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Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).

Adult↗

Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography.

We present a new approach for non-invasive localization of focal epileptogenic discharges in patients considered for surgical treatment. EEG-triggered functional MR imaging (fMRI) and 3D EEG source localization were combined to map the primary electrical source with high spatial resolution. The method is illustrated by the case of a patient with medically intractable frontal lobe epilepsy. EEG obtained in the MRI system allowed triggering of the fMRI acquisition by the patient's habitual epileptogenic discharges. fMRI revealed multiple areas of signal enhancement. Three-dimensional EEG source localization identified the same active areas and provided evidence of onset in the left frontal lobe. Subsequent electrocorticography from subdural electrodes confirmed spike and seizure onset over this region. This approach, i.e. the combination of EEG-triggered fMRI and 3D EEG source analysis, represents a promising additional tool for presurgical epilepsy evaluation allowing precise non-invasive identification of the epileptic foci.

Adolescent↗

Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional MRI.

RATIONALE: Physiological changes (such as heart rate and respiration rate) associated with strong pharmacological stimuli could change the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) mapping signals, independent of neural activity. OBJECTIVES: This study investigates whether the physiological changes per se associated with systemic cocaine administration (1 mg/kg) contaminate the BOLD fMRI signals by measuring BOLD and cerebral blood flow (CBF) fMRI and estimating the cerebral metabolic rate of oxygen (CMRO(2)) changes. MATERIALS AND METHODS: BOLD and CBF fMRI was performed, and changes in CMRO(2) were estimated using the BOLD biophysical model. RESULTS: After systemic cocaine administration, blood pressure, heart rate, and respiration rate increased, fMRI signals remained elevated after physiological parameters had returned to baseline. Cocaine induced changes in the BOLD signal within regions of the reward pathway that were heterogeneous and ranged from -1.2 to 5.4%, and negative changes in BOLD were observed along the cortical surface. Changes in CBF and estimated CMRO(2) were heterogeneous and positive throughout the brain, ranging from 14 to 150% and 10 to 55%, respectively. CONCLUSIONS: This study demonstrates a valuable tool to investigate the physiological and biophysical basis of drug action on the central nervous system, offering the means to distinguish the physiological from neural sources of the BOLD fMRI signal.

Algorithms↗

Gilles de la Tourette syndrome and voluntary movement: a functional MRI study.

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.

Adult↗

Modulation of signal changes in gradient-recalled echo functional MRI with increasing echo time correlate with model calculations.

Based on systematic in vivo studies analysed by fuzzy clustering, we prove the complex dependence of functional magnetic resonance imaging (fMRI) signal changes on echo time (TE) (ranging from 42 ms up to 160 ms) in the human visual cortex at 1.5 Tesla. We obtain a steady increase of signal enhancement with increasing TE, except at TE = 130 ms where the signal increase is significantly less than at 100 and 160 ms, respectively, caused by signal dephasing of spins in the vascular environment of the cortical region imaged. A comparison with model calculations reveals that vessels with a diameter of about 0.5 to 1 mm may be the main source of gradient-recalled echo fMRI signal changes at 1.5 Tesla at the given spatial resolution. In addition to conventional correlation analysis, fuzzy cluster analysis has been applied to evaluate fMRI data sets. Our results also indicate that, despite the similar temporal pattern of the functional response, it is possible to differentiate between areas which show higher signal enhancement (cluster 1, higher blood volume fraction) and lower signal enhancement (cluster 2, lower blood volume fraction), reflecting the different vascular environment. Therefore, fuzzy cluster analysis may help to extract functional information from activated areas closer to the actual neuronal activation.

Adolescent↗

Visual processing in infants and children studied using functional MRI.

