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How self-initiated memorized movements become automatic: a functional MRI study.

We used functional magnetic resonance imaging (fMRI) and dual tasks to investigate the physiology of how movements become automatic. Normal subjects were asked to practice some self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Our secondary task was a letter-counting task where subjects were asked to identify the number of times a target letter from the letter sequences was seen. Only the performances that achieved high accuracy in both single and dual tasks were considered automatic. The fMRI results before and after automaticity was achieved were compared. Our data showed that for both conditions, sequential movements activated similar brain regions. No additional activity was observed in the automatic condition. There was less activity in bilateral cerebellum, presupplementary motor area, cingulate cortex, left caudate nucleus, premotor cortex, parietal cortex, and prefrontal cortex during the automatic stage. These findings suggest that most of the motor network participates in executing automatic movements and that it becomes more efficient as movements become more automatic. Our results do not provide evidence for any area to become more activated for automatic movements.

Adult↗

Activation of human presupplementary motor area in learning of sequential procedures: a functional MRI study.

1. Using functional magnetic resonance imaging, we investigated the neural correlates of sequential procedural learning. During the test scans the subjects learned a new sequence (position or color) of button presses; during the control scans they pressed the buttons in any order. The comparison of the test and control scans was expected to reveal the neural activities related to learning, not sensory-motor processes. 2. We found that a localized area in what we regard to be the human homologue of the presupplementary motor area (pre-SMA) was particularly active for learning of new sequential procedures (either position or color sequences), not movements per se. 3. In contrast, the SMA proper (posterior to pre-SMA) was active for the performance of sequential movements, not learning. This was shown in another paradigm in which the subjects pressed the buttons in any order in the test scans and just watched the sequence in the control scans. 4. The learning-related pre-SMA region, which was consistent across different experiments in single subjects, was identified on only one side in each subject.

Humans↗

Dissociating the neural mechanisms of visual attention in change detection using functional MRI.

We investigated using functional magnetic resonance imaging (fMRI) the neural processes associated with performance of a change-detection task. In this task, two versions of the same picture are presented in alternation, separated by a brief mask interval. Even when the two pictures greatly differ (e.g., as when a building is in different locations), subjects report that identification of the change is difficult and often take 30 or more seconds to identify the change. This phenomenon of "change blindness" provides a powerful and novel paradigm for segregating components of visual attention using fMRI that can otherwise be confounded in short-duration tasks. By using a response-contingent event-related analysis technique, we successfully dissociated brain regions associated with different processing components of a visual change-detection task. Activation in the calcarine cortex was associated with task onset, but did not vary with the duration of visual search. In contrast, the pattern of activation in dorsal and ventral visual areas was temporally associated with the duration of visual search. As such, our results support a distinction between brain regions whose activation is modulated by attentional demands of the visual task (extrastriate cortex) and those that are not affected by it (primary visual cortex). A second network of areas including central sulcus, insular, and inferior frontal cortical areas, along with the thalamus and basal ganglia, showed phasic activation tied to the execution of responses. Finally, parietal and frontal regions showed systematic deactivations during task performance, consistent with previous reports that these regions may be associated with nontask semantic processing. We conclude that detection of change, when transient visual cues are not present, requires activation of extrastriate visual regions and frontal regions responsible for eye movements. These results suggest that studies of change blindness can inform understanding of more general attentional processing.

Adult↗

Episodic memory in left temporal lobe epilepsy: a functional MRI study.

Left medial temporal lobe epilepsy (MTLE) is associated with verbal memory impairment usually related to hippocampal damage. We used functional MRI (fMRI) to investigate the patterns of functional activity in healthy volunteers and MTLE patients engaged in verbal episodic memory tasks to look for evidence of a reallocation of verbal memory in epileptic patients. fMRI data were collected from seven MTLE patients with left-sided hippocampal sclerosis and 10 healthy right-handed control subjects on a 3T scanner. Subjects were instructed to learn a list of 17 words (encoding) and then to recall them (retrieval) on successive trials. Healthy volunteers and patients both exhibited bilateral activation (right higher than left) of the parahippocampal gyrus during the retrieval. This effect was more marked in the control subjects. In contrast to the control subjects, patients exhibited consistent and extensive left prefrontal activations in all the memory tasks. These findings show that verbal memory tasks did not involve the same functional patterns in patients and healthy volunteers. This may be interpreted as a dysfunctional response due to the epilepsy and left hippocampal sclerosis, and could reflect the early onset and progressive course of the disease.

