Characterization of Cerebellar Atrophy and Resting State Functional Connectivity Patterns in Sporadic Adult-Onset Ataxia of Unknown Etiology (SAOA).

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I-V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.

The role of muscle strength on tendon adaptability in old age.

PURPOSE: The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences. METHODS: The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 ± 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging. RESULTS: No between-leg differences in triceps surae muscle strength were identified between dominant (2798 ± 566 N) and non-dominant limb (2667 ± 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P < 0.05) of maximal AT force with AT stiffness (r = 0.500) and Young's modulus (r = 0.414), but only a tendency with the mean AT CSA. However, region-specific analysis revealed a significant relationship between maximal AT force and the proximal part of the AT, indicating that this region is more likely to display morphological adaptations following an increase in muscle strength in older adults. CONCLUSIONS: These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size.

Executive control processes are associated with individual fitness outcomes following regular exercise training: blood lactate profile curves and neuroimaging findings.

Cardiovascular training has been associated with neuroimaging correlates of executive control functions (ECF) in seniors and children/adolescents, while complementary studies in middle-aged populations are lacking. Ascribing a prominent role to cardiorespiratory fitness improvements, most studies concentrated on training-induced gains in maximal oxygen uptake (VO2max), although other fitness indices may provide complementary information. Here, we investigated the impact of long-term sub-maximal exercise training on interference control, considering individual training-induced shifts in blood lactate profile curves (BLC) and VO2max. Twenty-three middle-aged sedentary males (M = 49 years) underwent a six-month exercise program (intervention group, IG). Additionally, 14 individuals without exercise training were recruited (control group, CG, M = 52 years). Interference control was assessed before and after the intervention, using a functional magnetic resonance imaging (fMRI) flanker paradigm. Task performance and brain activations showed no significant group-by-time interactions. However, regression analyses in the IG revealed significant associations between individual fitness gains and brain activation changes in frontal regions, which were not evident for VO2max, but for BLC. In conclusion, training-induced plasticity of ECF-related brain activity can be observed in late middle adulthood, but depends on individual fitness gains. For moderate training intensities, BLC shifts may provide sensitive markers for training-induced adaptations linked to ECF-related brain function.

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume.

BACKGROUND: The apolipoprotein E4 allele (ApoE4) is an established genetic risk factor for Alzheimer's disease (AD). However, its effects on cognitive performance and brain structure in healthy individuals are complex. We investigated the effect of ApoE4 on cognitive performance and medial temporal lobe volumetric measures in cognitively unimpaired young elderly with and without subjective memory impairment (SMI), which is an at-risk condition for dementia.MethodAltogether, 40 individuals with SMI and 62 without were tested on episodic memory and on tasks of speed and executive function. All participants were ApoE genotyped. 21 subjects with SMI and 47 without received additional structural magnetic resonance imaging. Volumetric measures of the hippocampus, the entorhinal cortex and the amygdala were obtained manually. RESULTS: In the SMI group, ApoE4 carriers performed worse on the episodic memory (p=0.049) and showed smaller left hippocampal volumes (p=0.030). In the individuals without SMI, the ApoE4 carriers performed better on episodic memory (p=0.018) and had larger right hippocampal volumes (p=0.039). The interaction of group (SMI/no SMI) and ApoE genotype was significant for episodic memory (p=0.005) and right and left hippocampal volumes (p=0.042; p=0.035). There were no within-group differences or interaction effects on speed and executive function composite measures or other volumetric measures. CONCLUSIONS: The negative effect of ApoE4 on episodic memory and hippocampal volume in SMI supports SMI as a prodromal condition of AD. The positive effects of ApoE4 in subjects without SMI adds to a number of reports on positive ApoE4 effects in young and very old individuals.

[Cerebral MRI of preterm neonates at term equivalent age at 3 Tesla: hints at white matter damage on T2- and diffusion weighted images]. / Erfahrungen mit der MRT des Hirns bei Frühgeborenen--Hinweise auf Schädigung der weißen Substanz in T2- und Diffusionswichtung bei 3 Tesla.

BACKGROUND: MRI of the brain is reported to be very sensitive in the detection of diffuse white matter damage in preterm neonates. AIM: To review 3 Tesla-MRI studies of 21 preterm neonates at term equivalent age with regard to safety and detection of white matter changes. PATIENTS: In 21 preterm neonates (9 female, 12 male, mean age 96 days) an MRI of the brain was performed for clinical reasons with oral sedation. All examinations could be performed at 3 Tesla without any complication. In 7 of 21 noncystic periventricular white matter lesions could be found and in 14 hyperintensity of white matter (DEHSI) was observed. ADC-values of the white matter were considerably higher than reported for healthy children in literature. CONCLUSION: MRI at 3 Tesla can be performed safely in oral sedation at term equivalent age at 3 Tesla. T2-weighted and diffusion-weighted imaging is very sensitive for white matter changes.

