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PubMed1999

Spatial attention affects brain activity in human primary visual cortex.

Functional MRI was used to test whether instructing subjects to attend to one or another location in a visual scene would affect neural activity in human primary visual cortex. Stimuli were moving gratings restricted to a pair of peripheral, circular apertures, positioned to the right and to the left of a central fixation point. Subjects were trained to perform a motion discrimination task, attending (without moving their eyes) at any moment to one of the two stimulus apertures. Functional MRI responses were recorded while subjects were cued to alternate their attention between the two apertures. Primary visual cortex responses in each hemisphere modulated with the alternation of the cue; responses were greater when the subject attended to the stimuli in the contralateral hemifield. The attentional modulation of the brain activity was about 25% of that evoked by alternating the stimulus with a uniform field.

Attention↗

PubMed2003

Quantitative mapping of cerebral deoxyhemoglobin content using MR imaging.

In this study, we present a magnetic resonance imaging (MRI) method for quantifying cerebral deoxyhemoglobin content that is based on a measurement of the reversible contribution (R'2) of the transverse relaxation rate under the assumption of a quantitative relationship between R'2 and deoxyhemoglobin content. A numerical simulation was performed assuming a specific pulse sequence conventionally employed for R'2 measurement. The results showed a near linear relationship between R'2 and deoxyhemoglobin content in the physiological range of oxygen extraction for almost all sized vessels, although a large diffusion effect for capillary sized vessels compromised the relationship. Concerning the methodology for R'2 measurement, a theoretical analysis showed that multiexponential transverse signal decay of brain parenchyma may result in a considerable underestimation or overestimation of R'2, if a conventional method is employed for R'2 quantification. A modified method for correcting the effect of multiexponential signal decay was employed for R'2 measurement of the brain in normal volunteers. The results showed a high level of agreement between the R'2 values measured in our study and those estimated from physiological parameters obtained using other modalities such as PET. In the context of BOLD contrast-based functional MRI, the method proposed provides a quantitative mapping of baseline cerebral deoxyhemoglobin content, which is the essential physiological parameter for calibrating the stimulation-induced BOLD signal change and mapping neuronal activity in a quantitative manner by functional MRI.

Adult↗

PubMed2005

Brain correlates of negative and positive visuospatial priming in adults.

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.

Adolescent↗

PubMed2001

Depth of processing effects on neural correlates of memory encoding: relationship between findings from across- and within-task comparisons.

Neuroimaging studies have implicated the prefrontal cortex and medial temporal areas in the successful encoding of verbal material into episodic memory. The present study used event-related functional MRI to investigate whether the brain areas associated with successful episodic encoding of words in a semantic study task are a subset of those demonstrating depth of processing effects. In addition, we tested whether the brain areas associated with successful episodic encoding differ depending on the nature of the study task. At study, 15 volunteers were cued to make either animacy or alphabetical decisions about words. A recognition memory test including confidence judgements followed after a delay of 15 min. Prefrontal and medial temporal regions showed greater functional MRI activations for semantically encoded words relative to alphabetically encoded words. Two of these regions (left anterior hippocampus and left ventral inferior frontal gyrus) showed greater activation for semantically encoded words that were subsequently recognized confidently. However, other regions (left posterior hippocampus and right inferior frontal cortex) demonstrated subsequent memory effects, but not effects of depth of processing. Successful memory for alphabetically encoded words was also associated with greater activation in the left anterior hippocampus and left ventral inferior frontal gyrus. The findings suggest that episodic encoding for words in a semantic study task involves a subset of the regions activated by deep relative to shallow processing. The data provide little evidence that successful episodic encoding during a shallow study task depends upon regions different from those that support the encoding of deeply studied words. Instead, the findings suggest that successful episodic encoding during a shallow study task relies on a subset of the regions engaged during successful encoding in a deep task.

Acoustic Stimulation↗

PubMed1998

A critique of the use of the Kolmogorov-Smirnov (KS) statistic for the analysis of BOLD fMRI data.

