Cognitive interference processing in adult survivors of childhood acute lymphoblastic leukemia using functional magnetic resonance imaging.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group. MATERIAL: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years). METHODS: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT). RESULTS: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain. CONCLUSION: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.

Altered empathy processing in frontotemporal dementia A task-based fMRI study.

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the controls activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The controls rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informants ratings of the patients empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient's self-ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patients capacity to experience affective empathy.

Tract-based white matter hyperintensity patterns in patients with systemic lupus erythematosus using an unsupervised machine learning approach.

Currently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A total of 221 SLE patients with and without neuropsychiatric symptoms from two different sites were included in this study. WMH segmentations and lesion locations were acquired automatically. Cluster analysis was performed on the WMH distribution in 20 WM tracts. Our pipeline identified five distinct clusters with predominant involvement of the forceps major, forceps minor, as well as right and left anterior thalamic radiations and the right inferior fronto-occipital fasciculus. The patterns of the affected WM tracts were consistent over the SLE subtypes and sites. Our approach revealed distinct and robust tract-based WMH patterns within SLE patients. This method could provide a basis, to link the location of WMH with clinical symptoms. Furthermore, it could be used for other diseases characterized by presence of WMH to investigate both the clinical relevance of WMH and underlying pathomechanism in the brain.

Can resting-state functional MRI serve as a complement to task-based mapping of sensorimotor function? A test-retest reliability study in healthy volunteers.

PURPOSE: To investigate if resting-state functional MRI (fMRI) reliably can serve as a complement to task-based fMRI for presurgical mapping of the sensorimotor cortex. MATERIALS AND METHODS: Functional data were obtained in 10 healthy volunteers using a 3 Tesla MRI system. Each subject performed five bilateral finger tapping experiments interleaved with five resting-state experiments. Following preprocessing, data from eight volunteers were further analyzed with the general linear model (finger tapping data) and independent component analysis (rest data). Test-retest reliability estimates (hit rate and false alarm rate) for resting-state fMRI activation of the sensorimotor network were compared with the reliability estimates for task-evoked activation of the sensorimotor cortex. The reliability estimates constituted a receiver operating characteristics curve from which the area under the curve (AUC) was calculated. Statistical testing was performed to compare the two groups with respect to reliability. RESULTS: The AUC was generally higher for the task experiments, although median AUC was not significantly different on a group level. Also, the two groups showed comparable levels of within-group variance. CONCLUSION: Test-retest reliability was comparable between resting-state measurements and task-based fMRI, suggesting that presurgical mapping of functional networks can be a supplement to task-based fMRI in cases where patient status excludes task-based fMRI.

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging.

PURPOSE: To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT). METHODS: Twenty-eight CP patients (median age 34.5 [29.0-39.5] years) were investigated at median 20.5 (16.3-28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5-42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded. RESULTS: The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3-367.1] ms and 3.1 [1.6-5.6]%, respectively) and controls (309.1 [276.4-361.0] ms and 2.6 [1.6-4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6-353.4] ms and 4.2 [2.3-5.7]%, respectively) and without hypothalamic injury (355.7 [293.7-388.7] ms and 2.1 [1.0-5.2]%, respectively), respectively, and controls. CONCLUSION: Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.

Dimensionality reduction of fMRI time series data using locally linear embedding.

OBJECTIVE: Data-driven methods for fMRI analysis are useful, for example, when an a priori model of signal variations is unavailable. However, activation sources are typically assumed to be linearly mixed, although non-linear properties of fMRI data, including resting-state data, have been observed. In this work, the non-linear locally linear embedding (LLE) algorithm is introduced for dimensionality reduction of fMRI time series data. MATERIALS AND METHODS: LLE performance was optimised and tested using simulated and volunteer data for task-evoked responses. LLE was compared with principal component analysis (PCA) as a preprocessing step to independent component analysis (ICA). Using an example data set with known non-linear properties, LLE-ICA was compared with PCA-ICA and non-linear PCA-ICA. A resting-state data set was analysed to compare LLE-ICA and PCA-ICA with respect to identifying resting-state networks. RESULTS: LLE consistently found task-related components as well as known resting-state networks, and the algorithm compared well to PCA. The non-linear example data set demonstrated that LLE, unlike PCA, can separate non-linearly modulated sources in a low-dimensional subspace. Given the same target dimensionality, LLE also performed better than non-linear PCA. CONCLUSION: LLE is promising for fMRI data analysis and has potential advantages compared with PCA in terms of its ability to find non-linear relationships.

