P13. Dendato-thalamo-cortical pathways in association with otolith dysfunction

Introduction The processing of otolith information within the human cortex is still poorly understood (Lopez and Blanke, 2011). Two distinct anatomical otolith pathways within the thalamo-cortical vestibular network were proposed in patients with thalamic infarctions who presented with contra- or ipsiversive tilts of the subjective visual vertical (SVV) (Dieterich and Brandt, 1993; Baier et al., submitted for publication). Aim of this study was to investigate the dendato-thalamo-cortical pathways in association with otolith dysfunction by means of DTI (diffusion tensor imaging) based on the regions found in a recent patient study using statistical lesion-behavior mapping (Baier et al., subm…

Pain in chemotherapy-induced neuropathy – More than neuropathic?

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre …

Tight Link Between Our Sense of Limb Ownership and Self-Awareness of Actions

Background and Purpose— Hemiparetic stroke patients with disturbed awareness for their motor weakness (anosognosia for hemiparesis/-plegia [AHP]) may exhibit further abnormal attitudes toward or perceptions of the affected limb(s). The present study investigated the clinical relationship and the anatomy of such abnormal attitudes and AHP. Methods— In a new series of 79 consecutively admitted acute stroke patients with right brain damage and hemiparesis/ -plegia, different types of abnormal attitudes toward the hemiparetic/plegic limb (asomatognosia, somatoparaphrenia, anosodiaphoria, misoplegia, personification, kinaesthetic hallucinations, supernumerary phantom limb) were investigated. Re…

Insula and sensory insular cortex and somatosensory control in patients with insular stroke

Background In functional imaging studies, the insular cortex (IC) has been identified as an essential part of the processing of a whole spectrum of multimodal sensory input. However, there are no lesion studies including a sufficient number of patients, which would reinforce the functional imaging data obtained from healthy subjects. Such lesion studies should examine how damage to the IC affects sensory perception. We chose acute stroke patients with lesions affecting the IC in order to fill this gap. Methods A comprehensive sensory profiling by applying a quantitative sensory testing protocol was performed and a voxel-lesion behaviour mapping analysis in 24 patients with acute unilateral …

A Pathway in the Brainstem for Roll-Tilt of the Subjective Visual Vertical: Evidence from a Lesion–Behavior Mapping Study

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion–behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions…

Neuropsychological Symptoms After Anterior Cerebral Artery Ischemic Stroke.

Anatomical correlates of ocular motor deficits in cerebellar lesions

Humans are able to stabilize the images of moving targets on the retina by means of smooth pursuit eye movements. After the pontine level, all smooth pursuit pathways pass through the cerebellum. Previous animal studies gave evidence that two specific lesion sites within the cerebellum cause smooth pursuit disorders: those of the flocculus/paraflocculus and the vermis including lobule VI, VII, the uvula and the deep cerebellar nuclei. To date, there have been only a few lesion studies in patients with smooth pursuit disorders that do not allow direct comparison with a control group. In the present study, new lesion mapping techniques determined which cerebellar structures were involved in p…

Insular strokes cause no vestibular deficits.

Background and Purpose— In previous imaging studies, the posterior insular cortex (IC) was identified as an essential part for vestibular otolith perception and considered as a core region of a human vestibular cortical network. However, it is still unknown whether lesions exclusively restricted to the posterior IC suffice to provoke signs of vestibular otolith dysfunction. Thus, present data aimed to test whether patients with lesions restricted to the IC showed vestibular otolith dysfunction. Methods— We studied 10 acute unilateral stroke patients with lesions restricted to the IC which were tested for signs of vestibular otolith dysfunction, such as tilts of subjective visual vertical, …

Naloxone inhibits not only stress-induced analgesia but also sympathetic activation and baroreceptor-reflex sensitivity

Interactions between the sympathetic nervous system and pain are manifold and still have not been sufficiently characterized. Accordingly, several possible neuronal pathways have been described as being involved in mental stress-induced analgesia. We studied the role of the endogenous opioidergic system in stress-induced analgesia in 14 healthy participants in a double-blind cross-over trial. Naloxone or placebo was applied while electrical pain stimulation was started and electrical current increased. After reaching a constant stimulation at 30 mA, a color word interference test (Stroop task) was performed in a stressful and a non-stressful version. Blood pressure, heart rate and barorefle…

3.7. Are signs of ocular tilt reaction in cerebellar lesions mediated by the dentate nucleus?

The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients

Infratentorial lesions have been assigned an equivalent weighting to supratentorial plaques in the new McDonald criteria for diagnosing multiple sclerosis. Moreover, their presence has been shown to have prognostic value for disability. However, their spatial distribution and impact on network damage is not well understood. As a preliminary step in this study, we mapped the overall infratentorial lesion pattern in relapsing–remitting multiple sclerosis patients (N = 317) using MRI, finding the pons (lesion density, 14.25/cm3) and peduncles (13.38/cm3) to be predilection sites for infratentorial lesions. Based on these results, 118 fiber bundles from 15 healthy controls and a subgroup of 23 …

Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography.

