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Novel nonparametric approach to canonical correlation analysis with applications to low CNR functional MRI data.

Detection of activation in functional MRI (fMRI) is often complicated by the low contrast-to-noise ratio (CNR) in the data. The primary source of the difficulty is the fact that for activities that are subtle the signal can be hidden inside the inherent noise in the data. Classical univariate methods based on t-test or F-test are susceptible to noise, as they fail to harness systematic correlations in evoked responses within neighboring voxels. Here the power of a multivariate statistical analysis tool known as canonical correlation analysis (CCA) in fMRI studies is demonstrated where the CNR is low. As a further illustration of the power of the method, a comparative study of CCA and ordinary correlation analysis using simulated data under various noise levels is also performed. A novel nonparametric approach is introduced to calculate the P-values from the distribution of the complicated test statistic. The circumstances under which CCA is a better performer as well as when it is not the case are discussed. As an example, this method is applied to detect hippocampal activation from memory-related tasks.

Adult↗

Using visual advance information: an event-related functional MRI study.

Our event-related functional MRI (efMRI) study investigates whether visual advance information (AI) affects rather perceptual or central response-related processing areas. Twelve subjects were required to make a go/no-go decision to a conjunction of a specific color and motion direction. The stimuli were preceded by a cue, providing 100% valid advance information about motion direction. Partial and full advance information (PAI and FAI) predicted possible targets, respectively, certain nontargets, neutral cues (NAI) gave no prediction. The time between cue and stimulus (stimulus onset asynchrony, SOA) was varied. A response benefit was found after PAI as compared with NAI. The benefit was small with a short SOA (150 ms), increased with intermediate SOA (450 ms) and sustained with long SOA (750 ms). Perceptual and central processing areas were more active with increasing SOA, but only central response-related processing areas were selectively modulated by cue information. In particular, supplementary motor area and bilateral inferior parietal lobe were more active with PAI than with NAI. If comparing NAI with FAI, more errors were made and activity was larger in central processing areas. Our results suggest that, depending on the processing time, cues providing perceptual information modulate central response-related processes.

Adult↗

Mental rotation of objects retrieved from memory: a functional MRI study of spatial processing.

This functional MRI study examined how people mentally rotate a 3-dimensional object (an alarm clock) that is retrieved from memory and rotated according to a sequence of auditory instructions. We manipulated the geometric properties of the rotation, such as having successive rotation steps around a single axis versus alternating between 2 axes. The latter condition produced much more activation in several areas. Also, the activation in several areas increased with the number of rotation steps. During successive rotations around a single axis, the activation was similar for rotations in the picture plane and rotations in depth. The parietal (but not extrastriate) activation was similar to mental rotation of a visually presented object. The findings indicate that a large-scale cortical network computes different types of spatial information by dynamically drawing on each of its components to a differential, situation-specific degree.

Adult↗

Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study.

OBJECTIVE: To investigate, using functional MRI (fMRI), the neural network that is activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia. BACKGROUND: Mechanical hyperalgesia (i.e., pain to innocuous tactile stimuli) is a distressing symptom of neuropathic pain syndromes. Animal experiments suggest that alterations in central pain processing occur that render tactile stimuli capable of activating central pain-signaling neurons. A similar central sensitization can be produced experimentally with capsaicin. METHODS: In nine healthy individuals the cerebral activation pattern resulting from cutaneous nonpainful mechanical stimulation at the dominant forearm was imaged using fMRI. Capsaicin was injected adjacent to the stimulation site to induce secondary mechanical hyperalgesia. The identical mechanical stimulation was then perceived as painful without changing the stimulus intensity and location. Both activation patterns were compared to isolate the specific pain-related component of mechanical hyperalgesia from the tactile component. RESULTS: The pattern during nonpainful mechanical stimulation included contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII) activity. During hyperalgesia, significantly higher activation was found in the contralateral prefrontal cortex: the middle (Brodmann areas [BAs] 6, 8, and 9) and inferior frontal gyrus (BAs 44 and 45). No change was present within SI, SII, and the anterior cingulate cortex. CONCLUSIONS: Prefrontal activation is interpreted as a consequence of attention, cognitive evaluation, and planning of motor behavior in response to pain. The lack of activation of the anterior cingulate contrasts with physiologic pain after C-nociceptor stimulation. It might indicate differences in the processing of hyperalgesia and C-nociceptor pain or it might be due to habituation of affective sensations during hyperalgesia compared with acute capsaicin pain.

