Search

The study of pathological laughter and crying (PLC) allows insights into the neural basis of laughter and crying, two hallmarks of human nature. PLC is defined by brief, intense and frequent episodes of uncontrollable laughter or crying provoked by trivial stimuli. It occurs secondary to CNS disorders such as stroke, tumours or neurodegenerative diseases. Based on case studies reporting various lesions locations, PLC has been conceptualized as dysfunction in a cortico-limbic-subcortico-thalamo-ponto-cerebellar network. To test whether the heterogeneous lesion locations are indeed linked in a common network, we applied ‘lesion network-symptom-mapping’ to 70 focal lesions identified in a systematic literature search for case reports of PLC. In lesion network-symptom-mapping normative connectome data (resting state functional MRI, n = 100) is used to identify the brain regions that are likely affected by diaschisis based on the lesion locations. With lesion network-symptom-mapping we were able to identify a common network specific for PLC when compared with a control cohort (n = 270). This bilateral network is characterized by positive connectivity to the cingulate and temporomesial cortices, striatum, hypothalamus, mesencephalon and pons, and negative connectivity to the primary motor and sensory cortices. In the most influential pathophysiological model of PLC, a centre for the control and coordination of facial expressions, respiration and vocalization in the periaqueductal grey is assumed, which is controlled via two pathways: an emotional system that exerts excitatory control of the periaqueductal grey descending from the temporal and frontal lobes, basal ganglia and hypothalamus; and a volitional system descending from the lateral premotor cortices that can suppress laughter or crying. To test whether the positive and negative PLC subnetworks identified in our analyses can indeed be related to an emotional system and a volitional system, we identified lesions causing emotional (n = 15) or volitional facial paresis (n = 46) in a second literature search. Patients with emotional facial paresis show preserved volitional movements but cannot trigger emotional movements in the affected hemiface, while the reverse is true for volitional facial paresis. Importantly, these lesions map differentially onto the PLC subnetworks: the ‘positive PLC subnetwork’ is part of the emotional system and the ‘negative PLC subnetwork’ overlaps with the volitional system for the control of facial movements. Based on this network analysis we propose a two-hit model of PLC: a combination of direct lesion and indirect diaschisis effects cause PLC through the loss of inhibitory cortical control of a dysfunctional emotional system.

Background and Purpose: Poststroke depression is a common stroke sequel, yet its neurobiological substrates are still unclear. We sought to determine whether specific lesion locations are associated with depressive symptoms after stroke. Methods: In a prospective study, 270 patients with first ever stroke were repeatedly tested with the depression subscale of the Hospital Anxiety and Depression Scale within the first 4 weeks and 6 months after stroke. Voxel-based lesion behavior mapping based on clinical imaging was performed to test for associations between symptoms of depression and lesion locations. Results: Frequency of poststroke depression (Hospital Anxiety and Depression Scale-D score >7) after 6 months was 19.6%. Higher Hospital Anxiety and Depression Scale-D scores for depression within the first 4 weeks were the only independent predictor for poststroke depression after 6 months in a multiple logistic regression also including age, sex, lesion volume, stroke severity, Barthel-Index, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Nonparametric permutation-test based voxel-based lesion behavior mapping identified a cluster of voxels mostly within the left ventrolateral prefrontal cortex where lesions were significantly associated with more depressive symptoms after 6 months. No such association was observed within the right hemisphere despite better lesion coverage. Conclusions: Lesions in the left ventrolateral prefrontal cortex increase the risk of depressive symptoms 6 months poststroke. Lesions within the right hemisphere are unrelated to depressive symptoms. Recognition of left frontal lesions as a risk factor should help in the early diagnosis of poststroke depression through better risk stratification. The results are in line with evidence from functional imaging and noninvasive brain stimulation in patients without focal brain damage indicating that dysfunction in the left lateral prefrontal cortex contributes to depressive disorders.

