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A critique of functional localisers.

In this critique, we review the usefulness of functional localising scans in functional MRI studies. We consider their conceptual motivations and the implications for experimental design and inference. Functional localisers can often be viewed as acquiring data from cells that have been removed from an implicit factorial design. This perspective reveals their potentially restrictive nature. We deconstruct two examples from the recent literature to highlight the key issues. We conclude that localiser scans can be unnecessary and, in some instances, lead to a biased and inappropriately constrained characterisation of functional anatomy.

Brain Mapping↗

Neural basis of irony comprehension in children with autism: the role of prosody and context.

While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.

Adolescent↗

Dynamic magnetic resonance imaging of human Rolandic cortex.

Rolandic cortex was imaged with magnetic resonance (MR) in nine subjects while performing a motor activation task. Imaging was performed by a volumetric, T2-weighted pulse sequence in a conventional 1.5 Tesla scanner during both resting conditions and volitional toe flexion and extension of the dominant foot. Significant changes in MR signal intensity of 7.8 +/- 2.3% (mean +/- s.e.m.) were observed in the medial Rolandic cortex contralateral to the active foot. Changes were maximal in the vicinity of the central sulcus, but were also identified anteroposteriorly, across successive coronal planes. No significant changes were found in the ipsilateral Rolandic cortex or in other brain structures. Volumetric functional MRI strategies may provide an important non-invasive tool for assessment of cortical motor function.

Adolescent↗

The role of anterior cingulate cortex in working memory is shaped by functional connectivity.

The anterior cingulate (AC) cortex seems to be similarly engaged by attentional and memory processes. We tested the hypothesis that this common activation is best explained by changes in the regions interacting (functionally connected) with AC. Subjects were tested on two variants of a 2-back working memory task: a standard version with strong attentional demands, and a cued version that more strongly promoted memory retrieval. AC activation, measured with functional MRI, was found in both tasks, although more sustained in the standard condition. The regions functionally connected to the AC, and the relation of these activity patterns to memory performance, were completely different across tasks. In the standard task, the pattern related to a speed-accuracy tradeoff, whereas the connectivity pattern unique to the cued task related only to better accuracy. By virtue of these changing patterns of functional connectivity, the contribution of AC to attention- and memory-driven performance was similarly changed.

Adult↗

Magnetic resonace imaging study in major psychiatric disorders.

Magnetic resonance brain imaging provides good contrast between the three principal compartments of the brain: gray and white matter, and cerebrospinal fluid (CSF). Not only brain volumic and structural understanding, the application of magnetic imaging techniques as in Functional MRI (MRI), Magnetic resonance spectroscopy (MRS) also has greatly enhanced the range of findings in brain function of psychiatric patients. The objective of this paper was to present a brief review of the technological advances in magnetic neuroimaging, and to indicate how these techniques have impacted the study ofpsychiatry. Reviews of recent researches, examples of imaging techniques, and major findings for schizophrenia, affective disorder, anxiety, personality and other major psychiatric disorders are offered. In summary, the using of magnetic neuroimaging as an aid to diagnosis is discussed, and findings from the most accessible imaging techniques are reviewed.

Anxiety Disorders↗

Magnetic resonance imaging in multiple sclerosis.

Magnetic resonance imaging (MRI) has played a central role in the clinical management and scientific investigation of multiple sclerosis (MS) and has become the most important ancillary tool for diagnosing and monitoring the disease. Conventional MRI techniques are used to assess overt lesions and atrophy in the central nervous system and include spin-echo T2-weighted, pre- and post-gadolinium-enhanced spin-echo T1-weighted, and fluid-attenuated inversion-recovery images. Advanced MRI techniques such as diffusion-weighted imaging, magnetization transfer imaging, magnetic resonance spectroscopy, and functional MRI have increased our understanding of the pathogenesis of MS. The role of these newer techniques in clinical practice remains under investigation. In this review, we will focus on the role of MRI in the diagnosis and management of MS. We will also review how advanced MRI techniques contribute to our understanding of MS.

Atrophy↗

Role of fMRI in the decision-making process: epilepsy surgery for children.

Functional MRI (fMRI) is increasingly being used to evaluate children and adolescents who are candidates for surgical treatment of intractable epilepsy. It has the advantage of being noninvasive and well tolerated by young people. By identifying important functional regions within the brain, including unpredictable patterns of functional reorganization, it can aid in surgical decision-making. Here we illustrate this using a number of case studies from the pediatric epilepsy surgery program at our institution. We describe how fMRI, used in conjunction with conventional investigative methods such as neuropsychological assessment, MRI, and electrophysiology, can 1) help to improve functional outcome by enabling resective surgery that spares functional cortex, 2) guide surgical intervention by revealing when reorganization of function has occurred, and 3) show when abnormal cortex is also functionally active, and hence that surgery may not be the best option. Altogether, these roles have reduced the need for invasive procedures that can be both risky and distressing for young people with epilepsy. In our experience, fMRI has significantly contributed to the decision-making process, and improved the counseling and management of young people with intractable epilepsy.