Adult↗

Functional MRI activation of individual interictal epileptiform spikes.

We used spike-triggered functional MRI in a patient with localization-related epilepsy to determine whether individual (as opposed to averaged) focal interictal epileptiform discharges (spikes) were associated with hemodynamic changes detectable with blood oxygen level-dependent functional MRI (fMRI). It was found that 15 of 43 spikes (34.9%) were associated with significant focal fMRI activation. Single event-related fMRI of interictal spikes is feasible in selected patients, giving complementary information to that provided by averaged fMRI data.

Brain Mapping↗

MRI-clinical correlations in the primary progressive course of MS: new insights into the disease pathophysiology from the application of magnetization transfer, diffusion tensor, and functional MRI.

Despite patients with primary progressive multiple sclerosis (PPMS) experience a progressive disease course from onset, the burden and activity of lesions on conventional magnetic resonance imaging (MRI) scans of the brain are lower than in all other main clinical phenotypes of MS. This review outlines the major contributions given by magnetization transfer MRI, diffusion tensor MRI and functional MRI to the understanding of the pathophysiology of PPMS and provides evidence that, at least, three factors might explain this clinical/MRI discrepancy: (a) the presence of a diffuse tissue damage at a microscopic level; (b) a prevalent involvement of the cervical cord, and (c) an impairment of the adaptive capacity of the cortex to limit the functional consequences of subcortical structural damage.

Brain↗

Overt naming in aphasia studied with a functional MRI hemodynamic delay design.

The purpose of this study was to develop a functional MRI method to examine overt speech in stroke patients with aphasia. An fMRI block design for overt picture naming was utilized which took advantage of the hemodynamic response delay where increased blood flow remains for 4-8 s after the task [(Friston, K.J., Jezzard, P., Turner, R., 1994. Analysis of functional MRI time-series. Hum. Brain Mapp. 1, 153-171)]. This allowed task-related information to be obtained after the task, minimizing motion artifact from overt speech (Eden, G.F., Joseph, J., Brown, H.E., Brown, C.P., Zeffiro, T.A., 1999. Utilizing hemodynamic delay and dispersion to detect fMRI signal change without auditory interference: the behavior interleaved gradients technique. Magn. Reson. Med. 41, 13-20; Birn, RM., Bandettini, P.A., Cox, R.W., Shaker, R., 1999. Event-related fMRI of tasks involving brief motion. Hum. Brain Mapp. 7, 106-114; Birn, R.M., Cox, R.W., Bandettini, P.A., 2004. Experimental designs and processing strategies for fMRI studies involving overt verbal responses. NeuroImage 23, 1046-1058). Five chronic aphasia patients participated (4 mild-moderate and 1 severe nonfluent/global). The four mild-moderate patients who correctly named 88-100% of the pictures during fMRI, had a greater number of suprathreshold voxels in L supplementary motor area (SMA) than R SMA (P < 0.07). Three of these four mild-moderate patients showed activation in R BA 45 and/or 44; along with L temporal and/or parietal regions. The severe patient, who named no pictures, activated almost twice as many voxels in R SMA than L SMA. He also showed activation in R BA 44, but had remarkably extensive L and R temporal activation. His poor naming and widespread temporal activation may reflect poor modulation of the bi-hemispheric neural network for naming. Results indicate that this fMRI block design utilizing hemodynamic response delay can be used to study overt naming in aphasia patients, including those with mild-moderate or severe aphasia. This method permitted verification that the patients were cooperating with the task during fMRI. It has application for future fMRI studies of overt speech in aphasia.

Aged↗

Brain activation during semantic judgment of Chinese sentences: A functional MRI study.

A functional magnetic resonance imaging (fMRI) study was conducted to investigate whether the anatomic substrates of semantic memory may reflect categorical organization and to determine whether the left middle frontal gyrus (Brodmann area [BA] 9) plays a role in Chinese semantic judgment. Unlike previous studies using a word-retrieval task (e.g., word generation, naming, and word categorization), we used a typical task of semantic knowledge retrieval in cognitive psychology in which subjects were asked to determine whether a sentence describing an attribute of living things or nonliving things was true or not. The experimental conditions evoked extensive activation over several regions of the brain including a very strong activation in the left middle frontal region (BA9 and BA46). Our data show that there is no unique activation associated with living or nonliving things at the statistical threshold used in our study. The results imply that human semantic system is undifferentiated by category at the neural level. Our findings also corroborate and extend the claim that the left middle frontal gyrus plays an important role in reading Chinese at both the sentence and the word level.