The use of the Kolmogorov-Smirnov (KS) statistic for testing hypotheses regarding activation in blood oxygenation level-dependent functional MRI data is critiqued on both theoretical and empirical grounds. Theoretically, it is argued that the KS test is formally unable to support inferences of interest to most neuro-imaging studies and has reduced sensitivity compared with parametric alternatives. Empirically, false-positive rates yielded by the KS test in human data collected under the null hypothesis were significantly in excess of tabular values. These excessive false-positive rates could be explained by the presence of temporal autocorrelation. We also present evidence that the distribution of blood oxygenation level-dependent functional MRI data is only slightly nonnormal, questioning the initial impetus for the use of the KS test in this context. Finally, it is noted that parametric alternatives exist that do provide adequate control of the false-positive rate and can support inferences of interest.

Algorithms↗

PubMed1999

[The effect of the stimulus frequency, stimulus amplitude and blood pressure on the signal response in functional MRT: studies on an animal model].

PURPOSE: To examine the influence of frequency and amplitude of a stimulus and the effect of blood pressure on signal intensity changes in functional MRI. METHODS: Somatosensory stimulation of five (normotonic/hypotonic) anesthetized rats was performed with different stimulus frequencies and amplitudes. Measurements were performed with a 2.4 Tesla experimental scanner using a gradient-echo (GE) echo-planar imaging (EPI) sequence. RESULTS: The highest signal change was found at a frequency of 3 Hz and a stimulation amplitude of ten times the threshold value. A decrease of blood pressure to half the normotonic value gave rise to a decrease of the neuronal response of about 17%. CONCLUSION: Optimization of the stimulation frequency and stimulation amplitude maximizes signal changes in functional MRI of the somatosensory cortex. Even with a standardized paradigm, variations in measured neuronal activity may occur when blood pressure changes cannot be compensated by autoregulation.

Animals↗

PubMed1999

Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.

Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology.

Adult↗

PubMed1998

Functional analysis of primary visual cortex (V1) in humans.

Human area V1 offers an excellent opportunity to study, using functional MRI, a range of properties in a specific cortical visual area, whose borders are defined objectively and convergently by retinotopic criteria. The retinotopy in V1 (also known as primary visual cortex, striate cortex, or Brodmann's area 17) was defined in each subject by using both stationary and phase-encoded polar coordinate stimuli. Data from V1 and neighboring retinotopic areas were displayed on flattened cortical maps. In additional tests we revealed the paired cortical representations of the monocular "blind spot." We also activated area V1 preferentially (relative to other extrastriate areas) by presenting radial gratings alternating between 6% and 100% contrast. Finally, we showed evidence for orientation selectivity in V1 by measuring transient functional MRI increases produced at the change in response to gratings of differing orientations. By systematically varying the orientations presented, we were able to measure the bandwidth of the orientation "transients" (45 degrees).

Brain Mapping↗

PubMed2004

Cholinergic enhancement of frontal lobe activity in mild cognitive impairment.

Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept) on cognition and brain activity in patients with amnestic mild cognitive impairment (MCI), a diagnosis associated with a high risk of developing AD. Nine older adults with MCI were compared with nine healthy, demographically matched controls. At baseline, patients showed reduced activation of frontoparietal regions relative to controls during a working memory task. After stabilization on donepezil (5.7 +/- 1.7 weeks at 10 mg) patients showed increased frontal activity relative to unmedicated controls, which was positively correlated with improvement in task performance (r = 0.49, P = 0.05) as well as baseline hippocampal volume (r = 0.62, P < 0.05). The patients' overall cognitive function was stable or improved throughout the study. Short-term treatment with a cholinesterase inhibitor appears to enhance the activity of frontal circuitry in patients with MCI, and this increase appears to be related to improved cognition and to baseline integrity of the hippocampus. These relationships have implications for understanding the mechanisms by which cognition-enhancing medications exert their effects on brain function and for the use of functional MRI in early detection and treatment monitoring of AD and MCI.

Aged↗

PubMed2006

Application of k-space energy spectrum analysis to susceptibility field mapping and distortion correction in gradient-echo EPI.