Background and ObjectiveTheories assume that thalamic stroke may cause aphasia because of dysfunction in connected cortical networks. This takes into account that brain functions are organized in distributed networks, and in turn, localized damage may result in a network disorder such as thalamic aphasia. With this study, we investigate whether the integration of the thalamus into specific thalamocortical networks underlies symptoms after thalamic stroke. We hypothesize that thalamic lesions in patients with language impairments are functionally connected to cortical networks for language and cognition.MethodsWe combined nonparametric lesion mapping methods in a retrospective cohort of patients with acute or subacute first-ever thalamic stroke. A relationship between lesion location and language impairments was assessed using nonparametric voxel-based lesion-symptom mapping. This method reveals regions more frequently damaged in patients with compared with those without a symptom of interest. To test whether these symptoms are linked to a common thalamocortical network, we additionally performed lesion-network-symptom mapping. This method uses normative connectome data from resting-state fMRI of healthy participants (n = 65) for functional connectivity analyses, with lesion sites serving as seeds. Resulting lesion-dependent network connectivity of patients with language impairments was compared with those with motor and sensory deficits as baseline.ResultsA total of 101 patients (mean [SD] age 64.1 [14.6] years, 57 left, 42 right, and 2 bilateral lesions) were included in the study. Voxel-based lesion-symptom mapping showed an association of language impairments with damage to left mediodorsal thalamic nucleus lesions. Lesion-network-symptom mapping revealed that language compared with sensory deficits were associated with higher normative lesion-dependent network connectivity to left frontotemporal language networks and bilateral prefrontal, insulo-opercular, midline cingular, and parietal domain-general networks. Lesions related to motor and sensory deficits showed higher lesion-dependent network connectivity within the sensorimotor network spanning prefrontal, precentral, and postcentral cortices.DiscussionThalamic aphasia relates to lesions in the left mediodorsal thalamic nucleus and to functionally connected left cortical language and bilateral cortical networks for cognitive control. This suggests that dysfunction in thalamocortical networks contributes to thalamic aphasia. We propose that inefficient integration between otherwise undamaged domain-general and language networks may cause thalamic aphasia.

The loss and recovery of language functions are still incompletely understood. This longitudinal functional MRI study investigated the neural mechanisms underlying language recovery in patients with post-stroke aphasia putting particular emphasis on the impact of lesion site. To identify patterns of language-related activation, an auditory functional MRI sentence comprehension paradigm was administered to patients with circumscribed lesions of either left frontal (n = 17) or temporo-parietal (n = 17) cortex. Patients were examined repeatedly during the acute (≤1 week, t1), subacute (1–2 weeks, t2) and chronic phase (>6 months, t3) post-stroke; healthy age-matched control subjects (n = 17) were tested once. The separation into two patient groups with circumscribed lesions allowed for a direct comparison of the contributions of distinct lesion-dependent network components to language reorganization between both groups. We hypothesized that activation of left hemisphere spared and perilesional cortex as well as lesion-homologue cortex in the right hemisphere varies between patient groups and across time. In addition, we expected that domain-general networks serving cognitive control independently contribute to language recovery. First, we found a global network disturbance in the acute phase that is characterized by reduced functional MRI language activation including areas distant to the lesion (i.e. diaschisis) and subsequent subacute network reactivation (i.e. resolution of diaschisis). These phenomena were driven by temporo-parietal lesions. Second, we identified a lesion-independent sequential activation pattern with increased activity of perilesional cortex and bilateral domain-general networks in the subacute phase followed by reorganization of left temporal language areas in the chronic phase. Third, we observed involvement of lesion-homologue cortex only in patients with frontal but not temporo-parietal lesions. Fourth, irrespective of lesion location, language reorganization predominantly occurred in pre-existing networks showing comparable activation in healthy controls. Finally, we detected different relationships of performance and activation in language and domain-general networks demonstrating the functional relevance for language recovery. Our findings highlight that the dynamics of language reorganization clearly depend on lesion location and hence open new perspectives for neurobiologically motivated strategies of language rehabilitation, such as individually-tailored targeted application of neuro-stimulation.

The capacity to acquire and retain new motor skills is essential for everyday behavior and a prerequisite to regain functional independence following impairments of motor function caused by brain damage, e.g., ischemic stroke. Learning a new motor skill requires repeated skill practice and passes through different online and offline learning stages that are mediated by specific dynamic interactions between distributed brain regions including the cerebellum. Motor sequence learning is an extensively studied paradigm of motor skill learning, yet the role of the cerebellum during online and offline stages remains controversial. Here, we studied patients with chronic cerebellar stroke and healthy control participants to further elucidate the role of the cerebellum during acquisition and consolidation of sequential motor skills. Motor learning was assessed by an ecologically valid explicit sequential finger tapping paradigm and retested after an interval of 8 h to assess consolidation. Compared to healthy controls, chronic cerebellar stroke patients displayed significantly lower motor sequence performance independent of whether the ipsilesional or contralesional hand was used for task execution. However, the ability to improve performance during training (i.e., online learning) and to consolidate training-induced skill formation was similar in patients and controls. Findings point to an essential role of the cerebellum in motor sequence production that cannot be compensated, while its role in online and offline motor sequence learning seems to be either negligible or amenable to compensatory mechanisms. This further suggests that residual functional impairments caused by cerebellar stroke may be mitigated even months later by additional skill training.