Visuospatial perspective taking in a dynamic environment: perceiving moving objects from a first-person-perspective induces a disposition to act.

Spatial perspective taking is an everyday cognitive process that is involved in predicting the outcome of goal directed behavior. We used dynamic virtual stimuli and fMRI to investigate at the neural level whether motion perception interacts with spatial perspective taking in a life-like design. Subjects were asked to perform right-left-decisions about the position of either a motionless, hovering (STATic) or a flying ball (DYNamic), either from their own (1PP) or from the perspective of a virtual character (avatar, 3PP). Our results showed a significant interaction of STIMULUS TYPE and PERSPECTIVE with significantly increased activation in right posterior intraparietal sulcus (IPS) for 1PPDYN condition. As the IPS is critically involved in the computation of object-directed action preparation, we suppose that the simple perception of potentially action-relevant dynamic objects induces a 'readiness for (re)action', restricted to the 1PP. Results are discussed against the background of current theories on embodiment and enactive perception.

Distinct striatal regions for planning and executing novel and automated movement sequences.

The basal ganglia-thalamo-cortical circuits are viewed as segregated parallel feed back loops crucially involved in motor control, cognition, and emotional processing. Their role in planning novel, as compared to overlearned movement patterns is as yet not well defined. We tested for the involvement of the associative striatum (caudate/anterior putamen) in the generation of novel movement patterns, which is a critical cognitive requirement for non-routine motor behavior. Using event related functional MRI in 14 right-handed male subjects, we analyzed brain activity in the planning phase of four digit finger sequences. Subjects either executed a single overlearned four digit sequence (RECALL), or self-determined four digit sequences of varying order (GENERATE). In both conditions, RECALL and GENERATE, planning was associated with activation in mesial/lateral premotor cortices, motor cingulate cortex, superior parietal cortex, basal ganglia, insula, thalamus, and midbrain nuclei. When contrasting the planning phase of GENERATE with the planning phase of RECALL, there was significantly higher activation within this distributed network. At the level of the basal ganglia, the planning phase of GENERATE was associated with differentially higher activation located specifically within the associative striatum bilaterally. On the other hand, the execution phase during both conditions was associated with a shift of activity towards the posterior part of the putamen. Our data show the specific involvement of the associative striatum during the planning of non-routine movement patterns and illustrate the propagation of activity from rostral to dorsal basal ganglia sites during different stages of motor processing.

[Current stage of fMRI applications in newborns and children during the first year of life]. / Gegenwärtiger Stand der funktionellen MRT bei Neugeborenen und Kindern im ersten Lebensjahr.

Currently, a paradigm shift towards expanded early use of cranial MRI in newborns at risk and infants in the first year of life can be observed in neonatology. Beyond clinical MRI applications, there is progressive use of functional MRI (fMRI) in this age group. On the one hand, fMRI allows monitoring of functional developmental processes depending on maturational stage; on the other hand, this technique may provide the basis for early detection of pathophysiological processes as a prerequisite for functionally guided therapeutic interventions. This article provides a comprehensive review of current fMRI applications in neonates and infants during the first year of life and focuses on the associated methodological issues (e. g. signal physiology, sedation, safety aspects).

Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state.

BACKGROUND: Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se. METHOD: We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls. RESULTS: Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall. CONCLUSIONS: Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.

A role of the basal ganglia and midbrain nuclei for initiation of motor sequences.

The mesial premotor cortex is crucial for planning sequential procedures and movement initiation. With event-related (ER) functional magnetic resonance imaging (fMRI) it has been possible to separate mesial premotor activation before, during, and after self-initiated movements and, thereby, to distinguish advance planning from execution. The mesial premotor cortex is part of distributed cortico-basal ganglia-thalamo-cortical networks but, to date, the subcortical contributions to self-initiated movements are far less well understood. Using ER fMRI at 3T in 12 right-handed male volunteers, we studied the subcortical activation preceding an automated four-digit finger sequence that was either self-initiated or triggered externally by a visual cue. Beyond typical cortical activation increases in fronto-parietal regions, both initiation modes induced consistent subcortical activation in basal ganglia, midbrain (substantia nigra), and ipsilateral cerebellum. The planning phase of the internally initiated condition, when contrasted with the externally triggered condition, was associated with enhanced activity in frontal regions (mesial premotor cortex/rostral cingulate zone, dorsolateral prefrontal cortex), parietal regions (precuneus, inferior parietal cortex, encroaching onto V5/MT), insula, contralateral anterior putamen and midbrain (bilateral red nucleus/subthalamic nucleus). These data demonstrate the impact of initiation mode on planning-related activity in the ventral basal ganglia and interconnected midbrain nuclei, thereby stressing the crucial role of distributed cortico-basal ganglia-thalamo-cortical networks for self-initiated automated motor repertoires. Involvement of the substantia nigra during planning, as shown here, indicates dopaminergic gating of motor sequences.

