Echo-planar Functional Magnetic Resonance Research Articles

Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression

This study for the first time investigated resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder (BD) and compared them with findings in healthy controls and unipolar major depressive disorder (MDD) patient groups. Resting state correlations of low frequency BOLD fluctuations (LFBF) in echoplanar functional magnetic resonance (fMRI) data were acquired from a priori defined regions of interests (ROIs) in the pregenual anterior cingulate cortex (pgACC), dorsomedial thalamus (DMTHAL), pallidostriatum (PST) and amygdala (AMYG), to investigate corticolimbic functional connectivity in unmedicated BD patients in comparison to healthy subjects and MDD patients. Data were acquired from 11 unmedicated BD patients [six manic (BDM) and five depressed (BDD)], and compared with data available from 15 unmedicated MDD and 15 healthy subjects. BD patients had significantly decreased pgACC connectivity to the left and right DMTHAL, similar to findings seen in MDD. Additionally, BD patients had decreased pgACC connectivity with the left and right AMYG as well as the left PST. An exploratory analysis revealed that both BDD and BDM patients had decreased connectivity between the pgACC and DMTHAL. The results of the study indicate a common finding of decreased corticolimbic functional connectivity in different types of mood disorders.

Hyperresponsivity to Threat Stimuli in Domestic Violence Offenders

While spouse abuse research has almost exclusively adopted a social perspective, an increasing body of imaging research is documenting neural contributions to violence. To test the hypothesis that wife batterers are hyperresponsive to threatening stimuli, echo-planar functional magnetic resonance imaging was employed to assess brain function of 10 male batterers and 13 male matched controls during viewing of 4 types of visual stimuli: neutral, positive affect, aggressive-threat, and aggression against women. The study was conducted from September 2005 to August 2006. Compared to controls, batterers showed significantly higher neural hyperresponsivity to the threat stimuli in the hippocampus, fusiform gyrus, posterior cingulate gyrus, thalamus, and occipital cortex (p < .001). To a lesser extent, they also showed increased activation to the aggression against women stimuli, particularly in the precuneus bilaterally (p < .001), and also increased activation to positive affect stimuli in right hemisphere orbitofrontal, anterior cingulate, and inferior parietal cortical regions (p < .001). Findings indicate an affect-processing abnormality in wife batterers and suggest that hypersensitivity to mildly threatening affective provocations by their spouses may represent a neurobiological predisposition to spouse abuse in some men.

Influence of trait anxiety on brain activity during the acquisition and extinction of aversive conditioning

We examined how individual differences in trait anxiety (TA) influence the neural responses associated with the acquisition and extinction of anticipatory anxiety elicited through a context conditioning paradigm, with particular focus on the amygdala and the subgenual anterior cingulate cortex (sgACC). During two sessions of echo-planar functional magnetic resonance imaging (fMRI), 18 healthy volunteers completed a decision-making task with two randomly alternating 28-s to 32-s background screen colour blocks. One of the colours was associated with the presentation of an aversive noise (CTX+) and the other colour was 'safe' (CTX-). In the first session (Acquisition), 33% of CTX+ colour blocks were paired with noise and in the second session (Extinction) no noise was presented. The amygdala displayed an increased response to CTX+ compared to CTX- colour blocks during the Acquisition and Extinction sessions and the ACC displayed an increased response to CTX+ compared to CTX- colour blocks during Extinction only. In addition, a greater conditioned response (CTX+ minus CTX-) was observed in the ACC when comparing the Extinction and Acquisition sessions. Correlation analyses further showed that higher levels of TA were associated with a higher conditioned response in the amygdala during Extinction as well as a greater differential conditioned response (i.e. Extinction>Acquisition) in the ACC. Our results support the idea that individuals with high levels of anxiety-relevant traits and vulnerable to developing an anxiety disorder display a more resilient anxiety response during extinction that is characterized by hyper-responsivity in the amygdala.

Single-shot echo-planar functional magnetic resonance imaging of representations of the fore- and hindpaws in the somatosensory cortex of rats using an 11.7 T microimager

Most of functional magnetic resonance imaging (fMRI) experiments have been performed on horizontal bore magnets. Here, we present practical aspects of fMRI based on single-shot, spin-echo echo-planar imaging (EPI) using a widely available, cost effective 89 mm bore vertical 11.7 T microimager. It was demonstrated that reproducible, high-quality fMRI data can be obtained from α-chloralose anesthetized adult rat brain. Both coronal and the more extended horizontal EPI images were acquired to measure blood oxygenation level dependent (BOLD) responses to electrical stimulation of fore- and hindpaws. The BOLD patterns observed match the known representations of fore- and hindpaws in the somatosensory cortex in rats. Preliminary results on BOLD signal enhancement using aminophylline are also presented.

Gambling urges in pathological gambling: a functional magnetic resonance imaging study.

Gambling urges in pathological gambling (PG) often immediately precede engagement in self-destructive gambling behavior. An improved understanding of the neural correlates of gambling urges in PG would advance our understanding of the brain mechanisms underlying PG and would help direct research into effective treatments. Echoplanar functional magnetic resonance imaging was used to assess brain function during viewing of videotaped scenarios with gambling, happy, or sad content. Participants rated the quality and magnitude of their emotional and motivational responses. Men with PG (n = 10) reported mean +/- SD greater gambling urges after viewing gambling scenarios vs control subjects (n = 11) (5.20 +/- 3.43 vs 0.32 +/- 0.60; chi21,19 = 21.71; P<.001). The groups did not differ significantly in their subjective responses to the happy (P =.56) or sad (P =.81) videotapes. The most pronounced between-group differences in neural activities were observed during the initial period of viewing of the gambling scenarios: PG subjects displayed relatively decreased activity in frontal and orbitofrontal cortex, caudate/basal ganglia, and thalamus compared with controls. Distinct patterns of regional brain activity were observed in specific temporal epochs of videotape viewing. For example, differences localized to the ventral anterior cingulate during the final period of gambling videotape viewing, corresponding to the presentation of the most provocative gambling stimuli. Although group differences in brain activity were observed during viewing of the sad and happy scenarios, they were distinct from those corresponding to the gambling scenarios. In men with PG, gambling cue presentation elicits gambling urges and leads to a temporally dynamic pattern of brain activity changes in frontal, paralimbic, and limbic brain structures. When viewing gambling cues, PG subjects demonstrate relatively decreased activity in brain regions implicated in impulse regulation compared with controls.

Functional Fields in Human Auditory Cortex Revealed by Time-Resolved fMRI without Interference of EPI Noise

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields.

Effects of stimulus presentation rate on the activity of primary somatosensory cortex: a functional magnetic resonance imaging study in humans

To investigate the effect of stimulus presentation rate on the activity of primary somatosensory cortex, we performed echo-planar functional magnetic resonance imaging using a 1.5-tesla magnetic resonance system. Eight right-handed normal volunteers underwent functional magnetic resonance imaging during somatosensory stimulation with a 0.2 ms electrical square wave to the left index finger at 1, 4, 8, 16, and 32 Hz at constant intensity. Activated areas were located mainly around ‘the hand area’ of the right postcentral gyrus. Between 4 and 16 Hz, almost all subjects showed significant activation, but at 1 Hz and 32 Hz, five of eight subjects showed no activation. The average number of activated pixels in this area between 4 and 16 Hz were significantly greater than those at 1 Hz and 32 Hz, and the average percent signal increase had its activation peak at 8 Hz. Our results suggest that the existence of the optimal stimulation rate range may be a common phenomenon to a variety of sensory modalities. The electrical somatosensory stimulation rates from 4 Hz to 16 Hz are advisable to investigate the activation of the primary somatosensory cortex in human subjects.

Developmental and Lesion Effects in Brain Activation During Sentence Comprehension and Mental Rotation

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Effect of ethanol on BOLD response to acoustic stimulation: implications for neuropharmacological fMRI

The effects of ethanol on acoustically stimulated blood oxygenation level-dependent (BOLD) signal response in healthy humans was examined with echo planar functional magnetic resonance imaging (fMRI). An acquisition mode minimizing neuronal activation by scanner noise in combination with acoustic excitation by a pulsed 1000-Hz sine tone was used. Paradigms were repeated three times before and after the ingestion of 0.7 g of ethanol/kg body weight. Linear correlation analyses ( r≥0.40) revealed bilateral BOLD responses in the auditory cortex. Significant voxels covered a cortical volume of ∼3 ml that was reduced by ∼40% after ethanol. The BOLD signal change initially reaching ∼3% was reduced by 12–27%, depending on the definition of the region of interest for signal quantitation. Because ethanol produces vasodilation, the hemodynamic contribution to the BOLD signal change was estimated by modeling the relationship between regional cerebral blood flow (rCBF) and BOLD signal changes. Assuming a baseline flow increase by 10% after ethanol intake, the resulting ‘Flow-BOLD-Dependence’ (FBD) curve suggested that the ethanol-related BOLD signal reduction was ∼7–12% greater than the reduction contributed purely by vasodilation. However, simultaneous determination of rCBF and regional cerebral blood volume would be required for an exact quantitation of the neuronally induced BOLD response. Although the FBD model needs empirical validation, its cautious implementation appears to be helpful if fMRI is used in combination with vasoactive drugs.

Task-specific deactivation patterns in functional magnetic resonance imaging

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.

A Comparative fMRI Study of Cortical Representations for Thermal Painful, Vibrotactile, and Motor Performance Tasks

Cortical activity due to a thermal painful stimulus applied to the right hand was studied in the middle third of the contralateral brain and compared to activations for vibrotactile and motor tasks using the same body part, in nine normal subjects. Cortical activity was demonstrated utilizing multislice echo-planar functional magnetic resonance imaging (fMRI) and a surface coil. The cortical activity was analyzed based upon individual subject activity maps and on group-averaged activity maps. The results show significant differences in activations across the three tasks and the cortical areas studied. The study indicates that fMRI enables examination of cortical networks subserving pain perception at an anatomical detail not available with other brain imaging techniques and shows that this cortical network underlying pain perception shares components with the networks underlying touch perception and motor execution. However, the thermal pain perception network also has components that are unique to this percept. The uniquely activated areas were in the secondary somatosensory region, insula, and posterior cingulate cortex. The posterior cingulate cortex activity was in a region that, in the monkey, receives nociceptive inputs from posterior thalamic medial and lateral nuclei that in turn are targets for spinothalamic terminations. Discrete subdivisions of the primary somatosensory and motor cortical areas were also activated in the thermal pain task, showing region-dependent differences in the extent of overlap with the other two tasks. Within the primary motor cortex, a hand region was preferentially active in the task in which the stimulus was painful heat. In the primary somatosensory cortex most activity in the painful heat task was localized to area 1, where the motor and vibratory task activities were also coincident. The study also indicates that the functional connectivity across multiple cortical regions reorganizes dynamically with each task.

Time Course of fMRI-Activation in Language and Spatial Networks during Sentence Comprehension

Functional neuroimaging previously has been considered to provide inadequate temporal resolution to study changes of brain states as a function of cognitive computations; however, we have obtained evidence of differential amounts of brain activity related to high-level cognition (sentence processing) within 1.5 s of stimulus onset. The study used an event-related paradigm with high-speed echoplanar functional magnetic resonance imaging (fMRI) to trace the time course of the brain activation in the temporal and parietal regions as participants comprehended single sentences describing a spatial configuration. Within the first set of images, on average 1 s from when the participant begins to read a sentence, there was significant activation in a key cortical area involved in language comprehension (the left posterior temporal gyrus) and visuospatial processing (the left and right parietal regions). In all three areas, the amount of activation during sentence comprehension was higher for negative sentences than for their affirmative counterparts, which are linguistically less complex. The effect of negation indicates that the activation in these areas is modulated by the difficulty of the linguistic processing. These results suggest a relatively rapid coactivation in both linguistic and spatial cortical regions to support the integration of information from multiple processing streams.

Effects of repetition and competition on activity in left prefrontal cortex during word generation.

Neuroimaging studies have revealed an association between word generation and activity in the left inferior frontal gyrus (IFG) that is attentuated with item repetition. The experiment reported here examined the effects of repeated word generation, under conditions in which completion was either decreased or increased, on activity measured during whole-brain echoplanar functional magnetic resonance imaging. Activity in left IFG decreased during repetition conditions that reduced competition but increased during repetition conditions that increased competition; this pattern was contrasted to repetition effects observed in other cortical areas, specifically regions of left temporal cortex. The increase in left IFG activity, which is not predicted by a simple semantic retrieval account of prefrontal function, is consistent with the hypothesis that left IFG subserves the selection of semantic knowledge among competing alternatives.

Bilateral representation of sequential finger movements in human cortical areas

The spatial distribution of cortical neural clusters activated during movement of either hand (‘bilateral’ population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential finger opposition task, using echo-planar functional magnetic resonance imaging. ‘Bilateral’ clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral finger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral finger movements was detected. These findings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control.

Functional organization of activation patterns in children: Whole brain fMRI imaging during three different cognitive tasks

1. 1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children ( N = 6) and in one child with a left- hemisphere encephalomalacic lesion as sequellae from early stroke. 2. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. 3. There was evidence for significant bilateral activation m all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non- damaged hemisphere.

