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Cortical remapping in amputees and dysmelic patients: a functional MRI study.

OBJECTIVES: To investigate motor cortex function in upper and lower limb amputees and dysmelic patients using fMRI. MATERIAL AND METHODS: Five amputees and two dysmelic patients were examined. Motor and imagery tasks were defined according to each patient limb deficiency. Cortical activation patterns were analysed for each patient and compared between groups, integrating patients clinical data. RESULTS: There is a consistent pattern of cortical reorganization in all amputees: predominance of activation in the ipsilateral motor cortex and extension to premotor and sensory areas of the contralateral cortex. On the contrary, cortical maps of dysmelic patients were similar to those of healthy volunteers, predominantly with activation of contralateral primary motor cortex areas. CONCLUSIONS: fMRI discloses specific patterns of cortical reorganization on amputees and dysmelic patients, suggesting influence by prosthesis adaptation or stump use with dexterity. These findings could be further applied in influencing neurorehabilitation and development of prosthetic devices.

Aged↗

Neuroanatomy of language processing studied with functional MRI.

This article discusses recent data from functional magnetic resonance imaging (FMRI) studies of language. Although preliminary, these data suggest activation of the left prefrontal cortex across a variety of tasks, with less activation of posterior cortical areas known to play a role in language. Potential sources of error in functional imaging studies related to task subtraction techniques are briefly discussed. The semantic decision task used by the author and colleagues, which produces left lateralized activation of both prefrontal and temporoparietal areas, is presented in detail, and the activation pattern observed in these studies is discussed in the context of converging neuropsychological and positron emission tomography data. It is argued that superior temporal responses evoked by listening to speech represent sensory rather than language processes. The data bring into question the classical disconnection model of transcortical aphasia and confirm the participation of left prefrontal areas in comprehension. FMRI shows promise as an alternative to the intracarotid amobarbital test for language dominance.

Brain↗

Functional MRI of the kidney: tools for translational studies of pathophysiology of renal disease.

Magnetic resonance imaging (MRI) provides exquisite anatomic detail of various organs and is capable of providing additional functional information. This combination allows for comprehensive diagnostic evaluation of pathologies such as ischemic renal disease. Noninvasive MRI techniques could facilitate translation of many studies performed in controlled animal models using technologies that are invasive to humans. Such a translation is being recognized as essential because many proposed interventions and drugs that prove efficacious in animal models fail to do so in humans. In this article, we review the state-of-the-art functional MRI technique as applied to the kidneys.

Animals↗

Functional MRI for anticancer therapy assessment.

Anticancer drug discovery and development are experiencing a paradigm shift from cytotoxic therapies to more selective therapies that target underlying oncogenic abnormalities. Many newer therapies are cytostatic, for which objective tumour shrinkage is an inappropriate response parameter. There is a growing need to develop surrogate endpoints of drug efficacy to speed up the process of finding effective drug combinations for phase III trials. This review focuses on the developing field of functional magnetic resonance imaging (MRI) and its potential applications in the pharmacodynamic evaluation of existing and new cancer therapeutics. Dynamic contrast enhanced MRI, which is currently being used to evaluate anti-angiogenic, and anti-vascular agents in human trials will be reviewed in detail. The requirements that must be met before incorporating functional MRI techniques into clinical protocols are also discussed.

Antineoplastic Agents↗

Functional MRI in the evaluation of oesophageal motility: feasibility, MRI patterns of normality, and preliminary experience in subjects with motility disorders.

PURPOSE: The aim of this study was to introduce functional magnetic resonance imaging (fMRI) with T1-weighted turbo fast low-angle shot (FLASH) sequences in the evaluation of oesophageal motility and morphology, to formulate MRI patterns of normality in healthy subjects and to demonstrate the feasibility of the method by obtaining a preliminary experience in the study of subjects affected by oesophageal motility disorders. MATERIALS AND METHODS: Thirty healthy volunteers and seven patients with radiological and manometric diagnoses of oesophageal motility disorders underwent fMRI with dynamic T1- weighted turbo-FLASH (TFL) sequences during the administration of oral contrast material. RESULTS: Evaluation of oesophageal function and morphology proved possible in all subjects, as well as the formulation of normality patterns. In patients with motility disorders, fMRI correctly visualised the typical alterations in agreement with radiological and manometric findings. CONCLUSIONS: Functional MRI sequences acquired during the administration of oral contrast material can evaluate oesophageal transit, providing information on motility and morphology; furthermore, this modality can properly visualise the typical functional and morphological alterations of motility disorders.

Adult↗

Magnetic resonance imaging (MRI) detection of the murine brain response to light: temporal differentiation and negative functional MRI changes.

Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation.

Animals↗

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials.

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during hand-squeezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

Adult↗

A functional MRI study of three motor tasks in the evaluation of stroke recovery.