[Methodological aspects of functional neuroimaging at high field strength: a critical review]. / Methodische Aspekte der funktionellen Neurobildgebung im MRT-Hochfeldbereich: eine kritische Ubersicht.

The last few years have proven that high field magnetic resonance imaging (MRI) is superior in nearly every way to conventional equipment up to 1.5 tesla (T). Following the global success of 3T-scanners in research institutes and medical practices, a new generation of MRI devices with field strengths of 7T and higher is now on the horizon. The introduction of ultra high fields has brought MRI technology closer to the physical limitations and increasingly greater costs are required to achieve this goal. This article provides a critical overview of the advantages and problems of functional neuroimaging using ultra high field strengths. This review is principally limited to T2*-based functional imaging techniques not dependent on contrast agents. The main issues include the significance of high field technology with respect to SNR, CNR, resolution, and sequences, as well as artifacts, noise exposure, and SAR. Of great relevance is the discussion of parallel imaging, which will presumably determine the further development of high and ultra high field strengths. Finally, the importance of high field strengths for functional neuroimaging is explained by selected publications.

Encoding and retrieval related cerebral activation in continuous verbal recognition.

The differential neuronal activation related to encoding of novel and recognition of previously studied items and the effect of retrieval effort on neuronal activation were assessed in a event-related functional magnetic resonance imaging experiment. A verbal continuous recognition task with two repetitions of the target items was used. The interpretation of the results was focused on brain areas that have been previously reported to be involved in explicit memory. Encoding of novel words in comparison with the first repetition was associated with a stronger activation in the left parahippocampal and inferior frontal gyrus. Encoding of novel words compared to the second repetition was related to a greater bifrontal activation. Recognition of studied items was associated with greater activation in the medial and bilateral inferior parietal lobe at first repetition and in the medial and left inferior parietal lobe at second repetition in comparison with encoding of the novel items. Recognition at first repetition compared to recognition at second repetition was associated with greater bilateral frontal activation. The results are discussed in relation to current concepts of spatial differentiation of memory function and findings from event-related potentials studies of continuous recognition.

[Improved diagnosis of early cerebral infarct by the combined use of diffusion and perfusion]. / Verbesserte Diagnostik des frühen Hirninfarktes durch den kombinierten Einsatz von Diffusions- und Perfusionsbildgebung.

PURPOSE: To evaluate the feasibility and the diagnostic efficacy of multislice diffusion-weighted and perfusion imaging in addition to FLAIR-TSE, T2w-GraSE and MR-angiography in the diagnosis of acute stroke. METHODS: 18 patients with acute stroke were examined at 1.5 Tesla (Gyroscan ACS-NT, Philips Medical Systems) within 6 (n = 9) and 6-48 (n = 9) hours, respectively, and followed at regular intervals. For diffusion imaging we used a multislice multishot EPI-SE sequence with navigator echo correction and cardiac gating. Perfusion imaging was done by means of a FFE-EPI sequence after bolus injection of Gd-DTPA. RESULTS: The diagnostic value of diffusion-weighted and perfusion imaging was significantly higher compared with FLAIR-TSE (p = 0.0023) and GraSE (p = 0.0012) during the first 6 hours. With FLAIR-TSE and GraSE first pathologic changes were seen after 4 hours. We detected perfusion deficit (rCBV < 10%) and a corresponding drop of the ADC in all infarcts larger than 1 cm in diameter. Within the area of low rCBV the combined analysis of diffusion and perfusion imaging allows to identify an infarct region with characteristics of a penumbra and one with characteristics of the infarct core. TTP was increased in the surrounding tissue. However, parts of this area were rarely included in the infarct. The final extension of the untreated infarct, as revealed by computed tomography, corresponded well to the perfusion deficit. CONCLUSIONS: Early ischaemic cerebral infarcts can be diagnosed with diffusion and perfusion imaging before pathological changes are visualized with other imaging modalities. The combined use may allow to distinguish the infarct core from surrounding, potentially salvageable tissue.