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Introduction: Brain age, the estimation of a person's age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in clinical contexts. Here, we show how brain age predictions perform for the same individual at various time points and validate our findings with age-matched healthy controls., Methods: We used densely sampled T1-weighted MRI data from four individuals (from two densely sampled datasets) to observe how brain age corresponds to age and is influenced by acquisition and quality parameters. For validation, we used two cross-sectional datasets. Brain age was predicted by a pretrained deep learning model., Results: We found small within-subject correlations between age and brain age. We also found evidence for the influence of field strength on brain age which replicated in the cross-sectional validation data and inconclusive effects of scan quality., Conclusion: The absence of maturation effects for the age range in the presented sample, brain age model bias (including training age distribution and field strength), and model error are potential reasons for small relationships between age and brain age in densely sampled longitudinal data. Clinical applications of brain age models should consider of the possibility of apparent biases caused by variation in the data acquisition process., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: In the light of the ongoing replication crisis in the field of neuroimaging, it is necessary to assess the possible exogenous and endogenous factors that may affect functional magnetic resonance imaging (fMRI). The current project investigated time-of-day effects in the spontaneous fluctuations (<0.1 Hz) of the blood oxygenation level dependent (BOLD) signal. Method: Using data from the human connectome project release S1200, cross-spectral density dynamic causal modeling (DCM) was used to analyze time-dependent effects on the hemodynamic response and effective connectivity parameters. The DCM analysis covered three networks, namely the default mode network, the central executive network, and the saliency network. Hierarchical group-parametric empirical Bayes (PEB) was used to test varying design-matrices against the time-of-day model. Results: Hierarchical group-PEB found no support for changes in effective connectivity, whereas the hemodynamic parameters exhibited a significant time-of-day dependent effect, indicating a diurnal vascular effect that might affect the measured BOLD signal in the absence of any diurnal variations of the underlying neuronal activations and effective connectivity. Conclusion: We conclude that these findings urge the need to account for the time of data acquisition in future MRI studies and suggest that time-of-day dependent metabolic variations contribute to reduced reliability in resting-state fMRI studies.

Background: Small soft tissue masses are often falsely assumed to be benign and resected with failure to achieve tumor-free margins. Therefore, this study retrospectively investigated the distribution of histopathologic diagnosis to be encountered in small soft tissue tumors (≤ 5 cm) in a large series of a tertiary referral center., Methods: Patients with a soft tissue mass (STM) with a maximum diameter of 5 cm presenting at our institution over a period of 10 years, who had undergone preoperative Magnetic resonance imaging and consequent biopsy or/and surgical resection, were included in this study. A final histopathological diagnosis was available in all cases. The maximum tumor diameter was determined on MR images by one radiologist. Moreover, tumor localization (head/neck, trunk, upper extremity, lower extremity, hand, foot) and depth (superficial / deep to fascia) were assessed., Results: In total, histopathologic results and MR images of 1753 patients were reviewed. Eight hundred seventy patients (49.63%) showed a STM ≤ 5 cm and were therefore included in this study (46.79 +/- 18.08 years, 464 women). Mean maximum diameter of the assessed STMs was 2.88 cm. Of 870 analyzed lesions ≤ 5 cm, 170 (19.54%) were classified as superficial and 700 (80.46%) as deep. The malignancy rate of all lesions ≤ 5 cm was at 22.41% (superficial: 23.53% / deep: 22.14%). The malignancy rate dropped to 16.49% (20.79% / 15.32%) when assessing lesions ≤ 3 cm (p = 0.007) and to 15.0% (18.18% / 13.79%) when assessing lesions ≤ 2 cm (p = 0.006). Overall, lipoma was the most common benign lesion of superficial STMs (29.41%) and tenosynovial giant cell tumor was the most common benign lesion of deep STMs (23.29%). Undifferentiated pleomorphic sarcoma was the most common malignant diagnosis among both, superficial (5.29%) and deep (3.57%) STMs., Conclusions: The rate of malignancy decreased significantly with tumor size in both, superficial and deep STMs. The distribution of entities was different between superficial and deep STMs, yet there was no significant difference found in the malignancy rate.

