Investigating silent pauses in connected speech: integrating linguistic, neuropsychological, and neuroanatomical perspectives across narrative tasks in post-stroke aphasia.

Introduction: Silent pauses are regarded as integral components of the temporal organization of speech. However, it has also been hypothesized that they serve as markers for internal cognitive processes, including word access, monitoring, planning, and memory functions. Although existing evidence across various pathological populations underscores the importance of investigating silent pauses' characteristics, particularly in terms of frequency and duration, there is a scarcity of data within the domain of post-stroke aphasia. Methods: The primary objective of the present study is to scrutinize the frequency and duration of silent pauses in two distinct narrative tasks within a cohort of 32 patients with chronic post-stroke aphasia, in comparison with a control group of healthy speakers. Subsequently, we investigate potential correlation patterns between silent pause measures, i.e., frequency and duration, across the two narrative tasks within the patient group, their performance in neuropsychological assessments, and lesion data. Results: Our findings showed that patients exhibited a higher frequency of longer-duration pauses in both narrative tasks compared to healthy speakers. Furthermore, within-group comparisons revealed that patients tended to pause more frequently and for longer durations in the picture description task, while healthy participants exhibited the opposite trend. With regard to our second research question, a marginally significant interaction emerged between performance in semantic verbal fluency and the narrative task, in relation to the location of silent pauses-whether between or within clauses-predicting the duration of silent pauses in the patient group. However, no significant results were observed for the frequency of silent pauses. Lastly, our study identified that the duration of silent pauses could be predicted by distinct Regions of Interest (ROIs) in spared tissue within the left hemisphere, as a function of the narrative task. Discussion: Overall, this study follows an integrative approach of linguistic, neuropsychological and neuroanatomical data to define silent pauses in connected speech, and illustrates interrelations between cognitive components, temporal aspects of speech, and anatomical indices, while it further highlights the importance of studying connected speech indices using different narrative tasks.

Clinical feasibility of diffusion microstructure imaging (DMI) in acute ischemic stroke.

BACKGROUND: Diffusion microstructure imaging (DMI) is a fast approach to higher-order diffusion-weighted magnetic resonance imaging that allows robust decomposition and characterization of diffusion properties of brain tissue into intra-axonal, extra-axonal, and a free water-compartment. We now report the application of this technique to acute ischemic stroke and demonstrate its potential applicability to the daily clinical routine. METHODS: Thirty-eight patients diagnosed with acute ischemic stroke were scanned using an accelerated multi-shell diffusion-weighted imaging protocol (median delay between onset and MRI scan of 113 min). DMI metrics were calculated and the apparent diffusion coefficient (ADC) derived from conventional diffusion-weighted imaging was used for comparison. The resulting DMI parameter maps were analysed for their potential to improve infarct core delineation, and a receiver-operating characteristic (ROC) analysis was subsequently performed for automated infarct segmentation. RESULTS: Robust parameter maps for diffusion microstructure properties were obtained in all cases. Within the ischemic tissue, an increase in the volume fraction of the intra-axonal compartment was accompanied by a volume fraction reduction in the other two compartments. Moreover, diffusivity was reduced in all three compartments, with intra-axonal diffusivity showing the highest degree of contrast. The intra-axonal diffusion coefficient maps were subsequently found to perform better than single-shell ADC-derived segmentation in terms of automatic segmentation of the infarct core (area under the curve = 0.98 vs 0.92). CONCLUSIONS: The alterations to the ischemic core detected by DMI are in line with the "beading-model" of non-uniform neurite swelling under ischemic conditions. When compared to conventional single-shell diffusion-weighted imaging, DMI metrics are associated with improved discriminative power for delineating and characterizing ischemic changes. This might allow a more detailed assessment of infarct age, severity of damage, the degree of reversibility, and outcome.

Displaying the autonomic processing network in humans - a global tractography approach.

