Neuroimaging Paradigms Research Articles

Parkinson's disease patients show reduced cortical‐subcortical sensorimotor connectivity

Reduced dopamine input to cortical and subcortical brain structures, particularly those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The extent to which dopamine dysfunction affects connectivity within this and other brain networks remains to be investigated. The purpose of this study was to measure anatomical and functional connectivity in groups of PD patients and controls to determine whether connectivity deficits within the cortico-basal ganglia thalamocortical system could be attributed to PD, particularly in sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted magnetic resonance imaging (MRI) and resting-state functional MRI was implemented in a large cohort of PD patients and control subjects. Probabilistic tractography and functional correlation analyses were performed to map connections between brain structures and to derive indices of connectivity that were then used to compare groups. Anatomical connectivity deficits were demonstrated in PD patients, specifically for sensorimotor connections. Functional deficits were also found in some of the same connections. In addition, functional connectivity was found to increase in associative and limbic connections in PD patients compared with controls. This study lends support to findings regarding the dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and functional connectivity within this circuit were in some cases concordant in PD patients, a possible link between brain structure and function is suggested. Increases in functional connectivity in other cortico-basal ganglia thalamocortical circuits may be indicative of compensatory effects in response to system deficits elsewhere.

Modes and models in disorders of consciousness science.

The clinical assessment of non-communicative brain damaged patients is extremely difficult and there is a need for paraclinical diagnostic markers of the level of consciousness. In the last few years, progress within neuroimaging has led to a growing body of studies investigating vegetative state and minimally conscious state patients, which can be classified in two main approaches. Active neuroimaging paradigms search for a response to command without requiring a motor response. Passive neuroimaging paradigms investigate spontaneous brain activity and brain responses to external stimuli and aim at identifying neural correlates of consciousness. Other passive paradigms eschew neuroimaging in favour of behavioural markers which reliably distinguish conscious and unconscious conditions in healthy controls. In order to furnish accurate diagnostic criteria, a mechanistic explanation of how the brain gives rise to consciousness seems desirable. Mechanistic and theoretical approaches could also ultimately lead to a unification of passive and active paradigms in a coherent diagnostic approach. In this paper, we survey current passive and active paradigms available for diagnosis of residual consciousness in vegetative state and minimally conscious patients. We then review the current main theories of consciousness and see how they can apply in this context. Finally, we discuss some avenues for future research in this domain.

More than just tapping: Index finger-tapping measures procedural learning in schizophrenia

BackgroundFinger-tapping has been widely studied using behavioral and neuroimaging paradigms. Evidence supports the use of finger-tapping as an endophenotype in schizophrenia, but its relationship with motor procedural learning remains unexplored. To our knowledge, this study presents the first use of index finger-tapping to study procedural learning in individuals with schizophrenia or schizoaffective disorder (SCZ/SZA) as compared to healthy controls. MethodsA computerized index finger-tapping test was administered to 1169 SCZ/SZA patients (62% male, 88% right-handed), and 689 healthy controls (40% male, 93% right-handed). Number of taps per trial and learning slopes across trials for the dominant and non-dominant hands were examined for motor speed and procedural learning, respectively. ResultsBoth healthy controls and SCZ/SZA patients demonstrated procedural learning for their dominant hand but not for their non-dominant hand. In addition, patients showed a greater capacity for procedural learning even though they demonstrated more variability in procedural learning compared to healthy controls. Left-handers of both groups performed better than right-handers and had less variability in mean number of taps between non-dominant and dominant hands. Males also had less variability in mean tap count between dominant and non-dominant hands than females. As expected, patients had a lower mean number of taps than healthy controls, males outperformed females and dominant-hand trials had more mean taps than non-dominant hand trials in both groups. ConclusionsThe index finger-tapping test can measure both motor speed and procedural learning, and motor procedural learning may be intact in SCZ/SZA patients.

