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Neuroimaging in disorders of social and emotional functioning: what is the question?

Social and emotional processing uses neural systems involving structures ranging from the brain stem to the associational cortex. Neuroimaging research has attempted to identify abnormalities in components of these systems that would underlie the behavioral abnormalities seen in disorders of social and emotional processing, notably autism spectrum disorders, the focus of this review. However, the findings have been variable. The most replicated anatomic finding (a tendency toward large brains) is not modular, and metabolic imaging and functional imaging (although showing substantial atypicality in activation) are not consistent regarding specific anatomic sites. Moreover, autism spectrum disorder demonstrates substantial heterogeneity on multiple levels. Here evidence is marshaled from a review of neuroimaging data to support the claim that abnormalities in social and emotional processing on the autism spectrum are a consequence of systems disruptions in which the behaviors are a final common pathway and the focal findings can be variable, downstream of other pathogenetic mechanisms, and downstream of more pervasive abnormalities.

Adolescent↗

Neuroimaging studies of aggressive and violent behavior: current findings and implications for criminology and criminal justice.

With the availability of new functional and structural neuroimaging techniques, researchers have begun to localize brain areas that may be dysfunctional in offenders who are aggressive and violent. Our review of 17 neuroimaging studies reveals that the areas associated with aggressive and/or violent behavioral histories, particularly impulsive acts, are located in the prefrontal cortex and the medial temporal regions. These findings are explained in the context of negative emotion regulation, and suggestions are provided concerning how such findings may affect future theoretical frameworks in criminology, crime prevention efforts, and the functioning of the criminal justice system.

Aggression↗

Rehabilitation and functional neuroimaging dose-response trajectories for clinical trials.

BACKGROUND: In clinical trials, behavioral outcomes and physiological measures of activity-dependent plasticity that evolve with task-oriented therapies may fail to reach statistical significance. When significant, clinical effectiveness may not be robust enough to alter professional practices. OBJECTIVE: Provide the conceptual basis for a research design to optimize the effect of an experimental treatment. METHODS: Literature review. RESULTS: Research designs usually do not take into consideration the dynamic state of each subject's potential responsiveness to an intervention. Providing a rational, rather than convenient, intensity and duration of therapy may remedy this potential confounder for clinical trials. To determine whether a most effective dose of a therapy exists, investigators could assess subjects before the intervention, administer interim measures at planned intervals, and continue the intervention until the primary behavioral outcomes or functional imaging parameters or both reach a plateau for at least 15 h of additional treatment. CONCLUSION: Promising interventions ought to be continued in phase II/III trials until subjects reach an asymptote in the primary outcome for behavioral gains. For neuroimaging studies that aim to correlate brain-behavior measures during rehabilitation, the specific intervention should also continue until behavioral gains and cerebral adaptations have attained a persistent plateau. Future trials can investigate whether functional neuroimaging performed in parallel with repeated behavioral assessments can better inform researchers about the optimal duration of an experimental therapy and a subject's maximal capacity for intervention-induced cerebral reorganization.

Brain↗

Multimodality neuroimaging evaluation improves the detection of subtle cortical dysplasia in seizure patients.

The purpose of this study is to investigate if multimodality neuroimaging evaluation increases the detection of subtle focal cortical dysplasia as part of an epilepsy surgery evaluation. Three patients with normal magnetic resonance imaging and histopathological findings of focal cortical dysplasia were reviewed. Their magnetoencephalography recordings were performed on whole-head magnetoencephalography system. Magnetic resonance images were re-evaluated with special inspection in limited regions guided by magnetoencephalography spike localization. Two patients had ictal and interictal single photon emission computed tomography study after administration of Tc99m ECD. In two patients we found tiny focal abnormalities including slightly increased cortical thickness and blurred gray-white matter junction at the locations of interictal events after re-evaluation of the MR images indicating focal cortical dysplasia. The third patient showed focal atrophic change. All patients are seizure free after surgery. Both ictal and interictal single photon emission computed tomography showed hyperperfusion in the dysplastic cortex regions. Multimodality neuroimaging study can improve the detection of focal cortical dysplasia. Normal magnetic resonance images should be re-evaluated for subtle signs of focal cortical dysplasia especially when magnetoencephalography recording demonstrate focal epileptic discharges.

