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PubMed2004

The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.

Brain Mapping↗

PubMed2005

Neuroimaging and sleep medicine.

In sleep medicine, patients with sleep disorders are evaluated and treated. The primary assessment tool of the field has traditionally been polysomnography. While polysomnography has been helpful in the evaluation of some sleep disorders, such as sleep apnea syndrome and periodic limb movement disorder, it has been less helpful in others, such as the insomnias, or sleep disorders secondary to mental disorders. These disorders are presumed to stem from some alteration in brain function that disrupts sleep. The development of functional neuroimaging methods provides a means to understand brain function in patients with sleep disorders in a manner not accessible to polysomnography. This paper summarizes functional neuroimaging findings during healthy sleep, then, reviews available studies in sleep disorders patients, and studies addressing the pharmacology of sleep and sleep disorders. Areas in which functional neuroimaging methods may be helpful in sleep medicine, and in which future development is advised, include: (1) clarification of pathophysiology; (2) aid in differential diagnosis; (3) assessment of treatment response; (4) guiding new drug development; and (5) monitoring treatment response.

Brain↗

PubMed2005

The contribution of neuroimaging techniques to the understanding of supraspinal pain circuits: implications for orofacial pain.

The aim of this article was to give an overview of the current knowledge of supraspinal pain mechanisms derived from neuroimaging studies, and to present data related to chronic orofacial pain disorders. The available studies implied that the anterior cingulate cortex plays a role in the emotional-affective component of pain, as well as in pain-related attention and anxiety. The somatosensory cortices may be involved in encoding spatial, temporal, and intensity aspects of noxious input. The insula may mediate both affective and sensory-discriminative aspects of the pain experience. The thalamus appears to be a multifunctional relay system. The prefrontal cortex has been implied in the pain-related attention processing; it does not have intensity encoding properties. Chronic pain conditions were associated with increased activity in the somatosensory cortices, anterior cingulate cortex, and the prefrontal cortex, and with decreased activity in the thalamus. Few neuroimaging studies used experimental stimuli to the trigeminal system or included orofacial pain patients. However, the available studies appeared to be in agreement with those using stimuli to other body parts and those concerning other chronic pain conditions. Overall, the available data suggest that chronic (orofacial) pain states may be related to a dysfunctional brain network and may involve a compromised descending inhibitory control system. The somatosensory cortices, anterior cingulate cortex, thalamus, and prefrontal cortex may play a vital role in the pathophysiology of chronic pain and should be the main focus of future neuroimaging studies in chronic pain patients.

Brain↗

PubMed2001

Integrating cognitive psychology, neurology and neuroimaging.

In the last decade, there has been a dramatic increase in research effectively integrating cognitive psychology, functional neuroimaging, and behavioral neurology. This new work is typically conducting basic research into aspects of the human mind and brain. The present review features as examples of such integrations two series of studies by the author and his colleagues. One series, employing object recognition, mental motor imagery, and mental rotation paradigms, clarifies the nature of a cognitive process, imagined spatial transformations used in shape recognition. Among other implications, it suggests that when recognizing a hand's handedness, imagining one's body movement depends on cerebrally lateralized sensory-motor structures and deciding upon handedness depends on exact match shape confirmation. The other series, using cutaneous, tactile, and auditory pitch discrimination paradigms, elucidates the function of a brain structure, the cerebellum. It suggests that the cerebellum has non-motor sensory support functions upon which optimally fine sensory discriminations depend. In addition, six key issues for this integrative approach are reviewed. These include arguments for the value and greater use of: rigorous quantitative meta-analyses of neuroimaging studies; stereotactic coordinate-based data, as opposed to surface landmark-based data; standardized vocabularies capturing the elementary component operations of cognitive and behavioral tasks; functional hypotheses about brain areas that are consistent with underlying microcircuitry; an awareness that not all brain areas implicated by neuroimaging or neurology are necessarily directly involved in the associated cognitive or behavioral task; and systematic approaches to integrations of this kind.

Behavior↗

PubMed2001

Can neuroimaging really tell us what the human brain is doing? The relevance of indirect measures of population activity.

Neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) give an indication towards the localization of mental representations and processes in the human brain. It is not clear to what extent such global measures of neuronal activity, pooling across large populations of neurons, can reveal how certain computations are implemented by the neurons in such population ('computational neuroimaging'). Population activity is related tightly to single-cell activity when all neurons in the population have similar response properties. We describe some evidence from single-cell recordings in monkeys that indicates that neurons with similar response properties are not scattered randomly throughout the visual cortex. Notwithstanding this clustering, populations of nearby neurons are still rather heterogeneous, requiring some prudence in deriving single-cell response properties from population activity. The following review of recent neuroimaging studies of the visual system describes to what degree inferences about computations and representations can be drawn from these studies.

Animals↗

PubMed2004

Noninvasive neuroimaging of basilar artery dolichoectasia in a patient with an isolated abducens nerve paresis.

PURPOSE: To describe the neuroimaging findings in a patient with an isolated abducens nerve palsy caused by a dolichoectatic basilar artery. DESIGN: Retrospective case report. METHODS: A 65-year-old man presented with a 3-year history of gradually worsening horizontal double vision. He subsequently underwent magnetic resonance imaging, magnetic resonance angiography, and computed tomographic angiography. RESULTS: Neuroimaging revealed dolichoectasia of the basilar artery. The enlarged, tortuous vessel appeared to be compressing the subarachnoid portion of the nerve at its exit from the brainstem. CONCLUSION: Noninvasive neuroimaging studies are sufficient to establish a diagnosis of basilar artery dolichoectasia in patients with isolated cranial neuropathies.

Abducens Nerve Diseases↗

PubMed2002

Assessment of locus and extent of neurotoxic lesions in monkeys using neuroimaging techniques: a replication.

In a recent study, [Hippocampus 11 (2001) 361] demonstrated that in vivo neuroimaging techniques could be used to accurately quantify the extent of neuronal damage after ibotenic acid injections in non-human primates. The present study was undertaken to replicate these findings and to further estimate whether the concentration of ibotenic acid used (10-15 mg/ml) to produce the neuronal loss did not affect the fibers coursing within or around the targeted brain area. Magnetic resonance (MR) images (T1-weighted and FLAIR) were acquired in three monkeys before and after they received neurotoxic lesions of the hippocampal formation. The postsurgical FLAIR images were taken 7-10 days after surgery to visualize the hyperintense signals produced by increased edema at the injection sites. One year post-surgically, T1-weighted images were acquired and compared with T1-weighted images obtained pre-surgery to estimate reduction in hippocampal volume resulting from neuronal loss. Estimated neuronal loss was then compared with actual cell loss found during histological evaluation of brain tissue. Both neuroimaging techniques accurately estimated the extent of hippocampal damage and damage to surrounding structures. In addition, the concentration of ibotenic acid (10 mg/ml) used in the present study did not appear to have significantly damaged or de-myelinated fibers coursing through or around the hippocampal formation. Together with the previous results of [Hippocampus 11 (2001) 361], the present data strongly demonstrate that in vivo neuroimaging techniques provide powerful tools to estimate reliably and rapidly the extent and localization of brain lesions in non-human primates.

Animals↗

PubMed2001

SPECT neuroimaging in schizophrenia with religious delusions.

Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.

Adult↗

PubMed2004

Executive dysfunction in attention-deficit/hyperactivity disorder: cognitive and neuroimaging findings.

Attention-deficit/hyperactivity disorder has been associated with a prominent disturbance of executive functions. There is no pathognomic neuropsychological profile for the disorder, however. Nonetheless, results of neuropsychological testing, in concert with other clinical information,provide a more comprehensive and detailed picture of the individual patient's cognitive and emotional strengths and weaknesses than a psychiatric diagnostic interview alone. This approach to the evaluation of ADHD therefore can provide a strong objective basis from which to make patient-specific recommendations for compensatory strategies and treatment. It should be noted, however, that although executive dysfunction in the form of impaired response inhibition remains the most prominent cognitive theory of ADHD, other theories have been put forth that also deserve further investigation. These include a disturbance in delay aversion (referring to intolerance for waiting) and impaired temporal processing, among others [79]. The neural substrates of executive dysfunction in ADHD have begun to be revealed by a growing body of structural and functional neuroimaging research. Although still in its infancy, neuroimaging of ADHD is pointing toward disruption of FSTC circuitry and the cerebellum as being central to the cognitive and motor abnormalities seen in the disorder. Further research using cognitive tasks assessing executive functions in combination with functional imaging techniques will provide further insight into the etiology of the disorder. It is expected that advances in structural and functional neuroimaging will yield valuable information that will facilitate the differential diagnosis of ADHD. Evidence cited suggests that psychostimulant medication can improve executive functions and their underlying FSTC circuitry. Furthermore, a recent study of adults with ADHD found significant improvements in organization skills and other symptoms of ADHD following cognitive remediation targeting several executive and emotional aspects of the disorder [80]. Additional studies investigating the effects of treatment on executive dysfunction and brain integrity in ADHD will be necessary to determine the degree to which the structural and functional brain abnormalities observed are mutable. Finally, because the myriad cognitive, behavioral and emotional symptoms in ADHD likely reflect the interplay of multiple cognitive and psychosocial factors, development of treatments for ADHD likely will require a multi-modal approach.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder.

Functional neuroimaging studies have advanced the understanding of the brain mediation of OCD by orbitofrontal-subcortical circuitry, but much is still unknown. Phenotypic heterogeneity could account for many of the inconsistencies among previous neuroimaging studies of OCD. Current studies are seeking to find the neurobiological basis of OCD symptom subtypes and predictors of treatment response. Future studies combining genetics and basic neuroanatomic research with neuroimaging may clarify the cause and pathophysiology of OCD. Although many lines of evidence point to dysfunction of orbitofrontal-subcortical circuitry in patients with OCD, many questions remain unanswered. Some have suggested that orbitofrontal-subcortical hyperactivity in OCD may be the result of abnormal neuroanatomic development of these structures or a failure of pruning of neuronal connections between them, as occurs in normal development, but no postmortem neuroanatomic studies of OCD exist to delineate its pathophysiology. Interventions that directly alter the indirect-direct pathway balance within frontal-subcortical circuits will allow for direct testing of the pathophysiologic hypotheses presented here. The roles of various neurochemical systems in OCD are similarly unclear. Although an abundance of indirect evidence suggests serotonergic abnormalities in patients with OCD, no direct evidence demonstrates what those abnormalities are or whether they are primary or secondary phenomena in patients with OCD. Ongoing studies of 5-HT synthesis in the brains of patients with OCD may shed light on this question.

Brain↗

PubMed2002

Neuroimaging of emotion and personality: scientific evidence and ethical considerations.

Affective neuroscience has seen an explosion of research efforts using modern neuroimaging approaches to uncover the neural basis of emotion and personality. The first section of this paper reviews studies from the domains of affective and forensic neuroimaging. These studies illustrate some of the topics likely to be the subject of future ethical debates. The second section relates limitations of the neuroimaging approach to ethical considerations in predicting future psychopathology on the basis of brain state analysis.

Brain↗

PubMed2002

Legal and ethical issues in neuroimaging research: human subjects protection, medical privacy, and the public communication of research results.

Humans subjects research entails significant legal and ethical obligations. Neuroimaging researchers must be familiar with the requirements of human subjects protection, including evolving standards for the protection of privacy and the disclosure of risk in "non-therapeutic" research. Techniques for creating veridical surface renderings from volumetric anatomical imaging data raise new privacy concerns, particularly under the federal medical privacy regulation. Additionally, neuroimaging researchers must consider their obligation to communicate research results responsibly. The emerging field of neuroethics should strive to raise awareness of these issues and to involve neuroimaging researchers in the legal, ethical, and policy debates that currently surround human subjects research.

Brain↗

PubMed2000

Neuroimaging: do we really need new contrast agents for MRI?

The use of exogenous contrast media in magnetic resonance imaging of the brain has brought dramatic improvement in the sensitivity of detection and delineation of pathological structures, such as primary and metastatic brain tumors, inflammation and ischemia. Disruption of the blood brain barrier leads to accumulation of the intravenously injected contrast material in the extravascular space, leading to signal enhancement. Magnetic resonance angiography benefits from T(1)-shortening effects of contrast agent, improving small vessel depiction and providing vascular visualization even in situations of slow flow. High speed dynamic MRI after bolus injection of contrast media allows tracer kinetic modeling of cerebral perfusion. Progressive enhancement over serial post-contrast imaging allows modeling of vascular permeability and thus quantitative estimation of the severity of blood brain barrier disruption. With such an array of capabilities and ever improving technical abilities, it seems that the role of contrast agents in MR neuroimaging is established and the development of new agents may be superfluous. However, new agents are being developed with prolonged intravascular residence times, and with in-vivo binding of ever-increasing specificity. Intravascular, or blood pool, agents are likely to benefit magnetic resonance angiography of the carotid and cerebral vessels; future agents may allow the visualization of therapeutic drug delivery, the monitoring of, for example, gene expression, and the imaging evaluation of treatment efficacy. So while there is a substantial body of work that can be performed with currently available contrast agents, especially in conjunction with optimized image acquisition strategies, post processing, and mathematical analysis, there are still unrealized opportunities for novel contrast agent introduction, particularly those exploiting biological specificity. This article reviews the current use of contrast media in magnetic resonance neuroimaging, discusses some of the developing strategies for new applications of imaging with these agents and finally offers some views and indications for contrast agents currently under development, as well as some speculation on unsolved problems in neuroimaging, and opportunities for novel contrast agents.

Angiography↗

PubMed1997

Neuroimaging.

Nonenhanced CT scan remains the most valuable and available neuroimaging study available in the ED. Nonenhanced CT scans are excellent for identifying acute hemorrhage, mass lesions, hydrocephalus, and cerebral edema. It is of limited value in identifying old blood, small abscesses and tumors, arteriovenous malformations, and aneurysms; in these cases, either enhancement of the CT or MR imaging may be preferable. The role of MR imaging is evolving and is becoming a neuroimaging modality more easily available to the emergency physician. When available, it is the preferred neuroimaging study for ischemic infarcts, lacunar infarcts, and encephalitis.

Brain Diseases↗

PubMed1998

Beyond the single study: function/location metanalysis in cognitive neuroimaging.

Cognitive neuroimaging maps the brain locations of mental operations. This process is iterative, as no single study can fully characterize a mental operation or its brain location. This iterative discovery process, in combination with the location-reporting standard (i.e. spatial coordinates) of the cognitive neuroimaging community, has engendered a new form of metanalysis. Response locations from multiple studies have been analyzed collectively so as to better describe the spatial distribution of brain activations, with promising results. New hypotheses regarding elementary mental operations and their respective brain locations are being generated and refined via metanalysis. These hypotheses are being tested and confirmed by subsequent, prospective experiments. Function/location metanalysis is an important new tool for hypothesis generation in cognitive neuroimaging. This form of metanalysis is fundamentally different from the effect-size metanalyses prevalent in other literatures, with unique advantages and challenges.

Brain Mapping↗

PubMed2003

Evidence-based medicine: neuroimaging of seizures.

Evidence-based medicine is useful in epilepsy and neuroimaging (Figs. 1 and 2). An understanding of the pretest probability suggests that focal neurologic deficits are important in predicting the outcome of neuroimaging examinations. In cases of nonacute symptomatic seizures, confusion and postictal deficits should prompt MR evaluation. In remote symptomatic seizures, MR imaging should be performed in a child with unexplained cognitive or motor delays or a child less than 1 year of age. Patients with partial seizures, abnormal EEG, or generalized epilepsy also should be imaged. Acute seizures should be imaged with CT to exclude hemorrhage and because of the availability and speed of the modality. Ictal SPECT is the best neuroimaging examination to localize seizure activity. MR imaging can offer prediction of surgical outcome and may hold promise in the future for dimensional localization of seizure focus. Evidence-based medicine can only work if there is physician communication. The pretest probability is helpful only when an accurate history is provided to the consulting physician. This field will flourish if physicians can develop accurate methods of collating information and reporting it in a timely fashion in the literature.

Evidence-Based Medicine↗

PubMed2003

Neuroimaging in Alzheimer disease: an evidence-based review.

Current clinical criteria (DSM-IIIR and NINCDS-ADRDA) for the diagnosis of dementia and AD are reliable; however, these criteria remain to be validated by clinicians of different levels of expertise at different clinical settings. Structural neuroimaging has an important role in initial evaluation of dementia for ruling out potentially treatable causes. Although CT is the appropriate choice when brain tumors, subdural hematoma, or normal pressure hydrocephalus is suspected, MR imaging is more sensitive to the white-matter changes in vascular dementia. The diagnostic accuracy of PET, SPECT, 1H MRS, and MR volumetry of the hippocampus for distinguishing patients with AD from healthy elderly individuals is comparable to the accuracy of a pathologically confirmed clinical diagnosis. Sensitivity of PET for distinguishing patients with dementia with Lewy bodies from AD, however, is higher than that of clinical evaluation; similarly, SPECT and 1H MRS may be adjuncts to clinical evaluation for distinguishing patients with frontotemporal dementia from those with AD. Neuroimaging is valuable in predicting future development of AD in patients with MCI and in carriers of the ApoE epsilon 4 allele who are at a higher risk of developing AD than are cognitively normal elderly individuals. Quantitative MR techniques (e.g., MR volumetry, DWI, magnetization transfer MR imaging, and 1H MRS) and PET are sensitive to the structural and functional changes in the brains of patients with MCI, and hippocampal volumes on MR imaging are associated with future development of AD in these individuals. PET is also sensitive to the regional metabolic decline in the brains of carriers of the ApoE epsilon 4 allele. The longitudinal decrease of whole brain and hippocampal volumes on MR imaging, NAA levels on 1H MRS, cerebral glucose metabolism on PET, and cerebral blood flow on SPECT are associated with rate of cognitive decline in patients with AD. These neuroimaging markers may be useful for monitoring symptomatic progression in groups of patients with AD for drug trials. Furthermore, antemortem MR-based hippocampal volumes correlate with the pathologic stage of AD, and the rate of hippocampal volume loss on MR imaging correlates with clinical disease progression in the cognitive continuum from normal aging to MCI and to AD. Hence, as an in vivo correlate of pathologic involvement, structural imaging measures are potential surrogate markers for disease progression in patients with established AD and in patients with prodromal AD, who will benefit most from disease-modifying therapies underway.

Alzheimer Disease↗

PubMed2003

Diagnosis and exploration of massively univariate neuroimaging models.

The goal of this work is to establish the validity of neuroimaging models and inferences through diagnosis and exploratory data analysis. While model diagnosis and exploration are integral parts of any statistical modeling enterprise, these aspects have been mostly neglected in functional neuroimaging. We present methods that make diagnosis and exploration of neuroimaging data feasible. We use three- and one-dimensional summaries that characterize the model fit and the four-dimensional residuals. The statistical tools are diagnostic summary statistics with tractable null distributions and the dynamic graphical tools which allow the exploration of multiple summaries in both spatial and temporal/interscan aspects, with the ability to quickly jump to spatiotemporal detail. We apply our methods to a fMRI data set, demonstrating their ability to localize subtle artifacts and to discover systematic experimental variation not captured by the model.

Algorithms↗