Neural and Behavioral Correlates of Peritraumatic Dissociation in an Acutely Traumatized Sample

Peritraumatic dissociative responses have been identified as strong predictors of subsequent posttraumatic stress disorder development. We aimed to clarify the mechanism by which peritraumatic dissociation is related to PTSD development by exploring the neural correlates of peritraumatic dissociation during posttraumatic adjustment. We combined a prospective questionnaire study with a neuroimaging paradigm in an acutely traumatized sample recruited from the emergency department from 2004 until 2009. 121 acutely traumatized subjects were assessed for acute stress disorder, PTSD, and dissociative symptoms at 3 time points within the first 3 months post trauma. A subsample of 21 subjects underwent a script-driven 4-Tesla functional magnetic resonance imaging scan 2 to 4 months post trauma. Peritraumatic dissociation predicted PTSD diagnostic status at 5-6 weeks and 3 months over and above childhood trauma (Wald = 4.035, P = .045; Wald = 4.793, P = .029, respectively). Peritraumatic dissociation scores were positively correlated with activation in the right occipital lobe, ie, the lingual (Brodmann area [BA] 18, z = 3.37), fusiform (BA 19, z = 3.64), and parahippocampal (BA 19, z = 3.25) gyri. After covariation of dissociation at the time of the scan, peritraumatic dissociation remained positively correlated with activation in the right lingual (BA 18, z = 3.21) and fusiform (BA 19, z = 3.55) gyri. The neuroimaging findings indicate that peritraumatic dissociation is associated with greater activation of the right occipital lobe (BAs 18 and 19), a region previously implicated in vivid autobiographical memory recall of highly emotional events. These results suggest that peritraumatic dissociation directly leads to the formation of intrusive memories. Peritraumatic dissociation and childhood trauma emerged as valuable predictors of PTSD development and therefore can guide the identification of individuals at risk.

Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS

The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were "gain control" and "visual integration." CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development.

Neural circuitry underlying affective response to peer feedback in adolescence.

Peer feedback affects adolescents' behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents' emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9-17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents' perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.

A male advantage for spatial and object but not verbal working memory using the n-back task

Sex-related differences have been reported for performance and neural substrates on some working memory measures that carry a high cognitive load, including the popular n-back neuroimaging paradigm. Despite some evidence of a sex effect on the task, the influence of sex on performance represents a potential confound in neuroimaging research. The present study investigated sex-related differences in verbal, spatial, and common object versions of the high cognitive load “n-back” working memory task. Eighteen male and 18 female undergraduates completed all 3 versions of the task. A mixed ANOVA, with Sex (male and female) as the between-subjects factor and Condition (verbal, spatial, and object) as the within-subjects repeated measure revealed that males were significantly more accurate than females on the spatial and object versions of the n-back task and performed equivalently to females on the verbal version of the task. Although the expected female advantage for verbal working memory was not found using this effortful n-back task, these results support a male advantage for high cognitive load spatial and object working memory. Future research should take into account the influence of sex on performance of the n-back task, and examine sex-related differences in working memory using other paradigms.

Mapping Functional Circuits in Depression

Sigmund Freud, in Mourning and Melancholia (1917), described the difference between these states as the presence of self-loathing in depression and its absence in grief. This new study using a novel neuroimaging paradigm that examines activation of six brain circuits, originally identified in healthy individuals, has now identified neurophysiological correlates of hate in depression. In previous …

Towards a Neuroscience of Mind-Wandering

Mind-wandering (MW) is among the most robust and permanent expressions of human conscious awareness, classically regarded by philosophers, clinicians, and scientists as a core element of an intact sense of self. Nevertheless, the scientific exploration of MW poses unique challenges; MW is by nature a spontaneous, off task, internal mental process which is often unaware and usually difficult to control, document or replicate. Consequently, there is a lack of accepted modus operandi for exploring MW in a laboratory setup, leading to a relatively small amount of studies regarding the neural basis of MW. In order to facilitate scientific examination of MW the current review categorizes recent literature into five suggested strategies. Each strategy represents a different methodology of MW research within functional neuroimaging paradigms. Particular attention is paid to resting-state brain activity and to the “default-mode” network. Since the default network is known to exert high activity levels during off-task conditions, it stands out as a compelling candidate for a neuro-biological account of mind-wandering, in itself a rest-based phenomenon. By summarizing the results within and across strategies we suggest further insights into the neural basis and adaptive value of MW, a truly intriguing and unique human experience.