Adolescent↗

Controlling the familywise error rate in functional neuroimaging: a comparative review.

Functional neuroimaging data embodies a massive multiple testing problem, where 100,000 correlated test statistics must be assessed. The familywise error rate, the chance of any false positives is the standard measure of Type I errors in multiple testing. In this paper we review and evaluate three approaches to thresholding images of test statistics: Bonferroni, random field and the permutation test. Owing to recent developments, improved Bonferroni procedures, such as Hochberg's methods, are now applicable to dependent data. Continuous random field methods use the smoothness of the image to adapt to the severity of the multiple testing problem. Also, increased computing power has made both permutation and bootstrap methods applicable to functional neuroimaging. We evaluate these approaches on t images using simulations and a collection of real datasets. We find that Bonferroni-related tests offer little improvement over Bonferroni, while the permutation method offers substantial improvement over the random field method for low smoothness and low degrees of freedom. We also show the limitations of trying to find an equivalent number of independent tests for an image of correlated test statistics.

Brain↗

Substance use disorders and the orbitofrontal cortex: systematic review of behavioural decision-making and neuroimaging studies.

BACKGROUND: Orbitofrontal cortex dysfunctions have been frequently documented in people with substance use disorders. The exact role of this cortical region, however, remains unspecified. AIMS: To assess the functionality of the orbitofrontal cortex in people with substance use disorders. METHOD: Reports of studies using behavioural decision-making tasks and/or neuroimaging techniques to investigate orbitofrontal cortex functioning in cases of substance misuse were reviewed. Studies focusing exclusively on tobacco-smoking and gambling were excluded. RESULTS: Fifty-two research articles were evaluated. Most studies showed significant deficits in decision-making in people with substance use disorders. A consistent finding in the neuroimaging studies was hypoactivity of the orbitofrontal cortex after detoxification. The association between hyperactivity of this region and craving or cue reactivity was not consistent across studies. CONCLUSIONS: The orbitofrontal cortex has an important role in addictive behaviours. Further studies are needed to elucidate the underlying neuronal substrates of cue reactivity, craving and decision-making, and the implications for treatment and relapse prevention.

Brain Mapping↗

Functional neuroimaging of sympathetic innervation of the heart.

Many concepts about acute and chronic effects of stress depend on alterations in sympathetic nerves supplying the heart. Physiologic, pharmacologic, and neurochemical approaches have been used to evaluate cardiac sympathetic function. This article describes a fourth approach that is based on nuclear scanning to visualize cardiac sympathetic innervation and function and relationships between the neuroimaging findings and those from other approaches. Multiple-system atrophy with orthostatic hypotension (formerly the Shy-Drager syndrome) features normal cardiac sympathetic innervation and normal entry of norepinephrine into the coronary sinus (cardiac norepinephrine spillover), in contrast to Parkinson disease with orthostatic hypotension, which features neuroimaging and neurochemical evidence for loss of cardiac sympathetic nerves. This difference may have important implications not only for diagnosis but also for understanding the etiology of Parkinson disease. By analysis of curves relating myocardial radioactivity with time (time-activity curves) after injection of a sympathoneural imaging agent, it is possible to obtain information about cardiac sympathetic function. Abnormal time-activity curves are seen in common disorders such as heart failure and diabetic neuropathy and provide an independent, adverse prognostic index. Analogous abnormalities might help explain increased cardiovascular risk in psychiatric disorders such as melancholic depression.

