Functional network properties derived from wide-field calcium imaging differ with wakefulness and across cell type.

To improve 'bench-to-bedside' translation, it is integral that knowledge flows bidirectionally-from animal models to humans, and vice versa. This requires common analytical frameworks, as well as open software and data sharing practices. We share a new pipeline (and test dataset) for the preprocessing of wide-field optical fluorescence imaging data-an emerging mode applicable in animal models-as well as results from a functional connectivity and graph theory analysis inspired by recent work in the human neuroimaging field. The approach is demonstrated using a dataset comprised of two test-cases: (1) data from animals imaged during awake and anesthetized conditions with excitatory neurons labeled, and (2) data from awake animals with different genetically encoded fluorescent labels that target either excitatory neurons or inhibitory interneuron subtypes. Both seed-based connectivity and graph theory measures (global efficiency, transitivity, modularity, and characteristic path-length) are shown to be useful in quantifying differences between wakefulness states and cell populations. Wakefulness state and cell type show widespread effects on canonical network connectivity with variable frequency band dependence. Differences between excitatory neurons and inhibitory interneurons are observed, with somatostatin expressing inhibitory interneurons emerging as notably dissimilar from parvalbumin and vasoactive polypeptide expressing cells. In sum, we demonstrate that our pipeline can be used to examine brain state and cell-type differences in mesoscale imaging data, aiding translational neuroscience efforts. In line with open science practices, we freely release the pipeline and data to encourage other efforts in the community.

Food image-induced brain activation is not diminished by insulin infusion.

BACKGROUND/OBJECTIVES: The obesity epidemic appears to be driven in large part by our modern environment inundated by food cues, which may influence our desire to eat. Although insulin decreases food intake in both animals and humans, the effect of insulin on motivation for food in the presence of food cues is not known. Therefore, the aim of this study was to evaluate the effect of an intravenous insulin infusion on the brain response to visual food cues, hunger and food craving in non-obese human subjects. SUBJECTS/METHODS: Thirty-four right-handed healthy non-obese subjects (19F/15M, age: 29±8 years.; BMI: 23.1±2.1 kg m-2) were divided in two groups matched by age and BMI; the insulin group (18 subjects) underwent a hyperinsulinemic-euglycemic-clamp, and the control group (16 subjects) received an intravenous saline infusion, while viewing high and low-calorie food and non-food pictures during a functional MRI scan. Motivation for food was determined via analog scales for hunger, wanting and liking ratings. RESULTS: Food images induced brain responses in the hypothalamus, striatum, amygdala, insula, ventromedial prefrontal cortex (PFC), dorsolateral PFC and occipital lobe (whole brain correction, P<0.05). Wanting (P<0.001) and liking (P<0.001) ratings were significantly higher for the food than the non-food images, but not different between insulin and saline infusion groups. Hunger ratings increased throughout the MRI scan and correlated with preference for high-calorie food pictures (r=0.70; P<0.001). However, neither brain activity nor food cravings were affected by hyperinsulinemia or hormonal status (leptin and ghrelin levels) (P=NS). CONCLUSIONS: Our data demonstrate that visual food cues induce a strong response in motivation/reward and cognitive-executive control brain regions in non-obese subjects, but that these responses are not diminished by hyperinsulinemia per se. These findings suggest that our modern food cue saturated environment may be sufficient to overpower homeostatic hormonal signals, and thus contribute to the current obesity epidemic.

Application of BOLD Magnetic Resonance Imaging for Evaluating Regional Volumetric Foot Tissue Oxygenation: A Feasibility Study in Healthy Volunteers.