Regulation of the internal homeostasis is modulated by the central autonomic system. So far, the view of this system is determined by animal and human research focusing on cortical and subcortical grey substance regions. To provide an overview based on white matter architecture, we used a global tractography approach to reconstruct a network of tracts interconnecting brain regions that are known to be involved in autonomic processing. Diffusion weighted imaging data were obtained from subjects of the human connectome project (HCP) database. Resulting tracts are in good agreement with previous studies assuming a division of the central autonomic system into a cortical (CAN) and a subcortical network (SAN): the CAN consist of three subsystems that encompass all cerebral lobes and overlap within the insular cortex: a parieto-anterior-temporal pathway (PATP), an occipito-posterior-temporo-frontal pathway (OPTFP) and a limbic pathway. The SAN on the other hand connects the hypothalamus to the periaqueductal grey and locus coeruleus, before it branches into a dorsal and a lateral part that target autonomic nuclei in the rostral medulla oblongata. Our approach furthermore reveals how the CAN and SAN are interconnected: the hypothalamus can be considered as the interface-structure of the SAN, whereas the insula is the central hub of the CAN. The hypothalamus receives input from prefrontal cortical fields but is also connected to the ventral apex of the insular cortex. Thus, a holistic view of the central autonomic system could be created that may promote the understanding of autonomic signaling under physiological and pathophysiological conditions.

Ventral tegmental area connections to motor and sensory cortical fields in humans.

In humans, sensorimotor cortical areas receive relevant dopaminergic innervation-although an anatomic description of the underlying fiber projections is lacking so far. In general, dopaminergic projections towards the cortex originate within the ventral tegmental area (VTA) and are organized in a meso-cortico-limbic system. Using a DTI-based global tractography approach, we recently characterized the superolateral branch of the medial forebrain bundle (slMFB), a prominent pathway providing dopaminergic (and other transmitters) innervation for the pre-frontal cortex (Coenen et al., NeuroImage Clin 18:770-783, 2018). To define the connections between VTA and sensory-motor cortical fields that should contain dopaminergic fibers, we use the slMFB as a key structure to lead our fiber selection procedure: using a similar tracking-seed and tractography algorithm, we describe a dorsal extension of this slMFB that covers sensorimotor fields that are dorsally appended to pre-frontal cortical areas. This "motorMFB", that connects the VTA to sensorimotor cortical fields, can be further segregated into three sub-bundles with a seed-based fiber-selection strategy: A PFC bundle that is attendant to the pre-frontal cortex, passes the lateral VTA, runs through the border zone between the posterior and lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus. An MB bundle that is attendant to the mammillary bodies runs directly through the medial VTA, passes the lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus as well as the supplementary motor area (SMA) and the dorsal premotor cortex (dPMC). Finally, a BC bundle that is attendant to the brainstem and cerebellum runs through the lateral VTA, passes the anterior ventral thalamic nucleus, and covers the SMA, pre-SMA, and the dPMC. We, furthermore, included a fiber tracking of the well-defined dentato-rubro-thalamic tract (DRT) that is known to lie in close proximity with respect to fiber orientation and projection areas. As expected, the tract is characterized by a decussation at the ponto-mesencephal level and a projection covering the superior-frontal and precentral cortex. In addition to the physiological role of these particular bundles, the physiological and pathophysiological impact of dopaminergic signaling within sensorimotor cortical fields becomes discussed. However, some limitations have to be taken into account in consequence of the method: the transmitter content, the directionality, and the occurrence of interposed synaptic contacts cannot be specified.

Author Correction: Post-stroke insomnia in community-dwelling patients with chronic motor stroke: Physiological evidence and implications for stroke care.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Post-stroke insomnia in community-dwelling patients with chronic motor stroke: Physiological evidence and implications for stroke care.