Adolescent↗

Participation of the left posterior inferior temporal cortex in writing and mental recall of kanji orthography: A functional MRI study.

To examine the neuropsychological mechanisms involved in writing kanji (morphograms), we used functional MRI (fMRI) in 10 normal volunteers, all right-handed, native Japanese speakers. The experimental paradigms consisted of kana-to-kanji transcription, mental recall of kanji orthography and oral reading and semantic judgement of kana words. The first two tasks require manual and mental transcription of visually presented kana words into kanji, respectively, whereas the last two tasks involve language processing of the same set of stimulus words without recall of kanji. The transcription and mental recall tasks yielded lateralized activation of the left posterior inferior temporal cortex (PITC). By contrast, neither oral reading nor semantic judgement produced similar activation of the area. These results, in good accordance with lesion data, provide converging evidence that the left PITC plays an important role in writing kanji through retrieval of their visual graphic images, and suggest language-specific cerebral organization of writing. The set of fMRI experiments also provides new neuroimaging data on the cortical localization of basic language functions in people using a non-alphabetical language.

Adult↗

An improved method for spinal functional MRI with large volume coverage of the spinal cord.

PURPOSE: To develop a spinal functional MRI (fMRI) method with three-dimensional coverage of a large extent of the spinal cord with minimal partial volume effects MATERIALS AND METHODS: fMRI data of the cervical spinal cord were obtained at 1.5 T with a single-shot fast spin-echo imaging method, from thin contiguous sagittal slices spanning the cord. Thermal stimulation was applied to the palm of the hand in a block pattern with 15 degrees C for stimulation and 32 degrees C during baseline periods. Prior to analysis, the image data at each time point were reformatted into three-dimensional volumes and resliced perfectly transverse to the spinal cord. Smoothing was applied only in the superior-inferior (S/I) direction across uniform tissue types. Active voxels were then identified by means of a correlation to a model paradigm. RESULTS: The resulting activity maps demonstrate activity primarily in ipsilateral sensory areas and in some motor areas, consistent with the spinal cord neuroanatomy. These data also demonstrate detail of the subsegmental organization of the spinal cord, as well as anatomical detail of the spinous processes and positions of nerve roots. CONCLUSION: The spinal fMRI method described enables large volume coverage of the spinal cord in three dimensions, with reliable and reproducible results.

Humans↗

High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task.

Functional MRI (fMRI) studies of memory with coarse resolution of 4 x 4 x 5 mm often fail to demonstrate blood oxygenation level-dependent (BOLD) activation in the hippocampal formation. This failure occurs when nonactivating white matter is averaged with the signal from hippocampal gray matter, attenuating the total BOLD signal from a single voxel due to the "partial volume effect." In this study, we evaluated the suitability of high-resolution fMRI at 3T (voxel size 2 x 2 x 3 mm) for improved visualization of hippocampal activation during memory encoding in 21 healthy and 6 epilepsy subjects. We used a picture encoding task (block design) that involved memorization of indoor and outdoor scenes along with an appropriate resting task. Region-of-interest (ROI) analysis was performed; laterality indices (LIs) were calculated based on hippocampal ROIs (hROIs) or on global medial temporal ROIs (mtROIs). In 19 healthy subjects, robust bilateral BOLD signal changes within both ROIs were noted. The mean LI+/-SD for the hROIs is -0.12+/-0.06 and that for the medial temporal ROIs -0.12+/-0.05, with correlation between the LIs (r = 0.59, P = 0.009). Good concordance was noted between the surgical outcome and memory lateralization with the fMRI task employed in this study. The preliminary results are encouraging, and with continuing improvements in MRI scanner technology, we expect fMRI of the hippocampal formation at higher resolution to be possible and preferable. Furthermore, these results suggest that a larger study to test the utility of high-resolution fMRI in epilepsy presurgical evaluation is needed.

Adult↗

Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis.