Brain Mapping↗

Anesthesia during high-field intraoperative magnetic resonance imaging experience with 80 consecutive cases.

Intraoperative magnetic resonance imaging (MRI) has been used for years to update neuronavigation and for intraoperative resection control. For this purpose, low-field (0.1-0.2 T) MR scanners have been installed in the operating room, which, in contrast to machines using higher magnetic field strength, allowed the use of standard anesthetic and surgical equipment. However, these low-field MR systems provided only minor image quality and a limited battery of MR sequences, excluding functional MRI, diffusion-weighted MRI, or MR angiography and spectroscopy. Based on these advantages, a concept using high-field MRI (1.5 T) with intraoperative functional neuronavigational guidance has been developed that required adaptation of the anesthetic regimen to working in the close vicinity to the strong magnetic field. In this paper the authors present their experience with the first 80 consecutive patients who received anesthesia in a specially designed radio frequency-shielded operating room equipped with a high-field (1.5 T) MR scanner. We describe the MR-compatible anesthesia equipment used including ventilator, monitoring, and syringe pumps, which allow standard neuroanesthesia in this new and challenging environment. This equipment provides the use of total intravenous anesthesia with propofol and remifentanil allowing rapid extubation and neurologic examination following surgery. In addition, extended intraoperative monitoring including EEG monitoring required for intracranial surgery is possible. Moreover, problems and dangers related to the effects of the strong magnetic field are discussed.

Adolescent↗

[Intractable epilepsy--neurophysiological evaluation and indication for surgical treatment].

Medically intractable epilepsy, defined as the clinical attacks occurring at least once a month in spite of appropriate antiepileptic drug treatments, is one of the commonest disorders in the clinical neurology. Since surgical treatment of epilepsy is successful in selected patients, it is most important to delineate the epileptogenic focus and functions of adjacent cortical areas as precisely as possible. Recent advances in electrophysiology, magnetoencephalography, magnetic resonance imaging (MRI), functional imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have enabled us to elucidate the epileptogenic focus noninvasively without involving the conventional invasive EEG recording techniques. We evaluated 37 patients with intractable partial seizures by using prolonged video/EEG monitoring with sphenoidal or T1/T2 electrodes. MRI, ictal and interictal SPECT for blood flow measurement and interictal FDG-PET for glucose metabolism. Among 20 patients with intractable epilepsy who had a single ictal focus, PET, ictal SPECT and MRI findings were correlated with the ictal EEG finding with the concordance rate of 100, 86 and 75%, respectively. If all of those findings were convergent upon a single focus, then the surgical treatment with intraoperative corticography is most likely effective without employing any invasive recording. If those findings were divergent, then the invasive evaluation will be indicated.

Adolescent↗

Pharmacological applications of magnetic resonance imaging.

Magnetic resonance imaging (MRI) techniques are capable of spatial and temporal resolution and within subject repeatability that far exceed other currently available methods of noninvasively investigating brain functioning. While functional MRI (fMRI) techniques have traditionally been used to investigate sensory, motor, and cognitive functions, they are also very attractive for investigating the effects of pharmacological agents in the brain. However, because pharmacological agents may interfere with the very mechanisms that give rise to the fMRI signal, careful attention to experimental design and data analysis issues must be exercised. Specifically, introducing a drug into the system could potentially alter the coupling of neural activity with regional cerebral blood flow and/or the extraction of oxygen from blood, or may cause local or global cardiovascular changes unrelated to neural activity. These concerns notwithstanding, careful attention to experimental detail and verification procedures promises to make pharmacological MRI a valuable tool for understanding the actions of drugs on the brain at many levels. The physiological and biophysical bases of blood oxygen level-dependent, arterial spin labeling, cerebral blood flow, cerebral blood volume, and spectroscopy acquisition methods are presented to illustrate where confounds may arise when a drug is added to the system. Selected studies combining administration of pharmacological agents with MRI techniques are critically reviewed to illustrate both the challenges inherent in these applications and some possible solutions. Included are studies of acute direct effects of drugs, effects of drugs on task-related activation, chronic effects of drugs, effects of drugs on cerebral metabolism, and variable effects of drugs in different populations.

Animals↗

[MRI safety aspects and artifacts of atrial septal defect and patent foramen ovale occluders at 1.5 tesla: a phantom study].