Echo-planar imaging (EPI) is widely used in functional MRI studies. It is well known that EPI quality is usually degraded by geometric distortions, when there exist susceptibility field inhomogeneities. EPI distortions may be corrected if the field maps are available. It is possible to estimate the susceptibility field gradients from the phase reconstruction of a single-TE EPI image, after a successful phase-unwrapping procedure. However, in regions affected by pronounced field gradients, the phase-unwrapping of a single-TE image may fail, and therefore the estimated field maps may be incorrect. It has been reported that the field inhomogeneity may be calculated more reliably from T2*-weighted images corresponding to multiple TEs. However, the multi-TE MRI field mapping increases the scan time. Furthermore, the measured field maps may be invalid if the subject's position changes during dynamic scans. To overcome the limitations in conventional field mapping approaches, a novel k-space energy spectrum analysis algorithm is developed, which quantifies the spatially dependent echo-shifting effect and the susceptibility field gradients directly from the k-space data of single-TE gradient-echo EPI. Using the k-space energy spectrum analysis, susceptibility field gradients can be reliably measured without phase-unwrapping, and EPI distortions can be corrected without extra field mapping scans or pulse sequence modification. The reported technique can be used to retrospectively improve the image quality of the previously acquired EPI and functional MRI data, provided that the complex-domain k-space data are still available.

Artifacts↗

PubMed2003

Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.

Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.

Antineoplastic Agents↗

PubMed2004

Activation of the primary and association auditory cortex by the transition of sound intensity: a new method for functional examination of the auditory cortex in humans.

During functional MRI image acquisition, the scanning equipment generates substantial auditory noise, the effects of which are usually ignored. To investigate the neural activity in response to the transition of noise, we measured cerebral responses to short silent periods (1 and 5 s) during which the slice readout gradients were switched off. In all 15 normal volunteers, the 1 s silence bilaterally activated the primary and association auditory cortex. Subtraction of the response to the 1 s silent period from that to the 5 s silent period revealed the activation related to the onset (transition of sound from OFF to ON) event, indicating that the 1 s response is offset (transition of sound from ON to OFF) related. The complex response of the auditory cortex to the transition of the noise should be considered in designing functional MRI with auditory tasks.

Acoustic Stimulation↗

PubMed2000

Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults.

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI). BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy. METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation. RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca's area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults. CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.

Adolescent↗

PubMed1994

Functional magnetic resonance imaging at 1.5 T: activation pattern in schizophrenic patients receiving neuroleptic medication.

Activation of the cerebral cortex during motor task performance can be visualised with functional MRI. A modified FLASH sequence (TR/TE/alpha 100/60/40 degrees, first order flow rephased, fat suppression, reduced bandwidth 28 Hz/pixel, 120 repetitions, three cycles of rest and finger movement for each hand) on a standard 1.5 T clinical imager was used to investigate 10 schizophrenic patients receiving clozapine and 10 healthy volunteers. All subjects were right-handed. Color-coded statistical parametric maps (SPM) based on the Student's t-test were calculated. A grid overlay was used for global and regional quantification. Activation strength was defined as the mean t-value of the respective region. All patients and volunteers showed a significant activation in the contralateral and ipsilateral sensorimotor cortex during motor task performance. The schizophrenic patients showed a significantly reduced global activation strength compared with healthy volunteers (p < .005). Selective evaluation of left-hand compared to right-hand movement demonstrated an increase in global activation strength in volunteers in contrast to a decrease in patients. Furthermore a reduced coactivation in the dominant left hemisphere was found in patients compared to volunteers during movement of the ipsilateral (left) hand. We conclude that alterations of the right and left hemispheric balance can be detected in schizophrenic patients using functional MRI at 1.5 T. These changes may indicate a disturbed interhemispheric interaction in schizophrenia. The reduction in cortical activation may result from several causes, however, taken together with previous studies and the underlying physiological effects, the most likely explanation is a combined effect of the disease and the neuroleptic medication.

Adolescent↗

PubMed1995

Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: preliminary results.