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group su…

Keeping memory clear and stable--the contribution of human basal ganglia and prefrontal cortex to working memory.

Successful remembering involves both hindering irrelevant information from entering working memory (WM) and actively maintaining relevant information online. Using a voxelwise lesion-behavior brain mapping approach in stroke patients, we observed that lesions of the left basal ganglia render WM susceptible to irrelevant information. Lesions of the right prefrontal cortex on the other hand make it difficult to keep more than a few items in WM. These findings support basal ganglia-prefrontal cortex models of WM whereby the basal ganglia play a gatekeeper role and allow only relevant information to enter prefrontal cortex where this information then is actively maintained in WM.

Vestibular compensation of otolith graviceptive dysfunction in stroke patients

BACKGROUND AND PURPOSE A sensitive and frequent clinical sign of a vestibular tone imbalance is the tilt of the perceived subjective visual vertical (SVV). There are no data yet focusing on lesion location at the cortical level as a factor for predicting compensation from the tilt of the SVV. METHODS With modern voxelwise lesion behavior mapping analysis, the present study determines whether lesion location in 23 right-hemispheric cortical stroke patients with an otolith dysfunction could predict the compensation of a vestibular tone imbalance in the chronic stage. RESULTS Our statistical anatomical lesion analysis revealed that lesions of the posterior insular cortex are involved in vestib…

Vestibular thalamus: Two distinct graviceptive pathways.

Objective: To determine whether there are distinct thalamic regions statistically associated with either contraversive or ipsiversive disturbance of verticality perception measured by subjective visual vertical (SVV). Methods: We used modern statistical lesion behavior mapping on a sample of 37 stroke patients with isolated thalamic lesions to clarify which thalamic regions are involved in graviceptive otolith processing and whether there are distinct regions associated with contraversive or ipsiversive SVV deviation. Results: We found 2 distinct systems of graviceptive processing within the thalamus. Contraversive tilt of SVV was associated with lesions to the nuclei dorsomedialis, intrala…

The contribution of acetylcholine and dopamine to subprocesses of visual working memory--what patients with amnestic mild cognitive impairment and Parkinson׳s disease can tell us.

Attentional selection, i.e. filtering out of irrelevant sensory input and information storage are two crucial components of working memory (WM). It has been proposed that the two processes are mediated by different neurotransmitters, namely acetylcholine for attentional selection and dopamine for memory storage. However, this hypothesis has been challenged by others, who for example linked a lack in dopamine levels in the brain to filtering deficits. Here we tested the above mentioned hypothesis in two patient cohorts which either served as a proxy for a cholinergic or a dopaminergic deficit. The first group comprised 18 patients with amnestic mild cognitive impairment (aMCI), the second 22…

Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions.

Background: Disorders of gaze-holding—organized by a neural network located in the brainstem or the cerebellum—may lead to nystagmus. Based on previous animal studies it was concluded that one key player of the cerebellar part of this gaze-holding neural network is the flocculus. Up to now, in humans there are no systematic studies in patients with cerebellar lesions examining one of the most common forms of nystagmus: gaze-evoked nystagmus (GEN). The aim of our present study was to clarify which cerebellar structures are involved in the generation of GEN. Methods: Twenty-one patients with acute unilateral cerebellar stroke were analyzed by means of modern MRI-based voxel-wise lesion-behavi…

Anosognosia for hemiparesis after left-sided stroke

In patients with left-sided lesions, anosognosia for hemiparesis (AHP) seems to be a rare phenomenon. It has been discussed whether this rareness might be due to an inevitable bias due to language dysfunction and whether the left hemisphere's role for our self-awareness of motor actions thus is underestimated. By applying functional magnetic resonance imaging (fMRI) we examined whether patients with AHP following a left hemisphere stroke show a regular, left-sided or a reversed, right-sided lateralization of language functions. Only the former observation would argue for an original role of the left hemisphere in self-awareness about limb function. In a consecutive series of 44 acute left-s…

Evidence for modulation of opioidergic activity in central vestibular processing: A [(18)F] diprenorphine PET study.

