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.

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.

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.

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.

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.

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.

Brain stem activation in spontaneous human migraine attacks.

Evidence from animal experiments shows that the brain stem is involved in the pathophysiology of migraine. To investigate human migraine, we used positron emission tomography to examine the changes in regional cerebral blood flow as an index of neuronal activity in the human brain during spontaneous migraine attacks. During the attacks, increased blood flow was found in the cerebral hemispheres in cingulate, auditory and visual association cortices and in the brain stem. However, only the brain stem activation persisted after the injection of sumatriptan had induced complete relief from headache and phono- and photophobia. These findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control.

[Neuroimaging in medicine]. / Wissenschaftliche Neurobildgebung in der Medizin.

Neuroimaging has in recent years greatly contributed to our understanding of a wide range of aspects of central neurological diseases. These include the classification and localization of disease (e.g., in headache), the understanding of pathology (e.g., in Parkinson's disease), mechanisms of reorganization (e.g., in stroke), and the subclinical progress of disease (e.g., in degenerative diseases). Apart form presurgical mapping, clinical applications of fMRI are limited. However, functional imaging enables the formulation of neurobiological hypotheses that can be tested clinically and is suited to test classical clinical hypotheses about how the brain works. Understanding the mechanisms and the site of pathology, e.g., in cluster headaches, will lead and has led to new therapeutic strategies. New methodological developments for neuroscientific applications are aimed at the integration of functional and morphological connectivity through a combination of magnetic resonance techniques (fMRI, DTI) and electrophysiological (EEG, MEG) recordings. In addition to stimulus-dependent activations, resting state activity has found increasing interest, for example, in sleep research and various psychiatric diseases (e.g., schizophrenia, borderline).

[Diagnosing stroke aetiologies. Morphologic and functional analysis of the aorta and carotid arteries by MRI]. / Diagnostik von Schlaganfallursachen. Morphologische und funktionelle MRT-Darstellung der Aorta und der Karotiden.

Magnetic resonance imaging allows detailed visualization of the thoracic aorta and is not limited by air artefacts or insonation angles like transoesophageal echocardiography (TEE). Thus the aortic arch can be investigated with higher accuracy, and additional embolic high-risk sources such as complex plaques can be additionally detected by MRI in patients with cryptogenic stroke. Furthermore, MRI provides exact 3D plaque localisation and can be combined with multidirectional 3D MRI velocity mapping. In this way, previously not demonstrable retrograde flow paths originating at complex descending aortic plaques reaching the supra-aortic great arteries can be identified as the probable stroke mechanism in certain patients. The same technique can also be applied to the carotid arteries. This allows analysing the complex 3D helical flow within the internal carotid artery as well as measuring absolute flow velocities and wall shear stress in combination with data on vessel anatomy derived from conventional MR angiography. It is the purpose of this work to describe the state of the art of these modern MR imaging techniques and their potential to identify potential stroke mechanisms, and to analyse the particular role of individual haemodynamic factors on the development of local atherosclerosis.

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.

Reliability of aortic MRI at 3 Tesla in patients with acute cryptogenic stroke.

OBJECTIVES: To evaluate a new three dimensional (3D) MRI protocol for the reliable detection of aortic high risk plaques compared with transoesophageal echocardiography (TOE) and to test the reliability of additional MRI in stroke of undetermined aetiology. METHODS: 74 acute stroke patients were examined by both TOE and MRI at 3 Tesla with special regard to aortic high risk plaques (ie, > OR = 4 mm, superimposed thrombi). ECG synchronised pre- and post-contrast T1 weighted 3D imaging (spatial resolution approximately 1 mm3) covering the thoracic aorta was employed. In plaques > OR = 3 mm, additional two dimensional T2 imaging and time resolved (CINE) imaging sequences were performed. Aetiology of brain ischaemia was classified according to modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Aortic high risk embolic sources detected by MRI in patients with cryptogenic stroke were evaluated. RESULTS: Differences in maximum aortic wall thickness for TOE and MRI were not statistically significant for all aortic segments. The overall number of high risk plaques detected by MRI (n = 74) was substantially higher compared with TOE (n = 47). Most noticeably, MRI identified aortic high risk pathologies in 8/26 (30.8%) patients with cryptogenic stroke after standard diagnostics, including TOE (n = 2: dissection or thrombus; n = 6: plaques > OR = 4 mm). CONCLUSIONS: Our results demonstrate the feasibility of this 3D MRI protocol for the reliable detection of aortic high risk plaques in acute stroke patients. Because of improved visualisation of the aortic arch and the detection of additional embolic sources not seen by standard diagnostics, this novel technique may become a valuable tool for future patients with cryptogenic 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.

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.

No effect of a levodopa single dose on motor performance and motor excitability in chronic stroke. A double-blind placebo-controlled cross-over pilot study.

PURPOSE: Drugs that modulate neuronal transmission can influence motor recovery after stroke. Here, we tested if a single dose of levodopa could improve motor functions and change motor excitability in a group of chronic stroke patients. METHODS: Ten patients > 6 months after their stroke participated in a placebo-controlled double-blind trial. On two different occasions, they received either 100 mg levodopa or placebo in a randomized order. After drug intake, they participated in one hour of physiotherapy aimed at an improvement of dexterity. Motor functions were tested by application of the Nine-Hole-Peg Test, a dynamometer measuring grip strength and the Action Research Arm Test. In addition, transcranial magnetic stimulation (TMS) was applied to study intracortical excitability, stimulus response curves and silent periods. TMS studies and motor function measurements were performed before drug intake, 45 minutes after drug ingestion and after the physiotherapy. RESULTS: Compared to placebo, levodopa neither improved motor functions nor changed motor excitability as tested by TMS. CONCLUSION: These findings suggests that a single levodopa dose is not sufficient to improve motor function in chronic stroke. However, it cannot be excluded that the lack of a beneficial effect is related to the small study sample.

Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network.

Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception and the underlying mechanisms are finally beginning to be understood. According to pharmacological studies, the endogenous opioid system is essential for placebo analgesia. Recent functional imaging data provides evidence that the rostral anterior cingulate cortex (rACC) represents a crucial cortical area for this type of endogenous pain control. We therefore hypothesized that placebo analgesia recruits other brain areas outside the rACC and that interactions of the rACC with these brain areas mediate opioid-dependent endogenous antinociception as part of a top-down mechanism. Nineteen healthy subjects received and rated painful laser stimuli to the dorsum of both hands, one of them treated with a fake analgesic cream (placebo). Painful stimulation was preceded by an auditory cue, indicating the side of the next laser stimulation. BOLD-responses to the painful laser-stimulation during the placebo and no-placebo condition were assessed using event-related fMRI. After having confirmed placebo related activity in the rACC, a connectivity analysis identified placebo dependent contributions of rACC activity with bilateral amygdalae and the periaqueductal gray (PAG). This finding supports the view that placebo analgesia depends on the enhanced functional connectivity of the rACC with subcortical brain structures that are crucial for conditioned learning and descending inhibition of nociception.

Imaging recovery of function following brain injury.

The past years have seen significant advances in our understanding of recovery of function after brain lesions. This results from the development of sophisticated methods for exploring the human living brain, especially by using positron emission tomography scans. From the recent literature, it appears that two main mechanisms may participate in the recovery process: recruitment of cortical areas in the undamaged hemisphere and extension of specialized areas adjacent to the lesioned site.