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Reducing inhomogeneity artifacts in functional MRI of human brain activation-thin sections vs gradient compensation.

We evaluated two methods for correcting inhomogeneity-induced signal losses in magnetic resonance gradient-echo imaging that either use gradient compensation or simply acquire thin sections. The strategies were tested in the human brain in terms of achievable quality of T2*-weighted images at the level of the hippocampus and of functional activation maps of the visual cortex. Experiments were performed at 2.0 T and based on single-shot echo-planar imaging at 2. 0 x 2.0 mm(2) resolution, 4 mm section thickness, and 2.0 s temporal resolution. Gradient compensation involved a sequential 16-step variation of the refocusing lobe of the slice-selection gradient (TR/TE = 125/53 ms, flip angle 15 degrees ), whereas thin sections divided the 4-mm target plane into either four 1-mm or eight 0.5-mm interleaved multislice acquisitions (TR/TE = 2000/54 ms, flip angle 70 degrees ). Both approaches were capable of alleviating the inhomogeneity problem for structures in the base of the brain. When compared to standard 4-mm EPI, functional mapping in the visual cortex was partially compromised because of a lower signal-to-noise ratio of inhomogeneity-corrected images by either method. Relative to each other, consistently better results were obtained with the use of contiguous thin sections, in particular for a thickness of 1 mm. Multislice acquisitions of thin sections require minimal technical adjustments.

Adult↗

Human hippocampal activation in the delayed matching- and nonmatching-to-sample memory tasks: an event-related functional MRI approach.

The delayed matching-to-sample (DMS) and delayed nonmatching-to-sample (DNMS) memory tasks are standard tools used to probe visual recognition memory in human and nonhuman primates. Previous research indicates that structures within the medial temporal lobe, including the hippocampus, make up a crucial memory circuit for successful performance on these tasks. In the present investigation, event-related functional magnetic resonance imaging was used to examine activation in the hippocampus proper during these memory tasks relative to a perceptuomotor task involving the same stimuli. The results indicate that both memory tasks elicited greater activation in the right hippocampus during the encoding phase. These findings are consistent with the work from human patients and animal studies, indicating hippocampal involvement in the DMS and DNMS tasks.

Adult↗

Nicotine-induced limbic cortical activation in the human brain: a functional MRI study.

OBJECTIVE: Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates. METHOD: Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials. RESULTS: Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans. CONCLUSIONS: The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.

Adolescent↗

Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study.

BACKGROUND: Intense and rapidly changing mood states are a major feature of borderline personality disorder (BPD); however, there have only been a few studies investigating affective processing in BPD, and in particular no neurofunctional correlates of abnormal emotional processing have been identified so far. METHODS: Six female BPD patients without additional major psychiatric disorder and six age-matched female control subjects underwent functional magnetic resonance imaging (fMRI) to measure regional cerebral hemodynamic changes following brain activity when viewing 12 standardized emotionally aversive slides compared to 12 neutral slides, which were presented in random order. RESULTS: Our main finding was that BPD subjects but not control subjects were characterized by an elevated blood oxygenation level dependent fMRI signal in the amygdala on both sides. In addition, activation of the medial and inferolateral prefrontal cortex was seen in BPD patients. Both groups showed activation in the temporo-occipital cortex including the fusiform gyrus in BPD subjects but not in control subjects. CONCLUSIONS: Enhanced amygdala activation in BPD is suggested to reflect the intense and slowly subsiding emotions commonly observed in response to even low-level stressors. Borderline subjects' perceptual cortex may be modulated through the amygdala leading to increased attention to emotionally relevant environmental stimuli.

Affect↗

A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism.

Attending to rare stimuli interspersed among repetitive frequent stimuli produces a positive scalp potential at 300 to 600 ms after the target stimulus onset; this potential is known as the P300 wave. Although there is clear evidence of low visual P300 in subjects at high risk (HR) for developing alcoholism, the functional neuroanatomical correlates have not been studied. Functional and high-resolution anatomical magnetic resonance images were collected during the performance of a visual oddball task, from six control (low risk-LR) subjects with high P300s and eight HR subjects with low P300s. All the HR subjects were offspring of male alcoholics. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Target counts showed that all subjects performed the task comparably. Analysis of the functional magnetic resonance imaging (fMRI) data revealed two areas with significantly lower activation in the HR group when compared to the LR group: the bilateral inferior parietal lobule (BA 40), and the bilateral inferior frontal gyrus (BA 44). Inferior parietal lobule showed significantly lower activation in the HR group in contrast to the LR group, and inferior frontal gyrus was not activated in the HR group but was only activated in the LR group. This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system.