OBJECTIVE/BACKGROUND: To evaluate the feasibility and repeatability of applying blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the feet to quantify regional dynamic changes in tissue oxygenation during proximal cuff occlusion and reactive hyperemia. METHODS: Ten healthy male subjects underwent BOLD and T1-weighted imaging of the feet on two separate occasions, using a 3-T scanner. Dynamic changes in BOLD signal intensity were assessed before and during proximal cuff occlusion of the thigh and during reactive hyperemia, and BOLD time course data were evaluated for the time-to-half ischemic minimum, minimum ischemic value, peak hyperemic value, time-to-peak hyperemia, time-to-half peak hyperemia, and end value. T1-weighted images were used for segmentation of volumes of interest (VOI) in anatomical regions of the foot (heel, toes, dorsal foot, medial and lateral plantar foot). Repeatability of vascular responses was assessed for each foot VOI using semiautomated image registration and quantification of serial BOLD images. RESULTS: The heel VOI demonstrated a significantly higher peak hyperemic response, expressed as percent change from baseline BOLD signal intensity, compared with all other VOIs of the foot (heel, 7.4 ± 1.2%; toes, 5.6 ± 0.8%; dorsal foot, 5.7 ± 1.6%; medial plantar, 5.6 ± 1.7%; lateral plantar, 5.6 ± 1.5% [p < .05]). Additionally, the lateral plantar VOI had a significantly lower terminal signal intensity value (i.e., end value) when compared with all foot VOIs (p < .05). BOLD MRI was repeatable between visits in all foot VOIs, with no significant differences between study visits for any of the evaluated functional indices. CONCLUSION: BOLD MRI offers a repeatable technique for volumetric assessment of regional foot tissue oxygenation. Future application of BOLD imaging in the feet of patients with peripheral vascular disease may permit serial evaluation of regional tissue oxygenation and allow for improved assessment of therapeutic interventions targeting specific sites of the foot.

Groupwise whole-brain parcellation from resting-state fMRI data for network node identification.

In this paper, we present a groupwise graph-theory-based parcellation approach to define nodes for network analysis. The application of network-theory-based analysis to extend the utility of functional MRI has recently received increased attention. Such analyses require first and foremost a reasonable definition of a set of nodes as input to the network analysis. To date many applications have used existing atlases based on cytoarchitecture, task-based fMRI activations, or anatomic delineations. A potential pitfall in using such atlases is that the mean timecourse of a node may not represent any of the constituent timecourses if different functional areas are included within a single node. The proposed approach involves a groupwise optimization that ensures functional homogeneity within each subunit and that these definitions are consistent at the group level. Parcellation reproducibility of each subunit is computed across multiple groups of healthy volunteers and is demonstrated to be high. Issues related to the selection of appropriate number of nodes in the brain are considered. Within typical parameters of fMRI resolution, parcellation results are shown for a total of 100, 200, and 300 subunits. Such parcellations may ultimately serve as a functional atlas for fMRI and as such three atlases at the 100-, 200- and 300-parcellation levels derived from 79 healthy normal volunteers are made freely available online along with tools to interface this atlas with SPM, BioImage Suite and other analysis packages.

The intrinsic connectivity distribution: a novel contrast measure reflecting voxel level functional connectivity.

Resting-state fMRI (rs-fMRI) holds promise as a clinical tool to characterize and monitor the phenotype of different neurological and psychiatric disorders. The most common analysis approach requires the definition of one or more regions-of-interest (ROIs). However this need for a priori ROI information makes rs-fMRI inadequate to survey functional connectivity differences associated with a range of neurological disorders where the ROI information may not be available. A second problem encountered in fMRI measures of connectivity is the need for an arbitrary correlation threshold to determine whether or not two areas are connected. This is problematic because in many cases the differences in tissue connectivity between disease groups and/or control subjects are threshold dependent. In this work we propose a novel voxel-based contrast mechanism for rs-fMRI, the intrinsic connectivity distribution (ICD), that neither requires a priori information to define a ROI, nor an arbitrary threshold to define a connection. We show the sensitivity of previous methods to the choice of connection thresholds and evaluate ICD using a survey study comparing young adults born prematurely to healthy term control subjects. Functional connectivity differences were found in hypothesized language processing areas in the left temporal-parietal areas. In addition, significant clinically-relevant differences were found between preterm and term control subjects, highlighting the importance of whole brain surveys independent of a priori information.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Graph-theory based parcellation of functional subunits in the brain from resting-state fMRI data.

Resting-state fMRI provides a method to examine the functional network of the brain under spontaneous fluctuations. A number of studies have proposed using resting-state BOLD data to parcellate the brain into functional subunits. In this work, we present two state-of-the-art graph-based partitioning approaches, and investigate their application to the problem of brain network segmentation using resting-state fMRI. The two approaches, the normalized cut (Ncut) and the modularity detection algorithm, are also compared to the Gaussian mixture model (GMM) approach. We show that the Ncut approach performs consistently better than the modularity detection approach, and it also outperforms the GMM approach for in vivo fMRI data. Resting-state fMRI data were acquired from 43 healthy subjects, and the Ncut algorithm was used to parcellate several different cortical regions of interest. The group-wise delineation of the functional subunits based on resting-state fMRI was highly consistent with the parcellation results from two task-based fMRI studies (one with 18 subjects and the other with 20 subjects). The findings suggest that whole-brain parcellation of the cortex using resting-state fMRI is feasible, and that the Ncut algorithm provides the appropriate technique for this task.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures.