Adolescent↗

Within-subject reproducibility of category-specific visual activation with functional MRI.

We used functional magnetic resonance imaging (fMRI) to investigate within-subject reproducibility of activation in higher level, category-specific visual areas to validate the functional localization approach widely used for these areas. The brain areas investigated included the extrastriate body area (EBA), which responds selectively to human bodies, the fusiform face area (FFA) and the occipital face area (OFA), which respond selectively to faces, and the parahippocampal place area (PPA), which responds selectively to places and scenes. All six subjects showed significant bilateral activation in the four areas. Reproducibility was very high for all areas, both within a scanning session and between scanning sessions separated by 3 weeks. Within sessions, the mean distance between peak voxels of the same area localized by using different functional runs was 1.5 mm. The mean distance between peak voxels of areas localized in different sessions was 2.9 mm. Functional reproducibility, as expressed by the stability of T-values across sessions, was high for both within-session and between-session comparisons. We conclude that within subjects, high-level category-specific visual areas can be localized robustly across scanning sessions.

Adult↗

How does the brain accommodate to increased task difficulty in word finding? A functional MRI study.

In functional imaging of the brain, the difficulty of a task may be critical for the pattern of activation. Increased task difficulty could lead to increased activation in task-specific regions or to activation of additional, "compensatory" regions. A previous study with functional transcranial Doppler sonography (fTCD) showed no evidence that increased difficulty in word retrieval leads to a recruitment of areas homologous to language-related regions. The question remains how the brain accommodates increasing task difficulty. Because of limitations of fTCD method, we used functional magnetic resonance imaging (fMRI) in this study. We manipulated word retrieval difficulty in healthy subjects (n = 14) to determine whether the classical language-related brain regions are activated with increasing difficulty in word retrieval. fMRI demonstrated that with increased task difficulty (I) the lateralization of language-associated brain activation remained constant, (II) no additional activation of language-related regions of the dominant hemisphere, nor of homologous regions of the subdominant hemisphere, was evident, (III) additional activation was found in right posterior parietal cortex--typically associated with sustained attention and executive control. Thus, increased difficulty in word retrieval leads to coactivation of distinct brain areas, working together in a large cognitive network, rather than to increased activation of typically language-related areas.

Adult↗

Partial correlation for functional brain interactivity investigation in functional MRI.

Examination of functional interactions through effective connectivity requires the determination of three distinct levels of information: (1) the regions involved in the process and forming the spatial support of the network, (2) the presence or absence of interactions between each pair of regions, and (3) the directionality of the existing interactions. While many methods exist to select regions (Step 1), very little is available to complete Step 2. The two main methods developed so far, structural equation modeling (SEM) and dynamical causal modeling (DCM), usually require precise prior information to be used, while such information is sometimes lacking. Assuming that Step 1 was successfully completed, we here propose a data-driven method to deal with Step 2 and extract functional interactions from fMRI datasets through partial correlations. Partial correlation is more closely related to effective connectivity than marginal correlation and provides a convenient graphical representation for functional interactions. As an instance of brain interactivity investigation, we consider how simple hand movements are processed by the bihemispheric cortical motor network. In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions. We demonstrate the interest of this approach on real data.

Cerebral Cortex↗

Amygdala reactivity to emotional faces at high and low intensity in generalized social phobia: a 4-Tesla functional MRI study.

Using functional magnetic resonance imaging, we measured amygdala reactivity to faces varying on emotional intensity in subjects with generalized social phobia (GSP) and matched healthy controls, and observed greater bilateral activation to high (vs. low) intensity expressions in the phobic group, suggesting that more arousing social-emotional cues contribute to limbic hyperactivity in GSP.

Adult↗

Distributed neural systems for temporal production: a functional MRI study.

Using functional magnetic resonance imaging (fMRI), we investigated the neural substrates for computing time intervals. Five right-handed males were asked to judge if a digit probe belonged to a string of digits presented immediately before but to provide their response only after 1.5s had elapsed. This time estimation condition, compared with control working memory and motor tasks, was associated with increased activity in the middle occipital gyri, in the right inferior parietal lobe, and bilaterally in the prefrontal cortex. We argue that activity elicited in the occipital lobe provides duration information about visual stimuli that can be quantified at the level of the inferior parietal lobe. Comparison with time reference information depends on the bilateral prefrontal cortex.

