An fMRI Study Exploring the Overlap and Differences between Neural Representations of Physical and Recalled Pain

Implementing a recall paradigm without hypnosis, we use functional MRI (fMRI) to explore and compare nociceptive and centrally-driven pain experiences. We posit that a trace of a recent nociceptive event can be used to create sensory-re-experiencing of pain that can be qualified in terms of intensity and vividness. Fifteen healthy volunteers received three levels of thermal stimuli (warm, low pain and high pain) and subsequently were asked to recall and then rate this experience. Neuroimaging results reveal that recalling a previous sensory experience activates an extensive network of classical pain processing structures except the contralateral posterior insular cortex. Nociceptive-specific activation of this structure and the rated intensity difference between physical and recalled pain events allow us to investigate the link between the quality of the original nociceptive stimulus and the mental trace, as well as the differences between the accompanying neural responses. Additionally, by incorporating the behavioural ratings, we explored which brain regions were separately responsible for generating either an accurate or vivid recall of the physical experience. Together, these observations further our understanding of centrally-mediated pain experiences and pain memory as well as the potential relevance of these factors in the maintenance of chronic pain.     

The Neural Correlates of Identity Faking and Concealment: An fMRI Study

The neural basis of self and identity has received extensive research. However, most of these existing studies have focused on situations where the internal representation of the self is consistent with the external one. The present study used fMRI methodology to examine the neural correlates of two different types of identity conflict: identity faking and concealment. Participants were presented with a sequence of names and asked to either conceal their own identity or fake another one. The results revealed that the right insular cortex and bilaterally inferior frontal gyrus were more active for identity concealment compared to the control condition, whereas identity faking elicited a significantly larger percentage signal increase than the control condition in the right superior frontal gyrus, left calcarine, and right caudate. These results suggest that different neural systems associated with both identity processing and deception were involved in identity concealment and faking.     

An fMRI Study of Nicotine-Deprived Smokers' Reactivity to Smoking Cues during Novel/Exciting Activity

Engaging in novel/exciting (“self-expanding”) activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation.     

A Supramodal Neural Network for Speech and Gesture Semantics: An fMRI Study

In a natural setting, speech is often accompanied by gestures. As language, speech-accompanying iconic gestures to some extent convey semantic information. However, if comprehension of the information contained in both the auditory and visual modality depends on same or different brain-networks is quite unknown. In this fMRI study, we aimed at identifying the cortical areas engaged in supramodal processing of semantic information. BOLD changes were recorded in 18 healthy right-handed male subjects watching video clips showing an actor who either performed speech (S, acoustic) or gestures (G, visual) in more (+) or less (−) meaningful varieties. In the experimental conditions familiar speech or isolated iconic gestures were presented; during the visual control condition the volunteers watched meaningless gestures (G−), while during the acoustic control condition a foreign language was presented (S−). The conjunction of the visual and acoustic semantic processing revealed activations extending from the left inferior frontal gyrus to the precentral gyrus, and included bilateral posterior temporal regions. We conclude that proclaiming this frontotemporal network the brain''s core language system is to take too narrow a view. Our results rather indicate that these regions constitute a supramodal semantic processing network.     

Neural Circuits for Cognitive Appetite Control in Healthy and Obese Individuals: An fMRI Study

The mere sight of foods may activate the brain’s reward circuitry, and humans often experience difficulties in inhibiting urges to eat upon encountering visual food signals. Imbalance between the reward circuit and those supporting inhibitory control may underlie obesity, yet brain circuits supporting volitional control of appetite and their possible dysfunction that can lead to obesity remain poorly specified. Here we delineated the brain basis of volitional appetite control in healthy and obese individuals with functional magnetic resonance imaging (fMRI). Twenty-seven morbidly obese women (mean BMI = 41.4) and fourteen age-matched normal-weight women (mean BMI = 22.6) were scanned with 1.5 Tesla fMRI while viewing food pictures. They were instructed to inhibit their urge to eat the foods, view the stimuli passively or imagine eating the foods. Across all subjects, a frontal cortical control circuit was activated during appetite inhibition versus passive viewing of the foods. Inhibition minus imagined eating (appetite control) activated bilateral precunei and parietal cortices and frontal regions spanning anterior cingulate and superior medial frontal cortices. During appetite control, obese subjects had lower responses in the medial frontal, middle cingulate and dorsal caudate nuclei. Functional connectivity of the control circuit was increased in morbidly obese versus control subjects during appetite control, which might reflect impaired integrative and executive function in obesity.     