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 test the functional mechanisms associated with temporo-cerebellar connectivity, verifying these mechanisms for speech sounds. 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 reveal bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings imply that the encoding and modeling of rapidly modulated auditory spectro-temporal properties engage a temporo-cerebellar interface. The data further support the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.Significance StatementAsymmetric sampling in time, the principle of duration-sensitive hemispheric specialization of the cerebral cortex in the sensory decomposition of sound, is a widely tested hypothesis in auditory neuroscience. This functional organization is mirrored in the cerebellar cortex, implicated in the internal forward-modeling of sensory feedback that arises from motor actions. The potential structural and functional integration of these systems is not well understood. Using a unique combination of causal lesion-symptom mapping in persons with temporal lobe damage and diffusion-weighted magnetic resonance neuroimaging in healthy persons, we identify one key missing link and provide evidence for cross-lateral temporo-cerebellar connectivity using probabilistic white matter fiber tractography. These cerebellar-pontine-temporal cortex connections not only support asymmetric sampling in time but also establish the basis for a generalizable role of cerebellar forward-modeling in sensation beyond the monitoring of sensory feedback in the motor domain.

Surfactant proteins (SP) are multi-systemic proteins playing crucial roles in the regulation of rheological properties of physiological fluids, host defense, and the clearance of potentially harmful metabolites. Hydrocephalus patients suffer from disturbed central nervous system (CNS) fluid homeostasis and exhibit remarkably altered SP concentrations within the cerebrospinal fluid (CSF). A connection between CSF-SPs, CSF flow, and ventricular dilatation, a morphological hallmark of hydrocephalus, has been reported previously. However, currently there are no studies investigating the link between rheologically active SPs and periventricular white matter changes caused by impaired CSF microcirculation in hydrocephalic conditions. Thus, the aim of this study was to assess their possible relationships. The present study included 47 individuals (27 healthy subjects and 20 hydrocephalus patients). CSF specimens were analyzed for concentrations of SP-A, SP-C, and SP-D by using enzyme-linked immunosorbent assays (ELISAs). Axial T2w turbo inversion recovery magnitude (TIRM) magnetic resonance imaging was employed in all cases. Using a custom-made MATLAB-based tool for quantification of magnetic resonance signal intensities in the brain, parameters related to disturbed deep white matter CSF microcirculation were estimated (TIRM signal intensity (SI)-mean, minimum, maximum, median, mode, standard deviation, and percentiles, p10th, p25th, p75th, p90th, as well as kurtosis, skewness, and entropy of the SI distribution). Subsequently, statistical analysis was performed (IBM SPSS 24™) to identify differences between hydrocephalic patients and healthy individuals and to further investigate the connections between CSF-SP changes and deep white matter signal intensities. SP-A (0.38 ± 0.23 vs. 0.76 ± 0.49 ng/ml) and SP-C (0.54 ± 0.28 vs. 1.27 ± 1.09 ng/ml) differed between healthy controls and hydrocephalus patients in a statistically significant manner. Also, corresponding quantification of white matter signal intensities revealed statistically significant differences between hydrocephalus patients and healthy individuals: SImean (370.41 ± 188.15 vs. 222.27 ± 99.86, p = 0.001), SImax (1115.30 ± 700.12 vs. 617.00 ± 459.34, p = 0.005), SImedian (321.40 ± 153.17 vs. 209.52 ± 84.86, p = 0.001), SImode (276.55 ± 125.63 vs. 197.26 ± 78.51, p = 0.011), SIstd (157.09 ± 110.07 vs. 81.71 ± 64.94, p = 0.005), SIp10 (229.10 ± 104.22 vs. 140.00 ± 63.12, p = 0.001), SIp25 (266.95 ± 122.62 vs. 175.63 ± 71.42, p = 0.002), SIp75 (428.80 ± 226.88 vs. 252.19 ± 110.91, p = 0.001), SIp90 (596.47 ± 345.61 vs. 322.06 ± 176.00, p = 0.001), skewness (1.19 ± 0.68 vs. 0.43 ± 1.19, p = 0.014), and entropy (5.36 ± 0.37 vs. 4.92 ± 0.51, p = 0.002). There were no differences regarding SP-D levels in hydrocephalus patients vs. healthy controls. In the acute hydrocephalic subgroup, correlations were as follows: SP-A showed a statistically significant correlation with SImax (r = 0.670, p = 0.024), SIstd (r = 0.697, p = 0.017), SIp90 (r = 0.621, p = 0.041), and inverse correlation with entropy (r = - 0.700, p = 0.016). SP-C correlated inversely with entropy (r = - 0.686, p = 0.020). For the chronic hydrocephalus subgroup, the following correlations were identified: SP-A correlated with kurtosis of the TIRM histogram (r = - 0.746, p = 0.021). SP-C correlated with SImean (r = - 0.688, p = 0.041), SImax (r = - 0.741, p = 0.022), SImedian (r = - 0.716, p = 0.030), SImode (r = - 0.765, p = 0.016), SIstd (r = - 0.671, p = 0.048), SIp25 (r = - 0.740, p = 0.023), SIp75 (r = - 0.672, p = 0.048), and SIp90 (r = - 0.667, p = 0.050). SP-D apparently does not play a major role in CSF fluid physiology. SP-A and SP-C are involved in different aspects of CNS fluid physiology. SP-A appears to play an essential compensatory role in acute hydrocephalus and seems less involved in chronic hydrocephalus. In contrary, SP-C profile and white matter changes are remarkably connected in CSF of chronic hydrocephalus patients. Considering the association between CSF flow phenomena, white matter changes, and SP-C profiles, the latter may especially contribute to the regulation of paravascular glymphatic physiology.