Using fMRI, Hugdahl et al. (2015) reported the existence of a general-domain cortical network during active task-processing which was non-specific to the cognitive task being processed. They labelled this network the extrinsic mode network (EMN). The EMN would be predicted to be negatively, or anti-correlated with the classic default mode network (DMN), typically observed during periods of rest, such that while the EMN should be down-regulated and the DMN up-regulated in the absence of demands for task-processing, the reverse should occur when demands change from resting to task-processing. This would require alternating periods of task-processing and resting and analyzing data continuously when demands change from active to passive periods and vice versa. We were particularly interested in how the networks interact in the critical transition points between conditions. For this purpose, we used an auditory task with multiple cognitive demands in a standard fMRI block-design. Task-present (ON) blocks were alternated with an equal number of task-absent, or rest (OFF) blocks to capture network dynamics across time and changing environmental demands. To achieve this, we specified the onset of each block, and used a finite-impulse response function (FIR) as basis function for estimation of the fMRI-BOLD response. During active (ON) blocks, the results showed an initial rapid onset of activity in the EMN network, which remained throughout the period, and faded away during the first scan of the OFF-block. During OFF blocks, activity in the DMN network showed an initial time-lag where neither the EMN nor the DMN was active, after which the DMN was up-regulated. Studying network dynamics in alternating passive and active periods may provide new insights into brain network interaction and regulation., Competing Interests: The authors declare no conflict of interest. The co-authors KH, LE, RG and KS own shares in the company NordicNeuroLab Inc., which produced the headphones used for the presentation of the auditory stimuli. These authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To evaluate contrast-enhanced T1-weighted magnetic resonance (MR) images in histologically proven fibrous dysplasia (FD) for the prevalence of "milk cloud appearance" and its association with ground-glass appearance (GGA) on radiography or computed tomography (CT)., Methods: For this retrospective cohort study, 37 patients with histologically proven FD imaged preoperatively with contrast-enhanced MR imaging and radiography or CT were identified at our institution. Three radiologists independently evaluated MR images for the presence of milk cloud appearance on T1-weighted contrast-enhanced images, sites of skeletal involvement, type of bone involved, uni- vs. multifocality, mono- vs. polyostotic disease, maximum diameter, proportion of bone involved, expansile remodeling, and T2 homogeneity. The presence or absence of GGA on radiography or CT was determined in consensus. Inter-reader agreement was evaluated for milk cloud appearance using Cohen's kappa, and associations between milk cloud appearance and other imaging parameters were tested using Spearman's rho., Results: Among the 37 histologically proven FD lesions, GGA was identified in 70% of the lesions, while milk cloud appearance was found in 82% of the lesions. Inter-reader agreement for milk cloud appearance on MR imaging was good to excellent (κ 0.65, 0.82, and 0.8). A significant correlation was found between milk cloud appearance and GGA (ρ = 0.31, p < 0.001)., Conclusion: Milk cloud appearance is a characteristic sign of FD on contrast-enhanced T1-weighted MR images. Recognition of this feature may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of FD., Key Points: • Fibrous dysplasia displays a characteristic feature on contrast-enhanced T1-weighted MR imaging: milk cloud appearance. • Milk cloud appearance correlates well with the radiographic or CT finding of ground-glass appearance. • Recognition of milk cloud appearance on contrast-enhanced MR imaging may be helpful when radiographs are equivocal or unremarkable or when MR imaging is performed as the primary imaging modality in cases of fibrous dysplasia.

Purpose: To evaluate utility of magnetic resonance (MR) imaging in local staging of soft-tissue sarcoma, with an emphasis on assessment of neurovascular encasement., Materials and Methods: Institutional review board approval was obtained; informed consent requirement was waived. Preoperative MR images in 174 patients with soft-tissue sarcoma were analyzed by two readers. Tumor staging according to the American Joint Committee on Cancer/Union International Contre le Cancer and Enneking staging systems and analysis of osseous and articular invasion were performed. To assess neurovascular encasement, contact between tumor and arteries, between tumor and veins, and between tumor and nerves was classified (no contact, contact ≤90°, 91°-180°, 181°-270°, >271°). Interobserver agreement was determined; imaging findings were correlated with intraoperative findings and/or histopathologic findings (Pearson correlation coefficient [r] and Cohen κ coefficient)., Results: Intraoperative evaluation and/or histopathologic evaluation confirmed osseous, articular, and neurovascular invasion in 8.6%, 2.9%, and 25.3% of patients. Interobserver agreement was excellent for tumor staging (American Joint Committee on Cancer/Union International Contre le Cancer staging, κ = 0.811; Enneking staging, κ = 0.943) and osseous invasion (κ = 1.000). It was substantial for articular invasion (κ = 0.794). Sensitivity and specificity for osseous invasion were 100% and 98.7%, respectively (both readers). For articular invasion, sensitivity was 80% (both readers); specificities were 100% and 98.8% for readers 1 and 2, respectively. Interobserver agreement in quantifying contact between tumor and vessels and between tumor and nerves was excellent for arteries, veins, and nerves (κ = 0.845, 0.892, 0.893, respectively). Receiver operating characteristic analysis revealed optimal threshold of greater than 180° for prediction of arterial and venous encasement (both readers). For neural encasement, optimal threshold was greater than 180° (reader 1) and greater than 270° (reader 2). Sensitivities in diagnosing encasement for arteries, veins, and nerves were 84.6%, 84.6%, and 77.8% (reader 1) and 84.6%, 84.6%, and 72.2% (reader 2). Specificities for encasement of arteries, veins, and nerves, respectively, were 97.5%, 97.5%, and 93.2% (reader 1) and 93.8%, 94.7%, 97.3% (reader 2)., Conclusion: MR imaging allows reliable and accurate local staging of soft-tissue sarcoma. Encasement of arteries, veins, and nerves should be diagnosed, if the contact between tumor and vascular or neural circumference exceeds 180°., ((©) RSNA, 2015)