Functional brain imaging studies have provided insights into the processes related to motor recovery after stroke. The comparative value of different motor activation tasks for probing these processes has received limited study. We hypothesized that different hand motor tasks would activate the brain differently in controls, and that this would affect control-patient comparisons. Functional magnetic resonance imaging (MRI) was used to evaluate nine control subjects and seven patients with good recovery after a left hemisphere hemiparetic stroke. The volume of activated brain in bilateral sensorimotor cortex and four other motor regions was compared during each of three tasks performed by the right hand: index-finger tapping, four-finger tapping, and squeezing. In control subjects, activation in left sensorimotor cortex was found to be significantly larger during squeezing as compared with index-finger tapping. When comparing control subjects with stroke patients, patients showed a larger volume of activation in right sensorimotor cortex during index-finger tapping but not with four-finger tapping or squeezing. In addition, patients also showed a trend toward larger activation volume than controls within left supplementary motor area during index-finger tapping but not during the other tasks. Motion artifact was more common with squeezing than with the tapping tasks. The choice of hand motor tasks used during brain mapping can influence findings in control subjects as well as the differences identified between controls and stroke patients. The results may be useful for future studies of motor recovery after stroke.

Adult↗

Functional MRI of the rat somatosensory cortex: effects of hyperventilation.

Functional mapping of the rat somatosensory cortex was performed with T2*-sensitized MRI using a forepaw electrical stimulation model in alpha-chloralose-anesthetized rats at 7 T under both normocapnia and mild hyperventilation-induced hypocapnia. A highly localized activation area, consistent with the known somatosensory cortical region, was detected in all seven animals studied during hypocapnia and in five of the same animals during normocapnia. Quantitatively, hypocapnia was found to significantly increase both the size of the fMRI activation area (3.4 +/- 0.6 mm2 versus 1.5 +/- 0.6 mm2 in normocapnia, mean +/- standard error, n = 7, P < 0.03) and the average fMRI signal intensity increase (3.4 +/- 0.6% versus 2.7 +/- 0.4%, n = 5, P < 0.05). The increased sensitivity of fMRI to functional activation may reflect a widened arterial-venous oxygenation difference resulting from an increased effective oxygen extraction during hyperventilation. The dependence of the fMRI response on the ventilation state underscores the need to control for physiological parameters in animal fMRI studies.

Afferent Pathways↗

A weighted least-squares algorithm for estimation and visualization of relative latencies in event-related functional MRI.

The properties of the hemodynamic latencies in functional maps have been relatively unexplored. Accurate methods of estimating hemodynamic latencies are needed to take advantage of this feature of fMRI. A fully automated, weighted least-squares (WLS) method for estimating temporal latencies is reported. Using a weighted linear model, the optimal latency and amplitude of the fMRI response can be determined for those voxels that pass a detection threshold. There is evidence from previous studies that the hemodynamic response may be time-locked to the stimulus within certain limits, less variable earlier in its evolution, and able to resolve information about relative hemodynamic timing. This information can be used to test hypotheses about the sequence and spatial distribution of neural activity. The method can be used to weight the earliest evolution of the hemodynamic response more heavily and decrease bias resulting from the hemodynamic response function. Additionally, the WLS method can control for varying response shapes across the brain and improve latency comparisons between brain regions. The WLS method was developed to study the properties of hemodynamic latencies, which may be increasingly important as event-related fMRI continues to be advanced.

Algorithms↗

A functional MRI study on the neural substrates for writing.

Functional neuroanatomy of writing is relatively unknown compared to that of other linguistic processes. This study aimed at identifying brain regions crucial to the process of writing. Using functional magnetic resonance imaging (fMRI), brain hemodynamic activity was examined during three conditions that differentially engaged visual, linguistic, and/or motor functions: (1) writing names of pictures with the right index finger, (2) naming pictures silently, and (3) visually cued finger tapping. A writing minus naming comparison and a writing minus tapping comparison were performed, and brain regions commonly activated in these two contrasts were detected. Our main finding was that such common activation was observed in the anterior part of the left superior parietal lobule, the posterior part of the middle and superior frontal gyri, and the right cerebellum. The parietal and frontal regions were considered to subserve the process of writing as separated from that of naming and finger movements, which is consistent with the classical notion mainly proposed by studies of selective writing deficits called pure agraphia. The right cerebellar activation, on the other hand, was interpreted as the reflection of the execution of complex finger movements required for writing.

Adult↗

Diagnostic functional MRI: illustrated clinical applications and decision-making.

Functional magnetic resonance imaging (fMRI) has become a popular research tool, yet its use for diagnostic purposes and actual treatment planning has remained less widespread. The literature yields rather sparse evidence-based data on clinical fMRI applications and accordant decision-making. Notwithstanding, blood oxygenation level dependent (BOLD)- and arterial spin labeling (ASL)-fMRI can be judiciously combined with perfusion measurements, electroencephalographic (EEG) recordings, diffusion-weighted imaging (DWI), and fiber tractographies to assist clinical decisions. In this article we provide an overview of clinical fMRI applications based on illustrative examples. Assessment of cochlear implant candidates by fMRI is covered in some detail, and distinct reference is made to particular challenges imposed by brain tumors, other space-occupying lesions, cortical dysplasias, seizure disorders, and vascular malformations. Specific strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI studies in individual patients are highlighted.