Animal and functional imaging studies had identified cortical structures such as the parieto‐insular vestibular cortex, the retro‐insular cortex, or the anterior cingulate cortex belonging to a vestibular cortical network. Basic animal studies revealed that endorphins might be important transmitters involved in cerebral vestibular processing. The aim of the present study was therefore to analyse whether the opioid system is involved in vestibular neurotransmission of humans or not. Changes in opioid receptor availability during caloric air stimulation of the right ear were studied with [(18)F] Fluoroethyl‐diprenorphine ([(18)F]FEDPN) PET scans in 10 right‐handed healthy volunteers and compa…

Vestibular compensation in cerebellar stroke patients.

Background and purpose There is little evidence about the site where compensatory vestibular mechanisms in patients with cerebellar strokes take place. Methods To determine whether the location of a cerebellar lesion might be a crucial variable in vestibular compensation a sample of 22 patients with cerebellar stroke were tested for graviceptive function in the acute and chronic stage. Results Our statistical anatomical lesion analysis indicated that mainly lesions of the cerebellar hemispheres (lobule V, VI, VIIa) hinder vestibular compensation and might lead to an overcompensation. Conclusions Overcompensation-induced dysfunction can be explained by the absence of cerebellar inhibitory si…

Posterior insular cortex - a site of vestibular-somatosensory interaction?

Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilate…

Lesions to the posterior insular cortex cause dysarthria

Background:  Up to now, there are few systematic studies in a sufficient number of patients with lesions involving the insular cortex (IC) examining whether damage of the IC is directly related to dysarthria. Thus, this is the first study applying modern voxel-lesion behaviour mapping (VLBM) aimed to examine whether the IC is involved in dysarthria – and if so – which part of the IC is involved. Methods:  Twenty-five patients with acute stroke lesions affecting the IC and peri-insular region were investigated employing VLBM analysis. Results:  Present data indicated that dysarthria is associated with stroke lesions affecting the right- and left-sided posterior IC. Conclusions:  Owing to the…

Are signs of ocular tilt reaction in patients with cerebellar lesions mediated by the dentate nucleus?

A sensitive clinical sign of a vestibular tone imbalance in the roll plane is the ocular tilt reaction (OTR), a combination of skew deviation, ocular torsion and head and perceptual tilts such as tilts of the subjective visual vertical (SVV). Of these OTR components tilts of SVV are the most frequent. While these signs are regularly seen in patients with unilateral brainstem lesions, only a few case studies are available on their occurrence in patients with cerebellar lesions. Thus, the question arises whether cerebellar structures may be involved in contra- and/or ipsiversive tilts of the perceived vertical and other signs of OTR. We used lesion-mapping techniques in a total of 31 patients…

Vestibular-evoked myogenic potentials in "vestibular migraine" and Menière's disease: a sign of an electrophysiological link?

Characterizations of the signs and symptoms of "vestibular migraine" and of Meniere's disease seem to overlap, suggesting that both diseases might be due to a common peripheral vestibular dysfunction. Thus, the aim of the present study was to assess vestibular-evoked myogenic potentials (VEMPs) in both disorders to determine whether there might be an electrophysiological link between the two disorders. The amplitude and latency of VEMPs were measured from the sternocleidomastoid muscle in 63 patients with vestibular migraine (median age 47 years, range 24-70 years) and in 16 patients with Meniere's disease (median age 52 years, range 36-72 years), and compared with those of 63 sex- and age-…

Repetition suppression versus enhancement — it's quantity that matters

Upon repetition, certain stimuli induce reduced neural responses (i.e., repetition suppression), whereas others evoke stronger signals (i.e., repetition enhancement). It has been hypothesized that stimulus properties (e.g., visibility) determine the direction of the repetition effect. Here, we show that the very same stimuli can induce both repetition suppression and enhancement, whereby the only determining factor is the number of repetitions. Repeating the same, initially novel low-visible pictures of scenes for up to 5 times enhanced the blood oxygen level-dependent (BOLD) response in scene-selective areas, that is, the parahippocampal place area (PPA) and the transverse occipital sulcus…

Ocular tilt reaction: a clinical sign of cerebellar infarctions?

