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PubMed2005

What can functional neuroimaging tell the experimental psychologist?

I argue here that functional neuroimaging data--which I restrict to the haemodynamic techniques of fMRI and PET--can inform psychological theorizing, provided one assumes a "systematic" function-structure mapping in the brain. In this case, imaging data simply comprise another dependent variable, along with behavioural data, that can be used to test competing theories. In particular, I distinguish two types of inference: function-to-structure deduction and structure-to-function induction. With the former inference, a qualitatively different pattern of activity over the brain under two experimental conditions implies at least one different function associated with changes in the independent variable. With the second type of inference, activity of the same brain region(s) under two conditions implies a common function, possibly not predicted a priori. I illustrate these inferences with imaging studies of recognition memory, short-term memory, and repetition priming. I then consider in greater detail what is meant by a "systematic" function-structure mapping and argue that, particularly for structure-to-function induction, this entails a one-to-one mapping between functional and structural units, although the structural unit may be a network of interacting regions and care must be taken over the appropriate level of functional/structural abstraction. Nonetheless, the assumption of a systematic function-structure mapping is a "working hypothesis" that, in common with other scientific fields, cannot be proved on independent grounds and is probably best evaluated by the success of the enterprise as a whole. I also consider statistical issues such as the definition of a qualitative difference and methodological issues such as the relationship between imaging and behavioural data. I finish by reviewing various objections to neuroimaging, including neophrenology, functionalism, and equipotentiality, and by observing some criticisms of current practice in the imaging literature.

Arousal↗

PubMed2004

[Functional neuroimaging in adults].

A consensus has not been reached on the proper role of the different functional neuroimaging techniques available for the exploration of drug-resistant partial epilepsy, particularly in preparation for surgery. Several studies have suggested the potential contribution of positron emission tomography (PET) with [18F]-fluoro-deoxyglucose (FDG), [11C]-flumazenil (FMZ), or [11C]-alpha-methyl-tryptophane (AMT), single-photon emission computed tomography (SPECT) to measure ictal cerebral blood flow, magnetic resonance spectroscopy (MRS), and functional magnetic resonance imaging (fMRI) of language and memory functions, but to date there has been no impact study validating the clinical contribution of these different exploration techniques. The most robust data in the literature indicate that [18F]-FDG PET can help to predict surgical failures in patients with temporal lobe epilepsy. Studies with lesser power have suggested that SPECT measurement of ictal hyperperfusion blood flow, and [11C]-FMZ and [11C]-AMT PET can be useful in symptomatic neocortical epilepsy, particularly in patients with tuberous sclerosis explored with [11C]-AMT PET. Use of these different exploration techniques in epileptic patients with a normal MRI is warranted when complementary information could help in deciding on when and how to perform an invasive EEG, but there are significant risks of erroneous identification of the epileptogenic zone. Functional MRI assessment of language regions can be proposed as an alternative to the Wada test to determine hemispheric dominance in patients with temporal lobe epilepsy. Multicentric impact studies will be needed before evidence-based guidelines can be developed for the use of functional neuroimaging techniques in drug-resistant partial epilepsy.

Adult↗

PubMed2005

Functional magnetic resonance imaging in anesthetized patients: a relevant step toward real-time intraoperative functional neuroimaging.

OBJECTIVE: The introduction of intraoperative 1.5-T magnetic resonance imaging may provide up-to-date functional information in the surgical environment. However, feasible passive paradigms that allow the examination of anesthetized patients will be a precondition for intraoperative functional magnetic resonance imaging (fMRI). The aim of this study is to evaluate the feasibility of a recently developed passive fMRI paradigm for functional neuroimaging in anesthetized patients. METHODS: We investigated four anesthetized patients with intracranial pathological conditions not related to the sensorimotor cortex. All patients had been anesthetized with standard total intravenous anesthesia for more than 24 hours before the fMRI scan. Anesthesia and monitoring were sustained during the scanning procedure. A simultaneous electrical stimulation of the median and tibial nerves was applied to elicit a cortical activation using a custom-designed magnetoelectrically shielded conductor. Statistical evaluation using Statistical Parametric Mapping software (Wellcome Department of Imaging Neuroscience, University College, London, England) and the Talairach Daemon Client (Version 1.1; Research Imaging Center, University of Texas Health Science Center, San Antonio, TX) followed. RESULTS: Three of four patients showed a good activation of the sensorimotor cortex under anesthesia. In one patient, no significant activation was observed, presumably as a result of increased body impedance because of severe edema. Standard dosages of the narcotics did not influence the cortical response; however, stimulation intensity had to be increased compared with awake patients. We did not detect relevant interferences with magnetic resonance imaging arising from the technical setup. CONCLUSION: The method presented proved to be a feasible paradigm for fMRI evaluation of the sensorimotor cortex in anesthetized patients and thus forms a relevant step toward real intraoperative functional neuroimaging.

