to the ventral language pathway but relatively spared cortical language areas.

The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here, we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion-guided probabilistic tractography in healthy participants, we revealed bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings support the view that the encoding and modeling of rapidly modulated auditory spectro-temporal properties can rely on a temporo-cerebellar interface. We discuss these findings in view of the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.

Objective: In this retrospective, cross-sectional study we aimed to examine long-term memory deficits and gray matter volumes (GMV) in the hippocampus after transient global amnesia (TGA). Methods: 20 patients with a history of TGA (TGA+, mean 6.5 years after TGA) and 20 age-matched healthy controls (TGA-) underwent neurocognitive assessment (i.e. Mini-Mental State Examination (MMSE), visuospatial, verbal and episodic autobiographical memory and visuospatial learning/navigation [“human water maze”]) in combination with structural cerebral MRI. Voxel-based morphometry (VBM) was used to detect GMV in the hippocampus in TGA+ versus TGA-. Results: Besides slight differences in MMSE and visuo-spatial learning/navigation measured with a human water maze in TGA+ vs. TGA-, no other tests of visuo-spatial, verbal and autobiographical long-term memory differed between groups. VBM analyses yielded a statistically significant difference in bilateral hippocampal GMV with TGA+ compared to TGA- showing greater GMV in a region corresponding to bilateral CA1. However, none of the hippocampus-dependent cognitive measures correlated with hippocampal GMV. Conclusion: In the long-term course after TGA, only subtle neurocognitive deficits without microstructural damage of the hippocampus could be detected. Greater GMV in bilateral hippocampus in TGA+ vs. TGA- may indicate that TGA triggers hippocampal GMV increase rather than atrophy.

Anosognosia for hemiplegia (AHP) is known to be associated with lesions to the motor system combined with varying lesions to the right insula, premotor cortex, parietal lobe or hippocampus. Due to this widespread cortical lesion distribution, AHP can be understood best as a network disorder. We used lesion maps and behavioral data (n ​= ​49) from two previous studies on AHP and performed a lesion network-symptom-mapping (LNSM) analysis. This new approach permits the identification of relationships between behavior and regions connected to the lesion site based on normative functional connectome data. In a first step, using ordinary voxel-based lesion-symptom mapping, we found an association of AHP with lesions in the right posterior insula. This is in accordance with previous studies. Applying LNSM, we were able to additionally identify a region in the right posterior hippocampus where AHP was associated with significantly higher normative lesion connectivity. Notably, this region was spared by infarction in all patients. We therefore argue that remote neuronal dysfunction caused by disrupted functional connections between the lesion site and the hippocampus (i.e. diaschisis) contributed to the phenotype of AHP. An indirect affection of the hippocampus may lead to memory deficits which, in turn, impair the stable encoding of updated beliefs on the bodily state thus contributing to the multifactorial phenomenon of AHP.

Language is sustained by large-scale networks in the human brain. Stroke often severely affects function and network dynamics. However, the adaptive potential of the brain to compensate for lesions is poorly understood. A key question is whether upregulation of the right hemisphere is adaptive for language recovery. Targeting the potential for short-term reorganization in the lesioned brain, we applied 'virtual lesions' over left anterior or posterior inferior frontal gyrus (IFG) in post-stroke patients with left temporo-parietal lesions prior to functional neuroimaging. Perturbation of the posterior IFG selectively delayed phonological decisions and decreased phonological activity. The individual response delay was correlated with the upregulation of the lesion homologue, likely reflecting compensation. Moreover, stronger individual tract integrity of the right superior longitudinal fascicle was associated with lesser disruption. Our results provide evidence for functional and structural underpinnings of plasticity in the lesioned language network, and a compensatory role of the right hemisphere.

ObjectivePrevious research associated the left inferior frontal cortex with implicit structure learning. The present study tested patients with lesions encompassing the left inferior frontal gyrus (LIFG; including Brodmann areas 44 and 45) to further investigate this cognitive function, notably by using non-verbal material, implicit investigation methods, and by enhancing potential remaining function via dynamic attending. Patients and healthy matched controls were exposed to an artificial pitch grammar in an implicit learning paradigm to circumvent the potential influence of impaired language processing.MethodsPatients and healthy controls listened to pitch sequences generated within a finite-state grammar (exposure phase) and then performed a categorization task on new pitch sequences (test phase). Participants were not informed about the underlying grammar in either the exposure phase or the test phase. Furthermore, the pitch structures were presented in a highly regular temporal context as the beneficial impact of temporal regularity (e.g. meter) in learning and perception has been previously reported. Based on the Dynamic Attending Theory (DAT), we hypothesized that a temporally regular context helps developing temporal expectations that, in turn, facilitate event perception, and thus benefit artificial grammar learning.ResultsElectroencephalography results suggest preserved artificial grammar learning of pitch structures in patients and healthy controls. For both groups, analyses of event-related potentials revealed a larger early negativity (100-200 msec post-stimulus onset) in response to ungrammatical than grammatical pitch sequence events.ConclusionsThese findings suggest that (i) the LIFG does not play an exclusive role in the implicit learning of artificial pitch grammars, and (ii) the use of non-verbal material and an implicit task reveals cognitive capacities that remain intact despite lesions to the LIFG. These results provide grounds for training and rehabilitation, that is, learning of non-verbal grammars that may impact the relearning of verbal grammars.

The adaptive potential of the language network to compensate for lesions remains elusive. We show that perturbation of a semantic region in the healthy brain induced suppression of activity in a large semantic network and upregulation of neighbouring phonological areas. After perturbation, the disrupted area increased its inhibitory influence on another semantic key node. The inhibitory influence predicted the individual delay in response speed, indicating that inhibition at remote nodes is functionally relevant. Individual disruption predicted the upregulation of semantic activity in phonological regions. In contrast, perturbation over a phonological region suppressed activity in the network and disrupted behaviour without inducing upregulation. The beneficial contribution of a neighbouring network might thus depend on the level of functional disruption and may be interpreted to reflect a differential compensatory potential of distinct language networks. These results might reveal generic mechanisms of plasticity in cognitive networks and inform models of language reorganization.

Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.