Adult↗

A functional MRI study of the influence of practice on component processes of working memory.

Previous neuroimaging studies have shown that neural activity changes with task practice. The types of changes reported have been inconsistent, however, and the neural mechanisms involved remain unclear. In this study, we investigated the influence of practice on different component processes of working memory (WM) using a face WM task. Event-related functional magnetic resonance imaging (fMRI) methodology allowed us to examine signal changes from early to late in the scanning session within different task stages (i.e., encoding, delay, retrieval), as well as to determine the influence of different levels of WM load on neural activity. We found practice-related decreases in fMRI signal and effects of memory load occurring primarily during encoding. This suggests that practice improves encoding efficiency, especially at higher memory loads. The decreases in fMRI signal we observed were not accompanied by improved behavioral performance; in fact, error rate increased for high WM load trials, indicating that practice-related changes in activation may occur during a scanning session without behavioral evidence of learning. Our results suggest that practice influences particular component processes of WM differently, and that the efficiency of these processes may not be captured by performance measures alone.

Adult↗

Functional MRI study of semantic and phonological language processing in bilingual subjects: preliminary findings.

The objective of the study was to explore differences in regional fMRI activation topography and lateralization between semantic and phonological tasks performed in English and Spanish in bilingual individuals. Eight bilingual (primary Spanish and secondary English-speaking) individuals performed fMRI noun-verb association and rhyming tasks in both Spanish and English. Functional dataset analysis within Statistical Parametric Mapping (SPM99) with overlay on T1-weighted anatomic images was performed. Significantly higher laterality indices were noted in the semantic tasks as compared with the phonological tasks in the anterior regions of interest comprising the frontal and superior temporal lobes. A task subtraction analysis demonstrated right hemispheric (inferior frontal gyrus and supramarginal gyrus) foci of significantly increased activation in the combined language phonological tasks compared to the combined language semantic tasks; similarly prominent right hemispheric activation was seen in the English phonological-English semantic subtraction, but the analogous Spanish task subtraction revealed no task-related differences. This divergence in activation topography between semantic and phonological tasks performed in the nonnative language, but not in the primary language, suggests that neural networks utilized for phonological and semantic language processing in the nonnative language may not be as similar as those in the primary language.

Adult↗

An event-related functional MRI study comparing interference effects in the Simon and Stroop tasks.

The Stroop and Simon tasks typify a class of interference effects in which the introduction of task-irrelevant stimulus characteristics robustly slows reaction times. Behavioral studies have not succeeded in determining whether the neural basis for the resolution of these interference effects during successful task performance is similar or different across tasks. Event-related functional magnetic resonance imaging (fMRI) studies were obtained in 10 healthy young adults during performance of the Stroop and Simon tasks. Activation during the Stroop task replicated findings from two earlier fMRI studies. These activations were remarkably similar to those observed during the Simon task, and included anterior cingulate, supplementary motor, visual association, inferior temporal, inferior parietal, inferior frontal, and dorsolateral prefrontal cortices, as well as the caudate nuclei. The time courses of activation were also similar across tasks. Resolution of interference effects in the Simon and Stroop tasks engage similar brain regions, and with a similar time course. Therefore, despite the widely differing stimulus characteristics employed by these tasks, the neural systems that subserve successful task performance are likely to be similar as well.

Adult↗

Functional MRI evidence for an abstract, not perceptual, word-form area.

Previous studies have found an area in left ventral visual cortex that responds more to words and pseudowords than to consonant strings. Does this area respond to the perceptual form of wordlike stimuli, or is it responding to some more abstract, linguistic property, such as orthographic regularity (i.e., conformity with the spelling rules of the language)? During a functional magnetic resonance imaging experiment, participants read alternating-case words and pseudowords, which are orthographically regular but are perceptually unfamiliar. These stimuli activated the same area that was activated by pure-case words and pseudowords. These results suggest that the response of the so-called word-form area is not based on perceptual familiarity but rather on some more abstract feature such as orthographic regularity.

Adolescent↗

Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli.

