Event-related Functional MRI Research Articles

Noradrenaline and Movement Initiation Disorders in Parkinson's Disease: A Pharmacological Functional MRI Study with Clonidine.

Slowness of movement initiation is a cardinal motor feature of Parkinson’s disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson’s disease.

Emotional bias modification weakens game-related compulsivity and reshapes frontostriatal pathways.

Addiction is characterized by compulsive engagement despite adverse consequences. Psychobehavioural interventions targeting compulsivity in addictions are relatively rare, particularly for behavioural addictions like internet gaming disorder (IGD). Free from confounding drug-on-brain effects, IGD provides a promising model for understanding neuropsychological processes of addictions. IGD is a global concern in the setting of increasing internet use worldwide. Thus, developing interventions and understanding their mechanisms of action are important. Positive emotional association biases (EABs) towards addiction cues based on reward conditioning may underlie addiction-associated compulsivity. Here, we developed an EAB modification (EABM) protocol and examined whether modifying EABs via cognitive training would alter neurocognitive aspects of addiction-associated compulsivity in IGD. We recruited 90 IGD participants who were randomly assigned to receive EABM or sham training in a 1:1 ratio (clinicaltrials.gov identifier: NCT04068064). The EABM intervention involved six consecutive days of exposure to negative emotional terms linked to gaming stimuli and positive terms linked to non-gaming healthy-alternative stimuli. The sham training involved similar stimuli linked to neutral words. Participants underwent event-related functional MRI while performing a regulation-of-craving task and received several behavioural assessments pretraining and post-training. Primary efficacy measures were changes in gaming-related positive EABs, and compulsive gaming thoughts and behaviours. Behaviourally, EABM (versus sham) training decreased gaming-related positive EABs and compulsive gaming thoughts and behaviours. Neurally, EABM training involved decreased activation in the bilateral dorsal striatum in the regulation-of-craving task and altered left dorsal striatum-centric functional connectivity with ventral prefrontal cortical regions, which correlated with decreases in gaming-related EABs or compulsive gaming thoughts and behaviours. EABM training also implicated activation changes in the right medial frontal gyrus and posterior insula. EABM may reduce compulsive gaming thoughts and behaviours via reshaping functional organization of frontostriatal pathways and insular activity in IGD. The therapeutic potential of EABM should be examined in larger, longer-term studies, as should its application to other addictive disorders.

Behavioural and neural effects of eccentricity and visual field during covert visuospatial attention

The attentional priority map plays a key role in the distribution of attention, and is modulated by bottom-up sensory as well as top-down task-dependent factors. The intraparietal sulcus (IPS) is a key candidate to hold a neural representation of the attentional priority map. In the current study, we examined the role of the IPS during covert attention to spatial locations with high or low eccentricity in one or both visual hemifields. To this end, eighteen neurologically healthy participants performed a cued letter discrimination task in which they were endogenously cued to attend to a location at a 5 or 10° eccentricity in the left and/or right visual field. We briefly presented a four-letter target array and subsequently probed perceptual performance while acquiring event-related functional MRI data. While behavioural results showed greater letter discrimination performance at the low eccentricity compared to the high eccentricity location, no neural effect of eccentricity was observed. The results further showed that attending to one visual hemifield produced higher activation in the left parietal and occipital cortex compared to attending bilaterally. Future studies may consider increasing the involvement of top-down control of attention to the cued location to study the neural effect of eccentricity, e.g., through manipulating the task difficulty.

Event-related functional MRI of awake behaving pigeons at 7T

Animal-fMRI is a powerful method to understand neural mechanisms of cognition, but it remains a major challenge to scan actively participating small animals under low-stress conditions. Here, we present an event-related functional MRI platform in awake pigeons using single-shot RARE fMRI to investigate the neural fundaments for visually-guided decision making. We established a head-fixated Go/NoGo paradigm, which the animals quickly learned under low-stress conditions. The animals were motivated by water reward and behavior was assessed by logging mandibulations during the fMRI experiment with close to zero motion artifacts over hundreds of repeats. To achieve optimal results, we characterized the species-specific hemodynamic response function. As a proof-of-principle, we run a color discrimination task and discovered differential neural networks for Go-, NoGo-, and response execution-phases. Our findings open the door to visualize the neural fundaments of perceptual and cognitive functions in birds—a vertebrate class of which some clades are cognitively on par with primates.

