[Resting state functional MRI of the brain]. / Funktionelle MRT des Gehirns im Ruhezustand.

The article presents an introduction to studies of the brain using functional magnetic resonance imaging during rest (rsfMRI). These studies are based on the fact that the resting brain exhibits a certain level of constant background activity. These spontaneous rsfMRT activities are characterized by fluctuations of the blood oxygenation level-dependent (BOLD) signal (typically in the low frequency part of the power spectrum < 0.1 Hz), which correlate with the local neuronal activity and can be seen as a result of neuronal coupling of monosynaptic and polysynaptic connections. The first network, described in detail is the so-called default mode network (DMN). This includes the medial prefrontal cortex (MPC), the posterior cingulate cortex (PCC), the precuneus (PrC), parts of the medial temporal lobe and the lateral inferior parietal lobe. In addition, a number of other resting state networks (RSNs), such as a motor, somatosensory, visual, auditory and cognitive system has been described, which partly process long-term connections from the cerebral cortex to the diencephalon, brain stem and cerebellum.

Neuroimaging patterns associated with motor control in traumatic brain injury.

OBJECTIVE: To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor outcome in the functional maps of these patients? METHODS: In an exploratory cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. RESULTS: Compared to age-matched, healthy controls performing the same task, TBI patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to "poor clinical outcome" had decreased fMRI-signal change in the cSM1 during baseline. CONCLUSIONS: These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.

Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia.

BACKGROUND: Conditioning processes have been proposed to play a role in the development of anxiety disorders. As yet, the neurobiologic correlates of emotional learning have not been fully understood in these patients. Accordingly, brain activity was studied in subcortical and cortical regions involved in the processing of negative affect during differential aversive classical conditioning. METHODS: Twelve patients with social phobia and 12 healthy control subjects were presented with paired conditioned (CS; neutral facial expressions) and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional magnetic resonance imaging (fMRI) was utilized to examine regional cerebral activity during habituation, acquisition,a nd extinction trials. Activity was measured with echo-planar-imaging (EPI), and signal intensity in individually defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional valence to the CS indicated that behavioral conditioning occurred in both groups. The presentation of CS associated with negative odor led to signal decreases in the amygdala and hippocampus of normal subjects, whereas an opposite increased activation in both regions was observed in patients. Regional differences were not found during habituation and extinction. CONCLUSIONS: Results suggest that conditioned aversive stimuli are processed in subcortical regions, with phobic patients differing from control subjects.

Early left periventricular brain lesions induce right hemispheric organization of speech.

Right-hemispheric organization of speech has been observed following early left-sided brain lesions involving the language cortex. The authors studied speech organization in hemiparetic patients with pre- and perinatally acquired lesions in the left periventricular white matter using fMRI, and found that right-hemisphere activation correlated with left facial motor tract involvement. This suggests that the impairment of speech motor output from the left hemisphere plays an important role in this alteration of language representation.

Myelinoclastic diffuse sclerosis (Schilder's disease): cliniconeuroradiologic correlations.

We report a 17-year-old boy with myelinoclastic diffuse sclerosis (Schilder's disease) presenting with left leg paresis, visual loss, and behavioral changes. CT and MRI showed two large lesions in the subcortical white matter of the occipital and parietal lobes of both hemispheres and increased intracranial pressure. Histology disclosed large areas of demyelination and perivascular infiltrates. The patient improved with coincident oral prednisolone treatment.

Edema and the lack of blood perfusion produce opposite effects on the magnetic resonance characteristics of acutely ischemic rat kidneys.

Both kidneys of 28 rats were studied with magnetic resonance imaging (0.35 tesla, double spin-echo technique with echo-delay times [TEs] of 28 and 56 ms and repetition times [TRs] of 0.5 and 2.0 seconds). Kidneys were studied before and up to 4 hours after ligation of the abdominal aorta above the origin of the left renal artery (20 rats) or after ligation of the left renal artery (eight rats). Any changes in the relaxation times of cortex and medulla and in the cortex-to-medulla contrast (CMC) were correlated to histologic data and renal water content. After the first hour following ligation of either the abdominal aorta or the left renal artery, the cortex of the left kidneys showed a 20% shortening of the mean T2 relaxation time (P less than .001), a 16% shortening of the mean T1 relaxation time (P less than .001), a 73% increase in mean CMC on T2-weighted images (P less than .001) and a 42% decrease in mean CMC on T1-weighted images (P less than .001). There were no significant changes either in relaxation times of the medulla of the left kidneys or in relaxation times and CMC of the right kidneys. During the next three hours, relaxation times of cortex and CMC remained unchanged in the rats with ligated abdominal aorta. In the rats with ligated renal artery, relaxation times of cortex and CMC returned to normal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumin labeled with Gd-DTPA. An intravascular contrast-enhancing agent for magnetic resonance blood pool imaging: preparation and characterization.

