Freimut D. Juengling

The contribution of white and gray matter differences to developmental dyslexia : Insights from DTI and VBM at 3.0 T

Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming--among others--that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia.

Cortical grey matter alterations in idiopathic restless legs syndrome: An optimized voxel-based morphometry study.

An impairment of central somatosensory processing is assumed in restless legs syndrome (RLS). Although functional neuroimaging in RLS gave evidence to the presence of widespread functional changes in various brain areas, structural changes at the cortical level were not reported to be RLS‐associated to date. Here, an analysis of high‐resolution three‐dimensional magnetic resonance imaging (MRI) was performed in 63 patients with idiopathic RLS by use of optimized voxel‐based morphometry, in order to investigate if cortical areas might be altered in volume at group level according to the phenomenology of RLS. The comparison of the RLS patients versus controls yielded significant regional decreases of gray matter volume at corrected P < 0.05 in the bihemispheric primary somatosensory cortex, which additionally extended into left‐sided primary motor areas. All clusters correlated both with the severity of RLS symptoms and with disease duration. These results, for the first time, give in vivo evidence to structural neocortical gray matter alterations in RLS patients. The alterations in the sensorimotor cortices might add to the pathophysiological concepts of idiopathic RLS.

Quantification of brain atrophy in patients with myotonic dystrophy and proximal myotonic myopathy: a controlled 3-dimensional magnetic resonance imaging study

Myotonic dystrophy (DM1) and proximal myotonic myopathy (PROMM or DM2) are two distinct muscular disorders with multisystemic involvement. Both have previously been reported to be associated with cognitive impairment and white matter lesions detected by cerebral magnetic resonance imaging (MRI). In this study, the extent of brain atrophy was investigated in vivo in ten DM1 and nine PROMM patients in comparison to age-matched healthy controls for each group. The diagnosis was confirmed by DNA analysis of all patients. As a quantitative marker, the ratio of brain parenchymal to intracranial volume, called brain parenchymal fraction (BPF), was calculated from 3-dimensional MRI data using an automated analysis technique. Compared to age-matched healthy controls (mean BPF 0.852 +/- 0.032), the BPF in DM1 patients (0.713 +/- 0.031) was highly significantly decreased (P < 0.001). In contrast, the PROMM patients (mean BPF 0.792 +/- 0.029) showed only slightly decreased BPF values (P < 0.05). BPF was not significantly correlated to any of the clinical or genetic parameters in both diseases (disease duration, motor score, educational level, and number of CTG repeats in the expanded allele). In summary, global brain atrophy was demonstrated to occur in both diseases, but was more severely manifestated in DM1 patients.

Nondermatomal somatosensory deficits in patients with chronic pain disorder: clinical findings and hypometabolic pattern in FDG-PET.

ABSTRACT Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18‐fluordeoxyglucose positron emission tomography = FDG‐PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD‐17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a “trigger episode of somatic pain” on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG‐PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post‐central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain‐related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG‐PET. Abbreviations: ACC: anterior cingulate cortex; CRPS: complex regional pain syndrome; DLPFC: dorsolateral prefrontal cortex; DSM‐IV: diagnostic and statistical manual of mental disorders, fourth revision; FDG‐PET: 18‐fluordeoxyglucose positron emission tomography; fMRI: Functional magnetic resonance imaging; HAMD: Hamilton depression scale; ICD‐10: International classification of diseases, version 10; NDSD: nondermatomal somatosensory deficits; PFC: prefrontal cortex; PTSD: posttraumatic stress disorder; SPECT: single photon emission computerized tomography; SPM: Statistical parametric mapping; VAS: visual pain analogue scale.Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. The patients were assessed clinically and with conventional brain CT or MRI scan. In the last 11 patients functional neuroimaging was carried out (18-fluordeoxyglucose positron emission tomography = FDG-PET). Depressive symptoms were assessed with the Hamilton depression scale (HAMD-17) and pain intensity was rated with a visual analogue scale for pain (VAS). All patients suffered from mild to moderate depressive symptoms. All patients had experienced a prolonged antecedent phase of severe emotional distress; most of them remembered a ‘‘trigger episode of somatic pain” on the affected side. Somatosensory deficits were a replicable hyposensitivity to touch and heat perception of nondermatomal distribution. Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET. 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. No support and no potential conflict of interest. term refers to a slightly different historical understanding of dis-

Separating functional and structural damage in persistent vegetative state using combined voxel-based analysis of 3-D MRI and FDG-PET.

