Publications by authors named "Peter Mannfolk"

20 Publications

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

Acta Oncol 2021 Oct 12:1-8. Epub 2021 Oct 12.

Department of Oncology, Skåne University Hospital, Lund, Sweden.

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.
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http://dx.doi.org/10.1080/0284186X.2021.1987514DOI Listing
October 2021

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

Endocrine 2021 Jul 22. Epub 2021 Jul 22.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

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.
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http://dx.doi.org/10.1007/s12020-021-02824-9DOI Listing
July 2021

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

J Comp Neurol 2019 08 19;527(11):1837-1856. Epub 2019 Feb 19.

Division of Clinical Radiology, Department of Clinical Sciences, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1002/cne.24656DOI Listing
August 2019

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

Brain Res 2018 10 5;1697:76-82. Epub 2018 Jun 5.

Department of Linguistics, Centre for Languages and Literature, Lund University, Box 201, 221 00 Lund, Sweden. Electronic address:

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.
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http://dx.doi.org/10.1016/j.brainres.2018.06.004DOI Listing
October 2018

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

Brain Connect 2018 05 5;8(4):220-234. Epub 2018 Apr 5.

7 Department of Clinical Sciences , Lund/Memory Research Unit, Lund University, Lund, Sweden .

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.
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http://dx.doi.org/10.1089/brain.2017.0557DOI Listing
May 2018

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

Arthritis Res Ther 2018 02 7;20(1):21. Epub 2018 Feb 7.

Department of Clinical Sciences Lund/Diagnostic Radiology, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1186/s13075-018-1516-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803933PMC
February 2018

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

Brain Lang 2017 11;174:119-126

Department of Linguistics, Centre for Languages and Literature, Lund University, Box 201, 221 00 Lund, Sweden. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bandl.2017.08.004DOI Listing
November 2017

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

Neurosci Lett 2017 Sep 18;658:57-61. Epub 2017 Aug 18.

Department of Linguistics and Phonetics, Lund University, Sweden.

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.
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http://dx.doi.org/10.1016/j.neulet.2017.08.030DOI Listing
September 2017

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

Open Neuroimag J 2017 31;11:1-16. Epub 2017 Mar 31.

Department of Neurology and Clinical Sciences, Lund University Hospital, SE-221 85 Lund, Sweden.

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.
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http://dx.doi.org/10.2174/1874440001711010001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420180PMC
March 2017

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

Psychoneuroendocrinology 2016 11 1;73:157-165. Epub 2016 Aug 1.

Department of Diagnostic Radiology, Skåne University Hospital and Clinical Sciences, Lund University, Sweden; Lund University Bioimaging Centre (LBIC), Lund University, Sweden.

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 536cm, p<0.001) and grey matter (GM) volumes (525 vs 555cm, 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.
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http://dx.doi.org/10.1016/j.psyneuen.2016.07.222DOI Listing
November 2016

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

PLoS One 2016 29;11(1):e0147575. Epub 2016 Jan 29.

Department of Endocrinology, Skåne University hospital and IKVL, Lund University, Lund, Sweden.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732818PMC
July 2016

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

Brain Lang 2015 Nov 26;150:14-21. Epub 2015 Aug 26.

Department of Linguistics and Phonetics, Lund University, Sweden.

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.
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http://dx.doi.org/10.1016/j.bandl.2015.07.009DOI Listing
November 2015

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

J Brachial Plex Peripher Nerve Inj 2012 Oct 10;7(1). Epub 2012 Oct 10.

Departments of Hand Surgery, Lund University, Lund, Sweden.

Unlabelled:

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.
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http://dx.doi.org/10.1186/1749-7221-7-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3540024PMC
October 2012

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

J Magn Reson Imaging 2011 Sep 14;34(3):511-7. Epub 2011 Jul 14.

Department of Medical Radiation Physics, Clinical Sciences, Lund, Lund University, Sweden.

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.
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http://dx.doi.org/10.1002/jmri.22654DOI Listing
September 2011

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

Brain Imaging Behav 2011 Mar;5(1):1-11

Department of Neurology, Dept of Clinical Sciences, Lund University Hospital, 221 85, Lund, Sweden.

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.
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http://dx.doi.org/10.1007/s11682-010-9106-zDOI Listing
March 2011

Assessment of spatial BOLD sensitivity variations in fMRI using gradient-echo field maps.

Magn Reson Imaging 2010 Sep 22;28(7):947-56. Epub 2010 Jun 22.