A paramagnetic-labeled macromolecule, albumin-(Gd-DTPA), was prepared for use as an intravascular contrast agent for magnetic resonance imaging. An average of 19 Gd-DTPA chelates were covalently conjugated to human serum albumin through the bifunctional anhydride of DTPA. The albumin-(Gd-DTPA) was characterized with use of high-performance liquid chromatography, sodium dodecyl sulfate gel electrophoresis, atomic absorption, biuret and Bradford protein tests, and by its effect on proton relaxation (relaxivity). The average molecular weight was 92,000 daltons, indicating the albumin conjugate was predominantly monomeric. The T1 relaxivity of albumin-(Gd-DTPA) was 273 mM-1 sec-1 relative to carrier concentration, which corresponds to a relaxivity of 14.9 mM-1 sec-1 relative to gadolinium concentration. The average conditional stability constant for albumin-bound Gd-DTPA chelate was log K = 20.0. Spin-echo images of rats demonstrated persistent enhancement of vascular tissues and slowly flowing blood. Application of albumin-(Gd-DTPA) may augment the MR assessments of blood volume, tissue perfusion, and flow characteristics.

Magnetic resonance imaging in patients with central nervous system pathology: a comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA).

RATIONALE AND OBJECTIVES: The objective of the two pivotal phase 3 studies was to evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd-DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. METHODS: Two multicenter, randomized, double-blind, parallel group studies were conducted in 395 patients with known or suspected central nervous system pathology. Subjects were randomized to receive a single 0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug administration. Precontrast and postcontrast administration magnetic resonance scans were acquired using identical imaging planes and techniques. RESULTS: No deaths or unexpected adverse events were reported in either group. A comparison of adverse events by intensity and relation demonstrated no statistically significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were equivalent with respect to confidence in diagnosis, conspicuity, and border delineation. CONCLUSIONS: Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable efficacy profiles, and the safety profiles were considered similar.

Differential amygdala activation in schizophrenia during sadness.

Several studies have reported impaired emotion processing in schizophrenic patients. However, the corresponding functional cerebral correlates of such impairment have not been fully understood, leaving the neurobiological basis of their affective symptoms unknown. Functional magnetic resonance imaging (fMRI) was utilized to examine brain activity in subcortical and cortical regions of 13 medicated male schizophrenic patients and 13 matched healthy controls during happy and sad mood induction. Results show brain activity in the amygdala of normal controls during negative affect, which is in line with previous neuroimaging findings. Unlike controls, schizophrenic patients have not demonstrated amygdala activation during sadness despite matched ratings to normal controls indicating a similar negative affect. Recognizing that structural abnormalities exist in the amygdala of schizophrenic patients, our results provide new evidence of functional abnormalities in the limbic system.

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study.

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.

Dynamic pattern of brain activation during sequencing of word strings evaluated by fMRI.

An impaired ability to recite highly automated word strings (e.g., the names of the months of the year) in reverse order concomitant with preserved production of the conventional sequence has been considered a salient sign of frontal lobe dysfunction. Using functional magnetic resonance imaging (fMRI), the spatial and temporal pattern of brain activation during covert performance of these tasks was evaluated in healthy subjects. As compared to the response obtained during forward recitation, re-sequencing of the word string yielded additional activation of the bilateral middle and inferior frontal gyri, the posterior parietal cortex and the left anterior cingulate gyrus. The prefrontal responses are in accordance with the clinical findings referred to. However, the set of activated areas, as a whole, presumably reflects contribution of the various components of the working memory system to the sequencing of word strings. During successive periods of task administration, subjects showed a linear increase of production speed. Analysis of corresponding dynamic changes of regional hemodynamic responses revealed a significant increase at the level of the left inferior parietal cortex and a decrease within the mesial aspect of the left superior frontal gyrus. Presumably, the former finding reflects increasing demands on the phonological short-term memory store, due to faster updating of its content under increased word production rate. Decreasing activation within the superior frontal gyrus might indicate contribution of this area to the initiation of the cognitive processes subserving the sequencing of verbal items. These findings demonstrate the capability of fMRI as a powerful tool for the analysis of dynamic brain activation.