We studied the development of visual processing in 58 children, ranging from 1 d to 12 y of age (median age 29 mo), using functional magnetic resonance imaging. All but nine children had either been sedated using chloral hydrate (n = 12) or pentobarbital (n = 28). Nine children were studied under a full halothane/ N2O:O2 anesthesia. In the first postnatal month, 30% of the neonates showed a positive blood oxygenation level-dependent (BOLD) contrast signal, whereas, for infants between the ages of 1 mo and 1 y, 27% did so. Thirty-one percent of children between 1 and 6 y of age and 71% of children aged 6 y and above showed a positive BOLD contrast signal change to our visual stimulation paradigm. Besides the usual positive BOLD contrast signal change, we also noted that a large portion of the children measured displayed a negative BOLD contrast signal change. This negative BOLD contrast signal change was observed in 30% of children up to 1 mo of age, in 27% between 1 mo and 1 y of age, in 47% between 1 and 6 y of age, and in 14% of children 6 y and older. In the children in which we observed a negative correlating BOLD contrast signal change, the locus was more anterior and more lateral than the positive BOLD contrast signal, placing it in the secondary visual cortical area. The results indicate that when using functional magnetic resonance imaging on children, the primary visual cortical area does not respond functionally in the same manner as that of the adult until 1.5 y of age. This supports earlier clinical and electrophysiologic findings that different cortical mechanisms seem to contribute to visual perception at different times postnatally.

Adult↗

[Exploration of visual memory by functional MRI].

PURPOSE: The aim of our study was to evidence the location of the cortical area triggered by visual memory tasks by he mean of functional magnetic resonance imaging examination (fMRI). METHODS: Twelve healthy volunteers underwent fMRI examination on a 1.5 Tesla magnet with echoplanar imaging sequence during figurative and non-figurative memory tasks. An area was considered to be activated if at least 10 contiguous voxels activation was noted. Activated areas were defined for both tasks and the brain mapping was realized according to Talairach atlas. RESULTS: For all examinations a bilateral activity was evidenced (area 17 and 18). In addition, a frontal activation was also noted in 83% of the cases for both tasks. However, frontal activation was bilateral in 9/10 cases for the figurative task and 6/10 cases for the non-figurative task. CONCLUSION: FMRI was able to evidence activation of cerebral areas during visual memory tasks in all our study cases. Frontal activation was not discriminative of figurative or non figurative memory. This might be probably explain by inappropriate non-figurative tests. FMRI should allow a better knowledge of memory mechanisms as well as an enhancement of functional cerebral mapping before surgery.

Adult↗

Cortical motor activation in akinetic schizophrenic patients: a pilot functional MRI study.

Akinesia is associated with supplementary motor area (SMA) dysfunction in Parkinson's disease. We looked for a similar association in patients with schizophrenia. Using functional magnetic resonance imaging (fMRI), we compared motor activation in 6 akinetic neuroleptic-treated schizophrenic patients and 6 normal subjects. Schizophrenic patients had a defective activation in the SMA, left primary sensorimotor cortex, bilateral lateral premotor and inferior parietal cortices, whereas the right primary sensorimotor cortex and a mesial frontal area were hyperactive. SMA was hypoactive in akinetic schizophrenic patients, emphasizing the role of this area in motor slowness. Other abnormal signals likely reflect schizophrenia-related abnormal intracortical connections.

Adult↗

Functional MRI study of PASAT in normal subjects.

The paced auditory serial addition test (PASAT) is routinely used to evaluate the cognitive part of the multiple sclerosis functional composite (MSFC) score, the new reference index of patient disability. PASAT is sensitive to subtle cognitive impairment related to MS, although the cognitive components of this test still remain unclear. In order to better characterize brain systems involved during this complex task, functional magnetic resonance imaging (fMRI) experiments were conducted during PASAT in a population of ten normal subjects. The paradigm consisted of a series of 61 single-digit numbers delivered every 3 s. After each number, subjects were asked to overt vocalize the result of the addition of the two last numbers heard. A control task consisting of the repetition of the same series of single-digit numbers was used. Statistical group analysis was performed using the random effect procedure (SPM 99). Cortical activation was observed in the left prefrontal cortex, the supplementary motor area, the lateral premotor cortex, the cingulate gyrus, the left parietal lobe, the left superior temporal gyrus, the left temporal pole, and visual associative areas. fMRI activations underlying PASAT were consistent with an involvement of verbal working memory and the semantic memory retrieval network which could be related to arithmetic fact retrieval. This study on normal subjects could provide a base for the understanding of the potential abnormal cortical activation in MS patients performing this test for a cognitive evaluation.

Adult↗

Brain activation patterns during a verbal fluency test-a functional MRI study in healthy volunteers and patients with schizophrenia.

FMRI was used to study cortical activation patterns in nine healthy male subjects and nine high-functioning male schizophrenia patients during a letter verbal fluency task. Both groups showed similar patterns of activation, however, in controls the activation was primarily in the left broca area, while for schizophrenia patients, it was more bilateral. These data indicate that high-functioning schizophrenia patients show a reduced language lateralization of the frontal cortex compared to healthy controls.

