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Purpose To search for texture features of routine magnetic resonance imaging to predict tumor volume reduction and transient versus permanent tumor progression of vestibular schwannomas treated by Gamma Knife stereotactic radiosurgery. Materials and Methods Included were 23 patients with vestibular schwannomas treated in our center and followed over a period of 23.7–80.3 months (mean 42.7). Magnetic resonance imaging was performed on a 3-Tesla scanner and included T1-weighted images with and without contrast enhancement, T2-weighted, and fluid-attenuated inversion recovery images. Volumetric results were followed longitudinally over time and correlated to texture features as mean, minimum, maximum, standard deviation, skewness, and kurtosis of normalized signals taken from regions of interest covering the total tumor volume. Results In total, 14 tumors showed early progression during the first 5–18 months (2 cases permanent, 12 cases transient), whereas 9 tumors regressed immediately after SRS. Kurtosis of T2-weighted image intensity values turned out to predict progression best with a sensitivity and specificity of 71% and 78%. From all texture feature parameters, only the minimum of the normalized T2-weighted image intensity values correlated significantly to the final reduction of tumor volume per month (correlation coefficient = −0.634, P Conclusions Texture feature analysis helps to predict permanent versus transient enlargement and final volume reduction of schwannomas after SRS. Thus, alternative treatment strategies might be considered, mainly in large tumors, where further clinical deterioration cannot be excluded. To confirm these results, a prospective study including more cases and a longer follow-up period is necessary.

Recent neuroanatomical and functional neuroimaging studies indicate that the anterior part of the hippocampus, rather than the whole structure, may be specifically involved in episodic memory. In the present work, we examined whether anterior structural measurements are superior to other regional or global measurements in mapping functionally relevant degenerative alterations of the hippocampus in Alzheimer's disease (AD). Twenty patients with early AD (MMSE 25.7+/-1.7) and 18 healthy controls were studied using magnetic resonance and diffusion-tensor imaging. Using a regions-of-interest analysis, we obtained volumetric and diffusivity measures of the hippocampal head and body-tail-section as well as of the whole hippocampus. Detailed cognitive evaluation was based on the CERAD battery. All volumetric measures as well as diffusivity of the hippocampus head were significantly (p0.01) altered in patients as compared to controls. In patients, increased left head diffusivity significantly (p0.01) correlated with performance on free delayed verbal recall test (DVR) (r=-0.74, p=0.0002) and with the CERAD global score. Reduced volume of the left body-tail was also associated with performance on DVR (r=0.62, p=0.004). Stepwise regression analyses revealed that increased left head diffusivity was the only predictor for performance on DVR (R(2)=52%, p0.0005). These findings suggest that anterior hippocampus diffusivity is more closely related to verbal episodic memory impairment than other regional or global structural measures. Our data support the hypothesis of functional differentiation in general and the specific role of the anterior hippocampus in episodic memory in particular. Diffusivity measurements might be highly sensitive to functionally relevant degenerative alterations of the hippocampus.

The definition of neuropathic pain has recently been revised by an expert committee of the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) as "pain arising as direct consequence of a lesion or disease affecting the somatosensory system," and a grading system of "definite," "probable," and "possible" neuropathic pain has been introduced. This open case series of 5 outpatients (3 men, 2 women; mean age 48 +/- 12 years) demonstrates how the grading system can be applied, in combination with appropriate confirmatory testing, to diagnosis neuropathic conditions in clinical practice. The proposed grading system includes a dynamic algorithm that enhances the physician's ability to determine with a greater level of certainty whether a pain condition is neuropathic. Its clinical use should be further validated in prospective studies.