Functional and structural damage in postanoxic persistent vegetative state (PVS) was analysed using 18fluorodeoxyglucose PET (FDG-PET) coregistered to 3-D MRI in combination with morphometric 3-D MRI analysis (voxel-based morphometry, VBM). In five patients in late stages of non-traumatic PVS, combined analysis using statistical parametric mapping (SPM2) was performed to compare metabolic impairment and structural loss. FDG-PET showed widespread hypometabolism at p<0.001 (corrected) in the parietal, parietooccipital and frontotemporal cortices, cingulum, frontal medial and precentral gyrus, and within the bilateral thalamus. VBM revealed multilocal structural loss at p<0.001 (corrected) in the inferior parietal and superior/medial frontal cortices, insula and operculum, superior and medial temporal lobes, cingulum and fusiform gyrus, caudate, midbrain, dorsal pons, and the cerebellum, but to a lesser extent in the thalamus. The selective vulnerability of the brain in a sample of PVS patients could be mapped in vivo, indicating that a complex structural and functional lesion pattern of the cerebral networks seems to be associated with this condition.

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p‐HSP) and complicated forms (c‐HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p‐HSP (nu2003=u200321) and c‐HSP type (nu2003=u200312), and 30 age‐matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer‐independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (Pu2003<u20030.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c‐HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI‐based brain volume quantification, is a biological marker in HSP subtypes.

Patterns of Regional Brain Hypometabolism Associated with Knowledge of Semantic Features and Categories in Alzheimer's Disease

The study of semantic memory in patients with Alzheimers disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used a semantic verification task and resting 18-fluorodeoxyglucose positron emission tomography in a group of mild to moderate AD patients to investigate this issue. The four task conditions required semantic knowledge of (1) visual, (2) functional properties of living objects, and (3) visual or (4) functional properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmanns area [BA] 37/19). Effects of visual and functional property verification for non-living objects largely overlapped in the left anterior temporal (BA 38/20) and bilateral premotor areas (BA 6), with the visual condition extending more into left lateral precentral areas. There were no associations with functional property verification for living concepts. Our results provide strong support for anatomically separable representations of living and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas.

Comparison of voxel-based 3-D MRI analysis and subtraction ictal SPECT coregistered to MRI in focal epilepsy

While voxel-based 3-D MRI analysis methods as well as assessment of subtracted ictal versus interictal perfusion studies (SISCOM) have proven their potential in the detection of lesions in focal epilepsy, a combined approach has not yet been reported. The present study investigates if individual automated voxel-based 3-D MRI analyses combined with SISCOM studies contribute to an enhanced detection of mesiotemporal epileptogenic foci. Seven consecutive patients with refractory complex partial epilepsy were prospectively evaluated by SISCOM and voxel-based 3-D MRI analysis. The functional perfusion maps and voxel-based statistical maps were coregistered in 3-D space. In five patients with temporal lobe epilepsy (TLE), the area of ictal hyperperfusion and corresponding structural abnormalities detected by 3-D MRI analysis were identified within the same temporal lobe. In two patients, additional structural and functional abnormalities were detected beyond the mesial temporal lobe. Five patients with TLE underwent epileptic surgery with favourable postoperative outcome (Engel class Ia and Ib) after 3-5 years of follow-up, while two patients remained on conservative treatment. In summary, multimodal assessment of structural abnormalities by voxel-based analysis and SISCOM may contribute to advanced observer-independent preoperative assessment of seizure origin.

Different regional brain volume loss in pure and complicated hereditary spastic paraparesis: a voxel-based morphometric study.

Three‐dimensional magnetic resonance imaging of the brain was analyzed using optimized voxel‐based morphometry in 21 patients with pure hereditary spastic paraparesis (pHSP) and 12 patients with complicated HSP (cHSP). PHSP patients showed only small regional grey matter volume reduction, whereas significantly decreased grey matter volumes were localized pericentrally in cHSP. In the white matter, several small areas of regional volume reduction were observed in the pHSP patients, whereas the cHSP group exhibited large robust volume reduction involving the entire corpus callosum, a result that was reproduced by an additional region‐based MRI analysis. It could be demonstrated that the topography of cerebral volume changes differed markedly in pHSP or cHSP at group level. Corpus callosum thinning seems to be a general feature of cHSP.

Heterogeneity of voxel-based morphometry findings in Tourette's syndrome: An effect of age?

resonance images. Results before and after exercise therapy are summarized in the Table. Similar to previous reports, muscle phosphodiester ([PDE concentration]), and pH were elevated at rest and PCr t1/2 was prolonged. After 12 weeks of aerobic exercise therapy, PCr/inorganic phosphate and PCr recovery t1/2 improved. There was also a moderate increase in muscle volume. Resting pH and [PDE] remained unchanged. We support the notion that aerobic exercise therapy can improve muscle function in patients with myotonic dystrophy. Similar to Ørngreen and colleagues, we demonstrated that muscle volume improved after aerobic exercise therapy. The reduction in PCr recovery t1/2 and the increase in PCr/inorganic phosphate are indicative of improved mitochondrial function and suggest that maximal oxygen uptake is enhanced via this mechanism. The baseline elevation of [PDE] was noted and increased after exercise therapy. Future studies investigating the effectiveness of exercise therapy in patients with myotonic dystrophy should consider using P-MRS to evaluate changes in mitochondrial function and resting metabolites. Effective treatment to normalize elevated [PDE] remains to be elucidated.