Aged↗

PubMed2006

Post-lesional cerebral reorganisation: evidence from functional neuroimaging and transcranial magnetic stimulation.

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.

Animals↗

PubMedDate not supplied

When should functional neuroimaging techniques be used in the diagnosis and management of Alzheimer's dementia? A decision analysis.

BACKGROUND: Functional neuroimaging, including positron emission tomography (PET), has been proposed for use in diagnosing Alzheimer's disease-related dementia (AD). OBJECTIVE: The objective of this study was identify the circumstances under which PET scanning for the diagnosis of AD maximizes health outcomes. METHODS: A Markov-model-based decision analysis was conducted using estimates derived from the literature on AD epidemiology, the accuracy of PET, and donepezil treatment efficacy. The target population for the analysis was assumed to be US men and women who either have mild AD or are asymptomatic but at an elevated risk of developing AD owing to disease in a first-degree relative (parent or sibling). The time horizon was the patient lifetime. We compared treatment 1) based on an American Academy of Neurology (AAN) clinical evaluation either alone; 2) in combination with PET scanning; or 3) empirically based on a family history. Outcomes measures were life expectancy, quality-adjusted life-years (QALYs), and (severe) dementia-free life expectancy (SDFLE). RESULTS: For both patient populations, treating all patients based on an AAN evaluation without further testing using PET resulted in the greatest gains in life expectancy, QALYs, and SDFLEs. PET-based testing was the second preferred strategy compared to no intervention. The rankings of the strategies were sensitive to severity of treatment complications: analyses of hypothetical treatments with the potential for severe complications indicated that testing was preferred if the treatment was effective but had moderate complications. CONCLUSIONS: These results suggest that current treatments, which are relatively benign and may slow progression of disease, should be offered to patients who are identified as having AD based solely on an AAN clinical evaluation. A clinical evaluation that includes functional neuroimaging based testing will be warranted, however, when new treatments that are effective at slowing disease progression but have the potential for moderate to severe complications become available.

Aged↗

PubMed2006

Review of a mock research protocol in functional neuroimaging by Canadian research ethics boards.

OBJECTIVE: To examine how research ethics boards (REBs) review research projects in emerging disciplines such as functional neuroimaging. DESIGN: To compare the criteria applied and the decisions reached by REBs that reviewed the same mock research protocol in functional neuroimaging. PARTICIPANTS: 44 Canadian biomedical REBs, mostly working in public university or hospital settings. MAIN MEASUREMENTS: The mock research protocol "The Neurobiology of Social Behavior" included several ethical issues operating at all three levels: personal, institutional and social. Data consisting of responses to closed questions were analysed quantitatively. Qualitative analysis of open-question responses used mixed classification. RESULTS: Similar criteria were used by most participating REBs. Yet the project was unconditionally approved by 3 REBs, approved conditionally by 10 and rejected by 30. CONCLUSIONS: The results point to the difficulty for REBs of reviewing all kinds of research projects, regardless of field, by relying on international and national norms framed in general terms and a possible variation between REBs in the interpretation of their mandate for the protection of research subjects.

Canada↗

PubMed2002

Studies of altered social cognition in neuropsychiatric disorders using functional neuroimaging.

In this paper, we review studies using functional neuroimaging to examine cognition in neuropsychiatric disorders. The focus is on social cognition, which is a topic that has received increasing attention over the past few years. A network of brain regions is proposed for social cognition that includes regions involved in processes relevant to social functioning (for example, self reference and emotion). We discuss the alterations of activity in these areas in patients with autism, depression, schizophrenia, and posttraumatic stress disorders in relation to deficits in social behaviour and symptoms. The evidence to date suggests that there may be some specificity of the brain regions involved in these 4 disorders, but all are associated with dysfunction in the amygdala and dorsal cingulate gyrus. Although there is much work remaining in this area, we are beginning to understand the complex interactions of brain function and behaviour that lead to disruptions of social abilities.

Brain↗

PubMed2005

Functional neuroimaging of sleep.