Compensatory Effort Parallels Midbrain Deactivation during Mental Fatigue: An fMRI Study

Fatigue reflects the functioning of our physiological negative feedback system, which prevents us from overworking. When fatigued, however, we often try to suppress this system in an effort to compensate for the resulting deterioration in performance. Previous studies have suggested that the effect of fatigue on neurovascular demand may be influenced by this compensatory effort. The primary goal of the present study was to isolate the effect of compensatory effort on neurovascular demand. Healthy male volunteers participated in a series of visual and auditory divided attention tasks that steadily increased fatigue levels for 2 hours. Functional magnetic resonance imaging scans were performed during the first and last quarter of the study (Pre and Post sessions, respectively). Tasks with low and high attentional load (Low and High conditions, respectively) were administrated in alternating blocks. We assumed that compensatory effort would be greater under the High-attentional-load condition compared with the Low-load condition. The difference was assessed during the two sessions. The effect of compensatory effort on neurovascular demand was evaluated by examining the interaction between load (High vs. Low) and time (Pre vs. Post). Significant fatigue-induced deactivation (i.e., Pre>Post) was observed in the frontal, temporal, occipital, and parietal cortices, in the cerebellum, and in the midbrain in both the High and Low conditions. The interaction was significantly greater in the High than in the Low condition in the midbrain. Neither significant fatigue-induced activation (i.e., Pre<Post), nor its interaction with factor Load, was identified. The observed midbrain deactivation ([PreH – PostH]>[PreE– PostE]) may reflect suppression of the negative feedback system that normally triggers recuperative rest to maintain homeostasis.     

Neural substrates of data-driven scientific discovery: An fMRI study during performance of number series completion task

Although much has been known about how humans psychologically perform data-driven scientific discovery, less has been known about its brain mechanism. The number series completion is a typical data-driven scientific discovery task, and has been demonstrated to possess the priming effect, which is attributed to the regularity identification and its subsequent extrapolation. In order to reduce the heterogeneities and make the experimental task proper for a brain imaging study, the number magnitude and arithmetic operation involved in number series completion tasks are further restricted. Behavioral performance in Experiment 1 shows the reliable priming effect for targets as expected. Then, a factorial design (the priming effect: prime vs. target; the period length: simple vs. complex) of event-related functional magnetic resonance imaging (fMRI) is used in Experiment 2 to examine the neural basis of data-driven scientific discovery. The fMRI results reveal a double dissociation of the left DLPFC (dorsolateral prefrontal cortex) and the left APFC (anterior prefrontal cortex) between the simple (period length=1) and the complex (period length=2) number series completion task. The priming effect in the left DLPFC is more significant for the simple task than for the complex task, while the priming effect in the left APFC is more significant for the complex task than for the simple task. The reliable double dissociation may suggest the different roles of the left DLPFC and left APFC in data-driven scientific discovery. The left DLPFC (BA 46) may play a crucial role in rule identification, while the left APFC (BA 10) may be related to mental set maintenance needed during rule identification and extrapolation.     

Neural Correlates of Empathy with Pain Show Habituation Effects. An fMRI Study

Background

Neuroimaging studies have demonstrated that the actual experience of pain and the perception of another person in pain share common neural substrates, including the bilateral anterior insular cortex and the anterior midcingulate cortex. As many fMRI studies include the exposure of participants to repeated, similar stimuli, we examined whether empathic neural responses were affected by habituation and whether the participants'' prior pain experience influenced these habituation effects.

Method

In 128 trials (four runs), 62 participants (31 women, 23.0 ± 4.2 years) were shown pictures of hands exposed to painful pressure (pain pictures) and unexposed (neutral pictures). After each trial, the participants rated the pain of the model. Prior to the experiment, participants were either exposed to the same pain stimulus (pain exposure group) or not (touch exposure group). In order to assess possible habituation effects, linear changes in the strength of the BOLD response to the pain pictures (relative to the neutral pictures) and in the ratings of the model’s pain were evaluated across the four runs.

Results

Although the ratings of the model’s pain remained constant over time, we found neural habituation in the bilateral anterior/midinsular cortex, the posterior midcingulate extending to dorsal posterior cingulate cortex, the supplementary motor area, the cerebellum, the right inferior parietal lobule, and the left superior frontal gyrus, stretching to the pregenual anterior cingulate cortex. The participant’s prior pain experience did neither affect their ratings of the model’s pain nor their maintenance of BOLD activity in areas associated with empathy. Interestingly, participants with high trait personal distress and fantasy tended to show less habituation in the anterior insula.