Activation of right fronto-temporal cortex characterizes the 'living' category in semantic processing.

It is a vital ability for humans to distinguish between living and non-living objects. Whether the semantic features of these two classes of objects are represented in distinct brain areas, is unknown. In our study, words belonging to the categories 'living' and 'non-living' were presented visually to twelve right-handed volunteers, while brain activation was measured with event-related fMRI. Subjects had to judge whether the item belonged to one of these categories. Common areas of activation (P<0.05, corrected) during processing of both categories include the inferior occipital gyri bilaterally (BA 17/18), left inferior frontal gyrus (BA 44/45) and left inferior parietal lobe (BA 40). During processing of 'living' minus 'non-living' items, signal changes (P<0.05, corrected) were present in the the right inferior frontal (BA 47), middle temporal (BA 21) and fusiform gyrus (BA 19). Our results are in line with findings from patients with a deficit in semantic processing of living things, who specifically suffer from right hemispheric lesions.

The representation of articulation in the primary sensorimotor cortex.

Bilabial, alveolar and velar sounds are produced at different locations around the oral cavity. fMRI was used to localize cortical representation of articulation in seven healthy subjects during repetitive lip and vertical tongue movements as well as repetitive articulation of /pa/ (bilabial), /ta/ (alveolar), /ka/ (velar consonants) and a combination of all three in /pataka/. Centers of gravity (COG) analysis of fMRI activation in the primary motor (M1) and sensory cortex (S1) revealed /pa/- adjacent to lip representation and /ta/- articulation to tongue representation. The articulation of /pataka/ showed an activation pattern with a combination of the two M1/S1-components and additional activation in the supplementary motor area.

Functional lateralization of speech production at primary motor cortex: a fMRI study.

To evaluate lateralization of speech production at the level of the Rolandic cortex, functional magnetic resonance imaging (1.5 Tesla, 27 parallel axial slices, EPI-technique) was performed during a speech task (continuous silent recitation of the names of the months of the year). As control conditions, non-speech tongue movements and silent singing of a well-known melody with the syllable 'la' as its carrier were considered. Tongue movements produced symmetrical activation at the lower primary motor cortex. During automatic speech a strong functional lateralization to the left hemisphere emerged within the same area. In contrast, singing yielded a predominant right-sided activation of the Rolandic region. Functional lateralization of speech production therefore seems to include the precentral gyrus as well as Broca's area.

Opposite hemispheric lateralization effects during speaking and singing at motor cortex, insula and cerebellum.

Aside from spoken language, singing represents a second mode of acoustic (auditory-vocal) communication in humans. As a new aspect of brain lateralization, functional magnetic resonance imaging (fMRI) revealed two complementary cerebral networks subserving singing and speaking. Reproduction of a non-lyrical tune elicited activation predominantly in the right motor cortex, the right anterior insula, and the left cerebellum whereas the opposite response pattern emerged during a speech task. In contrast to the hemodynamic responses within motor cortex and cerebellum, activation of the intrasylvian cortex turned out to be bound to overt task performance. These findings corroborate the assumption that the left insula supports the coordination of speech articulation. Similarly, the right insula might mediate temporo-spatial control of vocal tract musculature during overt singing. Both speech and melody production require the integration of sound structure or tonal patterns, respectively, with a speaker's emotions and attitudes. Considering the widespread interconnections with premotor cortex and limbic structures, the insula is especially suited for this task.

Differential activation in parahippocampal and prefrontal cortex during word and face encoding tasks.

Episodic encoding is the first step in the formation of a memory trace. The relation between type of stimulus material and regional brain activation is not fully understood. We measured brain activation using fMRI in 12 healthy subjects during two experiments, word and face encoding. A widespread network of common activations in both tasks was present in the bilateral frontal (BA44/45), occipital (BA17/18/19) and fusiform gyri (BA37) as well as the right hippocampal formation (BA30). A region-of-interest-analysis for the hippocampal formation and dorsolateral prefrontal cortex (DLPFC) was performed additionally. During face encoding the right dorsal and during word encoding the bilateral ventral hippocampal region was activated. In the prefrontal cortex a lateralization to the left side was present only for word encoding. During encoding, activation in the inferior frontal and hippocampal cortex is modulated by the type of stimulus material.