To what degree resting state fMRI is stable or susceptible to internal mind states of the individual is currently an issue of debate. To address this issue, the present study focuses on sex differences and investigates whether resting state fMRI is stable in men and women or changes within relative short-term periods (i.e., across the menstrual cycle). Due to the fact that we recently reported menstrual cycle effects on cognitive control based on data collected during the same sessions, the current study is particularly interested in fronto-parietal resting state networks. Resting state fMRI was measured in sixteen women during three different cycle phases (menstrual, follicular, and luteal). Fifteen men underwent three sessions in corresponding time intervals. We used independent component analysis to identify four fronto-parietal networks. The results showed sex differences in two of these networks with women exhibiting higher functional connectivity in general, including the prefrontal cortex. Menstrual cycle effects on resting states were non-existent. It is concluded that sex differences in resting state fMRI might reflect sexual dimorphisms in the brain rather than transitory activating effects of sex hormones on the functional connectivity in the resting brain.

Objective: Primary hepatic angiosarcoma is a very rare and aggressive malignancy of vascular origin. We describe cross-sectional imaging findings of this entity with emphasis on dynamic contrast-enhanced (DCE) and diffusion-weighted (DWI) MR imaging., Methods: Seven cases of pathologically confirmed hepatic angiosarcoma were retrospectively reviewed (CT and MRI examinations were available in seven and six patients, respectively). Two radiologists evaluated lesion growth patterns, attenuation, signal intensity characteristics, contrast enhancement patterns, and apparent diffusion coefficients (ADCs)., Results: Multifocal hepatic disease was present in six patients by means of a mixed pattern of large dominant masses and multiple small nodules; one patient had a solitary large mass. Unenhanced images depicted hemorrhagic areas and a markedly heterogeneous internal architecture within large tumors. Contrast-enhanced early phase images showed variable patterns including patchy peripheral or bizarre shaped intralesional foci of enhancement, peripheral rim enhancement, and small lesions without enhancement. On DCE images, the majority of lesions presented with varying degrees of progressive enhancement. Small nodules frequently displayed homogeneous enhancement on delayed phase images due to complete fill-in. DWI revealed a high interlesional variability of ADC values (range 0.57-2.41 × 10(-3 )mm(2)/s, mean 1.37 × 10(-3 )mm(2)/s)., Conclusion: Cross-sectional imaging findings of hepatic angiosarcoma reflect the varied histopathological composition of the tumors. Multifocal disease, hemorrhage within large lesions, as well as progressive enhancement on DCE images are typical features of hepatic angiosarcoma. The mean ADC of lesions was found to be slightly elevated in comparison with other hepatic malignancies.

The independent component analysis (ICA) method was applied to fMRI data from two synaesthetes and their matched controls while they performed the coloured-word Stroop task and the single-letter (synaesthetic) Stroop task. ICA identified an 'attention' network, a 'perceptual' network as well as a 'conflict monitoring' network. Increased activity was observed in right V4 during the single-letter Stroop task for synaesthetes only. The finding confirms that the same neural substrate that is known to support the experience of physical colours also supports the experience of synaesthetic colours., (©2011 The British Psychological Society.)