Adult↗

Sparse imaging of the auditory oddball task with functional MRI.

Cortical reactions to rare task-related stimuli have been studied with electrophysiological methods in the assessment of the P300 component as well as in functional imaging studies with regard to oddball tasks. While functional magnetic resonance imaging studies using auditory stimuli have to deal with interference between auditory stimuli and scanner noise, the aim of our study was to assess auditory target processing with the sparse imaging method. Single volumes of echo-planar imaging were acquired 4 s following the onset of the stimuli of interest. In keeping with previous studies, target stimuli activated the insula, superior temporal gyrus, cingulate gyrus, middle frontal gyrus, parietal cortex and the cerebellum. Our results encourage the application of the sparse imaging method in experiments on cognitive processing elicited by auditory stimulation in a silent environment.

Acoustic Stimulation↗

Frontopolar and anterior temporal cortex activation in a moral judgment task: preliminary functional MRI results in normal subjects.

OBJECTIVE: To study the brain areas which are activated when normal subjects make moral judgments. METHOD: Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either "right" or "wrong". Half of the sentences had an explicit moral content ("We break the law when necessary"), the other half comprised factual statements devoid of moral connotation ("Stones are made of water"). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemodynamically modeled for event-related fMRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. RESULTS: Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (BA 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. CONCLUSIONS: These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct.

Adult↗

[Presurgical mapping with functional MRI: comparative study with transcranial magnetic stimulation and intraoperative mapping].

PURPOSE: The accuracy of preoperative mappings in patients with brain tumors near the central sulcus using functional magnetic resonance imaging (fMRI) or transcranical magnetic stimulation (TCS) was evaluated by comparative reference to intraoperative mapping. METHODS: The thumb movement was evoked by TCS for the mapping of the motor cortex. After the placement of the marker determined by TCS on the scalp, fMRI under motor tasks consisting of repetitive grasping was performed. For motor cortex activation, an axial oblique plane to maximize gray matter sampling in the rolandic cortex was employed in order to compare these different mapping techniques more precisely. Sixteen patients with brain tumors were included in this study. RESULTS: In nine patients, fMRI disclosed activation in one restricted gyrus or in the localized area around one restricted sulcus. Of these nine patients, preoperative TCS mapping corresponded closely with fMRI in six, while in the remaining three, the TCS marker fell between 1 and 2 cm apart from the fMRI-activated area. However, in these three patients, intraoperative electrocortical stimulation corresponded with the preoperative mapping with fMRI. In six patients, contigucus two gyri were activated by motor tasks. The TCS marker was disclosed on one of the two activated gyri. Of these six patients, the position of the TCS marker and fMRI-activated site corresponded with each other in four cases. They were found on the same gyrus but there was 1.0-2.0 cm distance between them in two cases. Intraoperative somatosensory evoked potential was monitored in two of these six cases. They corresponded well with the mapping by fMRI and TCS together. In only one patient, no significant activation area was obtained by fMRI because of excessive head motion during motor tasks. The TCS marker in this patient was identical with intraoperative electro-cortical stimulation mapping. CONCLUSION: For presurgical planning in patients with brain tumor near the central sulcus, comparative evaluation with fMRI and TCS is applicable and provides accurate functional mapping.

Adult↗

A quantitative comparison of functional MRI cluster analysis.

The aim of this work is to compare the efficiency and power of several cluster analysis techniques on fully artificial (mathematical) and synthesized (hybrid) functional magnetic resonance imaging (fMRI) data sets. The clustering algorithms used are hierarchical, crisp (neural gas, self-organizing maps, hard competitive learning, k-means, maximin-distance, CLARA) and fuzzy (c-means, fuzzy competitive learning). To compare these methods we use two performance measures, namely the correlation coefficient and the weighted Jaccard coefficient (wJC). Both performance coefficients (PCs) clearly show that the neural gas and the k-means algorithm perform significantly better than all the other methods using our setup. For the hierarchical methods the ward linkage algorithm performs best under our simulation design. In conclusion, the neural gas method seems to be the best choice for fMRI cluster analysis, given its correct classification of activated pixels (true positives (TPs)) whilst minimizing the misclassification of inactivated pixels (false positives (FPs)), and in the stability of the results achieved.