Conclusion

Neural structures showed a decrease of the BOLD signal, indicating habituation over the course of 45 minutes. This can be interpreted as a neuronal mechanism responding to the repeated exposure to pain depictions, which may be regarded as functional in a range of contexts.     

Working Memory in the Processing of the Iowa Gambling Task: An Individual Differences Approach

The Iowa Gambling Task (IGT) is a sequential learning task in which participants develop a tendency towards advantageous options arising from the outcomes associated with their previous decisions. The role of working memory in this complex task has been largely debated in the literature. On one hand, low working memory resources lead to a decrease in the number of advantageous decisions and make a significant part of participants unable to report explicitly which options are the most profitable. On the other hand, several studies have shown no contribution of working memory to the IGT decision patterns. In order to investigate this apparent incompatibility of results, we used an individual differences approach, which has proven an effective method to investigate the role of working memory in cognition. We compared the IGT decision patterns of participants as a function of their working memory capacity (WMC). As expected, contrary to low WMC participants, high WMC participants developed a tendency towards advantageous decisions. These findings lead us to discuss the role of WMC in decision making tasks.     

Emotion-Motion Interactions in Conversion Disorder: An fMRI Study

Objectives

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients.

Methods

An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups.

Results

We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the ‘freeze response’ to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area).

Conclusions

In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.     

Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

Background

Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors.

Methods/Principal Findings

To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG.

Conclusions

Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation.     

Glutathione-S-Transferase Activity in the Brain: Species, Sex, Regional, and Age Differences

Abstract: Glutathione- S -transferase activity in the brain of male mammals (rat and mouse) was found to be relatively lower than in that of females. In contrast, the male aves (pigeon, kite, vulture, and crow) exhibited comparatively higher activity of brain glutathione- S -transferase than the corresponding females. Postnatal development of cytosolic glutathione-S-transferase activity in the rat brain was also investigated. The day-7 rats showed a low activity of 48 nmol/min/mg protein that gradually increased 3.2-fold over the age of 28 days. No striking differences in brain enzyme activities were observed between the 35- and 90-day-old rats. Discrete brain regions of immature rats were found to possess considerable but lower quantities of glutathione- S -transferase activity than those of the adults. The activity increased with the onset of development and attained a steady state after 21 days of age.     

Sequential Coherence in Sentence Pairs Enhances Imagery during Comprehension: An Individual Differences Study

The present study investigates how sequential coherence in sentence pairs (events in sequence vs. unrelated events) affects the perceived ability to form a mental image of the sentences for both auditory and visual presentations. In addition, we investigated how the ease of event imagery affected online comprehension (word reading times) in the case of sequentially coherent and incoherent sentence pairs. Two groups of comprehenders were identified based on their self-reported ability to form vivid mental images of described events. Imageability ratings were higher and faster for pairs of sentences that described events in coherent sequences rather than non-sequential events, especially for high imagers. Furthermore, reading times on individual words suggested different comprehension patterns with respect to sequence coherence for the two groups of imagers, with high imagers activating richer mental images earlier than low imagers. The present results offer a novel link between research on imagery and discourse coherence, with specific contributions to our understanding of comprehension patterns for high and low imagers.     

An fMRI Study of the Neural Systems Involved in Visually Cued Auditory Top-Down Spatial and Temporal Attention

Top-down attention to spatial and temporal cues has been thoroughly studied in the visual domain. However, because the neural systems that are important for auditory top-down temporal attention (i.e., attention based on time interval cues) remain undefined, the differences in brain activity between directed attention to auditory spatial location (compared with time intervals) are unclear. Using fMRI (magnetic resonance imaging), we measured the activations caused by cue-target paradigms by inducing the visual cueing of attention to an auditory target within a spatial or temporal domain. Imaging results showed that the dorsal frontoparietal network (dFPN), which consists of the bilateral intraparietal sulcus and the frontal eye field, responded to spatial orienting of attention, but activity was absent in the bilateral frontal eye field (FEF) during temporal orienting of attention. Furthermore, the fMRI results indicated that activity in the right ventrolateral prefrontal cortex (VLPFC) was significantly stronger during spatial orienting of attention than during temporal orienting of attention, while the DLPFC showed no significant differences between the two processes. We conclude that the bilateral dFPN and the right VLPFC contribute to auditory spatial orienting of attention. Furthermore, specific activations related to temporal cognition were confirmed within the superior occipital gyrus, tegmentum, motor area, thalamus and putamen.     

Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the “classic” default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.     