Brain Diseases↗

Functional MRI of global and local processing in children.

Functional magnetic resonance imaging was used to examine developmental change in hemispheric biases for globally and locally directed analysis of hierarchical forms. In a previous reaction time (RT) study, which presented hierarchical stimuli to the visual hemifields, children 7 to 14 years of age demonstrated an emerging pattern of hemispheric differences. Initially children analyzed local elements more slowly, without a strongly lateralized advantage for local or global level processing. With age, children's development was marked by a left hemisphere advantage for local level processing that resembled an adult's and a trend toward a right hemisphere advantage for global. In the current study, 20 children 12 to 14 years old were imaged during attend-global and attend-local conditions to determine whether the developmental change in cognitive measures corresponded to a change in distribution of functional activation. Children formed two groups based on their RT performance, immature-bilateral (IB) or mature-lateralized (ML). The volume of task-related activation within lateral temporo-occipital regions of interest was compared for global and local conditions between the two groups. The IB children showed greater activation overall for local level processing, comparable activation across the two hemispheres for the global condition, and a trend of right greater than left hemisphere activation for local. In contrast, the ML children displayed right greater than left hemisphere activation during global analysis and the opposite during local processing. Importantly these patterns of functional activation mirror the profiles of RT performance. Together they demonstrate a shift from undifferentiated, bilateral processing toward hemispheric lateralization.

Aging↗

Functional MRI to study brain plasticity in clinical neurology.

Functional magnetic resonance imaging (fMRI) is being widely used to study recovery of function in patients with several neurological conditions, including multiple sclerosis, stroke and Alzheimer's disease. The application of this MR technique has shown that plastic cortical changes do occur after central nervous system (CNS) injury of different aetiology, that such changes are related to the extent of CNS damage and that they can contribute in limiting the clinical consequences of brain damage. Conversely, the failure or exhaustion of the adaptive properties of the cerebral cortex might be among the factors responsible for the accumulation of 'fixed' neurological deficits. New studies aimed at investigating the effect of therapies devoted to promote brain plasticity are now warranted.

Brain Diseases↗

Experimental design for functional MRI of scene memory encoding.

The use of functional imaging to identify encoding-related areas in the medial temporal lobe has previously been explored for presurgical evaluation in patients with temporal lobe epilepsy. Optimizing sensitivity in such paradigms is critical for the reliable detection of regions most closely engaged in memory encoding. A variety of experimental designs have been used to detect encoding-related activity, including blocked, sparse event-related, and rapid event-related designs. Although blocked designs are generally more sensitive than event-related designs, design and analysis advantages could potentially overcome this difference. In the present study, we directly contrast different experimental designs in terms of the intensity, extent, and lateralization of activation detected in healthy subjects. Our results suggest that although improved design augments the sensitivity of event-related designs, these benefits are not sufficient to overcome the sensitivity advantages of traditional blocked designs.

Adolescent↗

Modulation of the visual word retrieval system in writing: a functional MRI study on the Japanese orthographies.

We used functional magnetic resonance imaging (fMRI) to examine whether the act of writing involves different neuropsychological mechanisms between the two script systems of the Japanese language: kanji (ideogram) and kana (phonogram). The main experiments employed a 2 x 2 factorial design that comprised writing-to-dictation and visual mental recall for kanji and kana. For both scripts, the actual writing produced a widespread fronto-parietal activation in the left hemisphere. Especially, writing of kanji activated the left posteroinferior temporal cortex (lPITC), whereas that of kana also yielded a trend of activation in the same area. Mental recall for both scripts activated similarly the left parietotemporal regions including the lPITC. The writing versus mental recall comparison revealed greater activations in the left sensorimotor areas and right cerebellum. The kanji versus kana comparison showed increased responses in the left prefrontal and anterior cingulate areas. Especially, the lPITC showed a significant task-by-script interaction. Two additional control tasks, repetition (REP) and semantic judgment (SJ), activated the bilateral perisylvian areas, but enhanced the lPITC response only weakly. These results suggest that writing of the ideographic and phonographic scripts, although using the largely same cortical regions, each modulates the visual word-retrieval system according to their graphic features. Furthermore, comparisons with two additional tasks indicate that the activity of the lPITC increases especially in expressive language operations regardless of sensory modalities of the input stimulus.

Acoustic Stimulation↗

Real-time functional MRI: development and emerging applications.

Real-time functional magnetic resonance imaging (fMRI) is an emerging technique for assessing the dynamic and robust changes in brain activation during an ongoing experiment. Real-time fMRI allows measurement of several processes within the brain as they occur. The extracted information can be used to monitor the quality of acquired data sets, serve as the basis for neurofeedback training, and manipulate scans for interactive paradigm designs. Although more work is needed, recent results have demonstrated a variety of potential applications for real-time fMRI for research and clinical use. We discuss these developments and focus on methods enabling real-time analysis of fMRI data sets, novel research applications arising from these approaches, and potential use of real-time fMRI in clinical settings.

Algorithms↗