Sleep and sleep disorders have traditionally been viewed from a polysomnographic perspective. Although these methods provide information on the timing of various stages of sleep and wakefulness, they do not provide information regarding function in brain structures that have been implicated in the generation of sleep and that may be abnormal in different sleep disorders. Functional neuroimaging methods provide information regarding changes in brain function across the sleep-wake cycle that provides information for models of sleep dysregulation in a variety of sleep disorders. Early studies show reliable increases in function in limbic and anterior paralimbic cortex in rapid eye movement (REM) sleep and decreases in function in higher-order cortical regions in known thalamocortical networks during non-REM sleep. Although most of the early work in this area has been devoted to the study of normal sleep mechanisms, a collection of studies in diverse sleep disorders such as sleep deprivation, depression, insomnia, dyssomnias, narcolepsy, and sleep apnea suggest that functional neuroimaging methods have the potential to clarify the pathophysiology of sleep disorders and to guide treatment strategies.

Diagnostic Imaging↗

PubMed2001

Cognitive processing in literate and illiterate subjects: a review of some recent behavioral and functional neuroimaging data.

The study of illiterate subjects, which for specific socio-cultural reasons did not have the opportunity to acquire basic reading and writing skills, represents one approach to study the interaction between neurobiological and cultural factors in cognitive development and the functional organization of the human brain. In addition the naturally occurring illiteracy may serve as a model for studying the influence of alphabetic orthography on auditory-verbal language. In this paper we have reviewed some recent behavioral and functional neuroimaging data indicating that learning an alphabetic written language modulates the auditory-verbal language system in a non-trivial way and provided support for the hypothesis that the functional architecture of the brain is modulated by literacy. We have also indicated that the effects of literacy and formal schooling is not limited to language related skills but appears to affect also other cognitive domains. In particular, we indicate that formal schooling influences 2D but not 3D visual naming skills. We have also pointed to the importance of using ecologically relevant tasks when comparing literate and illiterate subjects. We also demonstrate the applicability of a network approach in elucidating differences in the functional organization of the brain between groups. The strength of such an approach is the ability to study patterns of interactions between functionally specialized brain regions and the possibility to compare such patterns of brain interactions between groups or functional states. This complements the more commonly used activation approach to functional neuroimaging data, which characterize functionally specialized regions, and provides important data characterizing the functional interactions between these regions.

Aged↗

PubMed2002

A model of the coupling between brain electrical activity, metabolism, and hemodynamics: application to the interpretation of functional neuroimaging.

In order to improve the interpretation of functional neuroimaging data, we implemented a mathematical model of the coupling between membrane ionic currents, energy metabolism (i.e., ATP regeneration via phosphocreatine buffer effect, glycolysis, and mitochondrial respiration), blood-brain barrier exchanges, and hemodynamics. Various hypotheses were tested for the variation of the cerebral metabolic rate of oxygen (CMRO(2)): (H1) the CMRO(2) remains at its baseline level; (H2) the CMRO(2) is enhanced as soon as the cerebral blood flow (CBF) increases; (H3) the CMRO(2) increase depends on intracellular oxygen and pyruvate concentrations, and intracellular ATP/ADP ratio; (H4) in addition to hypothesis H3, the CMRO(2) progressively increases, due to the action of a second messenger. A good agreement with experimental data from magnetic resonance imaging and spectroscopy (MRI and MRS) was obtained when we simulated sustained and repetitive activation protocols using hypotheses (H3) or (H4), rather than hypotheses (H1) or (H2). Furthermore, by studying the effect of the variation of some physiologically important parameters on the time course of the modeled blood-oxygenation-level-dependent (BOLD) signal, we were able to formulate hypotheses about the physiological or biochemical significance of functional magnetic resonance data, especially the poststimulus undershoot and the baseline drift.

Adenosine Triphosphate↗

PubMed2001

Interactions among neuronal systems assessed with functional neuroimaging.

Cortical organisation is based on the principles of functional specialisation and functional integration. Those two concepts exist at multiple spatial scales. For example at a macroscopic level, functionally segregated areas V1 and V5 are integrated within the dorsal visual stream. At a microscopic level, it is possible to infer the functional integration of (segregated) ocular dominance columns within area V1. At the macroscopic level functional specialisation and integration can be tested with functional neuroimaging, using fMRI/PET or EEG/MEG. A framework that allows making inferences on functional integration between brain regions using fMRI will be presented. The common feature of all techniques within that framework is that they can incorporate second order terms and therefore explicitly allow for contextual modulations. Two examples demonstrate how attention and paired associates learning can modulate effective connectivity within the visual system. Furthermore these models can incorporate non-linear modulatory (feedback) connections that can account for the changes in effective connectivity observed.

Attention↗

PubMed1998

Functional neuroimaging of attention in the auditory modality.