Using functional magnetic resonance imaging (fMRI), we investigated whether movement-associated functional changes of the brain are present in patients who are, most likely, at the earliest stage of multiple sclerosis (MS). Functional MRI exams were obtained from 16 patients at presentation with clinically isolated syndromes (CIS) suggestive of MS and 15 sex- and age-matched healthy volunteers during the performance of three simple and one more complex motor tasks with fully normal functioning extremities. fMRI analysis was performed using statistical parametric mapping (SPM99). Compared to healthy volunteers, CIS patients had increased activations of the contralateral primary sensorimotor cortex (SMC), secondary somatosensory cortex (SII), and inferior frontal gyrus (IFG), when performing a simple motor task with the dominant hand. The increased recruitment of the contralateral primary SMC was also found during the performance of the same motor task with the non-dominant hand and with the dominant foot. In this latter case, an anterior shift of the center of activation of this region was detected. During the performance of a complex motor task with the dominant upper and lower limbs, CIS patients had an increased recruitment of a widespread network (including the frontal lobe, the insula, the thalamus), usually considered to function in motor, sensory, and multimodal integration processing. The comparison of brain activations during the performance of simple vs. complex motor tasks showed that the movement-associated somatotopic organization of the cerebral and cerebellar cortices was retained in patients with CIS. Cortical reorganization occurs in patients at presentation with CIS highly suggestive of MS. Local synaptic reorganization, recruitment of parallel existing pathways, and reorganization of distant sites are all likely to contribute to the observed functional changes. Hum. Brain Mapping 21:106-115, 2004.

Adult↗

Functional MRI of visual cortex in sedated 18 month-old infants with or without periventricular leukomalacia.

Functional MRI (fMRI) of the visual cortex was evaluated in 42 sedated 18-month-old infants (mean corrected age; 31 males, 11 females) with or without periventricular leukomalacia (PVL). Data from 14 infants could not be evaluated because of movement artefacts. Ten of the remaining 28 infants showed no significant fMRI response upon visual stimulation. In 18 infants, a significant signal change upon stimulation was found in the visual cortex: in 17 a signal decrease and in one a signal increase. Functional changes were located mainly in the anterior part of the visual cortex. Seven of the 28 infants had normal MRI and 21 showed variable occipital PVL. An fMRI response was equally frequent in infants without PVL (4 of 7 infants) and with PVL (14 of 21 infants). In conclusion, fMRI was shown to be feasible in sedated infants. No correlation was found between functional activation and the presence or absence of occipital PVL. Type of fMRI response (signal decrease) and localization (anterior part of the visual cortex) are different from those seen in adults, probably reflecting a combination of sedation effects and immaturity of the visual system. At present, fMRI is a highly promising research tool; its clinical relevance still has to be established.

Case-Control Studies↗

Model-free functional MRI analysis based on unsupervised clustering.

Conventional model-based or statistical analysis methods for functional MRI (fMRI) are easy to implement, and are effective in analyzing data with simple paradigms. However, they are not applicable in situations in which patterns of neural response are complicated and when fMRI response is unknown. In this paper the "neural gas" network is adapted and rigourosly studied for analyzing fMRI data. The algorithm supports spatial connectivity aiding in the identification of activation sites in functional brain imaging. A comparison of this new method with Kohonen's self-organizing map and with a fuzzy clustering scheme based on deterministic annealing is done in a systematic fMRI study showing comparative quantitative evaluations. The most important findings in this paper are: (1) both "neural gas" and the fuzzy clustering technique outperform Kohonen's map in terms of identifying signal components with high correlation to the fMRI stimulus, (2) the "neural gas" outperforms the two other methods with respect to the quantization error, and (3) Kohonen's map outperforms the two other methods in terms of computational expense. The applicability of the new algorithm is demonstrated on experimental data.

Adult↗

Neural basis of endogenous and exogenous spatial orienting. A functional MRI study.

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Adult↗

Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations.

The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG). Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fMRI weighting of approximately 90% was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling.

Brain↗

Utilization of an intra-oral diamagnetic passive shim in functional MRI of the inferior frontal cortex.

Due to the presence of gross magnetic susceptibility artifacts, functional MRI (fMRI) has proved problematic in studies of the human inferior frontal cortex (IFC). There is a strong desire, therefore, to employ techniques that mitigate susceptibility artifacts in the IFC while preserving the imaging parameters of an fMRI study. It has been shown that the use of a single, strongly diamagnetic, intra-oral passive shim significantly improves the homogeneity of the static magnetic field (B(0)) and, as a result, alleviates the susceptibility artifacts within the IFC. In this study, practical issues regarding the use of an intra-oral passive shim are examined. We investigated B(0) instabilities within the IFC resulting from subject head motion in order to calculate the effects of an intra-oral passive shim on the temporal variance of an EPI time series. These studies show that the addition of an intra-oral passive shim improves both B(0) homogeneity and signal stability, and increases sensitivity to functional activation.