Previous neuroimaging studies demonstrated that a network of left-hemispheric frontal and temporal brain regions contributes to the integration of contextual information into a sentence. However, it remains unclear how these cortical areas influence and drive each other during contextual integration. The present study used dynamic causal modeling (DCM) to investigate task-related changes in the effective connectivity within this network. We found increased neural activity in left anterior inferior frontal gyrus (aIFG), posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and anterior superior temporal sulcus/MTG (aSTS/MTG) that probably reflected increased integration demands and restructuring attempts during the processing of unexpected or semantically anomalous relative to expected endings. DCM analyses of this network revealed that unexpected endings increased the inhibitory influence of left aSTS/MTG on pSTS/MTG during contextual integration. In contrast, during the processing of semantically anomalous endings, left aIFG increased its inhibitory drive on pSTS/MTG. Probabilistic fiber tracking showed that effective connectivity between these areas is mediated by distinct ventral and dorsal white matter association tracts. Together, these results suggest that increasing integration demands require an inhibition of the left pSTS/MTG, which presumably reflects the inhibition of the dominant expected sentence ending. These results are important for a better understanding of the neural implementation of sentence comprehension on a large-scale network level and might influence future studies of language in post-stroke aphasia after focal lesions.

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.

Objective Previous 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. Methods Patients 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. Results Electroencephalography 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. Conclusions These 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. © 2019 Jarret et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Post-stroke loss and recovery of language functions evolves in time and space. A high functional dynamic can be observed in the first days and weeks after stroke, which has been associated with reorganisation processes in the left-lateralised language network, its right-hemisphere homologues and in the vicinity of the lesion site. With the advances in in vivo neuroimaging techniques, mapping changes in the language network over time (e.g., lesion extent, structural integrity of grey or white matter, task-based activity, functional or structural connectivity) is currently the focus of ongoing investigations.Main Contribution: This review highlights the recent findings on the neurobiology of language recovery from the hyperacute to the subacute phase after stroke. It relates pathophysiological processes of stroke evolution and the spatio-temporal characteristics of recovery patterns within the anatomically distributed language network to the behavioural dynamics of early language recovery.Conclu...

To achieve precise timing, the brain needs to establish a representation of the temporal structure of sensory input and use this information to generate timely responses. These operations engage the basal ganglia. Current research in this direction is limited by reliance on animal models, motor and/or offline tasks, small sample sizes, the low temporal resolution of functional magnetic resonance imaging, and the study of progressive neurodegeneration. Here, we combine the excellent temporal resolution of electrophysiological potentials with the high spatial resolution of structural neuroimaging to investigate basal ganglia contributions to sensory timing. Chronic-stage lesion patients and healthy controls listened to pure-tone sequences differing exclusively in temporal regularity. Event-related potentials (ERPs) indicate a selective indifference against this manipulation in patients, attributable to the striatal part of the basal ganglia on the basis of a lesion-mapping approach. These findings provide evidence for a crucial contribution of the basal ganglia to basic sensory functioning.