PURPOSE: Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3-4-Hz spike-wave discharges (SWDs) on electroencephalography (EEG). Prior EEG-functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated. METHODS: We performed EEG-fMRI with simultaneous behavioral testing in 37 children with typical childhood absence epilepsy (CAE). Attentional vigilance was evaluated by a continuous performance task (CPT), and simpler motor performance was evaluated by a repetitive tapping task (RTT). RESULTS: SWD episodes were obtained during fMRI scanning from 9 patients among the 37 studied. fMRI signal increases during SWDs were observed in the thalamus, frontal cortex, primary visual, auditory, somatosensory, and motor cortex, and fMRI decreases were seen in the lateral and medial parietal cortex, cingulate gyrus, and basal ganglia. Omission error rate (missed targets) with SWDs during fMRI was 81% on CPT and 39% on RTT. For those seizure epochs during which CPT performance was impaired, fMRI changes were seen in cortical and subcortical structures typically involved in SWDs, whereas minimal changes were observed for the few epochs during which performance was spared. DISCUSSION: These findings suggest that typical absence seizures involve a network of cortical-subcortical areas necessary for normal attention and primary information processing. Identification of this network may improve understanding of cognitive impairments in CAE, and may help guide development of new therapies for this disorder.

Error-specific medial cortical and subcortical activity during the stop signal task: a functional magnetic resonance imaging study.

The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs. Previous studies have provided evidence indicating the importance of the medial cortical brain regions including the cingulate cortex in processing conflicting information. However, conflicting situations can be successfully resolved, or lead to errors, prompting a behavioral change in the observers. In particular, how does the brain use error signals specifically to adjust behavior on the fly? Here we employ a stop signal task (SST) to elicit errors approximately half of the time in high-conflict trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we show greater and, sequentially, less activation in the medial cortical regions when observers made an error, compared with when they successfully resolved high-conflict responses. Errors also evoked greater activity in the cuneus, retrosplenial cortex, insula, and subcortical structures including the thalamus and the region of the epithalamus (the habenula). We further showed that the error-related medial cortical activities are not correlated with post-error behavioral adjustment, as indexed by post-error slowing (PES) in go trial reaction time. These results delineate an error-specific pattern of brain activation during the SST. The results also suggest that the relationship between error-related activity and post-error behavioral adjustment may be more complicated than has been conceptualized by the conflict monitoring hypothesis.

Characterizing Attention with Predictive Network Models.

Recent work shows that models based on functional connectivity in large-scale brain networks can predict individuals' attentional abilities. While being some of the first generalizable neuromarkers of cognitive function, these models also inform our basic understanding of attention, providing empirical evidence that: (i) attention is a network property of brain computation; (ii) the functional architecture that underlies attention can be measured while people are not engaged in any explicit task; and (iii) this architecture supports a general attentional ability that is common to several laboratory-based tasks and is impaired in attention deficit hyperactivity disorder (ADHD). Looking ahead, connectivity-based predictive models of attention and other cognitive abilities and behaviors may potentially improve the assessment, diagnosis, and treatment of clinical dysfunction.

Reproducibility and accuracy of gated SPECT for determination of left ventricular volumes and ejection fraction: experimental validation using MRI.