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 predominance of the ipsilateral saccular-otolith projection, and (3) evaluate the impact of both factors on the temporo-parieto-insular activation pattern. A block design with three stimulation and rest conditions was applied: (1) 102 dB-VEMP stimulation; (2) 65 dB-control-acoustic stimulation, (3) 102 dB-white-noise-control stimulation. After subtraction of acoustic side effects, bilateral activations were found in the posterior insula, the superior/middle/transverse temporal gyri, and the inferior parietal lobule. The distribution of the saccular-otolith activations was influenced by the two factors but with topographic disparity: whereas the inferior parts of the temporo-parietal cortex were mainly influenced by the ipsilaterality of the pathways, the upper parts reflected the dominance of the non-dominant hemisphere. This is in contrast to the processing of acoustic stimulation, which showed a predominance of the contralateral pathways. Our study proves the importance of the hemispheric preponderance also in left-handers, which is of relevance in the superior parts of the insula gyrus V, the inferior parietal lobule, and the superior temporal gyri.

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., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). Of note, there is now increasing evidence of disturbed myelination in this illness--particularly in subcortical frontal lobe white matter (Konrad, A., Winterer, G. 2008. Disturbed structural connectivity in schizophrenia--primary factor in pathology or epiphenomenon? Schiz. Bull. [Electronic publication ahead of print]). Therefore, we investigated with diffusion tensor imaging (DTI) the impact of a tagging single nucleotide polymorphism (SNP) from the deCODE haplotype, i.e., SNP8NRG221533, on fractional anisotropy (FA), which reflects structural integrity of white matter. SNP8NRG221533 was selected because it gave the single best uncorrected association with schizophrenia in the original report by Stefansson et al. (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., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). As predicted, we found medial frontal FA to be significantly associated with this NRG1 gene variation. Using voxel-based morphometry (VBM), we could largely exclude the possibility that this genotype effect is indirectly caused by genotype-dependent effects on brain volume. This is the first demonstration that SNP8NRG221533 of the NRG1 gene affects medial frontal white matter microstructure in humans. As the degree of neuronal myelination contributes to structural integrity, our finding further supports a potential role of NRG1 in neuronal myelination in the human brain. By extension, our findings suggest that SNP8NRG221533 may contribute to the risk for the complex polygenic illness schizophrenia via its impact on myelination in frontal lobe white matter.

The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level.

Short tone bursts trigger a vestibular evoked myogenic potential (VEMP), an inhibitory potential which reflects a component of the vestibulocollic reflex (VCR). These potentials arise as a result of activation of the sacculus and are expressed through the vestibulo-collic reflex (VCR). Up to now, the ascending projections of the sacculus are unknown in humans, only the representation of the semicircular canals or the entire vestibular nerve has been demonstrated. The aim of this study was to determine whether a sacculus stimulus that evoked VEMPs could activate vestibular cortical areas in fMRI. To determine this, we studied the differential effects of unilateral VEMP stimulation in 21 healthy right-handers in a clinical 1.5 T scanner while wearing piezo electric headphones. A unilateral VEMP stimulus and two auditory control stimuli were given in randomized order over the stimulated ear. A random effects statistical analysis was done with SPM2 (p0.05, corrected). After exclusion of the auditory effects, the major findings were as follows: (i) significant activations were located in the multisensory cortical vestibular network within both hemispheres, including the posterior insular cortex, the middle and superior temporal gyri, and the inferior parietal cortex. (ii) The activation pattern was elicited bilaterally with a predominance of the right hemisphere in right-handers. (iii) Saccular vestibular projection was predominantly ipsilateral, whereas (iv) pure acoustic stimuli were processed with a predominance of the respective contralateral and mainly in the left hemisphere. This is the first demonstration by means of fMRI of the cortical representation of the saccular input at cortical level. The activation pattern is similar to that known from the stimulation of the entire vestibular nerve or the horizontal semicircular canal. Our data give evidence of a task-dependent separation of the processing within the vestibular otolith and the auditory systems in the two hemispheres.