Autoradiographic studies have shown that low dose ketamine produces increases in regional glucose utilisation and blood flow in the hippocampus, cerebral cortex, and olfactory lobe in the rat brain, probably due to antagonism at the NMDA receptor. Functional MRI using deoxyhaemoglobin contrast can be used to study changes in regional cerebral blood flow (rCBF). Long TE gradient-echo sequences were used to study changes in rCBF produced by low dose ketamine in rats anaesthetised with nitrous oxide, supplemented with either halothane (HAL) or fentanyl/fluanisone/midazolam (FFM) combination. Images from rats in the FFM group showed a 10-14% increase in signal intensity in the hippocampus, cerebral cortex, and olfactory lobe following either a single bolus or a low dose infusion of ketamine (p < .05). These changes were significantly reduced in the HAL group (p < .005). Halothane is known to attenuate the changes in regional glucose utilisation produced by the noncompetitive NMDA antagonist dizocilpine (MK-801), and its effects on ketamine-induced changes in rCBF seen in this study may be due to a similar effect. The potential use of functional MRI in studying the effect of pharmacological interventions on rCBF is discussed.

Anesthetics, Dissociative↗

PubMed1999

Neuropsychological functioning and MRI signal hyperintensities in geriatric depression.

OBJECTIVE: The purpose of this study was to examine the relationship between signal hyperintensities--a probable marker of underlying pathology--on T2-weighted magnetic resonance brain scans and neuropsychological test findings in elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R diagnosis of major depression (N=41) and normal elderly comparison subjects (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal hyperintensities in periventricular, deep white matter, and subcortical gray matter. Hard copies of scans were rated in random order by research psychiatrists blind to diagnosis; the modified Fazekas hyperintensity rating scale was used. Cognitive performance was independently assessed with a comprehensive neuropsychological battery. Clinical and demographic differences between groups were assessed by t tests and chi-square analysis. Relationships between neuropsychological performance and diagnosis and hyperintensities and their interaction were analyzed by using analysis of covariance, with adjustment for age and education. RESULTS: Elderly depressed subjects manifested poorer cognitive performance on several tests than normal comparison subjects. A significant interaction between hyperintensity location/severity and presence/absence of depression on cognitive performance was found: depressed patients with moderate-to-severe deep white matter hyperintensities demonstrated worse performance on general and delayed recall memory indices, executive functioning and language testing than depressed patients without such lesions and normal elderly subjects with or without deep white matter changes. CONCLUSIONS: Findings validate cognitive performance decrements in geriatric depression and suggest possible neuroanatomic vulnerabilities to developing particular neuropsychological dysfunction in depressed subjects.

Aged↗

PubMed1998

Preoperative functional magnetic resonance imaging (fMRI) of the motor system in patients with tumours in the parietal lobe.

Intracranial lesions may compromise structures critical for motor performance, and mapping of the cortex, especially of the motor hand area, is important to reduce postoperative morbidity. We investigated nine patients with parietal lobe tumours and used functional MRI sensitized to changes in blood oxygenation to define the different motor areas, especially the primary sensorimotor cortex, in relation to the localization of the tumour. Activation was determined by pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the primary sensorimotor cortex while performing a finger opposition task with the affected and unaffected side. In five patients the finger opposition task additionally activated the ipsilateral sensorimotor cortex and the supplementary motor area (SMA). Extension and flexion of the foot, additionally performed in two patients, also activated the sensorimotor cortex, in one case within the perifocal oedema of the tumour. Tumour localization near the central sulcus induced displacement of the sensorimotor cortex as compared to the unaffected side in all patients with a relevant mass effect. The results of our study demonstrate that functional MRI at 1.5 T with a clinically used tomograph can reproducibly localize critical brain regions in patients with intracranial lesions.

Adult↗

PubMed2001

An integrated visualization system for surgical planning and guidance using image fusion and an open MR.

A surgical guidance and visualization system is presented, which uniquely integrates capabilities for data analysis and on-line interventional guidance into the setting of interventional MRI. Various pre-operative scans (T1- and T2-weighted MRI, MR angiography, and functional MRI (fMRI)) are fused and automatically aligned with the operating field of the interventional MR system. Both pre-surgical and intra-operative data may be segmented to generate three-dimensional surface models of key anatomical and functional structures. Models are combined in a three-dimensional scene along with reformatted slices that are driven by a tracked surgical device. Thus, pre-operative data augments interventional imaging to expedite tissue characterization and precise localization and targeting. As the surgery progresses, and anatomical changes subsequently reduce the relevance of pre-operative data, interventional data is refreshed for software navigation in true real time. The system has been applied in 45 neurosurgical cases and found to have beneficial utility for planning and guidance. J. Magn. Reson. Imaging 2001;13:967-975.

Adolescent↗