Previous functional neuroimaging studies of attention have emphasized the visual modality. We developed an auditory version of the continuous performance test (CPT) that included simple, focused and divided attention conditions. Positron emission tomographic (PET) scans were acquired during CPT performance in normal young adults and then submitted to statistical parametric mapping. Simple attention brought about a large region of activation involving the anterior cingulate gyrus and the right anterior/mesial frontal lobe. Focused and divided attention CPT conditions were compared but there were few significant differences. The findings are consistent with activation of an anterior attention network during auditory attention, without involvement of posterior attention structures which are more likely to vary in accordance with sensory modality.

Acoustic Stimulation↗

PubMed2003

Functional neuroimaging of auditory processing.

There is a complex functional organization of the central auditory system from the brainstem to primary and associative auditory cortices. Functional neuroimaging has been used to visualize and confirm the spatial distribution of brain activation in temporal areas for the processing of simple acoustic stimuli. Brain activity is much more complex for words, and different networks can be recruited when phonological, lexical and semantic levels of processing are engaged.

Auditory Cortex↗

PubMed2006

In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging.

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior.

Brain Injuries↗

PubMed2003

Functional neuroimaging studies of motor recovery after stroke in adults: a review.

BACKGROUND: The precise mechanisms of and biological basis for motor recovery after stroke in adults are still largely unknown. Reorganization of the motor system after stroke as assessed by functional neuroimaging is an intriguing but challenging new field of research. Provocative but equivocal findings have been reported to date. SUMMARY OF REVIEW: We present an overview of functional neuroimaging studies (positron emission tomography or functional MRI) of motor tasks in patients recovered or still recovering from motor deficit after stroke. After a brief account of the connectivity of motor systems and the imaging findings in normal subjects, the literature concerning stroke patients is reviewed and discussed, and a general model is proposed. CONCLUSIONS: Both cross-sectional and longitudinal studies have demonstrated that the damaged adult brain is able to reorganize to compensate for motor deficits. Rather than a complete substitution of function, the main mechanism underlying recovery of motor abilities involves enhanced activity in preexisting networks, including the disconnected motor cortex in subcortical stroke and the infarct rim after cortical stroke. Involvement of nonmotor and contralesional motor areas has been consistently reported, with the emerging notion that the greater the involvement of the ipsilesional motor network, the better is the recovery. This hypothesis is supported by the enhanced activity of the ipsilesional primary motor cortex induced by motor training and acute pharmacological interventions, in parallel with improved motor function. Further longitudinal studies assessing the relationships between such changes and actual recovery, as well as manipulating such changes by rehabilitation or pharmacological maneuvers, should provide further information on these fundamental questions. This review closes with some perspectives for future research.

Adult↗

PubMed1999

Statistical limitations in functional neuroimaging. I. Non-inferential methods and statistical models.

Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference.

Bayes Theorem↗

PubMed1998

Functional neuroimaging studies of encoding, priming, and explicit memory retrieval.

Human functional neuroimaging techniques provide a powerful means of linking neural level descriptions of brain function and cognition. The exploration of the functional anatomy underlying human memory comprises a prime example. Three highly reliable findings linking memory-related cognitive processes to brain activity are discussed. First, priming is accompanied by reductions in the amount of neural activation relative to naive or unprimed task performance. These reductions can be shown to be both anatomically and functionally specific and are found for both perceptual and conceptual task components. Second, verbal encoding, allowing subsequent conscious retrieval, is associated with activation of higher order brain regions including areas within the left inferior and dorsal prefrontal cortex. These areas also are activated by working memory and effortful word generation tasks, suggesting that these tasks, often discussed as separable, might rely on interdependent processes. Finally, explicit (intentional) retrieval shares much of the same functional anatomy as the encoding and word generation tasks but is associated with the recruitment of additional brain areas, including the anterior prefrontal cortex (right > left). These findings illustrate how neuroimaging techniques can be used to study memory processes and can both complement and extend data derived through other means. More recently developed methods, such as event-related functional MRI, will continue this progress and may provide additional new directions for research.

Amnesia↗

PubMedDate not supplied

Contribution of functional neuroimaging to understanding neuropsychiatric side effects of interferon in hepatitis C.

Patients with hepatitis C who are treated with interferon may develop neuropsychiatric symptoms, including fatigue and depression. The authors discuss the potential use of functional neuroimaging in the identification and treatment of these patients. The authors provide an overview of functional neuroimaging studies of fatigue and depressive symptoms in various medical and psychiatric conditions and suggest future directions for research that may increase understanding of the specific neural substrates of neuropsychiatric side effects associated with hepatitis C and interferon treatment. This knowledge may help consultation-liaison psychiatrists identify patients at high risk for developing side effects related to hepatitis C and interferon, which would allow for implementation of validated strategies for prophylactic treatment of these patients.

Antineoplastic Agents↗