Hippocampus atrophy is a frequent finding in mild cognitive impairment (MCI), whereas diffusion-tensor-imaging (DTI) has demonstrated its value to detect subtle brain tissue changes in several neuropsychiatric diseases including MCI. To compare the diagnostic accuracy of both methods, high resolution MRI scans for hippocampus volumetry, and co-registered DTI-scans for ROI-based mean diffusivity (MD) and fractional anisotropy (FA) were carried out in 18 patients with amnestic MCI (7 females, age 67.3+/-8.7 years, MMSE 25.2+/-2.2) and 18 controls (age 66.9+/-9.0 years, MMSE 28.7+/-1.0). Diagnostic properties of normalized hippocampus volume (HV) and DTI measures with regard to MCI status were estimated by receiver operating characteristics (ROC) analyses and logistic regression. Parameters of the left hippocampus showed superior predictive power when compared to the right. At a specificity set to 80%, left HV had low sensitivity (50%); left hippocampal MD values revealed superior sensitivity (89%), similar to left hippocampal FA (78%). The results demonstrate higher sensitivity of DTI-derived left hippocampal parameters than volume measures in detecting subtle hippocampal abnormalities related to MCI.

Molecular and functional imaging techniques reveal evidence for lateralization of human cerebral function. Based on animal data, we hypothesized that asymmetry in dopamine neurotransmission declines during normal aging. In order to test this hypothesis, we measured dopamine D2/3 receptor availability with [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21 healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high-resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order to assess possible age-related decreases in NC and putamen volume. The calculated DMFP binding potentials (BP) showed a right-ward asymmetry in NC of young subjects that decreased with age (r = 0.577, p = 0.006; Pearson correlation; two-tailed). An age-independent analysis showed a right-ward asymmetry in NC of the whole subject group (left: 1.49+/-0.35; right: 1.65+/-0.43 [mean+/-S.D.]; p = 0.020). No such side lateralization or age-effects could be found in the putamen. Volumes tended to be asymmetric in the putamen (right: 4.85+/-0.56 cm3; left: 4.64+/-0.86 cm3 [mean+/-S.D.]; p = 0.063), but not in NC. The decline of putamen volume during aging was significant in the right putamen (r = -0.613; p = 0.007; Pearson correlation; two-tailed). There were no other significant correlations between striatal volumes and age or BP. Because ventral striatal dopamine neurotransmission is involved in cognitive processes, this loss of physiological asymmetry in NC dopamine transmission during aging might be involved in age-related declines of cognitive performance.

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri- and subgenual part of "classical ACC" only), midcingulate cortex (MCC, posterior part of "classical ACC"), putamen, caudate nucleus and the amygdala. BP for [(18)F]fluoroethyl-diprenorphine was lowest in the sensory motor strip (0.30). Highest BP was found in thalamus (1.36), basal ganglia (putamen 1.22, caudate 1.16) and amygdala (1.21). In the cingulate cortex, ACC (1.11) had higher BP than MCC (0.86). In the operculo-insular region, we found high BPs in all ROIs: anterior insula (1.16), posterior insula (1.05), frontal operculum (0.99) and parietal operculum (0.77). Factor analysis of interindividual variability of opiate receptor BP revealed four factors (95% explained variance): (1) operculo-insular areas, ACC, MCC and putamen, (2) amygdala and thalamus, (3) caudate and thalamus, (4) SI/MI and MCC. Nociceptive areas of the lateral pain system (frontoparietal operculum and insula) have opiate receptor BPs significantly higher than SI/MI, comparable to anterior and midcingulate areas of the medial pain system. These findings suggest that the cortical anti-nociceptive effects of opiates are not only mediated by ACC and MCC, but also by the operculo-insular cortex, if it can be assumed that opioid binding mediates anti-nociception in those structures.

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 (800 Hz carrier frequency, modulated at 24–36 Hz). Functional images were obtained with a 1.5-T scanner and were evaluated using SPM99. Sensitivity of fMRI activation in this unselected sample was 71% for tactile and 83% for auditory stimulation. Group analysis showed activation of SII/PV by tactile and activation of three locations in AI/AII by auditory stimuli. Distributions extended to the opposite side of the fissure (19–58% after tactile and 13–14% after auditory stimulation, depending on the side of stimulation/hemisphere). Morphometry of individual sulcal anatomy revealed that the course of the Sylvian fissure varied by 5.3 mm (SD) in vertical direction. Taking this into account, SII/PV was located 5.8 ± 2.7 mm above the Sylvian fissure, whereas AI/AII was located 6.3 ± 1.7 mm below the Sylvian fissure. Even in individual analysis, the most significant voxel after tactile stimuli in one subject was found on the “wrong” side of the fissure; this error could be ascribed to the spatial normalization procedure. These data show that fMRI signals may overlap substantially, even if the activated regions are separated by 12 mm across a major sulcus. Spatial normalization to an atlas template can introduce additional variance. Individual sulcal anatomy should be preferred over mean atlas locations.