Questionnaire studies suggest that stroke patients experience sustained problems with sleep and daytime sleepiness, but physiological sleep studies focussing specifically on the chronic phase of stroke are lacking. Here we report for the first time physiological data of sleep and daytime sleepiness obtained through the two gold-standard methods, nocturnal polysomnography and the Multiple Sleep Latency Test. Data from community-dwelling patients with chronic right-hemispheric stroke (>12 months) were compared to sex- and age-matched controls. Behavioural and physiological measures suggested that stroke patients had poorer sleep with longer sleep latencies and lower sleep efficiency. Patients further spent more time awake during the night, and showed greater high-frequency power during nonREM sleep than controls. At the same time the Multiple Sleep Latency Test revealed greater wake efficiency in patients than controls. Importantly these findings were not due to group differences in sleep disordered breathing or periodic limb movements. Post-stroke insomnia is presently not adequately addressed within the care pathway for stroke. A holistic approach to rehabilitation and care provision, that includes targeted sleep interventions, is likely to enhance long-term outcome and quality of live in those living with chronic deficits after stroke.

Neural correlates of visuospatial bias in patients with left hemisphere stroke: a causal functional contribution analysis based on game theory.

Stroke patients frequently display spatial neglect, an inability to report, or respond to, relevant stimuli in the contralesional space. Although this syndrome is widely considered to result from the dysfunction of a large-scale attention network, the individual contributions of damaged grey and white matter regions to neglect are still being disputed. Moreover, while the neuroanatomy of neglect in right hemispheric lesions is well studied, the contributions of left hemispheric brain regions to visuospatial processing are less well understood. To address this question, 128 left hemisphere acute stroke patients were investigated with respect to left- and rightward spatial biases measured as severity of deviation in the line bisection test and as Center of Cancellation (CoC) in the Bells Test. Causal functional contributions and interactions of nine predefined grey and white matter regions of interest in visuospatial processing were assessed using Multi-perturbation Shapley value Analysis (MSA). MSA, an inference approach based on game theory, constitutes a robust and exact multivariate mathematical method for inferring functional contributions from multi-lesion patterns. According to the analysis of performance in the Bells test, leftward attentional bias (contralesional deficit) was associated with contributions of the left superior temporal gyrus and rightward attentional bias with contributions of the left inferior parietal lobe, whereas the arcuate fascicle was contributed to both contra- and ipsilesional bias. Leftward and rightward deviations in the line bisection test were related to contributions of the superior longitudinal fascicle and the inferior parietal lobe, correspondingly. Thus, Bells test and line bisection tests, as well as ipsi- and contralesional attentional biases in these tests, have distinct neural correlates. Our findings demonstrate the contribution of different grey and white matter structures to contra- and ipsilesional spatial biases as revealed by left hemisphere stroke. The results provide new insights into the role of the left hemisphere in visuospatial processing.

Tractography of Association Fibers Associated with Language Processing.

INTRODUCTION: Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. METHODS: Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). RESULTS: We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. CONCLUSION: Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

Pharmacological therapies in post stroke recovery: recommendations for future clinical trials.

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials.

Wall shear stress distribution at the carotid bifurcation: influence of eversion carotid endarterectomy.

OBJECTIVES: To test the feasibility of four-dimensional (4D) flow MRI to quantify the systolic wall shear stress (WSSsystole) and oscillatory shear index (OSI) in high-grade internal carotid artery (ICA) stenosis before and after endarterectomy (CEA). METHODS: Twenty patients with ≥60 % ICA stenosis were prospectively and consequently included. Four-dimensional flow MRI was used to measure individual time-resolved 3D blood flow velocities. Segmental WSSsystole and OSI were derived at eight wall segments in analysis planes positioned along the ICA, common (CCA) and external carotid artery (ECA). RESULTS: Regional WSSsystole of all patients decreased after CEA (P < 0.05). Changes were most prominent at the ICA bulb but remained unchanged in the CCA and ECA. OSI was significantly lower after CEA in the lateral vessel walls (P < 0.05). For analysis planes at the stenosis in- and outlet, a reduction of mean WSSsystole by 32 % and 52 % (P < 0.001) and OSI distal to the stenosis (40 %, P = 0.01) was found after CEA. CONCLUSIONS: Our findings show the potential of in vivo 4D flow MRI to quantify haemodynamic changes in wall shear stress even in patients with complex flow conditions.

Differential effects of age on subcomponents of response inhibition.

