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Clustered functional MRI of overt speech production.

To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Acoustic Stimulation↗

Nonlinear cortical modulation of muscle fatigue: a functional MRI study.

Muscle fatigue has been studied for over a century, but almost no data are available to indicate how the brain perceives fatigue and modulates its signals to the fatiguing muscle. In this study, brain activation was measured by functional magnetic resonance imaging (fMRI) during a sustained (2-min) maximal-effort handgrip contraction while handgrip force and finger muscle electromyographic (EMG) data were recorded simultaneously by a magnetic resonance environment-adapted force-EMG measurement system. The results showed decoupled progresses in brain and muscle activities when muscle was fatigued and correlated behaviors among the cortical areas being analyzed. While handgrip force and EMG signals declined in parallel during the course of muscle fatigue, fMRI-measured brain activities first substantially increased and then decreased. This similar signal modulation occurred not only in the primary sensorimotor areas but also in the secondary and association cortices (supplementary motor, prefrontal, and cingulate areas). The nonlinear changes of brain signal may reflect an early adjustment to strengthen the descending command for force-loss compensation and subsequent inhibition by sensory feedback as fatigue became more severe. The close association in the activation pattern in many cortical regions may reflect integrated processing of information in the brain.

Afferent Pathways↗

Functional MRI correlates of the recall of unresolved life events in borderline personality disorder.

BACKGROUND: Patients with borderline personality disorder (BPD) frequently report unresolved life events but it is still poorly understood, how these experiences are represented in the brain. Using functional magnetic resonance imaging (fMRI), the present study aimed at investigating the neural correlates of the recall of unresolved life events in patients with BPD and healthy controls. METHOD: Twenty female BPD patients and 21 healthy control subjects underwent fMRI. During measurement subjects recalled unresolved and resolved negative life events. Individual cue words were used to stimulate autobiographical memory. After scanning, subjects rated their emotional states during the recall of both types of memories. RESULTS: When contrasting unresolved and resolved life events, patients showed significant bilateral activation of frontotemporal areas including the insula, amygdala, and the anterior cingulate cortex, the left posterior cingulate cortex, right occipital cortex, the bilateral cerebellum and the midbrain. In healthy subjects, no differential brain activation was related to these conditions. The 2 x 2 factorial analysis (DeltaBPD - Deltacontrols) revealed similar results with bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex, temporal activation including the amygdala, activation of the right occipital cortex, and parts of the cerebellum. Patients but not controls reported higher levels of anxiety and helplessness during the unresolved versus resolved memory condition. CONCLUSIONS: The activation of both, the amygdala and prefrontal areas, might reflect an increased effortful but insufficient attempt to control intensive emotions during the recall of unresolved life events in patients with BPD.

Adult↗

Amygdalar activation associated with happy facial expressions in adolescents: a 3-T functional MRI study.

OBJECTIVE: To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years. METHOD: Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions. RESULTS: Happy faces produced significant bilateral amygdalar activation when compared with neutral faces (p <.05, corrected). Sad faces relative to neutral did not produce significant amygdalar activation. CONCLUSIONS: These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared.

Adolescent↗

Frontal lobe activation during word generation studied by functional MRI.

AIMS: To further delimit the specific verbal operations occurring in the dorsolateral frontal cortex during the generation of words. METHODS: Different verbal fluency tasks guided by distinct specifications (phonological, semantic, or automatic production of words) were used in a functional magnetic resonance study. The study group comprised 10 right-handed normal subjects ranging in age from 23 to 27 years. Functional magnetic resonance images were obtained in a 1.5-Tesla magnet using a spoiled GRASS sequence. RESULTS: Noticeable activation was found during the word generation tasks in the dorsolateral frontal cortex. The region showing the most prominent activation was the posterior part of the left middle frontal gyrus. Nevertheless, the different tasks each had a different activation effect. The phonologically guided generation of words produced the most consistent activation of the middle frontal gyrus, which mainly involved the premotor cortex. CONCLUSION: The results suggest that operations concerned with the generation of sound sequences, rather than the amount of produced words or their semantics, are responsible for sustained focal activity observed in the frontal lobes during verbal fluency tasks.