PURPOSE: To investigate the magnetic resonance safety and magnetic resonance artifact intensities of patent foramen ovale and atrial septal occluders in a phantom study. MATERIALS AND METHODS: Seven different commercial occluder models (Amplatzer ASD, Angel Wing ASD, Helex Septal Occluder, Cardia PFO-Star Generation I & III, Sideris Buttoned Device, Starflex ASD) were tested in a 1.5 Tesla whole-body MR scanner. Following a deflection test, the non-magnetic devices were imaged using different MRI pulse sequences including conventional spin echo, spoiled gradient echo as well as fast refocused steady-state pulse sequences (trueFISP) commonly used for cardiac MRI. Additionally, device temperatures were measured in the MR scanner during two imaging protocols (trueFISP, HASTE) with an MR-compatible fiber-optical thermometer. RESULTS: One ferromagnetic device (Sideris Buttoned Device) did not pass the deflection test and was excluded from further experiments. For typical cardiac imaging protocols, the remaining non-ferromagnetic devices showed only minor image artifacts with artifact sizes not exceeding 2 mm next to a strut. Heating was not observed in the devices. CONCLUSION: Non-ferromagnetic occluder models used in this study can safely be imaged with typical cardiac MRI protocols at 1.5 Tesla. The device artifact sizes are small enough to allow anatomical and functional MRI even in the immediate vicinity of the occluders.

Artifacts↗

Analysis of magnetic resonance imaging acoustic noise generated by a 4.7 T experimental system.

High intensity acoustic noise is an undesirable side-effect in magnetic resonance imaging (MRI) that can cause discomfort and hearing loss in patients and may be an impediment in functional MRI (fMRI) studies of the auditory system. Experimental MRI systems with high magnetic field strengths may generate acoustic noise of higher sound pressure levels (SPLs) than conventional 1.0 and 1.5 T clinical systems. We measured the SPL and spectral content of the acoustic noise generated by the Bruker Biospect 47/40 4.7 T experimental MRI system during scanning sequences commonly used in animal testing. Each sequence generated acoustic noise of high SPL, rapid pulse rates, amplitude-modulated pulse envelopes and multi-peaked spectra. The rapid acquisition with enhancement sequence with a 0.25 mm slice thickness generated SPLs of up to 129 dB peak SPL and 130 dB (A). Fourier analysis of the spectral content of the acoustic noise generated by each MRI sequence showed a wide band of acoustic energy with spectral peaks from 0.2-5 kHz. The intense MRI acoustic impulse noise generated by the 4.7 T system may cause masking of stimuli used in fMRI of the auditory cortex, reduce the hearing acuity of experimental animals and present a risk for unprotected human ears.

Acoustics↗

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

Adult↗

Glaucoma and brain functional networks: a bidirectional Mendelian randomisation study.

OBJECTIVE: Glaucoma is a complex neurodegenerative ocular disorder accompanied by brain functional abnormalities that extend beyond the visual system. However, the causal association between the two remains unclear at present. This study aimed to investigate the potential causal relationships between glaucoma and brain functional networks in order to provide novel insights into the neuropathic mechanism of glaucoma. METHODS AND ANALYSIS: Based on the genome-wide association studies data of glaucoma and resting-state functional MRI (Rs-fMRI), a bidirectional Mendelian randomisation (MR) analysis was conducted between glaucoma and brain functional networks. Inverse variance weighting was applied as the primary method to estimate causality with false discovery rate correction. Additional sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Forward MR analysis suggested that glaucoma was causally associated with two brain networks between the subcortical cerebellum and the attention or visual network (p=0.022), as well as the default mode and central executive network (p=0.008), but without significance after false discovery rate correction (q>0.1). Reverse MR analysis revealed 19 Rs-fMRI traits related to glaucoma risk, including the salience or central executive network in the frontal region (p=0.0005, q=0.08) and the motor network (p=0.0009, q=0.08) with significant causality. CONCLUSIONS: This MR study revealed potentially causal relationships between glaucoma and brain functional networks. Especially, the functional connectivity of the motor network between the postcentral or precentral areas may potentially lead to increased risk of glaucoma.

Humans↗

fMRI of lexical-semantic priming in a chronic schizophrenia patient.

A neuropsychological hallmark of schizophrenia is a breakdown in semantic association networks that often impacts language and formal thought. Although computational models simulating this breakdown exist, studies have yet to investigate this phenomena using functional MRI (fMRI) coupled with an auditory lexical-decision semantic priming paradigm. Thus, this serves to functionally map brain activation to word pairs that differed with respect to a concept called "connectivity" in a patient with schizophrenia and a demographically matched control adult. Analyses revealed a striking difference with respect to the expected stepwise modulation of activation, with the control participant showing significantly greater areas of modulation than the participant with schizophrenia in regions classically implicated in language. Although the results are tentative because of the nature of this investigation (single-case study), they further support the characterization of schizophrenia as a breakdown in lexical-semantic association networks and represent one of the first fMRI studies of semantic priming in schizophrenia informed by a computer model.