FMRI assessment of language lateralization: An objective approach

Language lateralization based on functional magnetic resonance imaging (fMRI) is often used in clinical neurological settings. Currently, interpretation of the distribution, pattern and extent of language activation can be heavily dependent on the chosen statistical threshold. The aim of the present study was to 1) test the robustness of adaptive thresholding of fMRI data to yield a fixed number of active voxels, and to 2) develop a largely threshold-independent method of assessing when individual patients have statistically atypical language lateralization. Simulated data and real fMRI data in 34 healthy controls and 4 selected epilepsy patients performing a verbal fluency language fMRI task were used. Dependence of laterality on the thresholding method is demonstrated for simulated and real data. Simulated data were used to test the hypothesis that thresholding based upon a fixed number of active voxels would yield a laterality index that was more stable across a range of signal strengths (study power) compared to thresholding at a fixed p value. This stability allowed development of a method comparing an individual to a group of controls across a wide range of thresholds, providing a robust indication of atypical lateralization that is more objective than conventional methods. Thirty healthy controls were used as normative data for the threshold-independent method, and the remaining subjects were used as illustrative examples. The method could also be used more generally to assess relative regional distribution of activity in other neuroimaging paradigms (for example, one could apply it to the assessment of lateralization of activation in a memory task, or to the assessment of anterior–posterior distribution rather than laterality).

Functional imaging of hippocampal dysfunction among persons with Alzheimer’s disease: a proof-of-concept study

Cholinergic deficits are an early and functionally significant manifestation of Alzheimer’s disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed.

Assessing the neuroendocrine stress response in the functional neuroimaging context

Neural regulation of stress responses, and the feedback of stress hormones to the brain, reflect complex brain–body interactions that may underlie the effects of psychological stress on health. Elucidating the brain circuitry involved in the cortical control of limbic–hypothalamic–pituitary–adrenal axis, and the cortical “targets” of cortisol that in turn modulates brain function, requires careful assessment of glucocorticoid hormones, in the context of the neuroimaging paradigms. Here we discuss approaches for assessment of endocrine function in the context of neuroimaging, including methods of blood and saliva specimen collection, and methods for drug/hormone administration. We also briefly discuss important temporal considerations, including appropriate timing of sample collections for hormones with different time-courses of activation (e.g. ACTH vs. cortisol), the pharmacokinetics of both endogenous hormones and administered agents, and circadian considerations. These are crucial to experimental designs of rhythmic hormonal systems and multiple feedback loops. We briefly address psychological/behavioral ‘activation’ paradigms used for inducing endogenous LHPA axis responses within or in proximity to scanner, as well as strategies for administration of exogenous hormones or secretagogues. Finally, we discuss some of the analytical issues in terms of hormone responses (e.g. response and area under curve, diurnal variability) and strategies for linking measured levels of peripheral humoral factor to brain activity (e.g. hormone responses as between-subject regressors of BOLD activations, hormone levels as within-subject regressors in analyses of covariance of brain activity over time, etc.).