UNLABELLED: Quantitative gated SPECT (QGS) has been used for computation of left ventricular volumes and ejection fraction. This study evaluated, first, the effect of injected dose, time of imaging, and background activity on the reproducibility of QGS and, second, the accuracy of QGS, compared with cine MRI, for determining left ventricular volumes and ejection fractions in dogs with and without perfusion defects. METHODS: Sixteen dogs were subjected to either chronic occlusion of the circumflex artery (group I, no perfusion defect) or acute occlusion of the anterior descending coronary artery (group II, perfusion defect). Both groups underwent serial MRI and SPECT. RESULTS: ( QGS was very reproducible using the automated program (r = 0.99997). Correlation between left ventricular ejection fraction (LVEF) at 15 and 45 min was poor after the low-dose injection (r = 0.54; SE = 9%) and only fair after the high-dose injection (r = 0.77; SE = 5%). Correlation was poor in the presence of significant background activity (r = 0.36; SE = 12%). Correlation between QGS left ventricular volumes and MRI was good for group I (end-diastolic volume, r = 0.86; end-systolic volume, r = 0.81) and only fair for group II (end-diastolic volume, r = 0.66; end-systolic volume, r = 0.69). The overall LVEF correlation between QGS and MRI was poor (r = 0.51). QGS LVEF (mean +/- SD, 42% +/- 3%) overestimated MRI LVEF (29% +/- 2%). CONCLUSION: QGS provides a highly reproducible estimate of LVEF. However, QGS is affected by changes in background activity, time of imaging, and injected dose. In the presence of perfusion defects, QGS overestimated volume relative to MRI. The correlation between QGS- and MRI-derived LVEF was poor in this canine model.

Network analysis of brain activations in working memory: behavior and age relationships.

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging.

Analysis of J coupling-induced fat suppression in DIET imaging.

The DIET (or dual interval echo train) sequence, a modification of the fast spin echo (FSE) sequence that selectively reduces signal from fat in MR images, has been investigated. The DIET sequence uses an initial echo spacing longer than that of a conventional FSE sequence, thus allowing J coupling-induced dephasing to take effect. The sequence is evaluated theoretically, and its effectiveness on a hydrocarbon (1-pentene) is demonstrated numerically using density matrix calculations. The sequence is also evaluated experimentally using in vitro solutions and in vivo imaging. The efficacy of the sequence is compared for different lipid chemical structures, field strengths, and pulse sequence parameters.

MR of the head and neck: comparison of fast spin-echo and conventional spin-echo sequences.

PURPOSE: To compare conspicuousness of head and neck lesions on fast spin-echo sequences and conventional spin-echo sequences. METHODS: Forty consecutive patients with 61 head and neck lesions were evaluated. Lesion conspicuousness was qualitatively compared on conventional spin-echo and fast spin-echo sequences, using both spin-density and T2-weighted images. Thirty-six lesions had surgical or pathologic confirmation, and 25 were assigned a presumptive diagnosis based on clinical evaluation and imaging findings seen on conventional spin-echo T1- and T2-weighted sequences. Forty lesions were related to neoplasms; 21 lesions consisted of infectious, vascular, or inflammatory abnormalities. RESULTS: Fast spin-echo sequences provided improved lesion conspicuousness in 91% of spin-density images, in 77% of T2-weighted images, and in 84% of the combined spin-density and T2-weighted images. CONCLUSION: By providing shorter imaging times and equal or superior lesion conspicuousness, long-repetition-time fast spin-echo sequences can replace long-repetition-time conventional spin-echo sequences in evaluation of the head and neck.

Fast spin-echo MR imaging of the cervical spine: influence of echo train length and echo spacing on image contrast and quality.

PURPOSE: To examine the interaction of echo train length and interecho spacing and their effects on image quality and contrast in fast spin-echo sequences of the cervical spine. METHODS: Forty-three patients with suspected cervical disk disease were prospectively evaluated with fast spin-echo with varying echo train lengths and interecho spacing. A flow phantom was used to confirm findings related to cerebrospinal fluid pulsation. Parameters were manipulated to adjust contrast, signal-to-noise ratio, the effects of artifacts, and the speed of acquisition. RESULTS: In general, increasing echo train length increased homogeneity and high intensity of cerebrospinal fluid signal and reduced acquisition time; however, it decreased the signal-to-noise ratio of cerebrospinal fluid and cord and increased blurring, and, to a lesser extent, edge enhancement, and "truncation-type" artifact. Increasing interecho space permitted the use of longer echo times but minimally decreased contrast and signal-to-noise ratio of cord and cerebrospinal fluid. In addition, increasing echo spacing increased blurring, edge enhancement, truncation-type, magnetic susceptibility, and motion artifacts. CONCLUSIONS: For cervical spine imaging, a long echo train length and short echo spacing partially compensate for cerebrospinal fluid flow and produce the best myelographic effect but must be modulated by other constraints, such as artifact production or technical capabilities.

The cerebellum's role in reading: a functional MR imaging study.