Heart↗

Psychological, neuroimaging, and biochemical studies on functional association between impulsive behavior and the 5-HT2A receptor gene polymorphism in humans.

It has been suggested that impulsive behavior is caused by dysfunctional serotonergic 5-HT neurotransmission in the central nervous system (CNS). Brain neuroimaging studies have shown that behavioral inhibition is linked to the activation of cortex sites such as the ventral frontal cortex. Positron emission tomography (PET) imaging with [(18)F]altanserin to characterize 5-HT(2A) receptor binding revealed a reduction in 5-HT(2A) binding in the ventral frontal cortex in women who had recovered from impulsive diseases. These clinical, neuroimaging, and pharmacological studies appear to support the hypothesis that functional alteration of neurotransmission due to genetic polymorphisms of the 5-HT receptors may be involved in impulsive behavior modulation. Following evaluation by a self-reporting measure, it was proposed that a polymorphism in the promoter of the 5-HT(2A) receptor gene is the underlying cause of impulsive behavior; however, this hypothesis is not convincing. We examined whether the polymorphism in the 5-HT(2A) receptor gene promoter is involved in impulsive aggression by evaluating a behavioral task (Go/No-go task) in normal volunteers. The polymorphism of the 5-HT(2A) receptor gene promoter in lymphocytes from 71 volunteers was analyzed by using PCR. Impulsivity was defined as the number of commission errors (responding when one should not) recorded during a Go/No-go task; a larger number of commission errors indicate greater difficulty in inhibiting impulsive behavior. The subjects of the A-1438A allele group for the 5-HT(2A) receptor gene made more commission errors under the punishment-reward (PR)condition in a Go/No-go task than those in the G-1438G group. In the present review, we discuss and suggest the possible involvement of the A-1438A polymorphism of the 5HT2A receptor gene promoter in impulsive behavior. This hypothesis was evaluated by using a behavioral task measure that could directly reveal impulsive behavioral traits in humans.

Brain↗

Surveillance neuroimaging to detect relapse in childhood brain tumors: a Pediatric Oncology Group study.

PURPOSE: To investigate the prognostic significance of surveillance neuroimaging for detection of relapse among children with malignant brain tumors. PATIENTS AND METHODS: A historical cohort study examined all children who experienced relapse from 1985 to 1999 on one of 10 Pediatric Oncology Group trials for malignant glioma, medulloblastoma, or ependymoma. RESULTS: For all 291 patients (median age at diagnosis, 8.2 years), median time to first relapse was 8.8 months (range, 0.6 to 115.6 months). Ninety-nine relapses were radiographic, and 192, clinical; median time to relapse was 15.7 versus 6.6 months, respectively (P = .0001). When stratified by pathology, radiographic and clinical groups showed differences in median time to relapse for malignant glioma (7.8 v 4.3 months, respectively; P = .041) and medulloblastoma (23.6 v 8.9 months, respectively; P = .0006) but not ependymoma (19.5 v 13.3 months, respectively; P = .19). When stratified by early (< 8.8 months) or late (> or = 8.8 months) time to relapse, 115 early relapses were clinical, and 32, radiographic; for late relapses, 77 were clinical, and 67, radiographic (P = .001). Overall survival (OS) from relapse was significantly longer for radiographic compared with clinical detection (median, 10.8 months; 1-year OS, 46% v median, 5.5 months; 1-year OS, 33%; P = .002), but this trend did not retain significance when analyzed by pathology subgroups. CONCLUSION: Surveillance neuroimaging detects a proportion of asymptomatic relapses, particularly late relapses, and may provide lead time for other therapies on investigational trials. During the first year after diagnosis, radiographic detection of asymptomatic relapse was infrequent. A prospective study is needed to formulate a rational surveillance schedule based on the biologic behavior of these tumors.

Adolescent↗

Neural correlates of memory development and learning: combining neuroimaging and behavioral measures to understand cognitive and developmental processes.

