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A functional MRI protocol for localizing language comprehension in the human brain.

We describe a functional magnetic resonance imaging (fMRI) protocol to separate activation of areas in the brain associated with language comprehension from sensory areas activated as a result of the presentation of the language stimulus, by comparing cortical activation patterns during the presentation of similar or the same language stimulus via two different sensory modalities (auditory and visual), and identifying the regions of activation that are common to both modalities. The protocol can be implemented on any MR scanner capable of functional imaging, and has proven valuable for the reliable identification of the lateralization and location of language centres in patients being considered for neurosurgical procedures. As well, the method has potential for the study of cortical processing of auditory speech and written language in healthy subjects and in subjects suffering from language disorders.

Acoustic Stimulation↗

A functional MRI study of human amygdala responses to facial expressions of fear versus anger.

Functional magnetic resonance imaging (fMRI) of the human brain was used to compare changes in amygdala activity associated with viewing facial expressions of fear and anger. Pictures of human faces bearing expressions of fear or anger, as well as faces with neutral expressions, were presented to 8 healthy participants. The blood oxygen-level dependent (BOLD) fMRI signal within the dorsal amygdala was significantly greater to Fear versus Anger, in a direct contrast. Significant BOLD signal changes in the ventral amygdala were observed in contrasts of Fear versus Neutral expressions and, in a more spatially circumscribed region, to Anger versus Neutral expressions. Thus, activity in the amygdala is greater to fearful facial expressions when contrasted with either neutral or angry faces. Furthermore, directly contrasting fear with angry faces highlighted involvement of the dorsal amygdaloid region.

Adult↗

The representation of the human oral area in the somatosensory cortex: a functional MRI study.

The tactile sensation of the teeth is involved in various oral functions, such as mastication and speech. Using functional magnetic resonance imaging, we investigated the cortical sensory representation of the oral area, including the teeth. First, we identified the somatotopic representation of the lips, teeth and tongue in the postcentral gyrus (GpoC). Tactile stimuli were applied to the lower lip, tongue and teeth. The foci activated by each stimulus were characterized by the center of gravity (COG) of activated areas. Secondly, we examined the rostro-caudal changes in the somatotopic organization in the GPoC in terms of the overlap between each sensory representation. In the rostral portion of the GPoC, the COG of the representation of teeth was located significantly superior to that of the tongue and inferior to that of the lip, consistent with the classical 'sensory homunculus' proposed by Penfield; however, this somatotopic representation became unclear in the middle and caudal portions of the GPoC. The overlap between each representation in the middle and caudal portions of the GPoC was significantly greater than that in the rostral portion of the GPoC. These findings support the theory that the input from oral structures converges hierarchically across the primary somatosensory cortex.

Adult↗

Clinical applications of functional MRI in neuropsychiatry.

Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.

Brain↗

[Use of functional MRI in epilepsy].

For the purpose of examining pathophysiological mechanisms of a memory function in epileptic patients or an utility of fMRI for a presurgical assessment in neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or visual memory task were investigated in patient group of temporal lobe epilepsy and normal subject group. Patient group of temporal lobe epilepsy consisted of 7 cases, of which 3 and 3 cases had left and right temporal foci, respectively, except 1 case having undetermined laterality of temporal foci. Normal subjects were 16 cases. All the epileptic and normal subjects were right-handed except for 1 lefty normal subject. Verbal memory tasks were composed of covert and overt recall tasks of 10 words given auditorily, while visual ones were recall tasks of 6 figures given visually. Eventually, in normal subjects, the left side-dominant medial frontal lobes including the superior frontal and anterior cingulate gyri were mainly activated in fMRI during the covert recall tasks of verbal memory, while the left side-dominant inferior frontal and precentral gyri as the motor language areas were chiefly activated in addition to the medial frontal lobe during the overt recall tasks. Further, the bilateral occipital lobes were activated in fMRI during the recall tasks of visual memory. Also in patient groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks were the same as in normal subject group, regardless of the laterality of epileptic temporal foci. These results suggest that fMRI is useful for the determination of the lateralization of the cerebral hemisphere contributing to verbal memory function and therefore for the presurgical assessment of memory function in neurosurgical treatment of epilepsy.