Department of Medical Radiation Physics, Clinical Sciences Lund, Lund University, Barngatan 2B, Lund, Sweden.

Clinical blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is becoming increasingly valuable in, e.g., presurgical planning, but the commonly used gradient-echo echo-planar imaging (GE-EPI) technique is sometimes hampered by macroscopic field inhomogeneities. This can affect the degree of signal change that will occur in the GE-EPI images as a response to neural activation and the subsequent blood oxygenation changes, i.e., the BOLD sensitivity (BS). In this study, quantitative BS maps were calculated directly from gradient-echo field maps obtainable on most clinical scanners. In order to validate the accuracy of the calculated BS-maps, known shim gradients were applied and field maps and GE-EPI images of a phantom were acquired. Measured GE-EPI image intensity was then compared with the calculated (predicted) image intensity (pII) which was obtained from the field maps using theoretical expressions for image-intensity loss. The validated expressions for pII were used to calculate the corresponding predicted BOLD sensitivity (pBS) maps in healthy volunteers. Since the field map is assumed to be valid throughout an entire fMRI experiment, the influence of subject motion on the pBS maps was also assessed. To demonstrate the usefulness of such maps, pBS was investigated for clinically important functional areas including hippocampus, Broca's area and primary motor cortex. A systematic left/right pBS difference was observed in Broca's area and in the hippocampus, most likely due to magnetic field inhomogeneity of the particular MRI-system used in this study. For all subjects, the hippocampus showed pBS values above unity with a clear anterior-posterior gradient and with an abrupt drop to zero pBS in the anterior parts of hippocampus. It is concluded that GE field maps can be used to accurately predict BOLD sensitivity and that this parameter is useful to assess spatial variations which will influence fMRI experiments.
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http://dx.doi.org/10.1016/j.mri.2010.05.003DOI Listing
September 2010

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

MAGMA 2010 Dec 13;23(5-6):327-38. Epub 2010 Mar 13.

Department of Medical Radiation Physics, Clinical Sciences, Lund University, Barngatan 2B, 22185, Lund, Sweden.

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.
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http://dx.doi.org/10.1007/s10334-010-0204-0DOI Listing
December 2010

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

Magn Reson Imaging 2008 Feb 28;26(2):279-86. Epub 2007 Aug 28.

MR Department, Center for Medical Imaging and Physiology, Lund University Hospital, SE-221 85 Lund, Sweden.

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.
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http://dx.doi.org/10.1016/j.mri.2007.06.010DOI Listing
February 2008

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

Magn Reson Imaging 2007 Feb 28;25(2):188-96. Epub 2006 Nov 28.

Department of Diagnostic Radiology, Lund University, Lund, Sweden.

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.
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http://dx.doi.org/10.1016/j.mri.2006.09.044DOI Listing
February 2007

fMRI activity in the medial temporal lobe during famous face processing.

Neuroimage 2006 Apr 4;30(2):609-16. Epub 2005 Nov 4.

Division of Psychogeriatrics, Dept. of Clinical Sciences, Lund, Lund University Hospital, SE-221 85 Lund, Sweden.

The current event-related fMRI study examined the relative involvement of different parts of the medial temporal lobe (MTL), particularly the contribution of hippocampus and perirhinal cortex, in either intentional or incidental recognition of famous faces in contrast to unfamiliar faces. Our intention was to further explore the controversial contribution of MTL in the processing of semantic memory tasks. Subjects viewed a sequence of famous and unfamiliar faces. Two tasks were used encouraging attention to either fame or gender. In the fame task, the subjects were requested to identify the person when seeing his/her face and also to try to generate the name of this person. In the gender task, the subjects were asked to conduct a judgement of a person's gender when seeing his/her face. The visual processing was hence directed to gender and thereby expected to diminish attention to semantic information leading only to a "passive" registration of famous and non-familiar faces. Recognition of famous faces, in both contrasts, produced significant activations in the MTL. First, during the intentional recognition (the person identification task) increased activity was observed in the anterolateral part of left hippocampus, in proximity to amygdala. Second, during the incidental recognition of famous faces (the gender classification task), there was increased activity in the left posterior MTL with focus in the perirhinal cortex. Our results suggest that the hippocampus may be centrally involved in the intentional retrieval of semantic memories while the perirhinal cortex is associated with the incidental recognition of semantic information.
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http://dx.doi.org/10.1016/j.neuroimage.2005.09.060DOI Listing
April 2006
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