Three patients with acute large paramedian ponto-mesencephalic infarctions developed a bilateral retrograde degeneration of the medial cerebellar peduncles within 4 months after the insult. In an initial magnetic resonance imaging (MRI) within the first 2 weeks, the medial cerebellar peduncles showed normal intensities, but a control MRI after 4 months showed bright hyperintensities in the T2-TSE weighted images, and moderately increased signal intensities in echo planar imaging-diffusion weighted imaging were seen, possibly representing bilateral Wallerian degeneration of the cerebellar-pontine fibers.

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-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.

A new method is introduced to project the sulcal pattern of the brain surface onto a 2D plane. Twin brains are compared against each other using the planar representation. We obtained T1-weighted Flash-3D MRI volumes from 14 male twins (seven monozygotic, seven dizygotic) with 3 mm-thick coronal slices. The projection is based on potential theory: A virtual electrostatic field is calculated between the area of the segmented brain and a surrounding spherical electrode. Field lines starting from each border point of the segmented brain follow the gradient towards the sphere, leading to field line concentrations due to the underlying sulci. The unwrapped sphere surface with the number of field lines per area unit is used as the 2D representation of the sulcal pattern. The resulting brain projections show a distinctive pattern, and a visual assignment of the twin pairs from the unsorted set is possible because of a high similarity of the patterns between twin pairs. Global correlation coefficients for each pair of maps yield significantly higher values for matching monozygotic twin pairs (mean = 20.2, range 12.3-25.6) than for unmatched pairs (mean = 13.0, range 1.1-28.5). As a conclusion, our method allows us to map the location and depth of the sulci on a 2D plane. The resulting maps allow quantitative inter-individual comparisons on the entire brain or parts of the brain surface.

different papers and some eponyms used to characterize a certain neurological state differ from the original description. Except for Wallenberg‘s syndrome, classical brainstem syndromes are rarely seen in clinical practice. Lacunar brainstem syndromes are the consequence of infarcts, which involve long tracts and spare intra-axial cranial nerve segments. This group includes pure motor or pure sensory stroke, dysarthriaclumsy hand syndrome, or ataxic hemiparesis. Such infarcts may also cause body lateropulsion with or without limb ataxia, internuclear ophthalmoplgia, skew-torsion sign, or ocular tilt reaction. Small deep infarcts, which solely affect certain nuclei, may be followed by horizontal or vertical gaze palsies, upbeat nystagmus, isolated facial palsy, pseudoneuritis vestibularis, or isolated vomiting. Lacunar syndromes are more frequent than classical brainstem syndromes. Isolated cranial nerve dysfunctions are due to infarcts, which involve intra-axial cranial nerve segments and spare long tracts, and were reported for 3rd, 4th, 5th, 6th, 7th, or 8th nerves. This is the clinical manifestation of some percent of infarcts in the vertebrobasilar territory.

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 (SNPs) rs2289086 and rs4673628 were investigated by diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analysis in 51 healthy subjects (mean age 22.6±1.8 years). Reaction time (RT) was measured during an attentional paradigm (visual oddball). Results: For both rs2289086 and rs4673628, we found higher fractional anisotropy (FA) in the A/A genotype group in left temporal lobe white matter. In addition, higher FA in the rs4673628 A/A genotype group was demonstrated in the subventricular zone. Conclusions: As FA is considered to index structural integrity of WM, to which neuronal fiber myelination is contributing, our results suggest that variations of the ErbB4 genotype may confer risk for schizophrenia illness via its impact on structural connectivity in human brain. References: Konrad A, Winterer G (2007). Schizophr Bull (online). Nicodemus KK, et al. (2006). Mol Psychiatry 11(12): 1062–5. Silberberg G, et al. (2006). Am J Med Genet B Neuropsychiatr Genet 141(2): 142–8.