Adult↗

Assessment of cerebrocortical regions associated with sexual arousal in premenopausal and menopausal women by using BOLD-based functional MRI.

PURPOSE: The aim of this study was to compare the cerebral regions associated with sexual arousal between premenopausal and menopausal women by using functional magnetic resonance imaging (f MRI). MATERIALS AND METHODS: Ten premenopausal and 10 menopausal women underwent fMRI on a 1.5T MR scanner using the blood oxygen level dependent technique. To identify the activated brain regions associated with sexual response, brain activation was assessed during 1 minute of a nonerotic film, followed by 4 minutes of an erotic film. RESULTS: The overall activation ratios of the premenopausal women were greater than those of the menopausal women by approximately 8% on average. The limbic, temporal association areas, and parietal lobe showed greater enhancement of signal intensities in premenopausal women. However, signal enhancement in the genu of the corpus callosum and superior frontal gyrus was dominant in menopausal women. CONCLUSIONS: The activated brain center associated with visually evoked sexual arousal showed qualitative and quantitative differences between premenopausal and menopausal women.

Adult↗

Correlations between structural CNS damage and functional MRI changes in primary progressive MS.

In patients with primary progressive multiple sclerosis (PPMS), we investigated whether brain and cervical cord structural changes in lesions and normal-appearing brain tissue (NABT), measured using conventional, magnetization transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement-associated cortical activations measured using functional magnetic resonance imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f-MRI (flexion-extension of the last four fingers of the right hand). All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed greater activation bilaterally in the superior temporal gyrus, ipsilaterally in the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of cortical areas located in a widespread network for sensory-motor and multimodal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of cervical cord damage (as measured using MT MRI). This study shows that the pattern of cortical activation of PPMS patients is different from that of normal controls even when performing a motor task with clinically unaffected limbs. It also suggests that cortical reorganization might be able to limit the consequences of MS injury in the brain and cervical cord.

Adult↗

Unfolding the human hippocampus with high resolution structural and functional MRI.

The hippocampus is a region of the brain that is crucial to memory function. Functional neuroimaging allows for the noninvasive investigation of the neurophysiology of human memory by observing changes in blood flow in the brain. We have developed a technique that employs high-resolution functional magnetic resonance imaging (fMRI) in combination with cortical unfolding to provide activation maps of the hippocampal region that surpass in anatomic and functional detail other methods of in vivo human brain mapping of the medial temporal lobe. We explain the principles behind this method and illustrate its application to a novelty-encoding paradigm.

Brain Mapping↗

Evaluating the spatial relationship of event-related potential and functional MRI sources in the primary visual cortex.

The integration of electroencephalogram (EEG) recordings and functional magnetic resonance imaging (fMRI) can provide considerable insight into brain functionality. However, the direct relationship between neural and hemodynamic activity is still poorly understood. Of particular interest is the spatial correspondence between event-related potential (ERP) and fMRI sources. In the current study we localized sources generated by a checkerboard stimulus presented to eight subjects using both EEG and fMRI. The location of the sources of the visual evoked potential (VEP) were estimated at each timepoint and compared to the location of peak fMRI activity. In the majority of participants we found that the N75 dipole location coincides with a region of positive blood oxygenation level-dependent (BOLD) activation and the P100 dipole location coincides with a region of negative BOLD activation. These findings demonstrate the importance of including the negative BOLD response in combined EEG/fMRI studies.

Adult↗

In vivo measurement of changes in venous blood-oxygenation with high resolution functional MRI at 0.95 tesla by measuring changes in susceptibility and velocity.

High-resolution functional imaging experiments at 0.95 Tesla have been performed to determine the changes in oxygen saturation in pial veins during motor activation by measuring both flow and susceptibility changes in the blood. Averaging across subjects, mean values for the change of the oxygenation level, deltaY = 0.16 +/- 0.08 (n = 7) and deltaY = 0.13 +/- 0.09 (n = 4), were obtained from the susceptibility sensitive and the flow sensitive acquisitions, respectively. The results suggest that the increase in blood flow is largely uncoupled from the oxygen consumption. The quoted errors reflect mainly the intersubject variability. In addition, low-resolution echo planar imaging (EPI) measurements were performed on the same volunteers to quantify signal intensity changes. Using the measured change in oxygenation, the observed signal changes in the EPI experiments can be attributed to a 5% venous blood volume.

Adolescent↗

LOFA: software for individualized localization of functional MRI activity.

Although PET, SPECT, and fMRI studies have led to significant advances in functional mapping of the human brain, precise localization and quantification of activity in individual brains require additional procedures. Difficulties to be addressed by a localization strategy are: resolution of individual anatomic differences, differentiation of functional activity in closely juxtaposed brain regions, and management of multiple intricately shaped 3D anatomic structures. In this paper, we describe a localization tool, LOFA, which addresses these problems by forming ROIs with a user-driven interface. Using LOFA, complex 3D anatomy can be defined through open or closed loops and anatomic landmarks. Resulting partitions can be overlaid on top of each other to form multiple regions of interest (ROIs), and functional activity in these ROIs can be extracted individually, one after the other. LOFA introduces important paradigmatic advances over the other ROI analysis methods. The toolbox is interactive, fully compatible with AFNI (MCW), and requires Pv-Wave (VNI Inc.) license to run.

Brain↗

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Adolescent↗

Analysis of functional MRI data based on an estimation of the hemodynamic response in the human brain.

Functional magnetic resonance imaging (fMRI) data is usually analyzed using hemodynamic response data formulated with the aid of a gamma function. An fMRI response to stimuli can be mathematically modeled by convolution of the hemodynamic response and the presented stimulus. This approach is based on a linear system analysis. However, it is known that most biological systems are nonlinear and the nature of the hemodynamic response depends on both the subjects and brain regions under study. In this work, we estimated the hemodynamic responses of the fusiform face area (FFA) and the primary visual area (V1) using 1st- and 2nd-order Volterra kernels. The estimated hemodynamic responses were used to analyze fMRI data obtained from the corresponding regions. The results of the analysis of fMRI data using the estimated hemodynamic responses show a more significant activation than is obtained by conventional analysis using the hemodynamic response modeled by gamma function.

Brain↗

A functional MRI study of cortical activations associated with object manipulation in patients with MS.

Previous functional magnetic resonance imaging (fMRI) studies of simple motor tasks have shown that in patients with multiple sclerosis (MS), there is an increased recruitment of several regions part of a complex sensorimotor network. These studies have suggested that this might be the case because patients tend to activate, when performing a simple motor task, regions that are usually activated in healthy subjects during the performance of more complex tasks due to the presence of subcortical structural damage. In this study, we tested this hypothesis by comparing the patterns of cortical activations during the performance of two tasks with different levels of complexity from 16 MS patients and 16 age- and sex-matched controls. The first task (simple) consisted of flexion-extension of the last four fingers of the right hand, and the second task (complex) consisted of object manipulation. During the simple task, MS patients had, when compared to controls, more significant activations of the supplementary motor area (SMA), secondary sensorimotor area, posterior lobe of the cerebellum, superior parietal gyrus (SPG), and inferior frontal gyrus (IFG). These three latter regions are part of a fronto-parietal circuit, whose activation occurs typically in the contralateral hemisphere of healthy subjects during object manipulation, as shown also by the present study. During the performance of the complex task, MS patients showed an increased bilateral recruitment of several areas of the fronto-parietal circuit associated with object manipulation, as well of several other areas, which were mainly in the frontal lobes. This study confirms that some of the regions that are activated by MS patients during the performance of simple motor tasks are part of more complex pathways, recruited by healthy subjects when more complex and difficult tasks have to be performed.

Adult↗

Physiological noise reduction for arterial spin labeling functional MRI.

Three methods for the reduction of physiological noise in arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) are presented and compared. The methods are based upon a general linear model of the ASL measurement process and on a previously described retrospective image-based method (RETROICOR) for physiological noise reduction in blood oxygenation level dependent fMRI. In the first method, the contribution of physiological noise to the interleaved control and tag images that comprise the ASL time series are assumed to be equal, while in the second method this assumption is not made. For the third method, it is assumed that physiological noise primarily impacts the perfusion time series obtained from the filtered subtraction of the control and tag images. The methods were evaluated using studies of functional activity in the visual cortex and the hippocampal region. The first and second methods significantly improved statistical performance in both brain regions, whereas the third method did not provide a significant gain. The second method provided significantly better performance than the first method in the hippocampal region, whereas the differences between methods were less pronounced in visual cortex. The improved performance of the second method in the hippocampal region appears to reflect the relatively greater effect of cardiac fluctuations in this brain region. The proposed methods should be particularly useful for ASL studies of cognitive processes where the intrinsic signal to noise ratio is typically lower than for studies of primary sensory regions.

Adult↗

Demyelination and cortical reorganization: functional MRI data from a case of subacute combined degeneration.

Although it is accepted that functional changes of the cortex can occur in patients with white matter diseases of the brain and might have an adaptive role in limiting the clinical consequences of subcortical injury, the pathological substrates able to elicit such cortical changes are still unknown. This multiparametric magnetic resonance study of a patient with an early diagnosis of subacute combined degeneration suggests that demyelination alone does not necessarily induce adaptive functional changes of the cerebral cortex.

Cerebral Cortex↗

Method for functional MRI mapping of nonlinear response.

Nonlinear systems analysis combining blood oxygen level dependent (BOLD), functional magnetic resonance imaging (fMRI) and m-sequence stimulation paradigms are proposed as a new method for exploring neuronal responses and interactions. Previous studies of electrical activity in the human visual cortex have observed significant nonlinearities of task-induced activity with temporal dynamics on a timescale of 10-20 ms. Despite the confounding effect of the seconds-long hemodynamic response, it is demonstrated that BOLD fMRI can be used to probe neuronal interactions on a time scale of tens of ms. Visual activation experiments were performed with various stimuli, and amplitude maps of first and second order kernel coefficients were generated using correlation analysis. Second order nonlinearities in BOLD fMRI were observed and attributed to temporal contrast caused by transitions in the stimulus sequence. In addition, the kernel maps showed significant differences between second order nonlinearities of foveal and peripheral vision. By including a reference experiment with a slightly modified stimulus presentation, a distinction could be made between (fast) neuronal nonlinearities and hemodynamic effects on the time scale of the seconds. The results indicate that BOLD fMRI can probe fast neuronal nonlinearities.

Brain Mapping↗

Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1.

Most functional brain imaging studies use task-induced hemodynamic responses to infer underlying changes in neuronal activity. In addition to increases in cerebral blood flow and blood oxygenation level-dependent (BOLD) signals, sustained negative responses are pervasive in functional imaging. The origin of negative responses and their relationship to neural activity remain poorly understood. Through simultaneous functional magnetic resonance imaging and electrophysiological recording, we demonstrate a negative BOLD response (NBR) beyond the stimulated regions of visual cortex, associated with local decreases in neuronal activity below spontaneous activity, detected 7.15 +/- 3.14 mm away from the closest positively responding region in V1. Trial-by-trial amplitude fluctuations revealed tight coupling between the NBR and neuronal activity decreases. The NBR was associated with comparable decreases in local field potentials and multiunit activity. Our findings indicate that a significant component of the NBR originates in neuronal activity decreases.

Animals↗