The ventral striatum dissociates information expectation, reward anticipation, and reward receipt

Do dopaminergic reward structures represent the expected utility of information similarly to a reward? Optimal experimental design models from Bayesian decision theory and statistics have proposed a theoretical framework for quantifying the expected value of information that might result from a query. In particular, this formulation quantifies the value of information before the answer to that query is known, in situations where payoffs are unknown and the goal is purely epistemic: That is, to increase knowledge about the state of the world. Whether and how such a theoretical quantity is represented in the brain is unknown. Here we use an event-related functional MRI (fMRI) task design to disentangle information expectation, information revelation and categorization outcome anticipation, and response-contingent reward processing in a visual probabilistic categorization task. We identify a neural signature corresponding to the expectation of information, involving the left lateral ventral striatum. Moreover, we show a temporal dissociation in the activation of different reward-related regions, including the nucleus accumbens, medial prefrontal cortex, and orbitofrontal cortex, during information expectation versus reward-related processing.

Blunted medial prefrontal cortico-limbic reward-related effective connectivity and depression.

Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.

Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: an fMRI study.

The goal of this study is to investigate the neural correlates of working memory function associated with chemotherapy in pediatric cancer survivors using event-related functional MRI (fMRI) analysis. Fifteen pediatric cancer survivors treated with chemotherapy and 15 healthy controls were studied. Blood oxygenation level dependent (BOLD) fMRI was acquired. A visual n-back task was used to test working memory function during the fMRI scan. Responses were recorded via an MRI compatible button box for analysis. fMRI scans were analyzed using statistical parametric mapping software. All statistics were corrected for multiple comparisons by false discovery rate, with p < 0.05 as significance. Patients however gave more incorrect responses (p < 0.05), more no responses (p < 0.05), and longer response times (p < 0.05) compared with healthy controls. Correct responses generated significantly lower BOLD responses in the posterior cingulate for pediatric cancer survivors compared with controls (p < 0.05). Incorrect responses generated significantly greater BOLD responses in the angular gyrus in survivors (p < 0.05), and no response trials generated greater BOLD responses within the superior parietal lobule (p < 0.05) compared with controls. Working memory impairment appears to be due to an inability to manipulate information and to retrieve information from memory. The ability to delineate the affected neural circuits associated with chemotherapy-induced cognitive impairment could inform treatment strategies, identify patients at high risk of developing cognitive deficits, and pre-emptively tailor behavioral enrichment to overcome specific cognitive deficits.

Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder.

Heterogeneity within Major Depressive Disorder (MDD) has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A [(11C)WAY-100635], as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets.

Characterization of the hemodynamic response function in white matter tracts for event-related fMRI

Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Central pain processing in "drug-naïve" pain-free patients with Parkinson's disease.

Despite its clinical relevance, the pathophysiology of pain in Parkinson's disease (PD) is still largely unknown, and both central and peripheral mechanisms have been invoked. To investigate whether central pain processing is altered in "drug-naive" pain-free PD (dnPD) patients. Using event-related functional MRI (fMRI), functional response to forearm heat stimulation (FHS) at two different intensities (41°C and 53°C) was investigated in 20 pain-free dnPD patients, compared with 18 healthy controls (HCs). Secondary analyses were performed to evaluate associations between BOLD signal changes and PD clinical features and behavioral responses. During low-innocuous FHS (41°C), no activation differences were found between dnPD patients and HCs. During high-noxious FHS (53°C) a significantly increased activation in the left somatosensory cortex, left cerebellum, and right low pons was observed in dnPD patients compared to HCs. In the latter experimental condition, fMRI BOLD signal changes in the right low pons (p < .0001; R=-0.8) and in the cerebellum (p = .004; R = -0.7) were negatively correlated with pain intensity ratings only in dnPD patients. No statistically significant difference in experimental pain perception was detected between dnPD patients and HCs. Our findings suggest that a functional remodulation of pain processing pathways occurs even in the absence of clinically overt pain symptoms in dnPD patients. These mechanisms may eventually become dysfunctional over time, contributing to the emergence of pain symptoms in more advanced PD stages. The comprehension of pain-related mechanisms may improve the clinical approach and therapeutic management of this disabling nonmotor symptom.

Functional oxygen extraction fraction (OEF) imaging with turbo gradient spin echo QUIXOTIC (Turbo QUIXOTIC).

QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. The average cortical GM OEF was estimated as 0.38 ± 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 ± 0.04 at baseline and 0.35 ± 0.05 during activation, with an average %ΔOEF of -20%. These values are consistent with those of past studies. tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event-related functional MRI experiments. Magn Reson Med 79:2713-2723, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The effect of cerebellar tumor resection on pain perception in pediatric patients.

