Broad disruption of brain white matter microstructure and relationship with neuropsychological performance in male patients with severe alcohol dependence.

Aims In the last years, refined magnetic resonance diffusion tensor imaging (DTI) methods have become available to study microstructural alterations in the human brain. We investigated to what extent white matter tissue abnormalities are present in male patients after chronic, excessive alcohol consumption and if these alterations are correlated with measures of alcohol consumption and neuropsychological performance. Methods Twenty-four detoxified adult male patients with severe alcohol dependence and 23 healthy male control subjects were included in the study. Neuropsychological tests were assessed for executive function, attention, memory and visuospatial function. DTI was acquired and pr…

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia.

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 h…

Delayed feedback of somato-motor cortex activations modulates finger tapping results in real-time functional MR imaging

Neural correlates of hemispheric dominance and ipsilaterality within the vestibularsystem

Earlier functional imaging studies on the processing of vestibular information mainly focused on cortical activations due to stimulation of the horizontal semicircular canals in right-handers. Two factors were found to determine its processing in the temporo-parietal cortex: a dominance of the non-dominant hemisphere and an ipsilaterality of the neural pathways. In an investigation of the role of these factors in the vestibular otoliths, we used vestibular evoked myogenic potentials (VEMPs) in a fMRI study of monaural saccular-otolith stimulation. Our aim was to (1) analyze the hemispheric dominance for saccular-otolith information in healthy left-handers, (2) determine if there is a predom…

Cerebral activation in patients with somatoform pain disorder exposed to pain and stress: an fMRI study.

Patients with somatoform pain disorders are supposed to suffer from an early acquired defect in stress regulation. In order to look for common alterations of the pain- and stress-responsive cortical areas, we prospectively recorded cerebral activations induced by pin-prick pain, by cognitive stress and emotional stress using functional magnetic resonance imaging (fMRI) in a group of 17 patients and an age-matched control group. In addition, the hippocampal volumes of both groups were measured. Patients showed increased activations of the known pain-processing areas (thalamus, basal ganglia, operculo-insular cortex), but also of some prefrontal, temporal and parietal regions during first pai…

Cerebellar speech representation: lesion topography in dysarthria as derived from cerebellar ischemia and functional magnetic resonance imaging.

Background Lesion topography and the pathophysiological background of dysarthria due to focal cerebellar lesions have not yet been fully clarified. Objectives To investigate the lesion topography of dysarthria due to cerebellar ischemia and evaluate brainstem functions. Design Case studies. Patients Eighteen right-handed patients with sudden-onset dysarthria and cerebellar ischemia with and without brainstem involvement and 19 healthy, right-handed, monolingual, German-speaking volunteers. Methods In patients, we used multimodal electrophysiologic techniques to investigate brainstem functions. Functional magnetic resonance imaging (MRI) was performed in the 19 healthy volunteers. Activation…

Association of 5′ end neuregulin-1 ( NRG1 ) gene variation with subcortical medial frontal microstructure in humans

Animal data suggest that the gene neuregulin-1 (NRG1) is involved in neuronal myelination. A haplotype (deCODE) in the 5' end region of the gene was described to double the risk for schizophrenia in an Icelandic population (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A., Lemke, G., Sainz, J., Johannesson, G., Andresson, T., Gudbjartsson, D., Manolesc…

229 – ERBB4 genotype effects on human brain structure

Background:Disturbed functional and structural brain connectivity in schizophrenia has been shown in a large number of studies. There is evidence from several neuroimaging and post mortem studies that altered neuronal myelination may in part account for this deficit. Recent investigations have suggested that variations of the genes that encode the Neuregulin 1 (NRG1) ErbB4 receptor complex might be associated with schizophrenia illness. As NRG1 and ErbB4 have been implicated in myelination and neuronal proliferation. We investigated whether cerebral micro and macrostructure is predicted by two risk haplotypes of the ErbB4 gene. Methods: The effects of two single-nucleotide polymorphisms (SN…