Ocular tilt reaction (OTR) consists of head tilt, ocular torsion (OT), and skew deviation (SKD) combined with perceptual tilts such as deviations of the subjective visual vertical (SVV). Few case reports have shown that OTR also occurs in patients with cerebellar infarctions.1–4 However, no systematic clinical studies are available on the frequency of signs of OTR in patients with cerebellar lesions. Therefore, the questions arose as to whether OTR is a common clinical sign of an acute cerebellar lesion and whether the time course of its components is similar to those from brainstem infarctions. The cerebellar structures involved in 31 patients were studied in detail elsewhere.5 ### Methods…

Neural correlates of disturbed perception of verticality.

Objective: Perception of verticality can be perturbed after cortical stroke. However, a relationship between lesion location and pathologic perception of verticality is still a matter of debate since previous studies revealed contradictory results. Thus, the aim of the current study was to test whether specific cortical lesions were associated with tilts of subjective visual vertical (SVV) and to determine the critical brain areas that cause such tilts in the case of a lesion. Methods: SVV was systematically studied in 54 patients (22 patients with left-sided and 32 patients with right-sided lesions) with acute unilateral strokes, analyzed by modern voxel-wise lesion-behavior mapping techni…

The role of the thalamus in the human subcortical vestibular system1

Most of our knowledge concerning central vestibular pathways is derived from animal studies while evidence of the functional importance and localization of these pathways in humans is less well defined. The termination of these pathways at the thalamic level in humans is even less known. In this review we summarize the findings concerning the central subcortical vestibular pathways in humans and the role of these structures in the central vestibular system with regard to anatomical localization and function. Also, we review the role of the thalamus in the pathogenesis of higher order sensory deficits such as spatial neglect, pusher syndrome or thalamic astasia and the correlation of these p…

Anatomisches Korrelat der vertikalen Otolithenwahrnehmung: Topodiagnostische Erkenntnisse vom Hirnstamm bis zum Kortex

Die intakte vertikale Wahrnehmung ist eine wichtige Voraussetzung fur unsere Fahigkeit des aufrechten Gehens. Diese Fahigkeit ist multisensorisch, wobei der Signalverarbeitung der Otolithen eine dominante Rolle zukommt. Moderne Lasionsmethoden und funktionelle Bildgebungsdaten konnten zeigen, dass sowohl Strukturen im Kleinhirn, Hirnstamm und Thalamus als auch supratentorielle Regionen wie der insulare Kortex – Strukturen eines vestibularen Netzwerks – an der vestibular dominierten vertikalen Wahrnehmung beteiligt sind. Dieser Ubersichtsartikel beschreibt unseren aktuellen Kenntnisstand uber die anatomischen Regionen und Mechanismen, die eine intakte vestibulare vertikale Wahrnehmung beding…

Anatomical correlate of positive spontaneous visual phenomena: a voxelwise lesion study.

Objectives: Visual phenomena such as phosphenes, photopsias, or complex visual hallucinations occur in patients with lesions affecting the occipital, parietal, or temporal lobe. Whether these phenomena are provoked by lesions in specific anatomical regions is still uncertain. To determine which brain regions might be involved in such visual phenomena, we used new brain imaging and lesion analysis tools that allow a direct comparison with control patients. Methods: Visual phenomena were investigated in a total of 23 patients with acute infarctions along the visual pathways (6 patients with left-sided and 17 patients with right-sided lesions). Results: Ten of these 23 patients (43%) reported …

Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions

In the past years, claims of cognitive and attentional function of the cerebellum have first been raised but were later refuted. One reason for this controversy might be that attentional deficits only occur when specific cerebellar structures are affected. To further elucidate this matter and to determine which cerebellar regions might be involved in deficits of covert visual attention, we used new brain imaging tools of lesion mapping that allow a direct comparison with control patients. A total of 26 patients with unilateral right-sided cerebellar infarcts were tested on a covert visual attention task. Eight (31%) patients showed markedly slowed responses, especially in trials in which an…

The importance of the insular cortex for vestibular and spatial syndromes.

BACKGROUND AND PURPOSE The aim of the study was to identify the neuroanatomical correlates and associations of neuropsychological syndromes after acute unilateral right-hemisphere brain lesions. The neuropsychological syndromes considered were orientation in three-dimensional space such as tilts of the subjective visual vertical or of the subjective haptic vertical, pusher syndrome, visual neglect and unawareness of paresis (anosognosia for hemiparesis). These neuropsychological phenomena have been found to occur separately or in different combinations after lesions to the right insular cortex. METHOD Magnetic resonance imaging scans were obtained from 82 patients with acute right-hemispher…