126 Background: Acute cerebellar infarctions have been shown to lead to affective and cognitive deficits in pediatric patients. However, the consequences of cerebellar insult on pain processing are unknown. Recent evidence not only suggests that the cerebellum plays a role in affective processing, but it also demonstrates increased activity in this area when individuals experience experimental or clinical pain, particularly in the posterior cerebellum. The goal of this study is to evaluate the effect of cerebellar resection of low-grade astrocytomas in children on pain perception. Describing the impact of this treatment may be of particular importance in children, as it may alter sensory development into adulthood. Methods: Twelve pediatric patients treated with surgery only for non-malignant astrocytomas (mean age = 13.78 ± 5.64) and ten age-, gender-, race- and handedness-matched healthy controls (mean age = 14.52 ± 5.96) were evaluated using quantitative sensory testing and magnetic resonance imaging, comprising diffusion tensor imaging, resting state and event-related functional MRI scans. Five of these patients had tumors localized to the posterior cerebellar hemispheres. The psychophysical measures assessed included heat and cold detection thresholds (HDT, CDT), heat and cold pain thresholds (HPT, CPT), and cold pain tolerance using a cold pressor task. Results: Patients with lesions in the posterior cerebellum (n = 5) were shown to have a significantly lower tolerance to the cold pressor test than controls (n = 10). No significant differences were detected for the threshold measures. This suggests increased pain sensitivity in these patients to suprathreshold noxious stimuli compared to controls. Patients with lesions that did not include the posterior cerebellar hemispheres (n = 7) did not show significant differences with controls in terms of cold pain tolerance or thresholds. Conclusions: The differences in cold pain tolerance between patients and controls are presumed to result from damage to the posterior cerebellar hemispheres, potentially interfering with the modulation of pain pathways. Analysis of the preliminary imaging data is underway and recruitment is ongoing. Support: NIH/R21CA185870(EM)

The informativity of sound modulates crossmodal facilitation of visual discrimination: a fMRI study.

Many studies have investigated behavioral crossmodal facilitation when a visual stimulus is accompanied by a concurrent task-irrelevant sound. Lippert and colleagues reported that a concurrent task-irrelevant sound reduced the uncertainty of the timing of the visual display and improved perceptional responses (informative sound). However, the neural mechanism by which the informativity of sound affected crossmodal facilitation of visual discrimination remained unclear. In this study, we used event-related functional MRI to investigate the neural mechanisms underlying the role of informativity of sound in crossmodal facilitation of visual discrimination. Significantly faster reaction times were observed when there was an informative relationship between auditory and visual stimuli. The functional MRI results showed sound informativity-induced activation enhancement including the left fusiform gyrus and the right lateral occipital complex. Further correlation analysis showed that the right lateral occipital complex was significantly correlated with the behavioral benefit in reaction times. This suggests that this region was modulated by the informative relationship within audiovisual stimuli that was learnt during the experiment, resulting in late-stage multisensory integration and enhanced behavioral responses.

SNR dependence on hardware installation and patient immobilization in fMRI examinations. MR imaging protocol optimization

Introduction The primary form of fMRI uses the blood-oxygen-level dependent (BOLD) contrast imaging. In BOLD fMRI imaging, the signal-to-noise ratio (SNR) is extremely low and statistical methods are used to extract quantitative data. SNR of the images obtained has to be maintained as high as possible. Purpose The aim of this study is to estimate the SNR dependence on the video and audio device hardware as well as the patient immobilization in event related functional MRI examinations. Materials and methods A head mimicking phantom printed on a commercial 3D printer was scanned on a clinical 1.5 T whole-body clinical scanner utilizing a standard fMRI sequence protocol. Both anatomical and functional MR sequences were used for data acquisition. SNR parametric maps were produced and were fused on both anatomical and functional MR images obtained. The phantom was scanned before and after the installation of all the fMRI stimulus devices (visual and audio). Further examination conditions referring to immobilization of the phantom and cable looping were also studied separately. Results SNR is reduced down to 30% when the hardware cables were looped. Immobilization of the head mimicking phantom affected SNR by reducing its value to a level of 10%. The whole fMRI hardware installation also affected SNR with discrepancies at a level of 10%. Conclusion The fMRI hardware pre-installation and patient immobilization are important factors that have to be taken into consideration before performing an fMRI examination, as they can both affect the already extremely low SNR of the obtained images.

Slowness in Movement Initiation is Associated with Proactive Inhibitory Network Dysfunction in Parkinson's Disease.

Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Testing this hypothesis on the basis of direct neural-based evidence. Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia.

Effective connectivity of brain regions underlying third-party punishment: Functional MRI and Granger causality evidence

ABSTRACTThird-party punishment (TPP) for norm violations is an essential deterrent in large-scale human societies, and builds on two essential cognitive functions: evaluating legal responsibility and determining appropriate punishment. Despite converging evidence that TPP is mediated by a specific set of brain regions, little is known about their effective connectivity (direction and strength of connections). Applying parametric event-related functional MRI in conjunction with multivariate Granger causality analysis, we asked healthy participants to estimate how much punishment a hypothetical perpetrator deserves for intentionally committing criminal offenses varying in levels of harm. Our results confirmed that TPP legal decisions are based on two domain-general networks: the mentalizing network for evaluating legal responsibility and the central-executive network for determining appropriate punishment. Further, temporal pole (TP) and dorsomedial prefrontal cortex (PFC) emerged as hubs of the mentalizing network, uniquely generating converging output connections to ventromedial PFC, temporo-parietal junction, and posterior cingulate. In particular, dorsomedial PFC received inputs only from TP and both its activation and its connectivity to dorsolateral PFC correlated with degree of punishment. This supports the hypothesis that dorsomedial PFC acts as the driver of the TPP activation pattern, leading to the decision on the appropriate punishment. In conclusion, these results advance our understanding of the organizational elements of the TPP brain networks and provide better insights into the mental states of judges and jurors tasked with blaming and punishing legal wrongs.