Functional connectivity changes in core resting state networks are associated with cognitive performance in systemic lupus erythematosus.

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state-fMRI (rs-fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2-52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3-52.2 years) in conjunction with clinical examination and cognitive testing. Alterations in core resting state networks, not found in our healthy controls sample, correlated with cognitive performance gauged by neuropsychological tests in non-neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (NP). The observed pattern of increased functional connectivity in core resting state networks correlated with reduced cognitive performance on all cognitive domains tested and with a heavy focus on DM, CE, and DM-CE in the NP subgroup. Furthermore, we found that the observed alterations in memory and psychomotor speed correlated with disease duration. In SLE patients both with and without clinically overt neuropsychiatric manifestations, we found changes in the functional connectivity of core resting state networks essential to cognitive functions. These findings may represent a rewiring of functional architecture in response to neuronal damage and could indicate suboptimal compensatory mechanisms at play.

A two-compartment gel phantom for optimization and quality assurance in clinical BOLD fMRI.

Clinical applications of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) depend heavily on robust paradigms, imaging methods and analysis procedures. In this work, as a means to optimize and perform quality assurance of the entire imaging and analysis chain, a phantom that provides a well known and reproducible signal change similar to a block type fMRI experiment is presented. It consists of two gel compartments with slightly different T2 that dynamically enter and leave the imaged volume. The homogeneous gel in combination with a cylindrical geometry results in a well-defined T*2 difference causing a signal difference between the two compartments in T*2-weighted MR images. From time series data obtained with the phantom, maps of percent signal change (PSC) and t-values are calculated. As an example of image parameter optimisation, the phantom is demonstrated to be useful for accurate determination of the influence of echo time (TE) on BOLD fMRI results, taking the t-value as a measure of sensitivity. In addition, the phantom is proposed as a tool for quality assurance (QA) since reproducible time series and t-maps are obtained in a series of independent repeat experiments. The phantom is relatively simple to build and can therefore be used by any clinical fMRI center.

Rapid syntactic pre-activation in Broca's area: Concurrent electrophysiological and haemodynamic recordings.

Listeners are constantly trying to predict what the speaker will say next. We concurrently measured the electrophysiological and haemodynamic correlates of syntactic pre-activation, investigating when and where the brain processes speech melody cues to upcoming word order structure. Pre-activation of syntactic structure was reflected in a left-lateralised pre-activation negativity (PrAN), which was subserved by Broca's area in the left inferior frontal gyrus, as well as the contiguous left anterior insula.

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Altered white matter microstructure in lupus patients: a diffusion tensor imaging study.

BACKGROUND: The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms. METHODS: Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2-52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3-51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE). RESULTS: Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p < 0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report. CONCLUSIONS: We found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.

Flexible statistical modelling detects clinical functional magnetic resonance imaging activation in partially compliant subjects.

Clinical functional magnetic resonance imaging (fMRI) occasionally fails to detect significant activation, often due to variability in task performance. The present study seeks to test whether a more flexible statistical analysis can better detect activation, by accounting for variance associated with variable compliance to the task over time. Experimental results and simulated data both confirm that even at 80% compliance to the task, such a flexible model outperforms standard statistical analysis when assessed using the extent of activation (experimental data), goodness of fit (experimental data), and area under the operator characteristic curve (simulated data). Furthermore, retrospective examination of 14 clinical fMRI examinations reveals that in patients where the standard statistical approach yields activation, there is a measurable gain in model performance in adopting the flexible statistical model, with little or no penalty in lost sensitivity. This indicates that a flexible model should be considered, particularly for clinical patients who may have difficulty complying fully with the study task.

Forehearing words: Pre-activation of word endings at word onset.