Combined effects of attention and motivation on visual task performance: Transient and sustained motivational effects

We investigated how the brain integrates motivational and attentional signals by using a neuroimaging paradigm that provided separate estimates for transient cue- and target-related signals, in addition to sustained block-related responses. Participants performed a Posner-type task in which an endogenous cue predicted target location on 70% of trials, while motivation was manipulated by varying magnitude and valence of a cash incentive linked to task performance. Our findings revealed increased detection performance (d′) as a function of incentive value. In parallel, brain signals revealed that increases in absolute incentive magnitude led to cue- and target-specific response modulations that were independent of sustained state effects across visual cortex, fronto-parietal regions, and subcortical regions. Interestingly, state-like effects of incentive were observed in several of these brain regions, too, suggesting that both transient and sustained fMRI signals may contribute to task performance. For both cue and block periods, the effects of administering incentives were correlated with individual trait measures of reward sensitivity. Taken together, our findings support the notion that motivation improves behavioral performance in a demanding attention task by enhancing evoked responses across a distributed set of anatomical sites, many of which have been previously implicated in attentional processing. However, the effect of motivation was not simply additive as the impact of absolute incentive was greater during invalid than valid trials in several brain regions, possibly because motivation had a larger effect on reorienting than orienting attentional mechanisms at these sites.

Familial cerebral cavernous malformations: Rio de Janeiro study and review of the recommendations for management

Multiple cerebral cavernous malformation (CCM) is the hallmark of familial presentation of cavernous malformation in the brain. We describe an ongoing Familial Cerebral Cavernous Malformation Project in the Rio de Janeiro state showing genetic profile and the pattern of emergent neuroimaging findings of this particular population besides a review of the updated recommendations for management of familial CCM versus patients harboring sporadic lesions. Four families of our cohort of 9 families were genetically mapped showing mutational profile linked to CCM1. The neuroimaging paradigm was shifted from T2*gradient-echo (GRE) sequence to susceptibility weighting MR phase imaging (SWI). Only two index cases were subjected to surgery. There was no surgical intervention in any of the kindreds of our entire cohort of 9 families of our Neurovascular Program within seven years of follow-up. The genetic sequencing for mutational profile in four of these families has demonstrated only CCM1 gene affected. Our management of the familial CCM is according to the review of the literature recommendations. The Project of Familial Cerebral Cavernous Malformations of Rio de Janeiro detected mutations of the gene CCM1 in the first four families studied. Familial cavernous malformation are to be settled apart from the more common sporadic lesion. A set of recommendations was searched for in the literature in order to deal with these specific patients and kindreds.

Evolutionary neuromarketing: darwinizing the neuroimaging paradigm for consumer behavior

AbstractThe current paper serves two purposes. First, it reviews the neuroimaging literature most relevant to the field of marketing (e.g., neuroeconomics, decision neuroscience, and neuromarketing). Second, it posits that evolutionary theory is a consilient and organizing meta‐theoretical framework for neuromarketing research. The great majority of neuroimaging studies suffer from the illusion of explanatory depth namely the sophistication of the neuroimaging technologies provides a semblance of profundity to the reaped knowledge, which is otherwise largely disjointed and atheoretical. Evolutionary theory resolves this conundrum by recognizing that the human mind has evolved via the processes of natural and sexual selection. Hence, in order to provide a complete understanding of any given neuromarketing phenomenon requires that it be tackled at both the proximate level (as is currently the case) and the ultimate level (i.e., understanding the adaptive reason that would generate a particular neural activation pattern). Evolutionary psychology posits that the human mind consists of a set of domain‐specific computational systems that have evolved to solve recurring adaptive problems. Accordingly, rather than viewing the human mind as a general‐purpose domain‐independent organ, evolutionary cognitive neuroscientists recognize that many neural activation patterns are instantiations of evolved computational systems in evolutionarily relevant domains such as survival, mating, kin selection, and reciprocity. As such, an evolutionary neuromarketing approach recognizes that the neural activation patterns associated with numerous marketing‐related phenomena can be mapped onto the latter Darwinian modules thus providing a unifying meta‐theory for this budding discipline.Copyright © 2008 John Wiley & Sons, Ltd.

Functional Neuroimaging—Can It Contribute to Our Understanding of Processes of Change?