Rate-dependent activation of a prefrontal-insular-cerebellar network during passive listening to trains of click stimuli: an fMRI study.

Eight volunteers underwent fMRI during passive listening to click trains. Using a parametric approach, rate-response profiles across the frequency band considered (2-6 Hz) were determined. Several cerebral structures outside the central-auditory pathways and target areas displayed distinct activation patterns each: rate-response profiles resembling high-pass (left side) or low-pass filtered (right side) signal series emerged at the level of the anterior insula, band-pass like characteristics (center frequency: 3-4 Hz) were observed within the left inferior frontal gyrus, and click train rates > 4 Hz yielded enhanced activation of the right cerebellar hemisphere. A variety of clinical and experimental data indicate that the left and right cerebral hemispheres act as high- and low-pass filters, respectively, on auditory input (double filtering by frequency theory). In light of the present fMRI data, the anterior insula contributes to the assumed double filtering by frequency functions. Furthermore, these intrasylvian areas seem to join up with the right cerebellum and the left inferior frontal gyrus to a network subserving parsing/timing functions within the auditory-verbal domain.

fMRI reveals amygdala activation to human faces in social phobics.

Functional magnetic resonance imaging was used to determine the activation of the amygdala while seven social phobics and five healthy controls were exposed to slides of neutral faces as well as aversive odor stimuli. The amygdala was selectively activated in the social phobics during presentation of the face stimuli. The data show for the first time that the amygdala is active in human phobics when they are exposed to potentially fear-relevant stimuli. Further research is needed to determine the extent to which overactivation of the amygdala precedes or is a consequence of phobia.

Cavernous angioma of the optic tract.

A cavernous angioma of the right optic tract in a 35-year-old man is presented. The patient suffered from headaches and had a left homonymous visual field defect after subarachnoid haemorrhage and an intracerebral haematoma in the right temporomedial region, revealed by computed tomography (CT). Follow-up CT showed a small contrast-enhanced lesion in the right suprasellar and parasellar cistern. Angiography on three occasions did not reveal a vascular lesion. Magnetic resonance imaging was helpful both for diagnosis and planning surgical therapy. It showed typical signs of a cavernous angioma of the right optic tract; the diagnosis was confirmed by surgery and histological examination. This appears to be the first reported case of a cavernous angioma of the optic tract.

The influence of current direction on phosphene thresholds evoked by transcranial magnetic stimulation.

OBJECTIVES: To quantify phosphene thresholds evoked by transcranial magnetic stimulation (TMS) in the occipital cortex as a function of induced current direction. METHODS: Phosphene thresholds were determined in 6 subjects. We compared two stimulator types (Medtronic-Dantec and Magstim) with monophasic pulses using the standard figure-of-eight coils and systematically varied hemisphere (left and right) and induced current direction (latero-medial and medio-lateral). Each measurement was made 3 times, with a new stimulation site chosen for each repetition. Only those stimulation sites were investigated where phosphenes were restricted to one visual hemifield. Coil positions were stereotactically registered. Functional magnetic resonance imaging (fMRI) of retinotopic areas was performed in 5 subjects to individually characterize the borders of visual areas; TMS stimulation sites were coregistered with respect to visual areas. RESULTS: Despite large interindividual variance we found a consistent pattern of phosphene thresholds. They were significantly lower if the direction of the induced current was oriented from lateral to medial in the occipital lobe rather than vice versa. No difference with respect to the hemisphere was found. Threshold values normalized to the square root of the stored energy in the stimulators were lower with the Medtronic-Dantec device than with the Magstim device. fMRI revealed that stimulation sites generating unilateral phosphenes were situated at V2 and V3. Variability of phosphene thresholds was low within a cortical patch of 2x2cm(2). Stimulation over V1 yields phosphenes in both visual fields. CONCLUSIONS: The excitability of visual cortical areas depends on the direction of the induced current with a preference for latero-medial currents. Although the coil positions used in this study were centered over visual areas V2 and V3, we cannot rule out the possibility that subcortical structures or V1 could actually be the main generator for phosphenes.