Adult↗

Tracking cognitive processes with functional MRI mental chronometry.

Functional magnetic resonance imaging (fMRI) is used widely to determine the spatial layout of brain activation associated with specific cognitive tasks at a spatial scale of millimeters. Recent methodological improvements have made it possible to determine the latency and temporal structure of the activation at a temporal scale of few hundreds of milliseconds. Despite the sluggishness of the hemodynamic response, fMRI can detect a cascade of neural activations - the signature of a sequence of cognitive processes. Decomposing the processing into stages is greatly aided by measuring intermediate responses. By combining event-related fMRI and behavioral measurement in experiment and analysis, trial-by-trial temporal links can be established between cognition and its neural substrate.

Brain↗

Corticothalamic modulation during absence seizures in rats: a functional MRI assessment.

PURPOSE: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. METHODS: Blood-oxygenation-level-dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using gamma-butyrolactone (GBL; 200 mg/kg, intraperitoneal). RESULTS: The corticothalamic circuitry, critical for spike-wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. CONCLUSIONS: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.

Anesthesia↗

Cluster analysis of muscle functional MRI data.

Muscle functional magnetic resonance imaging (mfMRI) is frequently used to determine spatial patterns of muscle involvement in exercising humans. A frequent finding in mfMRI is that, even within synergistic muscle groups, signal intensity (SI) data from individual voxels can be quite heterogeneous. The purpose of this study was to develop a novel method for organizing heterogeneous mfMRI data into clusters whose members behave similarly to each other but distinctly from members of other clusters and apply it in studies of functional compartmentalization in the anterior compartment of the leg. An algorithm was developed that compared the SI time courses of adjacent voxels and grouped together voxels that were sufficiently similar. The algorithm's performance was verified by using simulated data sets with known regional differences in SI time courses that were then applied to experimental mfMRI data acquired from six male subjects (age 22.6 +/- 0.9 yr, mean +/- SE) who sustained isometric contractions of the dorsiflexors at 40% of maximum voluntary contraction. The experimental data were also characterized by using a traditional analysis (user-specified regions of interest from a single image), in which the relative change in SI and the contrast-to-noise ratio [CNR; 100%x(SI(RESTING) - SI(ACTIVE)/(noise standard deviation)] were measured. In general, clusters were found in areas in which the CNR exceeded 5. Cluster analysis made functional distinctions between regions of muscle that were not seen with traditional analysis. In conclusion, cluster analysis's use of the full SI time course provides more sensitivity to muscle functional compartmentation than traditional analysis.

Adult↗

Cortical language activation in aphasia: a functional MRI study.

BACKGROUND: Functional neuroimaging has been used in neurolinguistic research on normal subjects and on patients with brain damage. This study was designed to investigate the differences of the neural basis underlying language processing between normal subjects and aphasics. METHODS: Functional magnetic resonance imaging (fMRI) was used to map the language network in 6 normal subjects and 3 patients with aphasia who were in the stage of recovery from acute stroke. The participants performed a word generation task during multi-slice functional scanning for the measurement of signal change associated with regional neural activity induced by the task. RESULTS: In normal subjects, a distributed language network was activated. Activations were present in the frontal, temporal, parietal and occipital regions. In the patient group, however, no activation was detected in the left inferior frontal gyrus whether the patient had a lesion in the left frontal lobe or not. Two patients showed activations in some right hemisphere regions where no activation appeared in normal subjects. CONCLUSIONS: fMRI with word generation task is feasible for evaluating language function in aphasic patients. Remote effect of focal lesion and functional redistribution or reorganisation can be found in aphasic patients.

Adult↗

The effect of magnetization transfer on functional MRI signals.

A magnetization transfer (MT)-prepared echo-planar imaging (EPI) pulse sequence was developed to study motor cortex activation, using a finger tapping paradigm. MT weighting resulted in a reduction of both the activated area and, in the majority of activated pixels, the functional MRI signal, regardless of the correlation coefficient threshold used in generating the activation map. The magnetization transfer ratio (MTR) was higher during task activation than during rest. Because the MT effect is strongly tissue-dependent, these results support the hypothesis that incorporation of MT into functional MRI will help to understand the origin of the functional MRI signal.

Adult↗