Artifacts↗

Functional MRI localization of language in a 9-year-old child.

BACKGROUND: Localizing critical brain functions such as language in children is difficult and generally requires invasive techniques. Recently sensory, motor and language functions in adults have been mapped to specific brain locations using functional imaging techniques. Of these techniques, functional MRI (fMRI) is the least invasive and has the highest spatial and temporal resolution. Its use in adults is well documented but application to children has not been as well described. In the present study lateralization and localization of language was evaluated with fMRI prior to epilepsy surgery in a nine-year-old male with complex partial seizures, attentional difficulty and decreased verbal proficiency. METHODS: Two language paradigms well studied in adults (read, verb generation) and two additional language paradigms (antonym generation, latter fluency) were studied using whole brain fMRI after stimulus items and timing were adjusted to achieve the desired performance level during imaging. The patient was also conditioned to the magnet environment prior to imaging. RESULTS: Word reading and letter fluency tasks produced lateralized and localized activation similar to that seen in adults. The patient had no language deficits following an anterior 2/3 dominant temporal lobe resection. CONCLUSIONS: With modifications of protocols such as those detailed in this report, this non-invasive method for localizing language function is feasible for the presurgical evaluation of children as well being applicable for a variety of developmental language issues.

Brain↗

[Functional MRI in chronic liver disease of hepatitis B patients].

OBJECTIVE: To estimate the correlations between functional MRI (fMRI) parameters and the severity of chronic liver lesions of hepatitis B patients. METHODS: 47 hepatitis B patients [6 with chronic hepatitis, 41 with cirrhosis (14 with Child-Pugh class A cirrhosis; 12 with class B cirrhosis; and 15 with class C cirrhosis)] and 10 normal volunteers, referred for measurements of apparent diffusion coefficient (ADC) values of the liver, perfusion imaging parameters, portal flow parameters and serum markers of hepatic fibrosis were included in the study. Diffusion-weighted imaging (DWI) with different b values and b value remainder was performed. Time to peak (TP), maximum slope of increase (MSI) and distribution volume (DV) were measured with dynamic contrast material-enhanced MR imaging. Portal velocity and portal flow with phase contrast (PC) were measured. The patients' serum hepatic fibrosis markers, including hyaluronic acid (HA), type-III-procollagen (PC III), laminin (LN) and type-IV-collagen (C IV), were measured and analyzed together with the fMRI results. RESULTS: (1) The mean ADC3 in Child A, B, C cirrhosis patients was significantly lower than that in the controls (P < 0.05 in Child A, and P < 0.05 in Child B). (2) There was a significant increase of time to peak and a decrease of maximum slope of increase (P < 0.01) in the Child A, B, C patients than in the normal controls. (3) There was a significant decrease in portal velocity in cirrhotic patients as compared to that of the controls and chronic hepatitis patients (P < 0.01). (4) The mean HA in Child A, B, C cirrhosis patients was significantly higher than that in chronic hepatitis patients and in the controls (P < 0.01); The mean LN in Child A, B, C cirrhosis was also significantly higher than that in chronic hepatitis patients and in normal controls (P < 0.01); The mean PC III in Child A, B, C cirrhosis was significantly higher than that in the normal controls (P < 0.01). CONCLUSION: fMRI parameters can reflect some changes of the livers, therefore fMRI parameters are of value in clinical diagnosis and treatment of chronic hepatitis B patients.

Adult↗

A functional MRI study of mental image generation.

The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left.

Adolescent↗

Inflow versus deoxyhemoglobin effects in BOLD functional MRI using gradient echoes at 1.5 T.

Modified gradient-echo MR techniques were applied to study the effects of inflow on functional brain imaging studies using visual and motor cortex stimulation. The results demonstrate that the large signal changes, seen in previously reported gradient-echo studies at 1.5-2.0 T, are dominated by direct inflow effects, in particular when using a large flip angle and a thin slice. The findings suggest that inflow-based functional imaging, along with Blood Oxygenation Level Dependent (BOLD) functional MRI, may play an important role in future research towards the functional organization of the human brain.

Angiography↗

Functional MRI measurement of language lateralization in Wada-tested patients.

In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

Adult↗