Adult↗

Functional MRI of language: new approaches to understanding the cortical organization of semantic processing.

Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.

Brain Mapping↗

Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study.

BACKGROUND: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy. METHODS: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison. RESULTS: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully. CONCLUSIONS: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

Adolescent↗

Combined diffusion weighting and CSF suppression in functional MRI.

In this study, EPI pulse sequences with diffusion weighting for reduction of contributions from large vessels and inversion pulses in order to minimize the effects of CSF pulsations and CSF partial volume effects were developed for BOLD contrast investigations in functional MR imaging. One inversion recovery echo-planar imaging (IR-EPI) pulse sequence and one IR-EPI with additional diffusion weighting (DW-IR-EPI) were developed and compared to a standard gradient-echo EPI sequence in a cortical stimulation experiment in nine healthy volunteers. Stimulation of motor cortex was performed using a semi-complex finger-tapping paradigm in seven periods of alternating rest and stimulation. Comparison between the three pulse sequences was made by measuring the activated volume in each subject, as well as by calculating the relative signal increase during stimulation. Due to different baseline signal-to-noise levels in the images generated by the three pulse sequences, artificial noise was added so that the comparative investigation could be performed independently of the noise level. The activated volume was 128 +/- 73 pixels (mean +/- SD) using the standard EPI pulse sequence, 31 +/- 12 pixels using IR-EPI and 15 +/- 13 pixels when DW-IR-EPI was employed. The relative signal increase was 5.7 +/- 1.1% using standard EPI, 11.5 +/- 3.1% using IR-EPI and 9.9 +/- 2.4% using DW-IR-EPI. The activated volume obtained with the addition of extra noise, i.e. at equal S/N, was 70 +/- 50 pixels using the standard EPI, and when using IR-EPI, the activated volume was 28 +/- 13 pixels. At equal S/N, the signal increase was 7.3 +/- 1.4% using standard EPI and 12.0 +/- 3.6% using IR-EPI. In BOLD contrast imaging, a combination of diffusion weighting and inversion recovery appeared to reduce false activation caused by CSF pulsation and blood flow in large vessels.

Adult↗

Cognitive control in childhood-onset obsessive-compulsive disorder: a functional MRI study.

BACKGROUND: Failure to resist chronic obsessive-compulsive symptoms may denote an altered state of cognitive control. We searched for the cerebral regions engaged in this dysfunction. METHOD: Differences in brain regional activity were examined by event-related functional magnetic regional imaging (fMRI) in a group of adolescents or young adults (n = 12) with childhood-onset obsessive-compulsive disorder (OCD), relative to healthy subjects. Subjects performed a conflict task involving the presentation of two consecutive and possibly conflicting prime and target numbers. Patients' image dataset was further analysed according to resistance or non-resistance to symptoms during the scans. RESULTS: Using volume correction based on a priori hypotheses, an exploratory analysis revealed that, within the prime-target repetition condition, the OCD subjects activated more than healthy subjects a subregion of the anterior cingulate gyrus and the left parietal lobe. Furthermore, compared with 'resistant' patients, the 'non-resistant' OCD subjects activated a bilateral network including the precuneus, pulvinar and paracentral lobules. CONCLUSIONS: Higher regional activations suggest an abnormal amplification process in OCD subjects during the discrimination of repetitive visual stimuli. The regional distribution of functional changes may vary with the patients' ability to resist obsessions.

Adult↗

Functional MRI for neurofeedback: feasibility study on a hand motor task.

We present an fMRI-based method that enables subjects to monitor and actively modulate their own brain activity as a form of biofeedback. On a 1.5 T clinical MR scanner, functional areas during a simple hand motor task were delineated by detecting signal variations associated with the brain activity. Then, the subject adopted a different strategy to expand the activation in motor and somatosensory areas that were not activated previously. Statistical maps of brain activity were visually presented back to the subject, being updated at the end of each segmented rest-task block in near real-time manner. Our results suggest that the visual feedback of the functional brain activation maps guided subjects to adjust their task performance to achieve the desired modulation of cortical activity. This method may offer a potential utility for fMRI-based neurofeedback.