The present fMRI study attempts to identify brain areas that may underlie the effect of different background noises on functional brain asymmetry in a dichotic listening task. Previous studies have shown that the prominent right ear advantage in dichotic listening to consonant-vowel syllables is affected by background noise. To explore the underlying neuronal processes, haemodynamic brain responses using fMRI were recorded while participants performed the dichotic listening task in two different noisy backgrounds (conversational "babble" and traffic noise). The behavioural results showed a reduction of the right ear advantage in the background noise conditions, especially in the traffic noise condition. The behavioural results are discussed in terms of alertness-attentional mechanisms. The effects of background noise on brain activation involved significant activations in a speech-processing network. Specifically the changes in activations in the peri-Sylvian region of the superior temporal gyrus and in the temporo-parietal junction part in the left hemisphere, as well as in the superior temporal gyrus/sulcus area in the right hemisphere may mirror the effects of noise on behavioural performance. The effects of noise on brain activation are discussed with regard to pre-activation mechanisms.

In working memory (WM), functional imaging studies demonstrate cerebellar involvement indicating a cognitive role of the cerebellum. These cognitive contributions were predominantly interpreted as part of the phonological loop within the Baddeley model of WM. However, those underlying investigations were performed in the context of visual verbal WM which could pose a bias when interpreting the results. The aim of this fMRI study was to address the question of whether the cerebellum supports additional aspects of WM in the context of higher cognitive functions. Furthermore, laterality effects were investigated to further disentangle the cerebellar role in the context of the phonological loop and the visuospatial sketchpad. A direct comparison of verbal and abstract visual WM was performed in 17 young volunteers by applying a 2-back paradigm and extracting the % change in BOLD signal from the fMRI data. To minimize potential verbal strategies, Attneave and Arnoult shapes of non-nameable objects were chosen for the abstract condition. The analyses revealed no significant differences in verbal vs. abstract WM. Moreover, no laterality effects were demonstrated in both verbal and abstract WM. These results provide further evidence of a broader cognitive involvement of the cerebellum in WM that is not only confined to the phonological loop but also supports central executive subfunctions. The fact that no lateralization effects are found might be attributed to the characteristics of the n-back paradigm which emphasizes central executive subfunctions over the subsidiary slave systems.

In this fMRI-study, 6-year-old children considered at risk for dyslexia were compared with an age-/gender-matched control group for differences in brain activation when presented with visual stimuli differing in demands for literacy processing. Stimuli were nameable pictures, brand logos familiar to children, and written words - these were either regularly spelled using early-acquired rules ("alphabetic") or more complex ("orthographic"). Brain responses distinguished between the presentation conditions, as a function of group, within many cortical areas. Activation in the alphabetic and orthographic conditions in the left angular gyrus correlated with individual at-risk index scores, and activation in inferior occipito-temporal regions further indicated differential activation for the two groups related to orthographic processing, especially. Since similar patterns are reported in adult dyslexics when processing written words, it appears that sensitivity to the cortical differentiation of reading networks is established prior to formal literacy training.

The aim of the present fMRI study was to localize brain areas that were uniquely activated for phonological versus spatial working memory. Previous studies have reported inconsistent results, most likely because of methodological heterogeneity varying both stimuli and instructions in the same study. Here, identical consonant-vowel-consonant non-words were visually presented to the subjects in a 2-back paradigm under two different instructions; the subjects either had to memorize the non-words per se or their location. The results give evidence for a hemispheric organization of working memory, with dominance for processing of phonological information in the left hemisphere and frontal cortex, and spatial information in the right hemisphere and parietal cortex. The results also reflect a certain overlap between the neuronal network for working memory and processing of verbal and spatial material. These findings are discussed with regard to processing specificity and the extent that activated areas also may reflect perceptual processes.

The aim of this study was to use BOLD fMRI to evaluate the effect of alcohol intoxication on neuronal activation, when controlling for expectancy. Behavioural studies have shown that both alcohol intoxication and expectancy affect cognition, mood and behaviour. However, previous neuroimaging studies have not separated the effects of alcohol intoxication from the possible confounding effects of expectancy. Forty-five healthy male participants participated in the study. A balanced placebo design with four groups was used together with a working memory paradigm. Half of the participants consumed a soft-drink before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed an alcoholic beverage), and the other half consumed an alcoholic beverage before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed a soft-drink). A blood alcohol concentration (BAC) of 0.08% was used as the alcohol intoxication level. The most conspicuous result was that alcohol intoxication decreased neuronal activation especially in the dorsal anterior cingulate cortex (dACC) and in prefrontal areas, while expectancy increased neuronal activation in the same areas. This study shows that alcohol intoxication and expectancy have opposite effects on neuronal activation. The present results could have implications for pharmacological imaging studies.

