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Abstract Background Early tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC). Methods We screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response. Results The final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8–14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with

Cells of the pulmonary vasculature show a hyperproliferative phenotype in pulmonary arterial hypertension (PAH), thus contributing to the disease pathogenesis. Here the authors show that cyclin-dependent kinases are overactivated in PAH, and that their pharmacological inhibition attenuates the disease in two independent rodent models

A vivid discussion revolves around the role of the human mind in the quantum measurement process. While some authors argue that conscious observation is a necessary element to achieve the transition from quantum to classical states during measurement (Wigner, 1963), some go even further and propose a more active influence of the human mind on the probabilities of quantum measurement outcomes (e.g. Atmanspacher, Römer, & Walach, 2002; Penrose & Hameroff, 2011). This proposition was tested in micro-psychokinesis (micro-Pk) research were intentional observer effects on quantum random number generators (RNGs) were investigated. In the studies presented here we extended this line of research and tested the impact unconscious goals on micro-Pk. Our focus was cigarette addiction as an unconscious drive and hypothesized that regular cigarette smokers would influence the outcome of a quantum RNG that determined whether the participant was going to see a smoking-related or a neutral picture. Study 1 revealed strong evidence for micro-Pk (BF = 66.06) supporting the H1. As expected, no deviation from chance was found with non-smokers. In Study 2, a pre-registered highly powered replication attempt, failed to reproduce this result and showed strong evidence for H0 (BF = 11.07). When the data from both studies are combined a remarkable change in effect across time (resembling a combination of appearance followed by decline) can be seen only in the smoker’s subsample. Appearance-and-decline effects were absent in the non-smokers sample and in a simulation. Based on von Lucadou’s Model of Pragmatic Information we suggest that (micro-)Pk effects follow a systematic pattern comparable to a dampened harmonic oscillation. This concept may shed new light on past and future Pk research.

Background and Purpose: Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent., Materials and Methods: Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task., Results: Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values., Conclusion: Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.

Background and Purpose: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality., Materials and Methods: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality., Results: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively)., Conclusions: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

Twenty-four patients with proven benign and low-grade brain neoplasms each performed two iterations of four fMRI paradigms: language (word generation), primary and association auditory (text listening), upper limb fine motor control (alternating-limb bilateral finger tapping), and primary visual perception (reversing checkerboard). Activation clusters with varying thresholds were generated for each scan and used to calculate reproducibility parameters: Difference in the Center of Mass (COM) location, R(size), and R(overlap). The average difference in the COM, R(size), and R(overlap) values ranged from 1.70 +/- 0.53 mm -10.60 +/- 3.21 mm, 0.6 +/- 0.04-0.90 +/- 0.05 and 0.23 +/- 0.12 -1 +/- 0.16 respectively for all tasks. These values are within the range of, or higher than, previously published reports on fMRI test-retest precision. FMRI is indicated to be a noninvasive tool with acceptable reproducibility measures for assessing the localizations of multiple language and sensorimotor functions in patients scheduled for radiotherapy treatment.

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD.

Self-paced functional MR imaging (fMRI) paradigms, in which the task timing is determined by the subject's performance, can offer several advantages over commonly applied paradigms with predetermined stimulus timing. Independent component analysis (ICA) does not require specification of a timed response function, and could be an advantageous method of deriving results from fMRI data sets with varying response timings and durations. In this study normal volunteers (N = 10) each performed two self-paced fMRI motor and arithmetic paradigms. Individual data sets were analyzed with the Infomax spatial ICA algorithm. Conventional regression analysis was performed for comparison purposes. Spatial ICA effectively produced task-related components from each of the self-paced data sets, even in a few cases where regression analysis yielded non-specific functional maps. For the motor paradigm, these components consistently mapped to primary motor areas. ICA of the arithmetic paradigm yielded multiple task-related components that variably mapped to regions of parietal and frontal lobes. Regression analysis generally yielded similar spatial maps. The multiple task-related ICA components that were sometimes produced from each self-paced data set can be challenging to identify and evaluate for significance. These preliminary results indicate that ICA is useful as an exploratory and complementary method to conventional regression analysis for fMRI of self-paced paradigms.