BACKGROUND AND PURPOSE: Long considered to have a role limited largely to motor-related functions, the cerebellum has recently been implicated as being involved in both perceptual and cognitive processes. Our purpose was to determine whether cerebellar activation occurs during cognitive tasks that differentially engage the component processes of word identification in reading. METHODS: Forty-two neurologically normal adults underwent functional MR imaging of the cerebellum with a gradient-echo echo-planar technique while performing tasks designed to study the cognitive processing used in reading. A standard levels-of-processing paradigm was used. Participants were asked to determine whether pairs of words were written in the same case (orthographic processing), whether pairs of words and non-words rhymed with each other, respectively (phonologic assembly), and whether pairs of words belonged to the same category (semantic processing). Composite maps were generated from a general linear model based on a randomization of statistical parametric maps. RESULTS: During phonologic assembly, cerebellar activation was observed in the middle and posterior aspects of the posterior superior fissure and adjacent simple lobule and semilunar lobule bilaterally and in posterior aspects of the simple lobule, superior semilunar lobule, and inferior semilunar lobule bilaterally. Semantic processing, however, resulted in activation in the deep nuclear region on the right and in the inferior vermis, in addition to posterior areas active in phonologic assembly, including the simple, superior semilunar, and inferior semilunar lobules. CONCLUSION: The cerebellum is engaged during reading and differentially activates in response to phonologic and semantic tasks. These results indicate that the cerebellum contributes to the cognitive processes integral to reading.

Perturbation of the temperature distribution in microwave irradiated tissue due to the presence of metallic thermometers.

To date, satisfactory thermal dosimetry during the clinical application of localized hyperthermia can only be achieved using invasive thermometry. However the presence of commonly used metallic thermometers, such as thermocouples, may lead to the distortion of the temperature field due to self-heating of the probe under microwave irradiation. A computer simulation of the effect of this self-heating on the steady-state temperature distribution in plane-microwave irradiated homogeneous tissue has been undertaken and the significance of the effect for clinical hyperthermia dosimetry is assessed. The results indicate that a distortion of the temperature field in the neighborhood of the thermometer by several degrees can occur under adverse conditions.

Predicting reading performance from neuroimaging profiles: the cerebral basis of phonological effects in printed word identification.

This study linked 2 experimental paradigms for the analytic study of reading that heretofore have been used separately. Measures on a lexical decision task designed to isolate phonological effects in the identification of printed words were examined in young adults. The results were related to previously obtained measures of brain activation patterns for these participants derived from functional magnetic resonance imaging (fMRI). The fMRI measures were taken as the participants performed tasks that were designed to isolate orthographic, phonological, and lexical-semantic processes in reading. Individual differences in the magnitude of phonological effects in word recognition, as indicated by spelling-to-sound regularity effects on lexical decision latencies and by sensitivity to stimulus length effects, were strongly related to differences in the degree of hemispheric lateralization in 2 cortical regions.

Patterns of functional magnetic resonance imaging activation in association with structural lesions in the rolandic region: a classification system.

OBJECT: Functional magnetic resonance (fMR) imaging of the motor cortex is a potentially powerful tool in the preoperative planning of surgical procedures in and around the rolandic region. Little is known about the patterns of fMR imaging activation associated with various pathological lesions in that region or their relation to motor skills before surgical intervention. METHODS: Twenty-two control volunteers and 44 patients whose pathologies included arteriovenous malformations (AVMs; 16 patients), congenital cortical abnormalities (11 patients), and tumors (17 patients) were studied using fMR imaging and a hand motor task paradigm. Activation maps were constructed for each participant, and changes in position or amplitude of the motor activation on the lesion side were compared with the activation pattern obtained in the contralateral hemisphere. A classification scheme of plasticity (Grades 1-6) based on interhemispheric pixel asymmetry and displacement of activation was used to compare maps between patients, and relative to hand motor dexterity and/or weakness. There was 89.4% interobserver agreement on classification of patterns of fMR imaging activation. Displacement of activation by mass effect was more likely with tumors. Cortical malformations offer a much higher functional reorganization than AVMs or tumors. High-grade plasticity is recruited to compensate for severe motor impairment. CONCLUSIONS: Pattern modification of fMR imaging activation can be systematized in a classification of motor cortex plasticity. This classification has shown good correlation among grading, brain lesions, and motor skills. This proposal of a classification scheme, in addition to facilitating data collection and processing from different institutions, is well suited for comparing risks associated with surgical intervention and patterns of functional recovery in relation to preoperative fMR imaging categorization. Such studies are underway at the authors' institution.