L�sionsverteilung von Hirnstamminfarkten im MRT

Seit langer Zeit sind typische Hirnstammsyndrome bekannt. Eines der haufigsten ist das Wallenberg- Syndrom bei dorsolateralem Medulla-oblongata-Infarkt. Ursache ist hier meist ein Verschluss der ipsilateralen PICA. Die Vielzahl der Syndrome auf der einen Seite sowie die Klassifikation der Hirnstamminfarkte in Gruppen andererseits konnen als Hinweis darauf angesehen werden, dass die Hirnstamminfarkte regelmasig bestimmte Territorien und Gebiete bevorzugen. Inwieweit diese Hypothese zutrifft, sollte an einem Patientenklientel mit akuten Hirnstamminfarkten untersucht werden. Ziel unserer Arbeit war die Darstellung typischer Lasionsverteilungen bei Patienten mit akutem Hirnstamminfarkt. Bei 117…

Disturbed structural connectivity is related to inattention and impulsivity in adult attention deficit hyperactivity disorder

Inattention and impulsivity are the most prominent clinical features of attention deficit hyperactivity disorder (ADHD) in adulthood. Structural and functional neuroimaging studies of subjects with ADHD have demonstrated abnormalities in several brain areas, including fronto-striatal and fronto-cerebellar networks. Mostly, these studies were based on volumetric measurements and have been conducted in children. We investigated white matter (WM) integrity and correlation with measures of attention and impulsivity in adult patients with ADHD adopting diffusion tensor imaging (DTI). N = 37 (21 males) never-medicated adult patients with ADHD combined subtype and N = 34 (16 males) healthy control…

Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients with intracerebral tumors affecting the frontal lobe.

Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers se…

Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cere…

Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scan…

Combined spike-related functional MRI and multiple source analysis in the non-invasive spike localization of benign rolandic epilepsy.

Abstract Objective To localize the irritative zone in children by combined spike-related fMRI and EEG multiple source analysis (MSA) in children with benign rolandic epilepsy. Methods Interictal spikes were averaged and localized using MSA, and source locations were displayed in the anatomical 3D-MRI in 11 patients (5–12 yrs, median 10). Interictal spikes were additionally recorded during the fMRI acquisition (EEG-fMRI), and the fMRI sequences were correlated off-line with the EEG spikes. Results MSA revealed an initial central dipole in all patients, including the face or hand area. A second dipolar source was mostly consistent with propagated activity. BOLD activations from EEG-fMRI, cons…

VBM-DTI correlates of verbal intelligence: a potential link to Broca's area.

Abstract Human brain lesion studies first investigated the biological roots of cognitive functions including language in the late 1800s. Neuroimaging studies have reported correlation findings with general intelligence predominantly in fronto-parietal cortical areas. However, there is still little evidence about the relationship between verbal intelligence and structural properties of the brain. We predicted that verbal performance is related to language regions of Broca's and Wernicke's areas. Verbal intelligence quotient (vIQ) was assessed in 30 healthy young subjects. T1-weighted MRI and diffusion tensor imaging data sets were acquired. Voxel-wise regression analyses were used to correla…

A new method to investigate brain stem structural-functional correlations using digital post-processing MRI - reliability in ischemic internuclear ophthalmoplegia

We investigated the reliability of a new digital post-processing magnetic resonance imaging (MRI) technique in ischemic brain stem lesions to identify relations of the lesion to anatomical brain stem structures. The target was a medial longitudinal fasciculus (MLF) lesion, which was evident from ipsilateral internuclear ophthalmoplegia (INO). Sixteen patients with acute unilateral INO and an isolated acute brain stem lesion in T2- and EPI-diffusion weighted MRI within 2 days after the onset of symptoms were studied. The MRI slice direction was parallel and perpendicular to a slice selection of a stereotactic anatomical atlas. The individual slices were normalized and projected in the digita…

ErbB4 genotype predicts left frontotemporal structural connectivity in human brain.