Dichotic listening (DL) is one of the most frequently used paradigms to study hemispheric asymmetry and has been employed in several neuroimaging studies. The classic behavioral DL paradigm requires the subject to give a verbal response on each trial, which may cause image artifacts due to head movements when applied to an imaging environment. In order to avoid such artifacts most studies have used modified versions of the classic DL paradigm, where no verbal response is required. The purpose of the present study was to test a new DL paradigm, specifically developed for the fMRI environment, which is based on collecting verbal responses and thus being as close as possible to the classic DL behavioral task. By employing a sparse-sampling EPI acquisition schema we attempted to limit the negative impact of overt speech on image quality. A 5-s 'silent gap' allowed for stimulus presentation and collection of a verbal response to occur between subsequent image acquisitions and served as a high-pass filter that was optimized to detect activations of interest. Hence, the contribution of response-related activations to the measured signal was reduced. Twelve healthy volunteers (six males and six females) participated in the study. In order to obtain a measure of reliability, all participants went through the classic DL paradigm three times. The results, based on the estimation of the intraclass correlation coefficient, functional probability maps as well as on laterality maps, showed consistent activation in the right and left superior temporal gyrus, left middle temporal gyrus, and right inferior temporal gyrus, thus replicating previous results with visual display and motor response DL paradigms. It is concluded that an fMRI DL paradigm based on overt verbal responses is feasible and could have general implications for future fMRI studies of speech perception and product in general.

Concurrent event-related EEG-fMRI recordings pick up volume-conducted and hemodynamically convoluted signals from latent neural sources that are spatially and temporally mixed across the brain, i.e. the observed data in both modalities represent multiple, simultaneously active, regionally overlapping neuronal mass responses. This mixing process decreases the sensitivity of voxel-by-voxel prediction of hemodynamic activation by the EEG when multiple sources contribute to either the predictor and/or the response variables. In order to address this problem, we used independent component analysis (ICA) to recover maps from the fMRI and timecourses from the EEG, and matched these components across the modalities by correlating their trial-to-trial modulation. The analysis was implemented as a group-level ICA that extracts a single set of components from the data and directly allows for population inferences about consistently expressed function-relevant spatiotemporal responses. We illustrate the utility of this method by extracting a previously undetected but relevant EEG-fMRI component from a concurrent auditory target detection experiment.

The fractal dimension (FD) was used to reveal brain structure irregularities in patients with schizophrenia. FD provides a unique way of quantifying the shape complexity of cortical folding of the human brain. MR images were obtained from seven patients with schizophrenia that were compared with six healthy control subjects. The MR images were first segmented, and the FD was calculated for the grey/white matter boundary for the whole brain and the hemispheres separately, using the box-counting and Minkowski-Bouligand methods. The results showed that the patients had larger FD values than the controls, for the whole brain volume and right hemisphere.

Exploratory data analysis techniques such as independent component analysis (ICA) do not depend on a priori hypotheses and are able to detect unknown, yet structured spatiotemporal processes in neuroimaging data. We present fMRI data of two different subject-groups (young and old), which performed a modified Wisconsin Card Sorting Test (WCST). Spatiotemporal ICA and SPM-generated brain maps of the subject data are compared. For the group analysis a singular value decomposition approach was used. Spatiotemporal ICA reveals a frontoparietal network being activated while subjects performed different variants of the WCST. Contrary to the SPM analysis, ICA analysis revealed significant differences between young and old subjects as well as significant within-group differences.While young subjects showed with increasing task demands (A>>B>>C) increasing activation of the right lateral prefrontal cortex and of the medial orbito-frontal cortex, old subjects showed no such gradient in activation pattern and appeared to be more distributed.