Occurring at rates up to 6-7 syllables per second, speech perception and understanding involves rapid identification of speech sounds and pre-activation of morphemes and words. Using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the time-course and neural sources of pre-activation of word endings as participants heard the beginning of unfolding words. ERPs showed a pre-activation negativity (PrAN) for word beginnings (first two segmental phonemes) with few possible completions. PrAN increased gradually as the number of possible completions of word onsets decreased and the lexical frequency of the completions increased. The early brain potential effect for few possible word completions was associated with a blood-oxygen-level-dependent (BOLD) contrast increase in Broca's area (pars opercularis of the left inferior frontal gyrus) and angular gyrus of the left parietal lobe. We suggest early involvement of the left prefrontal cortex in inhibiting irrelevant left parietal activation during lexical selection. The results further our understanding of the importance of Broca's area in rapid online pre-activation of words.

Tone-grammar association within words: Concurrent ERP and fMRI show rapid neural pre-activation and involvement of left inferior frontal gyrus in pseudoword processing.

Using a concurrent ERP/fMRI paradigm, we investigated how listeners take advantage of morphologically relevant tonal information at the beginning of words to predict and pre-activate likely word endings. More predictive, low tone word stems gave rise to a 'pre-activation negativity' (PrAN) in the ERPs, a brain potential which has previously been found to increase along with the degree of predictive certainty as regards how a word is going to end. It is suggested that more predictive, low tone stems lead to rapid access to word endings with processing subserved by the left primary auditory cortex as well as the supramarginal gyrus, while high tone stems - which are less predictive - decrease predictive certainty, leading to increased competition between activated word endings, which needs to be resolved by the left inferior frontal gyrus.

A Functional MRI-Based Model for Individual Memory Assessment in Patients Eligible for Anterior Temporal Lobe Resection.

TITLE: A functional (f) MRI-based model for individual memory assessment in patients eligible for temporal lobe resection. AIM: To investigate if pre-operative fMRI memory paradigms, add predictive information with regard to post-surgical memory deficits. METHODS: Fourteen pharmacoresistant Temporal Lobe Epilepsy (TLE) patients accepted for Anterior Temporal Lobe Resection (ATLR) were included. A clinical risk assessment score (RAS 0-3) was constructed from structural MRI, neuropsychological testing and hemisphere dominance. fMRI lateralization indices (LIs) over frontal language and medial temporal regions were calculated. Predictive value from clinical risk scoring and added value from fMRI LIs were correlated to post-surgical memory change scores (significant decline -1 SD). Verbal memory outcome was classified either as expected (RAS 2-3 and post-operative decline; RAS 0-1 and intact post-operative verbal memory) or as unexpected (RAS 2-3 and intact post-operative verbal memory post-surgery; RAS 0-1 and post-operative decline). RESULTS: RAS for verbal memory decline exhibited a specificity of 67% and a sensitivity of 75%. Significant correlations were found between frontal language LIs and post-operative verbal memory (r = -0.802; p = 0.017) for left (L) TLE and between medial temporal lobe LIs and visuospatial memory (r = 0.829; p = 0.021), as well as verbal memory (r = 0.714; p = 0.055) for right (R) TLE. Ten patients had expected outcome and four patients had an unexpected outcome. In two MRI-negative RTLE patients that suffered significant verbal memory decline post-operatively, fMRI identified bilateral language and right lateralized medial temporal verbal encoding. In two LTLE patients with MRI pathology and verbal memory dysfunction, neither RAS nor fMRI identified the risk for aggravated verbal memory decline following ATLR. CONCLUSION: fMRI visualization of temporal-frontal network activation may add value to the pre-surgical work-up in epilepsy patients eligible for ATLR. Frontal language patterns are important for prediction in both L and RTLE. Strong left lateralized language in LTLE, as well as bilateral language combined with right lateralized encoding in RTLE, seems to indicate an increased risk for post-operative verbal memory decline.

Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.

Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.

Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood.

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27-46) years. All were treated with a CRT dose of 24Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p<0.001), memory (p<0.001), learning capacity (p<0.001), spatial ability (p<0.001), executive functions and attention (p<0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536cm3, p<0.001) and grey matter (GM) volumes (525 vs 555cm3, p=0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p=0.004), WM NAA+NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p<0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p=0.001) and GM NAA+NAAG/Cr (1.28 vs 1.34, p=0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p=0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA+NAAG/Cr (r=-0.4, p=0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.