Effect of temporal resolution and serial autocorrelations in event‐related functional MRI

To assess the impact of colored noise on statistics in event-related functional MRI (fMRI) (visual stimulation using checkerboards) acquired by simultaneous multislice imaging enabling repetition times (TRs) between 2.64 to 0.26 s. T-values within the visual cortex obtained with analysis tools that assume a first-order autoregressive plus white noise process (AR(1)+w) with a fixed AR coefficient versus higher-order AR models with spatially varying AR coefficients were compared. In addition, dependency of T-values on correction of physiological noise (respiration, heart rate) was evaluated. Optimal statistical power was obtained for a TR of 0.33 s, but T-values as obtained by AR(1)+w models were strongly dependent on the predefined AR coefficients in fMRI with short TRs which required higher-order AR models to achieve stable statistics. Direct estimation of AR coefficients revealed the highest values within the default mode network while physiological noise had little influence on statistics in cortical structures. Colored noise in event-related fMRI obtained at short TRs originates mainly from neural sources and calls for more sophisticated correction of serial autocorrelations which cannot be achieved with standard methods relying on AR(1)+w models with globally fixed AR coefficients. Magn Reson Med 76:1805-1813, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Neuropragmatics and irony processing in schizophrenia – Possible neural correlates of the meta-module of pragmatic meaning construction

The study investigates the pragmatics of irony processing and contextual effects in schizophrenia from a neurolinguistic perspective. Relying on neuroimaging (fMRI) techniques the research reveals the brain networks involved in social cognition and non-compositional processing, identifying an area with an integrative role, fulfilling basic tasks that serve as pillars of pragmatic meaning construction, in line with the hypothesized meta-module of pragmatic comprehension.Schizophrenic patients are known to be diagnosed with a typical Theory of Mind (ToM) mechanisms even during remission, which is believed to be responsible, or at least, to contribute to their deficit in pragmatic competence. Several studies reveal a connection between irony comprehension and ToM capacities in patients, who demonstrate difficulty in irony processing, which has been associated with their deficient mentalization skills. We examined the neural correlates of irony understanding in patients, as an indicator of ToM capacity, and evaluated how surface cues (linguistic help) affect irony comprehension. Patients and control subjects were submitted to event-related functional MRI scanning while performing three tasks: (1) irony, (2) irony with linguistic help and (3) control tasks. Results show that mentalizing skills are central for a fully-fledged pragmatic competence, and that linguistic surface cues enhance understanding of implicit content.

Brain activation during associative short-term memory maintenance is not predictive for subsequent retrieval.

Performance on working memory (WM) tasks may partially be supported by long-term memory (LTM) processing. Hence, brain activation recently being implicated in WM may actually have been driven by (incidental) LTM formation. We examined which brain regions actually support successful WM processing, rather than being confounded by LTM processes, during the maintenance and probe phase of a WM task. We administered a four-pair (faces and houses) associative delayed-match-to-sample (WM) task using event-related functional MRI (fMRI) and a subsequent associative recognition LTM task, using the same stimuli. This enabled us to analyze subsequent memory effects for both the WM and the LTM test by contrasting correctly recognized pairs with incorrect pairs for either task. Critically, with respect to the subsequent WM effect, we computed this analysis exclusively for trials that were forgotten in the subsequent LTM recognition task. Hence, brain activity associated with successful WM processing was less likely to be confounded by incidental LTM formation. The subsequent LTM effect, in contrast, was analyzed exclusively for pairs that previously had been correctly recognized in the WM task, disclosing brain regions involved in successful LTM formation after successful WM processing. Results for the subsequent WM effect showed no significantly activated brain areas for WM maintenance, possibly due to an insensitivity of fMRI to mechanisms underlying active WM maintenance. In contrast, a correct decision at WM probe was linked to activation in the “retrieval success network” (anterior and posterior midline brain structures). The subsequent LTM analyses revealed greater activation in left dorsolateral prefrontal cortex and posterior parietal cortex in the early phase of the maintenance stage. No supra-threshold activation was found during the WM probe. Together, we obtained clearer insights in which brain regions support successful WM and LTM without the potential confound of the respective memory system.