Brain↗

A truly simultaneous combination of functional transcranial Doppler sonography and H(2)(15)O PET adds fundamental new information on differences in cognitive activation between schizophrenics and healthy control subjects.

UNLABELLED: Working memory deficits are a cardinal feature of the pathophysiology of schizophrenia. Lesion studies and functional blood flow-dependent imaging methods with coarse temporal resolution, such as PET and functional MRI (fMRI), tend to paint a fairly static picture of the cortical regions involved. In contrast, functional transcranial Doppler sonography (fTCD) provides a high temporal resolution. Truly simultaneous fTCD-fMRI is not yet possible for technical reasons, but H(2)(15)O PET and fTCD can be used really simultaneously. However, this combination has not yet been used for cognitive activations in schizophrenia. We therefore investigated the extent to which there are both spatial (PET) and temporal changes (fTCD) in the activation patterns of schizophrenic patients. METHODS: Eleven clinically stable chronic schizophrenic, right-handed patients and 10 healthy, right-handed control subjects, matched for age, sex, education, and intelligence quotient, participated in the study. We selected stable chronic schizophrenic patients who could perform a working memory task (N-back task) as well as healthy volunteers to exclude the possibility of imaged artifacts due to poor performance. All subjects were examined with a truly simultaneous fTCD-H(2)(15)O PET combination under cognitive activation. RESULTS: Schizophrenic patients activate a significantly larger cortical volume for adequate task performance (P < 0.05), but with a significantly lower blood flow increase in this volume (P < 0.01), than do control subjects. Furthermore, they cannot significantly increase blood flow velocity during the time course of cognitive activation as control subjects do. There were only significant correlations between neuropsychologic performance and imaging parameters (fTCD changes, PET blood flow changes) in control subjects (all r >or= /0.65/; P < 0.05), but no significant correlations in schizophrenics (all r < /0.3/; P > 0.4). CONCLUSION: We demonstrated that schizophrenic patients exhibit qualitative differences in the spatial and temporal resolution of cognitive processing. All facts could be interpreted as a sign of alternative, less efficient problem-solving strategies in schizophrenia that lead to the working memory deficits observed during the further course of this disease. Truly simultaneous fTCD-PET can be used in neuroscience to add fundamental new information on spatial and temporal cognitive activation behavior to understand the true physiologic nature of the disease-specific differences of mental illnesses that are seen as disorders of the mind arising in the brain.

Adult↗

MRI measures of perfusion-related changes in human skeletal muscle during progressive contractions.

Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20-31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects (n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to approximately 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.

Adult↗

Uniting Kraepelin and Bleuler: the psychology of schizophrenia and the biology of temporal lobe abnormalities.

Bleuler and Kraepelin are described as icons of the aggressively psychological and aggressively biologic approaches to schizophrenia. We suggest that methodologic advances in studying the function and structure of the brain now allow a reconciliation of these seemingly dissimilar approaches, particularly in the temporal lobe. We begin with a brief historic overview of these different approaches to schizophrenia and then describe structural (magnetic resonance imaging [MRI]), functional (event-related potential [ERP]), and neuropsychological studies in this disorder, including a summary of work conducted in our own laboratory. Recent MRI investigations agree on the presence of volume reductions in schizophrenia in the medial temporal lobe structures of the hippocampus-amygdala complex and of the para-hippocampal gyrus. Furthermore, two recent studies also indicate volume reductions in the superior temporal gyrus (STG). These volume reductions are most prominent in male patients and in the left hemisphere of right-handed patients with schizophrenia. Along with structural studies, there has been a burgeoning interest in MRI-clinical correlations, with volume reductions in the anterior STG being associated with hallucinations and those in the posterior STG being associated with thought disorder. Functional ERP studies also implicate the importance of the temporal lobe in schizophrenia; in addition, ERP abnormalities have been directly associated with a left greater than right MRI volume reduction of the posterior STG. Neuropsychological studies in nonpsychiatric patients are also consistent with a pattern of functional deficits shown to arise from temporal lobe abnormalities, whereas direct MRI-neuropsychological correlations in schizophrenic patients show that decreased performance on tests of verbal memory, abstraction, and categorization correlates with reduced MRI volume of left and right temporal lobe structures. Integration of these findings with those from basic neuroscience suggests a possible role of excitatory amino acid neurotransmission dysregulation and excitotoxicity in the pathology of schizophrenia. A data-based pathophysiologic characterization of schizophrenia is now becoming a reality, and the next few years should see a further unification of the Kraepelinian and Bleulerian approaches to this disorder.

Brain Mapping↗