Diminished left frontotemporal connectivity is among the most frequently reported findings in schizophrenia and there is evidence that altered neuronal myelination may in part account for this deficit. Several investigations have suggested that variations of the genes that encode the Neuregulin 1 (NRG1)-ErbB4 receptor complex are associated with schizophrenia illness. As NRG1--ErbB4 has been implicated in neuronal myelination, we investigated with diffusion tensor imaging (DTI) whether fractional anisotropy (FA)--a putative measure of neuronal myelination--is predicted by a risk haplotype of the ErbB4 gene. The effects of the ErbB4 genotype were investigated in healthy subjects (N=59; mean …

3.4. Functional brainstem infarction studies: Previous results and new ways of lesion coregistration

Diffusionsgewichtetes MRT bei vertebrobasil�ren Isch�mien

The aim of this study was to evaluate the applicability, sensitivity, and predictive power of diffusion-weighted MR imaging (DWI) in the diagnosis of vertebrobasilar infarction. From 1997 to 2002, we prospectively recruited 268 patients with acute signs and symptoms suspective of vertebrobasilar ischemia. The patients underwent biplanar EPI-T2 and EPI DWI within 24 h after onset of symptoms and high-resolution MRI as a control within 7 days. One hundred twenty-one patients had additional CT scanning. The DWI revealed acute vertebrobasilar infarction in 71.0%. The mean time exposure of DWI was 8 min and thus no more than that of CT imaging. It showed significantly more acute lesions than CT …

Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD.

Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) have shown abnormalities in several brain areas including the frontostriatal circuitry and were mostly conducted in children and adolescents. We investigated 30 never-medicated adult ADHD patients (16 males) and 30 matched healthy control individuals. Functional magnetic resonance imaging was acquired during a working memory paradigm (n-back). Group activation maps and group differences of activation were calculated using voxel-based analyses. The generic activation pattern was more extended in the control group. In ADHD patients, significantly decreased activation was found in the right inferior parietal cortex. Distur…

Diffusion weighted magnetic resonance imaging in the diagnosis of reversible ischaemic deficits of the brainstem

Objectives: To evaluate the sensitivity of diffusion weighted magnetic resonance imaging (MRI) for the diagnosis of clinically suspected reversible ischaemic deficits of the brainstem. Methods: A total of 158 consecutive patients presenting with acute signs of brainstem dysfunction were investigated using EPI diffusion weighted MRI within 24 hours of the onset of symptoms. High resolution T1 and T2 weighted imaging was performed as a follow up after a median of six days Results: Fourteen of the 158 patients had a complete clinical recovery within 24 hours (transitory ischaemic attack (TIA)), and 19 patients recovered in less than one week (prolonged reversible neurological deficit (RIND)). …

Association of attentional network function with exon 5 variations of the CHRNA4 gene

Mutational analyses in xenopus oocyte and mice models indicate that the positive effect of nicotine on attention may be modulated by genetic variations within exon 5 of the alpha4 subunit of the nicotinergic acetylcholine receptor gene CHRNA4. The potential relevance of exon 5 is further emphasized by two recent family-based association studies of nicotine dependence because subgroups of nicotine-dependent subjects are thought to 'self-medicate' attentional deficits with nicotine. We investigated a synonymous single nucleotide polymorphisms (SNP): rs1044396, which has recently been associated with nicotine-dependence, plus two adjacent synonymous SNPs rs1044394 and rs1044393 in exon 5 of n …

Distributed BOLD-response in association cortex vector state space predicts reaction time during selective attention.

Human cortical information processing is thought to be dominated by distributed activity in vector state space (Churchland, P.S., Sejnowski, T.J., 1992. The Computational Brain. MIT Press, Cambridge.). In principle, it should be possible to quantify distributed brain activation with independent component analysis (ICA) through vector-based decomposition, i.e., through a separation of a mixture of sources. Using event-related functional magnetic resonance imaging (fMRI) during a selective attention-requiring task (visual oddball), we explored how the number of independent components within activated cortical areas is related to reaction time. Prior to ICA, the activated cortical areas were d…

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…

93. Structural brain abnormalities in attention-deficit/hyperactivity disorder: A voxel-based MRI study in adult patients