Background: The sporadic adult onset ataxias of unknown etiology (SAOA) denote the non-hereditary degenerative adult onset ataxias that are distinct from multiple system atrophy (MSA)., Objective: To define and characterize the clinical phenotype of sporadic adult onset ataxia of unknown etiology (SAOA)., Design: A survey of clinical features, nerve conduction and evoked potentials, autonomic tests, and magnetic resonance imaging (MRI)-based brain morphometry was conducted in patients with SAOA., Patients: Study subjects were a consecutive sample of 27 patients (11 male, 16 female) who met the diagnostic criteria for SAOA (age 55 +/- 13 years; age at disease onset 47 +/- 14 years; disease duration 8 +/- 7 years)., Results: All patients presented with a cerebellar syndrome. The most frequent extracerebellar symptoms were decreased vibration sense in 70% and decreased or absent ankle reflexes in 33% of the patients. Nerve conduction studies revealed a polyneuropathy in 26% of the patients. Somatosensory evoked potentials were abnormal in 44%, and central motor conduction time in 17% of patients. Autonomic testing revealed an affected autonomic nervous system in 58% of patients. Voxel-based brain morphometry showed a predominant reduction of gray matter in the cerebellum which was significantly correlated with disease stages. A loss of white matter was found in both middle cerebellar peduncles and the outer edge of the pons., Conclusions: The data show that SAOA is a predominantly, but not exclusively cerebellar disorder. Clinical, electrophysiological, and imaging findings showed some similarities with multiple system atrophy which raises the question of an overlap of these two disorders.

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.

The specific role of particular cerebral regions with regard to executive functions remains elusive. We conducted a functional magnetic resonance imaging (fMRI) study to segregate different network components underlying the Wisconsin Card Sorting Test (WCST), a test widely applied clinically to assess executive abilities. Three different test variants of the WCST, differing in task complexity (A > B > C), were contrasted with a high-level baseline condition (HLB). Cognitive subcomponents were extracted in a serial subtraction approach (A-C, A-B, B-C). Imaging data were further subjected to a correlational analysis with individual behavioral parameters. Contrasting A with the HLB revealed the entire neural network underlying WCST performance, including frontoparietal regions and the striatum. Further analysis showed that, within this network, right ventrolateral prefrontal cortex related to simple working memory operations, while right dorsolateral prefrontal cortex related to more complex/manipulative working memory operations. The rostral anterior cingulate cortex (ACC) and the temporoparietal junction bilaterally represented an attentional network for error detection. In contrast, activation of the caudal ACC and the right dorsolateral prefrontal cortex was associated with increased attentional control in the context of increasing demands of working memory and cognitive control. Non-frontal activations were found to be related to (uninstructed relative to instructed) set-shifting (cerebellum) and working memory representations (superior parietal cortex, retrosplenium). The data provide neural correlates for the different cognitive components involved in the WCST. They support a central role of the right dorsolateral prefrontal cortex in executive working memory operations and cognitive control functions but also suggest a functional dissociation of the rostral and caudal ACC in the implementation of attentional control.

Previous neuroimaging studies have consistently reported bilateral activation to speech stimuli in the superior temporal gyrus (STG) and have identified an anteroventral stream of speech processing along the superior temporal sulcus (STS). However, little attention has been devoted to the possible confound of individual differences in hemispheric dominance for speech. The present study was designed to test for speech-selective activation while controlling for inter-individual variance in auditory laterality, by using only subjects with at least 10% right ear advantage (REA) on the dichotic listening test. Eighteen right-handed, healthy male volunteers (median age 26) participated in the study. The stimuli were words, syllables, and sine wave tones (220-2600 Hz), presented in a block design. Comparing words > tones and syllables > tones yielded activation in the left posterior MTG and the lateral STG (upper bank of STS). In the right temporal lobe, the activation was located in the MTG/STS (lower bank). Comparing left and right temporal lobe cluster sizes from the words > tones and syllables > tones contrasts on single-subject level demonstrated a statistically significant left lateralization for speech sound processing in the STS/MTG area. The asymmetry analyses suggest that dichotic listening may be a suitable method for selecting a homogenous group of subjects with respect to left hemisphere language dominance.

Voxel-based relaxometry (VBR) is a novel morphometric method that analyses the relaxation rate R2 derived from multi-echo T2-weighted images on a voxel-by-voxel basis. We used VBR to study the brain morphology of 14 patients suffering from multiple-system atrophy of cerebellar type (MSA-C) and compared the results with those obtained by voxel-based morphometry (VBM) of T1-weighted images. VBR analysis revealed reduction of relaxation rate R2 in the cerebellum and brainstem reflecting infratentorial brain atrophy. The affected regions largely corresponded to those regions in which VBM showed reductions of grey and white matter. In addition, R2 was increased in the putamen, a region in which VBM did not show abnormalities. Our data show that the combination of VBR and VBM provided convergent and complimentary information about the brain morphology of MSA-C.