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. DOI: http://dx.doi.org/10.7554/eLife.25964.001, eLife digest Taking part in a conversation requires us to extract meaning from a complex series of sounds by recognising words and phrases. We then need to decide on a response, and plan and execute the lip and tongue movements necessary to generate that response. Each of these processes – from analysing the meaning of words to producing speech – requires a distinct set of brain regions to work together. However, we know relatively little about how these regions interact with one another during specific language processes, or about what happens when key regions are damaged. Hartwigsen et al. have now used a technique called TMS in healthy volunteers to temporarily disrupt the activity of individual brain regions with a role in language. TMS involves applying small magnetic fields to the scalp over a target brain area. The magnetic fields induce electrical currents in the underlying brain tissue and temporarily scramble its activity. Hartwigsen et al. examined how this affected the volunteers’ performance on a language task, as well as the activity of other language areas. Temporarily disrupting a single brain region involved in analysing the meaning of words reduced the activity of multiple other areas in the brain’s language networks. The greater this reduction in activity, the more poorly the volunteers performed on a language task. However, not all brain regions showed reduced activity. Areas adjacent to the disrupted region, which normally process the sounds of words, increased their activity. This increase may have partially compensated for the effects of the TMS to help limit the language impairments. These findings offer insights into how the brain reacts and adapts when key language areas are damaged, for example as a result of stroke. The next step is to determine the extent to which healthy brain tissue can take over from damaged regions, and whether we can target this process to improve recovery after stroke. DOI: http://dx.doi.org/10.7554/eLife.25964.002

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.

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form ('what') and stimulus occurrence ('when'). Consequently, behaviour is optimal when we can anticipate both the 'what' and 'when' dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention.2014 The Author(s) Published by the Royal Society. All rights reserved.

Background Poststroke aphasia recovery evolves in time. Increased perilesional activity associated with treatment-related language improvements has been confirmed in the chronic phase ( Fridriksson et al., 2011 ), but has not yet been systematically demonstrated during the early phases of stroke recovery. The pathophysiology of stroke suggests that perilesional reorganisation evolves within days, lasting for months after stroke, while increased neuronal excitability might provide a basis for perilesional neuroplasticity ( Schiene et al., 1999 ). Methods We compared fMRI BOLD response to speech (SP) and reversed speech (REV) using an auditory comprehension paradigm ( Saur et al., 2006 ) administered repeatedly (acute (t1) ⩽ 1 week, subacute (t2) = 1–2 weeks, chronic (t3) > 6 months post-onset) to patients with stroke affecting left frontal (FC, N = 17) or temporoparietal cortex (TPC, N = 17). Language activation (SP > REV) obtained from three perilesional ROIs expanding stepwise to 39 mm beyond the lesion (DISTANCE) was compared across TIME and to the improvement of language comprehension/production. Results An ANOVA revealed a significant TIME × DISTANCE interaction (F(4) = 2.9, p = .025) with increased activation from t1 to t3 and t2 to t3 (p). Conclusion To conclude, a remapping of cortical language representations in undamaged left cortices is likely to commence during subacute phase of recovery and improvements of specific language functions differentially involve frontal or temporal perilesional areas.

Background Poststroke aphasia recovery evolves in space and time. Substantial language improvements can be observed within the first days after stroke. However, underlying changes in the functional status of the language network during the acute phase remain to be demonstrated. Methods In a resting-state functional connectivity (RSFC) fMRI study we assessed changes in functional connectivity repeatedly (acute( t 1) = 2 ± 1, subacute( t 2) = 10 ± 2 days post-onset) in aphasic patients ( N = 12, 62 ± 14 years, 10 male) with left temporoparietal stroke. Language comprehension and production scores were calculated based on the Aachener Aphasie-Test. For RSFC analysis 9mm spherical ROIs reflecting core language regions in the left anterior inferior frontal (aIFG: x = −54 y = 32 z = 1, MNI-space), posterior middle temporal gyrus (pMTG: x = −54 y = −43 z = 4) and their right hemisphere homologous were selected. Results Seed-to-whole-brain analysis from left aIFG or pMTG revealed RSFC to right hemisphere homologous frontal or temporal areas at t 1 and t 2 ( p > .05, FWE corrected). Longitudinally, RSFC from left pMTG to left aIFG as well as RSFC from left aIFG to left frontal (operculum, insula, premotor cortex) and to right frontal (IFG, premotor cortex) areas increased significantly from t 1 to t 2 ( p > .001, uncorrected). Subsequent ROI-to-ROI analysis revealed increased RSFC between left aIFG and pMTG from t 1 to t 2 associated with improved language production ( r = .579, p = .049). During the acute phase ( t 1) better scores for language comprehension and production were predicted by higher RSFC between left aIFG and right aIFG ( r = .736 p = .006). Conclusion We observed early ipsi- and contralesional changes in the language network’s functional connectivity and associated language improvements indicative of acute diaschisis and subsequent reorganization within the distributed language network.