Word tones cueing morphosyntactic structure: Neuroanatomical substrates and activation time-course assessed by EEG and fMRI.

Previous studies distinguish between right hemisphere-dominant processing of prosodic/tonal information and left-hemispheric modulation of grammatical information as well as lexical tones. Swedish word accents offer a prime testing ground to better understand this division. Although similar to lexical tones, word accents are determined by words' morphosyntactic structure, which enables listeners to use the tone at the beginning of a word to predict its grammatical ending. We recorded electrophysiological and hemodynamic brain responses to words where stem tones matched or mismatched inflectional suffixes. Tones produced brain potential effects after 136 ms, correlating with subject variability in average BOLD in left primary auditory cortex, superior temporal gyrus, and inferior frontal gyrus. Invalidly cued suffixes activated the left inferior parietal lobe, arguably reflecting increased processing cost of their meaning. Thus, interaction of word accent tones with grammatical morphology yielded a rapid neural response correlating in subject variability with activations in predominantly left-hemispheric brain areas.

Reconstruction of sciatic nerve after traumatic injury in humans - factors influencing outcome as related to neurobiological knowledge from animal research.

BACKGROUND: The aim was to evaluate what can be learned from rat models when treating patients suffering from a sciatic nerve injury. METHODS: Two patients with traumatic sciatic nerve injury are presented with examination of motor and sensory function with a five-year follow-up. Reconstruction of the nerve injury was performed on the second and third day, respectively, after injury using sural nerve grafts taken from the injured leg. The patients were examined during follow-up by electromyography (EMG), MRI and functionalMRI (fMRI) to evaluate nerve reinnervation, cell death in dorsal root ganglia (DRG) and cortical activation; factors that were related to clinical history in the patients. RESULTS: One patient regained good motor function of the lower leg and foot, confirmed by EMG showing good activation in the leg muscles and some reinnervation in the foot muscles, as well as some sensory function of the sole of the foot. The other patient regained no motor (confirmed by EMG) or sensory function in the leg or foot. Factors most influential on outcome in two cases were type of injury, nerve gap length and particularly type of reconstruction. A difference in follow-up and rehabilitation likely also influence outcome. MRI did not show any differences in DRG size of injured side compared to the uninjured side. fMRI showed normal activation in the primary somatosensory cortex as a response to cutaneous stimulation of the normal foot. However, none of the two patients showed any activation in the primary somatosensory cortex following cutaneous stimulation of the injured foot. CONCLUSIONS: In decision making of nerve repair and reconstruction data from animal experiments can be translated to clinical practice and to predict outcome in patients, although such data should be interpreted with caution and linked to clinical experience. Rat models may be useful to identify and study factors that influence outcome after peripheral nerve repair and reconstruction; procedures that should be done correctly and with a competent team. However, some factors, such as cognitive capacity and coping, known to influence outcome following nerve repair, are difficult to study in animal models. Future research has to find and develop new paths and techniques to study changes in the central nervous system after nerve injury and develop strategies to utilize brain plasticity during the rehabilitation.

fMRI memory assessment in healthy subjects: a new approach to view lateralization data at an individual level.

We present a comprehensive and clinically applicable fMRI test-including both a verbal and a visuospatial task-for assessment of hemispheric specific memory in the medial temporal lobe (MTL). fMRI data was collected from 15 healthy right-handed volunteers. Whole-brain activation was analyzed as well as activation in two regions of interest: the MTL and the anterior speech area. Laterality indices (LI) and LI-curves were calculated using the LI toolbox of Wilke and Lidzba, 2007. The fMRI paradigms successfully visualized memory-related activity in the MTL, the verbal memory measure also provided information of language lateralization. Eleven subjects showed left lateralized verbal encoding in the MTL, visuospatial memory activation was divided equally between left and right, and 14/15 subjects had left lateralized language. Lateralization data at the group level were consistent with previous studies, but a variety of activation effects were found at the individual level indicating differences in strategy during verbal and visuospatial processing. Further studies using the presented method are needed to determine its clinical usefulness.