The present study used functional and structural MRI to investigate differences in neuronal substrates underlying shifts of attention in young and old subjects, studied with dichotic listening. Two different consonant-vowel syllables were presented and the subjects were instructed to attend to and report from either the left or right ear stimulus. Typically, a right-ear advantage is observed when attending to the right-ear stimulus, and a left-ear advantage when attending to the left-ear stimulus. The behavioral results showed that the old group had difficulties with attentional modulation of the right-ear advantage in the attend left condition. This is interpreted as a failure of an important aspect of attentional control; the top-down biasing of attention for selection of task-relevant stimulus. The fMRI results showed that an area in the left middle frontal gyrus was more activated in the young group compared to the old group in the attend left condition. The structural MRI data showed reduced gray matter density of the same area in the old group. Based on these converging findings, we suggest that the left middle frontal gyrus plays an important role in top-down biasing of selecting task-relevant stimuli, and to inhibit processing of task-irrelevant stimuli. To our knowledge, this is one of the first studies addressing the question on how age-related changes in attentional processing is reflected in both functional and structural differences in the brain.

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia. We had the possibility, using the same fMRI paradigm, to study seven cases with left middle cerebral artery (MCA) infarction and partial recovery of comprehension > or =6 months after presentation with global aphasia on acute assessment. Lateralization of activation did not differ significantly between patients and controls. The most consistent regions of activation included the left extrasylvian posterior temporal and the right posterior parietal cortex. Recovery of language comprehension was associated predominantly with activations in regions, which were also activated in several normal subjects. We suggest that a redundancy recovery mechanism within multiple representations of closely related functions was more important than take-over of function by previously unrelated areas (vicariation) as the basis of recovery of word comprehension in our patients in spite of extensive left hemispheric damage. We conclude that redundancy within the lexical-semantic system seems to make an important contribution to recovery of comprehension even in severe aphasia.

In patients with alertness deficits due to right hemispheric vascular brain damage, training induced changes in the individual functional networks involved in intrinsic alertness were assessed in a longitudinal positron emission tomography (PET)/fMRI activation study. Patients were trained by administering the alertness routine of the AIXTENT computerized attention training or, in the control condition, by using a computerized training of verbal and topological memory. Before and after the training, both a PET/fMRI and a neuropsychological assessment were carried out. In this paper, we are presenting four patients after alertness training: three, whose alertness performance improved significantly after training, and one, who did not improve. In the patients showing behavioural improvement, the PET/fMRI activation after training revealed partial restitution of the right hemisphere (RH) functional network known to subserve intrinsic alertness in normal subjects, especially in the right dorsolateral or medial frontal cortex. For the patient without behavioural improvement, the PET activation after training showed an increase of activation only in the left hemisphere. Out of the four patients in the memory training control group only one showed significant improvement of alertness. Another patient had an increase of right frontal activation after the training but this did not correspond to behavioural improvement. In a control group of six normal participants, repetition of the alertness activation paradigm in fMRI revealed a decrease of right frontal and parietal activation from the first to a second measurement after 3 weeks, in contrast to the observed training induced effects in the patients.

Purpose: To investigate the reliability of functional magnetic resonance imaging (fMRI), an approach for mapping and quantifying reliably activated voxels was developed., Materials and Methods: First, a SPM99 analysis was performed, and the resulting statistical maps were taken as the basis for subsequent analyses of reliability. Several approaches were demonstrated using 1). a voxel-wise intraclass correlation coefficient (ICC); 2). an analysis of scatter plots, calculating the correlation of contrast t-values for pairs of activation maps; and 3). the ratio of overlapping volumes as suggested in the literature. The methods were applied to an fMRI study in which subjects were asked to vary their attentional effort during watching a flickering checkerboard pattern with varying letters in the center. The subjects had to ignore or attend to the presentation, or they had to detect a target letter within the checkerboard., Results: The imaging data showed good reliability in terms of ICC for regions of visual processing, as well as for frontal areas, especially in the letter detection task. Furthermore, the size of reliable clusters depended on the presumed attentional effort of the subjects., Conclusion: Application of the method demonstrated that the activation due to visual stimulation could also be detected very consistently during a no-attend condition, but the reliability of the activations were best during the attended tasks., (Copyright 2003 Wiley-Liss, Inc.)