Preliminary studies have shown that psychotherapeutic and pharmacological treatments of psychiatric disorders lead to measurable changes in the activity of the brain, particularly when they successfully reduce depression, fears, or obsessions. The purpose of this paper is to review the potential of functional neuroimaging in the understanding and evaluation of psychotherapy. Following an overview of basic neuroimaging concepts and procedures, promising neuroimaging paradigms probing mind–brain function are presented together with selected results on psychiatric patients and control subjects. Neuroimaging studies conducted pre- and post-psychotherapy are reviewed. Conclusions are formulated regarding an interdisciplinary dialogue between psychoanalysts and neuroscientists. Most likely, modulations of connections within the limbic system by higher cortical (prefrontal) networks are instrumental in the changes depicted in various studies. Overall, current developments open new avenues for bridging the gap between psychodynamic and biological psychiatry. Based on the studies presented and the emerging plasticity of the brain, the distinction between somatic treatments having an impact on the brain and psychological treatments with more elusive subjective effects has become obsolete. It must be assumed that psychoanalysis also has a measurable impact on brain functioning, insofar as it successfully ameliorates symptoms, changes relationship patterns, or increases mentalizing abilities.

Synaesthesia is associated with enhanced, self-rated visual imagery

Although the condition known as synaesthesia is currently undergoing a scientific resurgence, to date the literature has largely focused on the heterogeneous nature of synaesthesia across individuals. In order to provide a better understanding of synaesthesia, however, general characteristics need to be investigated. Synaesthetic experiences are often described as occurring ‘internally’ or in the ‘mind’s eye’, which is remarkably similar to how we would describe our experience of visual mental imagery. We assessed the role of visual imagery in synaesthesia by sampling a large group of synaesthetes and found that they report experiencing more vivid mental images than controls. These findings have important implications for our general understanding of synaesthesia and, in particular, emphasize the need to control for visual imagery in behavioural and neuroimaging paradigms.

Dysfunctional action monitoring hyperactivates frontal–striatal circuits in obsessive–compulsive disorder: an event-related fMRI study

Converging evidence suggests that hyperactivity in frontal-striatal circuits and in action-monitoring processes characterizes obsessive-compulsive disorder (OCD). It remains unclear, however, just how these abnormalities in brain function translate into the cognitive, affective, and behavioral manifestations of OCD. One possibility is that exaggerated or false error signals generated by the anterior cingulate (ACC) underlie compulsive behaviors by triggering the feeling that things are "not just right" even when no actual error has been made. Since recurrent compulsive behavior typically follows correct completion of a behavioral task (e.g., hand washing), ACC hyperactivity should be observed during correctly completed, high-conflict trials as well as during error trials. Frontal-striatal regions would also be expected to be activated during both trial types, as these regions are robustly associated with OCD across multiple neuroimaging paradigms. To test this hypothesis, 14 OCD patients and 14 matched controls completed a speeded reaction time task during functional magnetic resonance imaging (fMRI). Only correctly rejected, high-conflict trials produced excessive activation in both action monitoring (rostral and caudal ACC, LPFC) and frontal striatal regions (lateral orbitofrontal cortex (OFC), caudate, and thalamus) among OCD patients when compared to healthy controls. Portions of the posterior cingulate were also hyperactive among OCD patients. These results suggest that correctly rejected, high-conflict trials that require response inhibition may provide a better model than error trials of compulsive behaviors in OCD.

Amusia and musicogenic epilepsy.

Amusia and musicogenic epilepsy are clinical disorders that provide a window into the localization of music in the brain. Classic clinical studies of patients with these disorders, coupled with more recent studies employing modern neuroimaging and sophisticated neuropsychologic paradigms, have converged in helping to elucidate the complex neural systems that are utilized in decoding music. The notion of cerebral dominance for music has been replaced by a concept of modular but interconnected networks that have wide bilateral localization in the brain and that are molded both by genetics and experience. These disorders also provide insight into the important interface between music and emotion.

Neuroimaging studies of amygdala function in anxiety disorders.

Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive-behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains.