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Human functional neuroimaging connectivity research in dependence.

Functional and effective connectivity are relatively new techniques in the analysis of functional neuroimaging studies in humans. They have previously been used in studies of 'normal' psychological and neurological processes such as vision before gradually transferring into use in pathological disease states such as schizophrenia. These techniques are now beginning to extend into the field of substance misuse and dependence. So far, most functional neuroimaging studies in this field have shown consistent patterns of activation in several brain regions, and theories are emerging based upon these and animal models. Studies of brain connectivity can now begin to help further unravel the tangle of disparate brain regions and their connections that underpin the psychopharmacological processes of dependence.

Brain↗

[Functional neuroimaging in psychotherapy research].

Only recently has functional neuroimaging been used increasingly in the context of psychotherapy research. Based on a literature survey, procedures, methodological underpinnings and paradigms relevant for psychotherapy research are explored regarding functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Current studies on changes of brain functions and potential mechanisms are presented based on obsessive-compulsive disorders, depression, phobia, panic and borderline personality disorders. Findings and implications are discussed regarding the use of functional neuroimaging in psychotherapy research. Systematic changes of brain activation were demonstrated following successful psychotherapy, partially resembling and partially differing from those induced by psychopharmacological treatments. Thus the traditional split between pharmacological procedures "acting on the brain" and psychological procedures making the patient "feel better" has been rendered obsolete. Procedures of functional neuroimaging have been developed to such an extent that they can be used to study issues of great relevance for psychotherapy, e. g. biological underpinnings of psychiatric disorders, plasticity of neural networks, mechanisms of change and prognostic factors of psychotherapy, etc.

Biomedical Research↗

Functional neuroimaging in mental disorders.

Recent advances in functional neuroimaging allow us to map neural activity in the living human brain with precise spatial and temporal resolution and provide an unprecedented opportunity to examine the neurocognitive components of mental disorders. In this article we aim to summarize the main functional neuroimaging findings in the major psychiatric disorders and the different methodological approaches that have been used to study them. We will discuss studies of the resting state and of activation during the performance of cognitive tasks, and studies focused on specific psychiatric symptoms. We will also review work on functional connectivity, discuss future directions in the field and consider how functional neuroimaging may contribute to clinical practice.

Journal Article↗

The counting Stroop: an interference task specialized for functional neuroimaging--validation study with functional MRI.

The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P < or = 10(-4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories.

Adult↗

Functional neuroimaging of autistic disorders.

Functional neuroimaging methods hold promise for elucidating the neurobiology of autistic disorders, yet they present difficult practical and scientific challenges when applied to these complex and heterogeneous syndromes. Single-state studies of brain metabolism and blood flow thus far have failed to yield consistent findings, but suggest considerable variability in regional patterns of cerebral synaptic activity. Patients with idiopathic autism are less likely to show abnormalities than are patients with comorbid illness or epilepsy. Activation studies have begun to suggest alterations in brain organization for language and cognition. Neurotransmitter studies using positron emission tomography (PET) suggest abnormalities of serotonergic and dopaminergic function. Studies using magnetic resonance spectroscopy (MRS) have begun to document metabolic deficits in the frontal cortex and cerebellum. A single study using magnetoencephalography suggests a high incidence of epileptiform activity in children with autistic regression. Research needs include well-controlled developmental studies, particularly of young subjects and relatively homogeneous subgroups, which balance scientific rigor with ethical constraints. Investigations of the serotonergic and dopaminergic systems, limbic-based memory and emotional systems, and the role of epileptiform activity in autism represent priorities for future research.

Autistic Disorder↗

Functional neuroimaging in child psychiatry.

Functional neuroimaging in child psychiatry presents unique scientific, ethical, and technical challenges. The study of childhood disorders presupposes knowledge of neurodevelopment and brain maturation. However, much of human brain science is based on inferences from animal work and indirect neurochemical measures from body fluids. Neuroimaging can examine brain development directly in humans. The benefits can be enormous for learning how and when to intervene to prevent or treat a disorder. These unprecedented potential gains are countered by complex and difficult ethical issues. Technical advances can reduce ethical concerns by minimizing risks. They also promise to enhance the sensitivity and specificity of the measures (eg, by improving spatial and temporal resolution). Judiciously designed investigations will permit the testing of a priori hypotheses built on rational models of neuropathology. Finally, it is the integration of scientific knowledge across the various fields of neuroscience and clinical research that will push the limits of our understanding of health and disease.

Adolescent↗

Functional neuroimaging and cognitive rehabilitation for people with traumatic brain injury.

Cognitive deficits are a common consequence of traumatic brain injury. Although such deficits are amenable to rehabilitation, methods for individualizing cognitive interventions are still unrefined. Functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging are emerging as possible technologies for measuring and monitoring the cerebral consequences of plasticity associated with brain injury and for evaluating the effectiveness of rehabilitation interventions. Functional neuroimaging may even enable more customized and efficient selection, design, or adaptation of individual cognitive rehabilitation programs. We review the current literature on functional neuroimaging after traumatic brain injury, relating these findings to cognitive rehabilitation. Overall, functional neuroimaging after traumatic brain injury has shown reliable differences in brain activity within several regions of frontal cortex, partly but not uniformly consistent with neuropsychological and structural findings in traumatic brain injury. We also outline a number of promising research opportunities for applying functional neuroimaging in traumatic brain injury settings, along with associated challenges.

Brain Injuries↗

A role for sleep in the processing of memory traces. Contribution of functional neuroimaging in humans.

Sleep is thought to participate in the consolidation of recent memory traces. We tested this hypothesis in humans, using functional neuroimaging (functional magnetic resonance imaging and positron emission tomography). First, following the training on a procedural visuo-motor learning task (pursuit task), total sleep deprivation on the first post-training night significantly deteriorates the gain in performance, which is usually observed after one complete night of sleep. In parallel, sleep deprivation hampers the changes in functional segregation and connectivity, which underpin the gain in performance usually observed in subjects allowed to sleep on the first post-training night. Second, following the training on an implicit memory task (probabilistic serial reaction time task), some brain areas are reactivated during REM sleep on the first post-training night. The reactivation was shown to be related to the processing of high-level material and to be modulated by the amount of learning achieved during the training session. These changes in activity do not involve isolated brain areas but entire macroscopic cortico-subcortical networks. Taken together, the results suggest an off-line processing of recent memory traces during sleep.

Brain↗

The neural bases of prosopagnosia and pure alexia: recent insights from functional neuroimaging.

PURPOSE OF REVIEW: To discuss whether recent functional neuroimaging results can account for clinical phenomenology in visual associative agnosias. RECENT FINDINGS: Functional neuroimaging studies in healthy human subjects have identified only two regions of ventral occipitotemporal cortex that invariantly respond to individual faces and visual words, respectively. The signature of face identity coding in the fusiform neural response was shown to be missing in a patient with prosopagnosia. Another case study established that a surgical lesion close to the region sensitive to visual words can result in pure alexia. SUMMARY: Evidence is increasing that functional specialization for processing face identity and visual word forms is restricted to two specialized sensory modules in the occipitotemporal cortex. A structural or functional lesion to face-sensitive and word-sensitive regions in the ventral occipitotemporal cortex can provide the most parsimonious account for the clinical syndromes of prosopagnosia and agnosic alexia. This review suggests that functional specialization should be considered in terms of whether exclusively one brain region (instead of many) underpins a defined function and not as whether this brain region underpins exclusively one cognitive function. Such functional specialization seems to exist for at least two higher-order visual perceptual functions, face and word identification.

Dyslexia↗

The role of functional neuroimaging in pediatric brain injury.

The aim of this article is to review empirical studies published in the last 10 years that used various functional neuroimaging techniques to assess pediatric patients with brain injury. Overall, these studies have demonstrated the ability of functional neuroimaging to offer unique information concerning the diagnosis, clinical outcome, and recovery mechanisms after pediatric brain injury. Future research using functional neuroimaging is recommended to better understand the functional reorganization and neurodevelopmental consequences resulting from brain injury. Such research might allow clinicians to design tailored early-intervention and rehabilitation programs to maximize the recovery process for pediatric patients. Limitations and advantages associated with the use of functional neuroimaging in pediatric populations are discussed.

Brain Injuries↗

Episodic memory meets working memory in the frontal lobe: functional neuroimaging studies of encoding and retrieval.

Recent functional-neuroimaging studies have provided a wealth of new information suggesting that regions of the prefrontal cortex play a role in episodic memory encoding and retrieval. This review seeks to evaluate the results of these studies in the context of one general model that has proposed that the left prefrontal cortex is preferentially involved in episodic memory encoding, whereas the right prefrontal cortex is preferentially involved in episodic memory retrieval, irrespective of the type (e.g., modality) of information being remembered. The origins of this framework are considered in some detail and then all relevant functional-neuroimaging studies are critically reviewed. The results of this review fail to provide support for the functional-asymmetry model, suggesting instead that episodic memory encoding and retrieval may actually involve similar regions of the lateral prefrontal cortex when all factors relating to the type of stimulus material (i.e., modality), are appropriately controlled.

Brain Mapping↗

Functional neuroimaging of normal human sleep by positron emission tomography.

Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this 'canonical' sleep may be summarized as follows. In slow-wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid-eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.

Animals↗

The anatomy of language: contributions from functional neuroimaging.

This article illustrates how functional neuroimaging can be used to test the validity of neurological and cognitive models of language. Three models of language are described: the 19th Century neurological model which describes both the anatomy and cognitive components of auditory and visual word processing, and 2 20th Century cognitive models that are not constrained by anatomy but emphasise 2 different routes to reading that are not present in the neurological model. A series of functional imaging studies are then presented which show that, as predicted by the 19th Century neurologists, auditory and visual word repetition engage the left posterior superior temporal and posterior inferior frontal cortices. More specifically, the roles Wernicke and Broca assigned to these regions lie respectively in the posterior superior temporal sulcus and the anterior insula. In addition, a region in the left posterior inferior temporal cortex is activated for word retrieval, thereby providing a second route to reading, as predicted by the 20th Century cognitive models. This region and its function may have been missed by the 19th Century neurologists because selective damage is rare. The angular gyrus, previously linked to the visual word form system, is shown to be part of a distributed semantic system that can be accessed by objects and faces as well as speech. Other components of the semantic system include several regions in the inferior and middle temporal lobes. From these functional imaging results, a new anatomically constrained model of word processing is proposed which reconciles the anatomical ambitions of the 19th Century neurologists and the cognitive finesse of the 20th Century cognitive models. The review focuses on single word processing and does not attempt to discuss how words are combined to generate sentences or how several languages are learned and interchanged. Progress in unravelling these and other related issues will depend on the integration of behavioural, computational and neurophysiological approaches, including neuroimaging.

Brain↗

Functional neuroimaging in Alzheimer's type dementia.

This article aims to review the role of the functional neuroimaging modality of positron emission tomography (PET) in the early diagnosis of Alzheimer's disease (AD). Clinical diagnosis in the early disease stages is difficult and treatments are emerging which rather than reversing structural damage are likely to slow or halt the disease process. While currently no routine diagnostic test confirms AD presence, imaging techniques are an important expanding field in biological neuropsychiatry. The challenge for neuroimaging methods is to achieve high specificity and sensitivity in early disease stages. Glucose metabolic PET imaging with fluorodeoxyglucose (FDG) has the potential to detect very early neocortical dysfunction before even abnormal neuropsychological testing is obtainable. The implications are for the identification of minimally symptomatic patients that could benefit most from treatment strategies, as well as the monitoring of treatment response and possible therapeutic deceleration of the disease. FDG PET correlates with AD neuropathology and is able to indicate disease progression or severity, meeting both functional neuroimaging prerequisites in diagnosing AD. A combination of functional neuroimaging with different techniques should be able to provide highest diagnostic specificity in diagnosing dementia. This may even lead to a new classification of dementias according to differences in the causative aetiology.

Aged↗

Functional neuroimaging of hallucinations in schizophrenia: toward an integration of bottom-up and top-down approaches.

Hallucinations in schizophrenia represent an important clinical problem, an interesting neuropsychological enigma, and a significant challenge for neuroscientific research. Functional neuroimaging techniques allow the in vivo, systems-level study of brain dysfunction underlying this debilitating symptom. Clinical and scientific vantage points that can inform the design and interpretation of functional neuroimaging studies of schizophrenic hallucinations are outlined. These include considerations of the phenomenology of hallucinations, the relationship of hallucinations to other symptoms of schizophrenia, and the neuropsychological functions that are thought to be disrupted in hallucinations. They also include the anatomical and chemical brain systems in which abnormalities are implicated in schizophrenia, the neurologic conditions in which hallucinations may occur, the neurochemical contexts that are associated with hallucinations, and the methodologic details of the functional neuroimaging techniques employed. Bottom-up and top-down functional neuroimaging strategies for the investigation of schizophrenic hallucinations with positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) are reviewed. Bottom-up approaches start with or measure the biology associated with hallucinations. Top-down approaches start from the specific neuropsychological dysfunctions thought to be associated with hallucinations. The distributed brain regions, systems and functions implicated in schizophrenic hallucination formation are then discussed in the context of an integration of bottom-up and top-down approaches. Focus is placed upon abnormalities in the functions of, and interactions among, auditory-linguistic association cortices, caudal and rostral limbic/paralimbic systems, prefrontal cortices, ventral striatum and (non-specific projection and associative) thalamic nuclei, as well as upon the glutamatergic, GABAergic and ventral tegmental dopaminergic modulation of these systems.

Brain Mapping↗

The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain.

Little is known about the function of the retrosplenial cortex and until recently, there was no evidence that it had any involvement in emotional processes. Surprisingly, recent functional neuroimaging studies show that the retrosplenial cortex is consistently activated by emotionally salient words. A review of the functional neuroimaging literature reveals a previously overlooked pattern of observations: the retrosplenial cortex is the cortical region most consistently activated by emotionally salient stimuli. Evidence that this region is also involved in episodic memory suggests that it might have a role in the interaction between emotion and episodic memory. Recognition that the retrosplenial cortex has a prominent role in the processing of emotionally salient stimuli invites further studies to define its specific functions and its interactions with other emotion-related brain regions.

Brain Mapping↗

High-resolution spatio-temporal functional neuroimaging of brain activity.

The past decades have shown extraordinary progress in our ability to noninvasively image the functions of the human brain. Of particular interest is the recent trend in combining information from electrophysiological and magnetic resonance imaging, which we termed eMRI, to achieve high-resolution functional neuroimaging in both space and time domains. In this article, we review the recent progress in high-resolution functional neuroimaging, in particular the multimodal integration of electroencephalography (EEG) and magnetic resonance imaging (MRI). The state-of-the-art EEG inverse solutions based on different brain electric source models and various approaches to integrate the information from MRI are reviewed. The remaining challenges, future trends, and potential applications of the high-resolution functional neuroimaging research are discussed.

Action Potentials↗

Functional neuroimaging: a new generation of human brain studies in obesity research.

Obesity is predominantly caused by overeating, an abnormal behaviour for which there is no unequivocal neurophysiological explanation. Functional neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have recently emerged as new tools to search for regions of the brain that are involved in the regulation of eating behaviours and those that are involved in the pathophysiology of obesity. Using these techniques, a limited number of studies have provided the first in vivo images of the human hypothalamic response to nutritional stimuli and revealed the complexity of the human brain response to hunger, taste, and satiation. Selective differences have been reported in the functional architecture of the brain of obese and lean individuals. We discuss current use and possible future developments of functional neuroimaging applied to obesity research. We conclude that functional neuroimaging provides an increasingly important tool for investigating how different regions of the brain work in concert to orchestrate normal eating behaviours and how they conspire to produce obesity and other eating disorders.

Energy Intake↗