Background: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored., Objective: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery., Methods: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values)., Results: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%., Conclusion: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

In a previous functional magnetic resonance imaging (fMRI) study with normal subjects, we demonstrated regions related to conceptual-semantic word processing around the first frontal sulcus (BA 9) and the posterior parietal lobe (BA 7/40) in agreement with several previous reports. We had the possibility, using the same fMRI paradigm, to study two consecutive cases with left middle cerebral artery (MCA) infarction (RC and HP) and lesions affecting either solely the pre-frontal (HP) or both the pre-frontal and posterior parietal part of the network activated in normal subjects (RC). Both patients showed transcortical sensory aphasia (TSA) on acute assessment. This contradicts classical disconnection accounts of the syndrome stating intact conceptual representations in TSA. Their recovery of language comprehension was associated with activation of a left hemispheric network. Mainly activations of left perilesional pre-frontal regions (RC), left Wernicke's area (RC and HP) or the left posterior middle and inferior temporal cortex (HP) were demonstrated in the TSA patients. The latter findings suggest that in our cases of TSA functional take-over has occurred in regions with related functions ('redundancy recovery') rather than in previously unrelated areas ('vicarious functioning'). Our data support distributed models of conceptual-semantic word processing and multiple left hemispheric representations of closely related functions.

This study examined the neural areas involved in the recognition of both emotional prosody and phonemic components of words expressed in spoken language using echo-planar, functional magnetic resonance imaging (fMRI). Ten right-handed males were asked to discriminate words based on either expressed emotional tone (angry, happy, sad, or neutral) or phonemic characteristics, specifically, initial consonant sound (bower, dower, power, or tower). Significant bilateral activity was observed in the detection of both emotional and verbal aspects of language when compared to baseline activity. We found that the detection of emotion compared with verbal detection resulted in significant activity in the right inferior frontal lobe. Conversely, the detection of verbal stimuli compared with the detection of emotion activated left inferior frontal lobe regions most significantly. Specific analysis of the anterior auditory cortex revealed increased right hemisphere activity during the detection of emotion compared to activity during verbal detection. These findings illustrate bilateral involvement in the detection of emotion in language while concomitantly showing significantly lateralized activity in both emotional and verbal detection, in both the temporal and frontal lobes.

Whole-head functional MR images were acquired while 10 subjects were asked to tap with their right index finger in synchrony with a visual stimulus appearing regularly with a frequency of 1.5 Hz, or irregularly with a mean frequency of 1.5 Hz. Performance data show that during regular tapping most taps were close to stimulus onset. However, when the subjects paced their tapping according to the irregular stimuli, most taps appeared about 300 ms after the onset of the pacing stimuli. Comparing the brain activations resulting from regular tapping with those from irregular tapping, we found increased activation in left precuneus only. Comparing irregular versus regular tapping shows increased activity in right cerebellar nuclei and vermis, left ventrolateral thalamus, left sensorimotor cortex, left and right pre-SMA and left SMA proper. These results show that during irregular pacing the motor areas are more strongly activated than during regular pacing. In addition, further neural systems are involved in the motor control during irregular pacing: cerebellar vermis and a cerebello-thalamo-cortical system. The latter is supposedly involved in error correction in the context of visually guided movements.

We studied the effects of different speeds of unimanual and bimanual movements on functional magnetic resonance signal changes in the cerebellum. Six healthy consistently right-handed subjects were scanned at rest and while executing a sequential finger-to-thumb-opposition task either unimanually (left or right hand) or bimanually. Movement frequency was paced by an auditory signal at rates of either 1 or 3 Hz. Significant frequency-dependent blood oxygen level-dependent signal increases were demonstrated ipsilaterally and contralaterally in the intermediate and lateral portions of the anterior cerebellum for bimanual movements and for unimanual movements with the subdominant hand. There was only a weak frequency-dependent effect for unimanual movements performed with the dominant hand. In addition, signals were stronger on the right intermediate zone of the anterior cerebellum for movements involving the right (dominant) hand while there was stronger activity on the left cerebellar hemisphere for movements involving the left (subdominant) hand. Taken together, these results suggest that rate and movement task effects on cerebellar activation are differentially sensitive to subdominant and dominant hand movements., (Copyright 1999 Academic Press.)

Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition. [ABSTRACT FROM AUTHOR]

Abstract: Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann''s areas 17 and 18 brought into stereotaxic space—where and how variable? NeuroImage 11, 66–84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure κ was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. κ = 1 means the hypothesis is fully true, κ = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, κ was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas. [Copyright &y& Elsevier]