Inhibitory deficits contribute to cognitive decline in the aging brain. Separating subcomponents of response inhibition may help to resolve contradictions in the existing literature. A total of 49 healthy participants underwent functional magnetic resonance imaging (fMRI) while performing a Go/no-go-, a Simon-, and a Stop-signal task. Regression analyses were conducted to identify correlations of age and activation patterns. Imaging results revealed a differential effect of age on subcomponents of response inhibition. In a simple Go/no-go task (no spatial discrimination), aging was associated with increased activation of the core inhibitory network and parietal areas. In the Simon task, which required spatial discrimination, increased activation in additional inhibitory control regions was present. However, in the Stop-signal task, the most demanding of the three tasks, aging was associated with decreased activation. This suggests that older adults increasingly recruit the inhibitory network and, with increasing load, additional inhibitory regions. However, if inhibitory load exceeds compensatory capacity, performance declines in concert with decreasing activation. Thus, the present findings may refine current theories of cognitive aging.

Comparison of blood flow velocity quantification by 4D flow MR imaging with ultrasound at the carotid bifurcation.

BACKGROUND AND PURPOSE: 4D flow MR imaging is an emerging technique that allows visualization and quantification of 3D blood flow in vivo. However, representative studies evaluating its accuracy are lacking. Therefore, we compared blood flow quantification by using 4D flow MR imaging with US within the carotid bifurcation. MATERIALS AND METHODS: Thirty-two healthy volunteers (age 25.3 ± 3.4 years) and 20 patients with ≥50% ICA stenosis (age 67.7 ± 7.4 years) were examined preoperatively and postoperatively by use of 4D flow MR imaging, with complete coverage of the left and right carotid bifurcation. Blood flow velocities were assessed with standardized 2D analysis planes distributed along the CCA and the ICA and were compared with US at baseline and postoperatively in patients. In addition, we tested reproducibility and interobserver agreement of 4D MR imaging in 10 volunteers. RESULTS: Overall, 101 CCAs and 79 ICAs were available for comparison. MR imaging underestimated (P < .05) systolic CCA and ICA blood flow velocity by 26% (0.79 ± 0.29 m/s vs 1.06 ± 0.31 m/s) and 19% (0.72 ± 0.21 m/s vs 0.89 ± 0.27 m/s) compared with US. Diastolic blood flow velocities were similar for MR imaging and US (differences, 9% and 3%, respectively; not significant). Reproducibility and interobserver agreement of 4D flow MR imaging was excellent. CONCLUSIONS: 4D flow MR imaging allowed for an accurate measurement of blood flow velocities in the carotid bifurcation of both volunteers and patients with only moderate underestimation compared with US. Thus, 4D flow MR imaging seems promising for a future combination with MRA to comprehensively assess ICA stenosis and related hemodynamic changes.

Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke.

OBJECTIVES: Cerebral autoregulation is particularly challenged in acute ischemic stroke. We investigated (1) clinical and radiological factors related to dynamic cerebral autoregulation (DCA) in acute stroke and (2) the relationship between DCA and clinical outcome of stroke. METHODS: A total of 45 patients with middle cerebral artery (MCA) stroke were analyzed pooling two previous studies. DCA was measured by transcranial Doppler in both MCAs early (within 48 h from onset) and late (day 5-7) using low-frequency phase and correlation analysis (index Mx). Outcome was assessed by modified Rankin scale after a mean period of 4 months. RESULTS: Mx increased (i.e. autoregulation worsened) between the early and late measurement, more so on affected (P = 0.005) than on unaffected sides (P = 0.014). Poorer autoregulation as indicated by lower ipsilateral phase (early and late) and higher Mx (late measurement) were significantly related to larger infarction. More severe stroke was significantly related to poorer ipsilateral Mx and phase. Ipsilateral phase in the early (P = 0.019) and Mx in the late measurement (P =0..016) were related to poor clinical outcome according to univariate analysis. CONCLUSIONS: Impairment of DCA ipsilateral to acute ischemic stroke is associated with larger infarction. Dysautoregulation tends to worsen and spread to the contralateral side over the first days post-stroke and is associated with poor clinical outcome.