This special issue includes 4 articles addressing the general theme of neural correlates of memory development and learning. Taken together, the articles represent a broad range of development, including infants, children, adolescents, and adults as participants. Each line of research examines relations between brain activity and cognitive functions using both physiological measures, event-related potentials or functional magnetic resonance imaging, and behavioral measures of memory and learning. This introduction sets the stage by briefly reviewing historical trends in memory development research, discussing major issues associated with neuroimaging research, and providing an integrated perspective of some specific contributions of the investigations included in this special issue, arguing that combining neuroimaging and behavioral measures advances research on memory development and learning in terms of understanding cognitive and developmental processes. The article concludes with a brief discussion of potential future directions for this type of research.

Brain↗

Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival.

OBJECTIVE: To define neuroimaging characteristics of peroxisome biogenesis disorders (PBD) with prolonged survival belonging to the Zellweger spectrum (ZeS). METHODS: The authors studied MR images of 25 patients surviving the first year. Neuroimages were compared to neurologic profiles, PBD-ZeS specific compound developmental scores, and two common PEX1 mutations. RESULTS: Three groups are defined based on normal findings, developmental anomalies, and regressive changes. Regressive changes consisting of leukoencephalopathy were identified in patients who had either stable clinical course or progressive deterioration. Concomitant neocortical atrophy was encountered in a minority. Leukoencephalopathy with stable clinical course represents the largest subgroup (48%). The authors found the central cerebellar white matter a focus for early changes in both asymptomatic and symptomatic leukoencephalopathy. A relationship between white matter involvement in clinically stable leukoencephalopathy and degree of developmental failure could not be established. The common homozygous PEX1 G843D mutation is represented in the three main outcome groups. This result points to variable phenotypic expression of the most common PEX1 mutation. CONCLUSIONS: MR findings in ZeS patients surviving the first year differ from Zellweger syndrome in predominance of regressive over developmental changes. Distribution pattern suggests identical pathomechanisms for symptomatic and asymptomatic leukoencephalopathy.

ATPases Associated with Diverse Cellular Activitie↗

NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia.

OBJECTIVE: To determine the utility of the neuroimaging component within the National Institute of Neurological Disorders and Stroke (NINDS) Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for vascular dementia for distinguishing between patients with and without dementia in the context of cerebrovascular disease. METHOD: One hundred twenty-five poststroke patients age > or =75 (27 with and 98 without poststroke dementia) from representative hospital-based stroke registers in the North East of England were evaluated using a 1.5 T MR scanner. The proportion of patients with and without poststroke dementia meeting the imaging component of the NINDS AIREN criteria was determined, and hippocampal atrophy (measured using the Schelten scale) was compared between the two groups. RESULTS: There were no significant differences between the patients with and without poststroke dementia on any criteria of the imaging parameters within the NINDS AIREN criteria. In addition, there were no significant differences in the number or size of cortical or subcortical infarcts between the two groups, with 13 patients without dementia having cortical infarcts >50 mm. Patients with dementia had greater hippocampal atrophy (right: Mann-Whitney U test, Z = 2.5, p = 0.01; left: Mann-Whitney U test, Z = 2.5, p = 0.01). CONCLUSION: The neuroimaging component of the NINDS AIREN criteria does not distinguish between older patients with and without poststroke dementia.

Aged↗

Anti-Ro(SS-A) autoantibodies in central nervous system disease associated with Sjögren's syndrome (CNS-SS): clinical, neuroimaging, and angiographic correlates.