Patterns of Spontaneous Brain Activity in Amyotrophic Lateral Sclerosis: A Resting-State fMRI Study

By detecting spontaneous low-frequency fluctuations (LFF) of blood oxygen level–dependent (BOLD) signals, resting-state functional magnetic resonance imaging (rfMRI) measurements are believed to reflect spontaneous cerebral neural activity. Previous fMRI studies were focused on the examination of motor-related areas and little is known about the functional changes in the extra-motor areas in amyotrophic lateral sclerosis (ALS) patients. The aim of this study is to investigate functional cerebral abnormalities in ALS patients on a whole brain scale. Twenty ALS patients and twenty age- and sex-matched healthy volunteers were enrolled. Voxel-based analysis was used to characterize the alteration of amplitude of low frequency fluctuation (ALFF). Compared with the controls, the ALS patients showed significantly decreased ALFF in the visual cortex, fusiform gyri and right postcentral gyrus; and significantly increased ALFF in the left medial frontal gyrus, and in right inferior frontal areas after grey matter (GM) correction. Taking GM volume as covariates, the ALFF results were approximately consistent with those without GM correction. In addition, ALFF value in left medial frontal gyrus was negatively correlated with the rate of disease progression and duration. Decreased functional activity observed in the present study indicates the underlying deficits of the sensory processing system in ALS. Increased functional activity points to a compensatory mechanism. Our findings suggest that ALS is a multisystem disease other than merely motor dysfunction and provide evidence that alterations of ALFF in the frontal areas may be a special marker of ALS.     

Functional Activation during the Rapid Visual Information Processing Task in a Middle Aged Cohort: An fMRI Study

The Rapid Visual Information Processing (RVIP) task, a serial discrimination task where task performance believed to reflect sustained attention capabilities, is widely used in behavioural research and increasingly in neuroimaging studies. To date, functional neuroimaging research into the RVIP has been undertaken using block analyses, reflecting the sustained processing involved in the task, but not necessarily the transient processes associated with individual trial performance. Furthermore, this research has been limited to young cohorts. This study assessed the behavioural and functional magnetic resonance imaging (fMRI) outcomes of the RVIP task using both block and event-related analyses in a healthy middle aged cohort (mean age = 53.56 years, n = 16). The results show that the version of the RVIP used here is sensitive to changes in attentional demand processes with participants achieving a 43% accuracy hit rate in the experimental task compared with 96% accuracy in the control task. As shown by previous research, the block analysis revealed an increase in activation in a network of frontal, parietal, occipital and cerebellar regions. The event related analysis showed a similar network of activation, seemingly omitting regions involved in the processing of the task (as shown in the block analysis), such as occipital areas and the thalamus, providing an indication of a network of regions involved in correct trial performance. Frontal (superior and inferior frontal gryi), parietal (precuenus, inferior parietal lobe) and cerebellar regions were shown to be active in both the block and event-related analyses, suggesting their importance in sustained attention/vigilance. These networks and the differences between them are discussed in detail, as well as implications for future research in middle aged cohorts.     

Brain Deactivation in the Outperformance in Bimodal Tasks: An fMRI Study

While it is known that some individuals can effectively perform two tasks simultaneously, other individuals cannot. How the brain deals with performing simultaneous tasks remains unclear. In the present study, we aimed to assess which brain areas corresponded to various phenomena in task performance. Nineteen subjects were requested to sequentially perform three blocks of tasks, including two unimodal tasks and one bimodal task. The unimodal tasks measured either visual feature binding or auditory pitch comparison, while the bimodal task required performance of the two tasks simultaneously. The functional magnetic resonance imaging (fMRI) results are compatible with previous studies showing that distinct brain areas, such as the visual cortices, frontal eye field (FEF), lateral parietal lobe (BA7), and medial and inferior frontal lobe, are involved in processing of visual unimodal tasks. In addition, the temporal lobes and Brodmann area 43 (BA43) were involved in processing of auditory unimodal tasks. These results lend support to concepts of modality-specific attention. Compared to the unimodal tasks, bimodal tasks required activation of additional brain areas. Furthermore, while deactivated brain areas were related to good performance in the bimodal task, these areas were not deactivated where the subject performed well in only one of the two simultaneous tasks. These results indicate that efficient information processing does not require some brain areas to be overly active; rather, the specific brain areas need to be relatively deactivated to remain alert and perform well on two tasks simultaneously. Meanwhile, it can also offer a neural basis for biofeedback in training courses, such as courses in how to perform multiple tasks simultaneously.