Acoustic Stimulation↗

Functional MRI of the rat lumbar spinal cord involving painful stimulation and the effect of peripheral joint mobilization.

PURPOSE: To examine neuronal activation in the spinal cord due to secondary hyperalgesia resulting from intrajoint capsaicin injection, and the effect of physiotherapy manipulation, using functional magnetic resonance imaging (fMRI), in alpha-chloralose anesthetized rats. MATERIALS AND METHODS: FMRI of the rat lumbar spinal cord was performed at 9.4 Tesla. Stimuli included injection of 25 microL of capsaicin (128 microg/mL in 7.5% dimethyl sulfoxide [DMSO]) into the right forepaw or 75 microL into the right ankle joint followed by a light touch stimulus, with and without physiotherapy manipulation. RESULTS: Activation of pain areas of the spinal cord (dorsal horn) was found in all animals after injection of capsaicin into the plantar surface of the rat hindpaw and ankle joint. Overlay maps depicting activations and deactivations showed significant reproducibility between experiments. Greater overlay of activations were observed for intrajoint compared to intradermal capsaicin injection. The distribution of activations after stimulation of the hindpaw using a light touch stimulus was somewhat more varied; activation of the dorsal horn was evident, with greater overlap resulting when joint mobilization was not performed. CONCLUSION: Results suggest a trend toward decreased areas of activation in the spinal cord associated with pain, as a result of hyperalgesia, following physiotherapy joint mobilization.

Animals↗

Cortical and subcortical activation with monaural monosyllabic stimulation by functional MRI.

Few reports have characterized auditory processing in monaural stimulation, which is important to the understanding of auditory brain activity in subjects with hearing loss. We therefore measured regional brain activity in response to monaural stimulation of 95 dB SPL monosyllables using functional magnetic resonance imaging (fMRI) in subjects with normal hearing and five with unilateral deafness as controls for 'cross-hearing'. Images were analyzed by statistical parametric mapping software. In subjects without hearing loss, the stimuli elicited cortical activation in the primary auditory (BA 41) and auditory association regions (BA 42, 22), particularly contralaterally where extent of activation was approximately 2.5 times the ipsilateral extent. All patients with profound unilateral deafness showed no statistically apparent response in the primary auditory and auditory association regions, ruling out an important influence from cross-hearing. We found fMRI to be a useful technique for analysis of auditory processing that should be applicable to patients with various hearing abnormalities.

Acoustic Stimulation↗

A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction.

OBJECTIVES: Even when euthymic bipolar disorder patients can have persistent deficits in working memory, but the neural basis of this deficit remains unclear. We undertook an functional magnetic resonance imaging investigation of euthymic bipolar disorder patients performing two working memory paradigms; the two-back and Sternberg tasks, selected to examine the central executive and the phonological loop respectively. We hypothesized that neuronal dysfunction would be specific to the network underlying the executive rather than the phonological loop component of working memory. METHODS: Twelve right-handed euthymic bipolar I males receiving lithium carbonate monotherapy were matched with 12 controls. The two-back task comprised a single working memory load contrasted with baseline vigilance condition. The Sternberg paradigm used a parametric design incorporating variable working memory load with fixed delay between presentation of an array of items to be remembered and a target item. Functional activation data were acquired during performance of the tasks and were analysed to produce brain activation maps representing significant group differences in activation (ANOVA). Load-response curves were derived from the Sternberg task data set. RESULTS: There were no significant between-group differences (t-test) in performance of the two-back task, or in 2 x 5 group by memory load ANOVA for the performance data from Sternberg task. In the two-back task, compared with controls bipolar disorder patients showed reductions in bilateral frontal, temporal and parietal activation, and increased activations with the left precentral, right medial frontal and left supramarginal gyri. No between-group differences were observed in the Sternberg task at any working memory load. CONCLUSIONS: Our findings support the notion that, in euthymic bipolar disorder, failure to engage fronto-executive function underpins the core neuropsychological deficits.