OBJECTIVE: To examine in Sjögren's syndrome (SS) the interrelationship between the presence of the anti-Ro(SS-A) antibody response and (1) concomitant presence and type (ie, focal or nonfocal) of CNS disease (CNS-SS), (2) cross-sectional brain MRI or CT, and (3) abnormal cerebral angiography. METHODS: Neurologic, neuroimaging, and angiographic features of CNS-SS patients were correlated with the presence of precipitating anti-Ro(SS-A) autoantibodies detected by gel double-immunodiffusion or quantitative ELISA, which detects antibodies directed against the 60-kd peptide. Statistical analyses were performed using Fisher's exact test (two-tailed) with Haldane's adjustment and odds ratio with Cornfield 95% confidence intervals. RESULTS: Precipitating antibodies against the Ro(SS-A) antigen, determined by gel double-immunodiffusion, were present in an increased frequency in CNS-SS patients with (1) documented clinical CNS disease, (2) focal clinical CNS manifestations and serious complications, (3) large regions of increased signal intensity, consistent with ischemia/infarcts on brain MRI scans or regions of decreased attenuation consistent with infarcts on CT, and (4) abnormal cerebral angiograms consistent with small-vessel angiitis. Finally, the anti-Ro(SS-A) antibody response in CNS was directed against the 60-kd peptide specificity, determined by ELISA. CONCLUSIONS: Clinical, neuroimaging (cerebral CT), and angiographic observation suggest that a subset of anti-Ro(SS-A) antibody-positive, in contrast with -negative, CNS-SS patients have more serious and extensive CNS disease, some with frank cerebral angiopathy. Anti-Ro(SS-A) antibodies are postulated to play a role in mediating or potentiating vascular injury in CNS-SS.

Autoantibodies↗

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↗

Fiswidgets: a graphical computing environment for neuroimaging analysis.

Current fMRI neuroimaging software programs offer the researcher a wealth of analysis methods and tools. However, the incompatibilities in user interface, data format, and computing environment in these tools make it difficult if not impossible for most researchers to take advantage of the full set of resources available for neuroimaging analyses. We describe a graphical computing environment, Functional Imaging Software Widgets (fiswidgets), which was developed to address these interoperability and usability problems. This environment provides a desktop style framework into which 100 subcomponents from a number of widely used fMRI analysis software packages (e.g., AFNI, AIR) are incorporated. It is an open-source, extensible environment available for reuse and modification by other software developers. A discussion of the design criteria (open architecture, modularity, wrapper technology, commercial utilities) that support such loosely integrative computing environments, and the problems entailed in maintaining them (development overhead, distribution logistics, format incompatibilities, graphics vs scripting tradeoffs, and appropriate acknowledgment of software developers) follows.

Computer Graphics↗

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↗

Comparative study of the neuropsychological and neuroimaging evaluations in children with dyslexia.

We analyzed retrospectively the neuroimaging exams of children with a confirmed diagnosis of dyslexia and correlated our findings with the evaluation of higher cortical functions. We studied 34 medical files of patients of the Ambulatory of Neuro-difficulties in Learning, FCM/UNICAMP. All of them had been sent to the ambulatory with primary or secondary complaints of difficulties at school and were submitted to neuropsychological evaluation and imaging exam (SPECT). From the children evaluated 58.8% had exams presenting dysfunction with 47% presenting hypoperfusion in the temporal lobe. As for the higher cortical functions, the most affected abilities were reading, writing and memory. There was significance between the hypoperfused areas and the variables schooling, reading, writing, memory and mathematic reasoning. The SPECTs showed hypoperfusion in areas involved in the reading and writing processes. Both are equivalent in terms of involved functional areas and are similar in children with or without specific dysfunctions in neuroimaging.

Adolescent↗

Neuroimaging in traumatic brain imaging.

Traumatic brain injury (TBI) is a common and potentially devastating clinical problem. Because prompt proper management of TBI sequelae can significantly alter the clinical course especially within 48 h of the injury, neuroimaging techniques have become an important part of the diagnostic work up of such patients. In the acute setting, these imaging studies can determine the presence and extent of injury and guide surgical planning and minimally invasive interventions. Neuroimaging also can be important in the chronic therapy of TBI, identifying chronic sequelae, determining prognosis, and guiding rehabilitation.

Animals↗