Positron emission tomography studies have provided evidence for the involvement of the thalamus and cortex in pain and temperature perception. However, the involvement of these structures in pain and temperature perception of individual subjects has not been studied in detail with high spatial resolution imaging. As a first step toward this goal, we have used functional magnetic resonance imaging (fMRI) to locate discrete regions of the thalamus, insula, and second somatosensory cortex (S2) modulated during innocuous and noxious thermal stimulation. Results were compared with those obtained during tactile stimulation of the palm. High resolution functional images were acquired on a 1.5 T echospeed GE MR system with an in-plane resolution of 1.7 mm. A modified peltier-type thermal stimulator was used to deliver innocuous cool and warm and noxious cold and hot stimuli for 40-60 s to the thenar eminence of normal male and female volunteers. Experimental paradigms consisted of four repetitions of interleaved control and task stimuli. A pixel by pixel statistical analysis of images obtained during each task versus control (e.g., noxious heat vs. warm, warm vs. neutral temperature, etc.) was used to determine task-related activations. Painful thermal stimuli activated discrete regions within the lateral and medial thalamus, and insula, predominantly in the anterior insula in most subjects, and the contralateral S2 in 50% of subjects. The innocuous thermal stimuli did not activate the S2 in any of the subjects but activated the thalamus and posterior insula in 50% of subjects. By comparison, innocuous tactile stimulation consistently activated S2 bilaterally and the contralateral lateral thalamus. These data also demonstrate that noxious thermal and innocuous tactile-related activations overlap in S2. The data also suggest that innocuous and noxious-related activations may overlap within the thalamus but may be located in different regions of the insula. Therefore, we provide support for a role of the anterior insula, S2, and thalamus in the perception of pain; whereas the posterior insula appears to be involved in tactile and innocuous temperature perception. These data demonstrate the feasibility of using fMRI for studies of pain, temperature, and mechanical stimuli in individual subjects, even in small regions such as thalamic nuclei. However, the intersubject variability should be considered in future single subject imaging studies and studies that rely on averaged group responses.

Adult↗

Functional MRI of the brain during orgasm in women.

Women diagnosed with complete spinal cord injury (SCI) at T10 or higher report sensations generated by vaginal-cervical mechanical self-stimulation (CSS). In this paper we review brain responses to sexual arousal and orgasm in such women, and further hypothesize that the afferent pathway for this unexpected perception is provided by the Vagus nerves, which bypass the spinal cord. Using functional magnetic resonance imaging (fMRI), we ascertained that the region of the medulla oblongata to which the Vagus nerves project (the Nucleus of the Solitary Tract or NTS) is activated by CSS. We also used an objective measure, CSS-induced analgesia response to experimentally induced finger pain, to ascertain the functionality of this pathway. During CSS, several women experienced orgasms. Brain regions activated during orgasm included the hypothalamic paraventricular nucleus, amygdala, accumbens-bed nucleus of the stria terminalis-preoptic area, hippocampus, basal ganglia (especially putamen), cerebellum, and anterior cingulate, insular, parietal and frontal cortices, and lower brainstem (central gray, mesencephalic reticular formation, and NTS). We conclude that the Vagus nerves provide a spinal cord-bypass pathway for vaginal-cervical sensibility and that activation of this pathway can produce analgesia and orgasm.

Brain↗

Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test--a functional MRI study on healthy volunteers and schizophrenics.

It has been demonstrated by single photon emission computed tomography (SPECT) and positron emission tomography (PET) that frontal brain regions are stimulated during performance of the Wisconsin Card Sorting Test (WCST). The WCST is also regarded as one of the standard tests for the assessment of frontal activity in brain imaging studies of schizophrenia. In this study cerebral activation was assessed by means of functional magnetic resonance imaging (fMRI). In healthy volunteers WCST stimulation resulted in a right lateralized frontal activation. In 13 chronic schizophrenics on stable neuroleptic medication, a lack of activation in the right prefrontal cortex and--as a trend--an increased left temporal activity during execution of the WCST was noted compared to controls. Since a one-slice technique was used, no information about the activation pattern in adjacent brain regions was obtained. However, as fMRI possesses a superior spatial resolution compared to SPECT and PET, the anatomical localization of the activation effect in the measured slice can be defined more precisely. Beside these methodological considerations, the results are discussed in relation to prior findings of a reduced ability of schizophrenics to coordinate cerebral function.

Adult↗

Functional MRI activity in the thalamus and occipital cortex of anesthetized dogs induced by monocular and binocular stimulation.

The neuroanatomy of the mammalian visual system has received considerable attention through electrophysiological study of cats and non-human primates, and through neuroimaging of humans. Canine neuroanatomy, however, has received much less attention, limiting our understanding of canine vision and visual pathways. As an early step in applying blood oxygenation level dependant (BOLD) functional magnetic resonance imaging (fMRI) for veterinary use, we compared visual activity in the thalamus and occipital cortex of anesthetized dogs presented with binocular and monocular visual stimuli. Activity in the left and right thalamus and occipital cortex during monocular stimulation was also compared. Six beagles were presented with a vertical grating visual stimulus and scanned at 4 Tesla. Each dog was scanned twice under each of 3 anesthetic protocols (isoflurane, propofol, and fentanyl/midazolam). We found: 1) significant BOLD activation in the lateral geniculate nucleus (LGN) of the thalamus and the occipital cortex; 2) a significantly larger area of activation in the LGN during monocular stimulation than during binocular stimulation; and 3) that activity in the hemisphere contralateral to the stimulus was not significantly greater than that ipsilateral to it.

Anesthetics↗

Differential amygdalar response to novel versus newly familiar neutral faces: a functional MRI probe developed for studying inhibited temperament.

BACKGROUND: As a prelude to future studies of subjects with different temperaments, we sought to develop a probe to measure differential amygdalar responses to novel versus familiar stimuli. Prior neuroimaging studies of the amygdala in humans to date have focused principally on responses to emotional stimuli, primarily aversive, rather than to novelty per se. METHODS: Eight normal subjects aged 22.4 +/- 1.3 years were scanned using functional magnetic resonance imaging (fMRI) during passive viewing of novel and familiar faces. RESULTS: Using this newly developed paradigm, we found greater fMRI blood oxygenation level dependent (BOLD) signal response within the right amygdala to novel versus familiar faces--all with neutral expression. Furthermore, although a new facial identity was always presented in the novel condition, signal in the amygdala declined over time as it did for the familiar condition. CONCLUSIONS: These results suggest that at least one primary function of the amygdala is to detect and process unexpected or unfamiliar events that have potential biological import, of which stimuli symbolic of fear or threat are but one possible example. We propose that this experimental paradigm will be useful for examining brain responses to novelty in different temperamental groups, as well as various psychiatric disorders.

Adult↗

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects.

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.

Adult↗

Alcohol intoxication effects on simulated driving: exploring alcohol-dose effects on brain activation using functional MRI.

Driving while intoxicated is a major public health problem. We investigated impaired driving using a simulated driving skill game that presents an 'in-car' view of a road and a readout of speed. We explored brain activation and behavioral alterations from baseline at two blood alcohol concentrations (BACs). Participants received single-blind individualized doses of beverage alcohol designed to produce blood alcohol content (BAC) of 0.04 and 0.08 or placebo. Scanning occurred on a 1.5 Tesla Philips MRI scanner after training to asymptote performance. Analysis was performed using independent component analysis (ICA) to isolate systematically nonoverlapping 'networks' and their time courses. Imaging results revealed seven separate driving-related brain networks with different time courses. Several significant findings were observed for the imaging data. First, dose-dependent functional magnetic resonance imaging (fMRI) changes were revealed in orbitofrontal (OF) and motor (but not cerebellar) regions; visual and medial frontal regions were unaffected. Second, cerebellar regions were significantly associated with driving behavior in a dose-dependent manner. Finally, a global disruptive effect of alcohol on the ICA time courses was observed with highly significant differences in OF and motor regions. Alcohol thus demonstrated some behavioral effects and unique, disruptive, dose-dependent effects on fMRI signal within several brain circuits. The fMRI data also suggest that the deficits observed in alcohol intoxication may be modulated primarily through OF/anterior cingulate, motor and cerebellar regions as opposed to attentional areas in frontoparietal cortex.

Adult↗

Atypical hemispheric dominance for attention: functional MRI topography.

The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.

Adult↗

Left ventricular function: MRI assessment.

Biplane left ventricular (LV) angiography has always been considered the standard of reference to measure LV volumes and ejection fraction (EF): however, angiographic measurements depend on the assumption of geometric models derived from two-dimensional information. MRI is the best technique to evaluate cardiac volumes and mass providing direct non geometric analysis of the ventricles with a high contrast resolution. Standard cine MRI is considered a time-consuming technique for acquisition and measurements; breath hold cine MRI and echoplanar imaging (EPI) non gated sequences are useful to reduce the acquisition time from a few minutes to a few seconds. The evaluation of the heart linear parameters (diameters, thickness), areas, volumes and mass is essential in the diagnosis of many heart diseases and in the assessment of the ventricular function. The modalities to evaluate LV measurements and to obtain functional parameters, the acquisition technique and flow analysis were analyzed in this study.

Angiography↗