Bipolar Disorder↗

Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients.

BACKGROUND/OBJECTIVES: A previous fMRI study demonstrated increased brain activation during working memory tasks in patients with HIV with mild dementia. The current study aims to determine whether patients who are HIV-1 positive and have normal cognitive function also show increased brain activation on fMRI. METHODS: Blood oxygenation level-dependent (BOLD) fMRI was performed in 10 patients with HIV (CD <500) and 10 age-, sex-, education-, and handedness-matched seronegative subjects. Each subject performed a battery of neuropsychological tests and fMRI with three tasks (0-back, 1-back, and 2-back) that required different levels of attention for working memory. RESULTS: Compared with control subjects, patients with HIV showed greater magnitude of brain activation (BOLD signal intensity changes, p <or= 0.001) in the lateral prefrontal cortex, with normal performance during fMRI and on a battery of neuropsychological tests. The patients with HIV also showed increased activated brain volume in the lateral prefrontal cortex (p = 0.007) but not in other activated regions, including the posterior parietal cortex, supplementary motor area, thalamus, caudate, and occipital cortex. The increase in activated brain volume was independent of task difficulty. CONCLUSION: Increased brain activation in subjects who are positive for HIV precedes clinical signs or deficits on cognitive tests. Early injury to the neural substrate may necessitate increased usage of brain reserve to maintain normal cognitive function. BOLD fMRI appears to be more sensitive than clinical and neuropsychological evaluations for detecting early HIV-associated brain injury.

AIDS Dementia Complex↗

Multi-slice perfusion-based functional MRI using the FAIR technique: comparison of CBF and BOLD effects.

Perfusion-weighted imaging techniques employing blood water protons as an endogenous tracer have poor temporal resolution because each image should be acquired with an adequate spin 'tagging' time. Thus, perfusion-based functional magnetic resonance imaging studies are typically performed on a single slice. To alleviate this problem, a multi-slice flow-sensitive alternating inversion recovery technique has been developed. Following a single inversion pulse and a delay time, multi-slice echo-planar images are acquired sequentially without any additional inter-image delay. Thus, the temporal resolution of multi-slice FAIR is almost identical to that of single slice techniques. The theoretical background for multi-slice FAIR is described in detail. The multi-slice FAIR technique has been successfully applied to obtain three-slice cerebral blood flow based functional images during motor tasks. The relative CBF change in the contralateral motor/sensory area during unilateral thumb-digit opposition is 45.0+/-12.2% (n=9), while the blood oxygenation level dependent signal change is 1.5+/-0.4 SD%. Relative changes of the oxygen consumption rate can be estimated from CBF and BOLD changes using FAIR. The BOLD signal change is not correlated with the relative CBF increase, and thus caution should be exercised when interpreting the BOLD change as a quantitative index of the CBF change, especially in inter-subject comparisons.

Brain↗

Functional MRI of human hypothalamic responses following glucose ingestion.

The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.

Adult↗

Disruption of the neural response to rapid acoustic stimuli in dyslexia: evidence from functional MRI.

The biological basis for developmental dyslexia remains unknown. Research has suggested that a fundamental deficit in dyslexia is the inability to process sensory input that enters the nervous system rapidly and that deficits in processing rapid acoustic information are associated with impaired reading. Functional magnetic resonance imaging (fMRI) was used to identify the brain basis of rapid acoustic processing in normal readers and to discover the status of that response in dyslexic readers. Normal readers showed left prefrontal activity in response to rapidly changing, relative to slowly changing, nonlinguistic acoustic stimuli. Dyslexic readers showed no differential left frontal response. Two dyslexic readers participated in a remediation program and showed increased activity in left prefrontal cortex after training. These fMRI results identify left prefrontal regions as normally being sensitive to rapid relative to slow acoustic stimulation, insensitive to the difference between such stimuli in dyslexic readers, and plastic enough in adulthood to develop such differential sensitivity after intensive training.

Acoustic Stimulation↗

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Adult↗