Altered effective connectivity in drug free schizophrenic patients

The present fMRI study aimed to investigate effective connectivity within a cortical-subcortical-cerebellar information processing network in drug free schizophrenic patients while performing a 2-back working memory task. The finding of enhanced thalamo-cortical and cortico-cortical intrahemispheric connectivity could be interpreted as a compensatory increase of neuronal connection strength consistent with a model of cortical inefficiency in schizophrenic patients. Additionally, the result could be integrated into a model of deficient thalamo-cortical filter functions. Conversely, lower interhemispheric connectivity of the frontal and parietal association cortex appears to be the functional…

Correlation of brain white matter diffusion anisotropy and mean diffusivity with reaction time in an oddball task.

<i>Background:</i> Reaction time (RT) is a frequently used measure of information processing speed, but the underlying physiological and anatomical conditions are not yet fully understood. A correlation between measures of white matter (WM) ultrastructural properties and RT is expected – particularly for those WM tracts that are involved in the attentional system of the brain. <i>Methods:</i> Diffusion tensor imaging data were acquired in 43 unrelated healthy subjects (age: 22.7 ± 1.8 years), and RT was measured during an attention-requiring visual oddball task in the same scanning session. Voxel-by-voxel and region of interest analyses were performed for the large a…

EEG-related Functional MRI in Benign Childhood Epilepsy with Centrotemporal Spikes

The localization of epileptic foci is an important issue in children with extratemporal epilepsies. However, the value of noninvasive methods such as the EEG-assisted functional magnetic resonance imaging (fMRI) has not been sufficiently investigated in children. As a model of extratemporal epilepsies, we studied 7 patients aged 5 to 12 (median 10) years with benign childhood epilepsy and centrotemporal (rolandic) spikes. Interictal spikes were recorded during the fMRI acquisition on a MR-compatible battery-powered digital EEG system with 16 channels. The fMRI sequences were correlated off-line with the EEG spikes and analyzed with the software Statistical Parametrical Mapping SPM99. The fM…

58. White matter abnormalities in attention-deficit/hyperactivity disorder: A diffusion tensor imaging study in adult patients

Spatial resolution of fMRI in the human parasylvian cortex: Comparison of somatosensory and auditory activation

Abstract In spite of its outstanding spatial resolution, the biological resolution of functional MRI may be worse because it depends on the vascular architecture of the brain. Here, we compared the activation patterns of the secondary somatosensory and parietal ventral cortex (SII/PV) with that of the primary auditory cortex and adjacent areas (AI/AII). These two brain regions are located immediately adjacent to each other on opposite banks of the Sylvian fissure, and are anatomically and functionally distinct. In 12 healthy subjects, SII/PV was activated by pneumatic tactile stimuli applied to the index finger (0.5 cm 2 contact area, 4 bar pressure), and AI/AII by amplitude-modulated tones…

COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits.

Abstract Objective: Prefrontal dopamine (DA) is catabolized by the COMT (catechol- O -methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide polymorphism (SNP) in the COMT gene predicts executive cognition in humans with Val carriers showing poorer performance due to less available synaptic DA. Recent fMRI studies are thought to agree with these studies having demonstrated prefrontal hyperactivation during n -back and attention-requiring tasks. This was interpreted as “less efficient” processing due to impaired signal-to-noise ratio (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR in primates and humans imply that prefrontal cortex…

Direction‐dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study)

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion‐sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction‐dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compa…

Topodiagnostic value of blink reflex R1 changes: a digital postprocessing MRI correlation study.

The aim of the study was to investigate the relation of the blink reflex R1 arc to known anatomical brainstem structures. Acute vascular brainstem lesions as identified by magnetic resonance imaging (MRI) of patients with isolated R1 pathology were superimposed into a stereotactic anatomical atlas using a new method of digital postprocessing. Isolated acute brainstem lesions were documented by diffusion-weighted MRI in 12 of 24 patients with unilateral R1 pathology. The lesions were located in the ipsilateral mid- to lower pons. In three patients only, the lesion had partial contact with the principal sensory nucleus of the trigeminal nerve (PSN) on at least one level. In two patients, the …