Background and Purpose: The purpose of this study was to determine the incidence of susceptibility artifacts on functional MR imaging (fMRI) studies and their effect on fMRI readings. We hypothesized that the availability of the signal intensity maps (SIMs) changes the interpretation of fMRI studies in which susceptibility artifacts affected eloquent brain regions., Methods: We reviewed 152 consecutive clinical fMRI studies performed with a SIM. The SIM consisted of the initial echo-planar images (EPI) in each section thresholded to eliminate signal intensity from outside the brain and then overlaid on anatomic images. The cause of the artifact was then determined by examining the images. Cases with a susceptibility artifact in eloquent brain were included in a blinded study read by four readers, first without and then with the SIM. For each reader, the number of times the interpretation changed on viewing the SIM was counted., Results: Of 152 patients, 44% had signal intensity loss involving cerebral cortex and 18% involving an eloquent brain region. Causes of the artifacts were: surgical site artifact, blood products, dental devices, calcium, basal ganglia calcifications, ICP monitors, embolization materials, and air. When provided with the SIM, readers changed interpretations in 8-38% of patient cases, depending on reader experience and size and location of susceptibility artifact., Conclusion: Patients referred for clinical fMRI have a high incidence of susceptibility artifacts, whose presence and size can be determined by inspection of the SIM but not anatomic images. The availability of the SIM may affect interpretation of the fMRI.

The Hooper Visual Organization Test (VOT), a commonly applied neuropsychological test of visual spatial ability, is used for assessing patients with suspected right hemisphere, or parietal lobe involvement. A controversy has developed over whether the inferences of this test metric can be assumed to involve global, lateralized, or regional functionality. In this study, the characteristic visual organization and object naming aspects of the VOT task presentation were adapted to a functional MR imaging (fMRI) paradigm to probe the neuroanatomic correlates of this neuropsychological test. Whole brain fMRI mapping results are reported on a cohort of normal subjects. Bilateral fMRI responses were found predominantly in the posterior brain, in regions of superior parietal lobules, ventral temporal-occipital cortex, and posterior visual association areas, and to a lesser extent, the frontal eye fields bilaterally, and left dorsolateral prefrontal cortex. The results indicate a general brain region or network in which VOT impairment, due to its visuospatial and object identification demands, is possible to be detected. Discussion is made of interpretive limitations when adapting neuropsychological tests to fMRI analysis.

Background and Purpose: Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA., Methods: Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group., Results: None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant., Conclusion: A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Independent component analysis (ICA) has been demonstrated to be an effective data-driven method for analyzing fMRI data. However, a method for objective differentiation of task-related components from those that are artifactually non-relevant is needed. We propose a method of constant-cycle (periodic) fMRI task paradigm combined with ranking of spatial ICA components by the magnitude contribution of their temporal aspects to the fundamental task frequency. Power spectrum ranking shares some similarity to correlation with an a priori hemodynamic response, but without a need to presume an exact timing or duration of the fMRI response. When applied to a complex motor task paradigm with auditory cues, multiple task-related activations are successfully identified and separated from artifactual components. These activations include sensorimotor, auditory, and superior parietal areas. Comparisons of task-related component time courses indicate the temporal relationship of fMRI responses in functionally involved regions. Results indicate the sensitivity of ICA to short-duration hemodynamics, and the efficacy of a power spectrum ranking method for identification of task-related components., (Copyright 2002 Wiley-Liss, Inc.)

Object: Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region., Methods: Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits. In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007)., Conclusions: Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.

Object: Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms., Methods: Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case., Conclusions: Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Typically, fMRI data is processed in the time domain with linear methods such as regression and correlation analysis. We propose that the theory of phase synchronization may be used to more completely understand the dynamics of interacting systems, and can be applied to fMRI data as a novel method of detecting activation. Generalized synchronization is a phenomenon that occurs when there is a nonlinear functional relationship present between two or more coupled, oscillatory systems, whereas phase synchronization is defined as the locking of the phases while the amplitudes may vary. In this study, we developed an application of phase synchronization analysis that is appropriate for fMRI data, in which the phase locking condition is investigated between a voxel time series and the reference function of the task performed. A synchronization index is calculated to quantify the level of phase locking, and a nonparametric permutation test is used to determine the statistical significance of the results. We performed the phase synchronization analysis on the data from five volunteers for an event-related finger-tapping task. Functional maps were created that provide information on the interrelations between the instantaneous phases of the reference function and the voxel time series in a whole-brain fMRI activation data set. We conclude that this method of analysis is useful for revealing additional information on the complex nature of the fMRI time series., (Copyright 2002 Wiley-Liss, Inc.)

This study was designed to compare the test-retest precision of functional magnetic resonance imaging (fMRI) data processed with independent component analysis (ICA) and the same data analyzed with a conventional model-dependent method (Student's- t mapping). Volunteers underwent two or three iterations of visual and auditory stimuli, while data were collected for fMRI scans. The scan data were separately processed with ICA and with Student's- t mapping (STM). As a measure of test-retest precision, concurrence ratios were calculated for each subject and each task as the number of voxels that were activated by two iterations of a task divided by the average number of voxels activated in each repetition. In 28 test-retest comparisons, the average concurrence ratio was 0.69+/-0.10 for ICA and 0.65+/-0.13 for the conventional method, a statistically insignificant difference. In fMR image data of block stimulus paradigms, ICA had similar test-retest precision to a conventional model-dependent method.

Background and Purpose: With independent component analysis (ICA), regions of activation can be identified on functional MR (fMR) images without a priori knowledge of expected hemodynamic responses. The purpose of this study was to compare the results of fMR imaging data processed with spatial ICA with results obtained with conventional hypothesis-driven analysis., Methods: Eleven patients with focal cerebral lesions and one with agenesis of the corpus callosum were enrolled. Each patient performed text-listening, finger-tapping, and word-generation tasks. Conventional activation maps were generated by fitting time courses of each voxel to a boxcar reference function. Maps were created from the same image data with ICA techniques. To compare the maps, a concurrence ratio (CR) (number of voxels activated on both maps to number of voxels activated on either map) was calculated., Results: In the ICA analysis, maps with appropriate spatial and temporal features for auditory, sensorimotor, or language cortices were identified in most patients. Images processed with ICA resembled images processed with conventional means. In patients who moved or performed the task incorrectly, ICA produced a map that resembled the expected activation pattern but differed from the conventional image. CRs averaged 70% for all comparisons in the 12 patients., Conclusion: fMR imaging maps for auditory, sensorimotor, and language tasks produced with ICA and conventional techniques were similar in most cases. Differences were consistent with the particular characteristics of the method. In data sets corrupted by motion or incorrect task performance, ICA may produce more accurate maps.

Background and Purpose: Functional MR (fMR) imaging of word generation has been used to map Broca's area in some patients selected for craniotomy. The purpose of this study was to measure the reliability, precision, and accuracy of word-generation tasks to identify Broca's area., Methods: The Brodmann areas activated during performance of word-generation tasks were tabulated in 34 consecutive patients referred for fMR imaging mapping of language areas. In patients performing two iterations of the letter word-generation tasks, test-retest reliability was quantified by using the concurrence ratio (CR), or the number of voxels activated by each iteration in proportion to the average number of voxels activated from both iterations of the task. Among patients who also underwent category or antonym word generation or both, the similarity of the activation from each task was assessed with the CR. In patients who underwent electrocortical stimulation (ECS) mapping of speech function during craniotomy while awake, the sites with speech function were compared with the locations of activation found during fMR imaging of word generation., Results: In 31 of 34 patients, activation was identified in the inferior frontal gyri or middle frontal gyri or both in Brodmann areas 9, 44, 45, or 46, unilaterally or bilaterally, with one or more of the tasks. Activation was noted in the same gyri when the patient performed a second iteration of the letter word-generation task or second task. The CR for pixel precision in a single section averaged 49%. In patients who underwent craniotomy while awake, speech areas located with ECS coincided with areas of the brain activated during a word-generation task., Conclusion: fMR imaging with word-generation tasks produces technically satisfactory maps of Broca's area, which localize the area accurately and reliably.

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Background and Purpose: In subjects performing no specific cognitive task ("resting state"), time courses of voxels within functionally connected regions of the brain have high cross-correlation coefficients ("functional connectivity"). The purpose of this study was to measure the contributions of low frequencies and physiological noise to cross-correlation maps., Methods: In four healthy volunteers, task-activation functional MR imaging and resting-state data were acquired. We obtained four contiguous slice locations in the "resting state" with a high sampling rate. Regions of interest consisting of four contiguous voxels were selected. The correlation coefficient for the averaged time course and every other voxel in the four slices was calculated and separated into its component frequency contributions. We calculated the relative amounts of the spectrum that were in the low-frequency (0 to 0.1 Hz), the respiratory-frequency (0.1 to 0.5 Hz), and cardiac-frequency range (0.6 to 1.2 Hz)., Results: For each volunteer, resting-state maps that resembled task-activation maps were obtained. For the auditory and visual cortices, the correlation coefficient depended almost exclusively on low frequencies (<0.1 Hz). For all cortical regions studied, low-frequency fluctuations contributed more than 90% of the correlation coefficient. Physiological (respiratory and cardiac) noise sources contributed less than 10% to any functional connectivity MR imaging map. In blood vessels and cerebrospinal fluid, physiological noise contributed more to the correlation coefficient., Conclusion: Functional connectivity in the auditory, visual, and sensorimotor cortices is characterized predominantly by frequencies slower than those in the cardiac and respiratory cycles. In functionally connected regions, these low frequencies are characterized by a high degree of temporal coherence.

Background and Purpose: Independent component analysis (ICA), unlike other methods for processing functional MR (fMR) imaging data, requires no a priori assumptions about the hemodynamic response to the task. The purpose of this study was to analyze the temporal characteristics and the spatial mapping of the independent components identified by ICA when the subject performs a finger-tapping task., Methods: Ten healthy subjects performed variations of the finger-tapping task conventionally used to map the sensorimotor cortex. The scan data were processed with ICA, and the temporal configuration of the components and their spatial localizations were studied. The locations with activation were tabulated and compared with locations known to be involved in the organization of motor functions in the brain., Results: Components were identified that correlated to varying degrees with the conventional boxcar reference function. One or more of these components mapped to the sensorimotor cortex, supplementary motor area (SMA), putamen, and thalamus. By means of ICA components, sensorimotor cortex, supplementary motor area, and superior cerebellar activation were identified bilaterally in 100% of the subjects; thalamus activation was contralateral to the active hand in 80%; and putamen activation was contralateral to the active hand in 60%., Conclusion: ICA processing of multislice fMR imaging data acquired during finger tapping identifies the sensorimotor cortex, SMA, cerebellar, putamen, and thalamic activation. ICA appears to be a method that provides information on both the temporal and spatial characteristics of activation. Multiple task-related components can be identified by ICA, and specific activation maps can be derived from each separate component.

Background and Purpose: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks., Methods: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps., Results: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz., Conclusion: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

A new approach in studying interregional functional connectivity using functional magnetic resonance imaging (fMRI) is presented. Functional connectivity may be detected by means of cross correlating time course data from functionally related brain regions. These data exhibit high temporal coherence of low frequency fluctuations due to synchronized blood flow changes. In the past, this fMRI technique for studying functional connectivity has been applied to subjects that performed no prescribed task ("resting" state). This paper presents the results of applying the same method to task-related activation datasets. Functional connectivity analysis is first performed in areas not involved with the task. Then a method is devised to remove the effects of activation from the data using independent component analysis (ICA) and functional connectivity analysis is repeated. Functional connectivity, which is demonstrated in the "resting brain," is not affected by tasks which activate unrelated brain regions. In addition, ICA effectively removes activation from the data and may allow us to study functional connectivity even in the activated regions.

Background and Purpose: Repetitive motor tasks that produce sustained neuronal activity in the sensorimotor cortex produce transient neuronal activity in subcortical regions. We tested the hypothesis that a reference function modeling a transient hemodynamic response would more reliably detect activation in the basal ganglia than would a conventional reference function, which models a sustained hemodynamic response., Methods: Functional MR imaging data were acquired in eight subjects performing an alternating-hand finger-tapping task. Postprocessing was performed by cross-correlation to two types of reference functions: one that models a sustained hemodynamic response to finger tapping and one that models an initial transient hemodynamic response. Activation in the sensorimotor cortex, supplementary motor area, cerebellum, thalamus, and corpus striatum was tabulated for each reference function., Results: With the conventional boxcar reference function, activation was detected in the sensorimotor cortex, supplementary motor area, and cerebellum, but intermittently in the corpus striatum in all subjects. With the reference function for a transient response, activation in the corpus striatum was not detected in all subjects., Conclusion: In the corpus striatum, activation is detected more frequently with a reference function that models a transient response. Activated cortical and subcortical regions can be mapped with an alternating-hand finger-tapping paradigm and a combination of reference functions.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.

Functional MR imaging, similar to positron-emission tomography, shows the regions in which cerebral blood flow changes as neurons are active in the performance of cognitive tasks. Blood flow increases (activation) exceed that needed to supply oxygen for the increased metabolic needs for the increased neuronal activity. Therefore, in regions with activation, the deoxyhemoglobin concentration in the capillary blood decreases below levels found in the brain where neurons are not active.

The overall goal of this study was the development and application of a less motion sensitive, single-shot MRI technique for use on a standard clinical system in a dynamic imaging setting, such as cardiac scanning. Time encoding, a single-shot line scanning technique, has been used to produce single-shot, small field-of-view cardiac images without the use of presaturation pulses. The major advantages of this method are: (1) as a line scanning technique, time encoding is minimally sensitive to motion when compared with 2D Fourier methods, and (2) aliasing will not occur if the object being imaged extends beyond the field of view.