Algorithms↗

Linking semantic priming effect in functional MRI and event-related potentials.

The aim of this study is to examine the neural substrates involved in semantic priming using a combined event-related functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) study. Twelve subjects were instructed to judge whether the presented target word was a real word or a nonword. Under the related condition, target words were preceded by a semantically related prime word. On the other hand, under the unrelated condition, prime words did not have semantic relatedness with the target word. The reaction time for reaching a judgment was longer under the unrelated condition than under the related condition, indicating that the recognition of target words is promoted by semantic priming under the related condition. In the fMRI results, we found reduced activity in the dorsal and ventral left inferior frontal gyrus, the anterior cingulate, and left superior temporal cortex for related versus unrelated conditions (i.e., the repetition suppression effect). ERP analysis revealed that the amplitude of the N400 component was reduced under the related condition compared with the unrelated condition (i.e., the N400 priming effect). Correlation analysis between the BOLD repetition suppression effect and the N400 priming effect decomposed by independent component analysis (ICA) across subjects showed significant correlation in the left superior temporal gyrus. This finding is consistent with the recent MEG data suggesting that the source of N400 is judged to be the bilateral superior temporal lobe. We discussed this finding herein in relation to the modulation of access to the phonological representation caused by semantic priming.

Adult↗

Functional MRI and novel picture-learning among older patients with chronic schizophrenia: abnormal correlations between recognition memory and medial temporal brain response.

The relationship between disordered brain function and learning deficits in chronic schizophrenia is unclear. The authors compared correlations of brain response to picture encoding with subsequent recognition memory between samples of clinically stable patients over age 45 with schizophrenia and demographically similar healthy individuals. Subjects were studied with functional magnetic resonance imaging during novel picture encoding and a control condition. Comparison subjects showed an inverse relationship between subsequent recognition memory and brain response in medial temporal areas. Among schizophrenia patients, brain response in these regions was positively correlated with recognition memory. Brain-behavior relationships during learning were thus found to be qualitatively different between schizophrenic patients and healthy subjects.

Aged↗

Pulmonary functional MRI: an animal model study of oxygen-enhanced ventilation combined with Gd-DTPA-enhanced perfusion.

BACKGROUND: The assessment of regional pulmonary ventilation and perfusion is essential for the evaluation of a variety of lung disorders. Pulmonary ventilation MRI using inhaled oxygen as a contrast medium can be obtained with a clinical MR scanner, without additional equipment, and has been demonstrated to be a feasible means of assessing ventilation in animal models and some clinical patients. However, few studies have reported on MR ventilation-perfusion imaging. In this study, we evaluated the usefulness of oxygen-enhanced ventilation in combination with first-pass Gd-DTPA-enhanced perfusion MRI in a canine model of pulmonary embolism and airway obstruction. METHODS: Peripheral pulmonary embolisms were produced in eight dogs by intravenous injection of gelfoam strips at the pulmonary segmental arterial level, and airway obstructions were created in five of the dogs by inserting a self-designed balloon catheter into a secondary bronchus. Oxygen-enhanced MR ventilation images were produced by subtracting images from before and after inhalation of pure oxygen. Pulmonary perfusion MR images were acquired with a dynamic three-dimensional fast gradient-echo sequence. MR ventilation and perfusion images were read and contrasted with results from general examinations of pathological anatomy, ventilation-perfusion scintigraphy, and pulmonary angiography. RESULTS: Regions identified as having airway obstructions matched using both MR ventilation and perfusion imaging, but regions of pulmonary embolisms were mismatched. The area of airway obstruction defects was smaller using MR ventilation imagery than that using ventilation scintigraphy. Abnormal perfusion regions due to pulmonary embolisms were divided into defective regions and reduced regions based on the time course of signal intensity changes. In the diagnosis of pulmonary embolisms with the technique of ventilation and perfusion MRI, sensitivity and specificity were 75.0% and 98.1%, respectively, and the diagnostic results of this MRI technique were in agreement with the results of ventilation-perfusion scintigraphy and pulmonary angiography (K: 0.899, 0.743). CONCLUSIONS: Oxygen-enhanced ventilation in combination with pulmonary perfusion MRI can be used to diagnose abnormalities of airways and blood vessels in the lungs, and can provide regional functional information with high spatial and temporal resolution. This method possesses great potential value for clinical applications.

Airway Obstruction↗