Improved auditory cortex imaging using clustered volume acquisitions

The effects of the noise of echo-planar functional magnetic resonance imaging on auditory cortex responses were compared for two methods of acquiring functional MR data. Responses observed with a distributed volume acquisition sequence were compared to those obtained with a clustered volume acquisition sequence. In the former case, slices from the volume were acquired at equal intervals within the repetition time, whereas the latter acquired all slices in rapid succession at the end of the imaging period. The clustered volume acquisition provides a period of quiet during which a stimulus may be presented uninterrupted and uncontaminated by the noise of echo-planar imaging. Both sequences were implemented on a General Electric Signa imager retrofitted for echo-planar imaging by Advanced NMR Systems, Inc. The sequences were used to acquire 60 images per slice of a fixed volume of cerebral cortex while subjects were presented an instrumental music stimulus in an On vs. Off paradigm. Data were acquired for both sequences using TR values of 2, 3, 4, 6 and 8 sec. The clustered volume acquisition sequence was found to yield greater measures of dynamic range (percent signal change, mean statistical power per unit imaging time) across the tested range of TR values. Observations of more consistent spatial extent of responses, greater mean signal changes, and higher and more consistent values of mean t-statistic per unit imaging time demonstrate the efficacy of using a clustered volume acquisition for fMRI of auditory cortex.

Improved auditory cortex imaging using clustered volume acquisitions

The effects of the noise of echo-planar functional magnetic resonance imaging on auditory cortex responses were compared for two methods of acquiring functional MR data. Responses observed with a distributed volume acquisition sequence were compared to those obtained with a clustered volume acquisition sequence. In the former case, slices from the volume were acquired at equal intervals within the repetition time, whereas the latter acquired all slices in rapid succession at the end of the imaging period. The clustered volume acquisition provides a period of quiet during which a stimulus may be presented uninterrupted and uncontaminated by the noise of echo-planar imaging. Both sequences were implemented on a General Electric Signa imager retrofitted for echo-planar imaging by Advanced NMR Systems, Inc. The sequences were used to acquire 60 images per slice of a fixed volume of cerebral cortex while subjects were presented an instrumental music stimulus in an On vs. Off paradigm. Data were acquired for both sequences using TR values of 2, 3, 4, 6 and 8 sec. The clustered volume acquisition sequence was found to yield greater measures of dynamic range (percent signal change, mean statistical power per unit imaging time) across the tested range of TR values. Observations of more consistent spatial extent of responses, greater mean signal changes, and higher and more consistent values of mean t-statistic per unit imaging time demonstrate the efficacy of using a clustered volume acquisition for fMRI of auditory cortex. Hum. Brain Mapping 7:89–97, 1999. © 1999 Wiley-Liss, Inc.

The constructive nature of vision: direct evidence from functional magnetic resonance imaging studies of apparent motion and motion imagery.

Echoplanar functional magnetic resonance imaging was used to monitor activation changes of brain areas while subjects viewed apparent motion stimuli and while they were engaged in motion imagery. Human cortical areas MT (V5) and MST were the first areas of the 'dorsal' processing stream which responded with a clear increase in signal intensity to apparent motion stimuli as compared with flickering control conditions. Apparent motion of figures defined by illusory contours evoked greater activation in V2 and MT/MST than appropriate control conditions. Several areas of the dorsal pathway (V3A, MT/MST, areas in the inferior and superior parietal lobule) as well as prefrontal areas including FEF and BA 9/46 responded strongly when subjects merely imagined moving stimuli which they had seen several seconds before. The activation during motion imagery increased with the synaptic distance of an area from V1 along the dorsal processing stream. Area MT/MST was selectively activated during motion imagery but not during a static imagery control condition. The comparison between the results obtained with objective motion, apparent motion and imagined motion provides further insights into a complex cortical network of motion-sensitive areas driven by bottom-up and top-down neural processes.

Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study

Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS−). CS+ and CS− trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat ( Quirk et al. 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.

Functional imaging of mirror and inverse reading reveals separate coactivated networks for oculomotion and spatial transformations.

Echoplanar functional magnetic resonance imaging (fMRI) was used to localize the cortical areas involved in the analysis of spatially transformed letter strings. Significant increases of the blood oxygen level-dependent (BOLD) signal for transformed vs normal reading were observed in the superior parietal lobule (SPL), along the intraparietal sulcus (IPS), in the frontal eye fields (FEF), and in the latero-occipital area LO. The respective contributions of oculomotor and spatial transformation areas to this activation pattern were separated by means of a control condition involving the execution and suppression of eye movements. Areas activated in association with the control of eye movements included the superior parietal lobule and the frontal eye fields. The cooperation of different brain areas was analysed by correlating the time course of task-dependent BOLD signal changes in these areas. This correlation analysis revealed coactivation of occipitotemporal object recognition areas and a spatial transformation area in the intraparietal sulcus during the reading of transformed letter strings. We suggest that cortical systems that are coactivated during complex cognitive tasks can be differentiated by the correlation analysis of BOLD signal time courses in spatially separate brain areas.