Naho Ichikawa

Association of neural and physiological responses during voluntary emotion suppression.

Recent neuroimaging studies have shown that several prefrontal regions play critical roles in inhibiting activation of limbic regions during voluntary emotion regulation. The present study aimed to confirm prior findings and to extend them by identifying the frontal neural circuitry associated with regulation of peripheral physiological responses during voluntary emotion suppression. Ten healthy female subjects were presented with affectively positive, neutral, and negative pictures in each of an Attending and Suppression task. Regional cerebral blood-flow changes were measured using 15O-water positron emission tomography, and autonomic (heart rate: HR, skin conductance response: SCR) and endocrine (adrenocorticotropic hormone: ACTH) indices were measured during both tasks. The left amygdala and the right anterior temporal pole were activated during the Attending task, whereas activation was observed in the left lateral prefrontal cortex (LPFC), including the adjacent medial prefrontal cortex (MPFC), and medial orbitofrontal cortex (MOFC) during the Suppression task. In the Attending task, activation in the amygdala and MOFC positively correlated with magnitudes of the SCR and ACTH responses. Emotion suppression elicited enhancement of SCR and the strength of the effect positively correlated with activation in the MOFC. These results suggest that the MOFC plays a pivotal role in top-down regulation of peripheral physiological responses accompanying emotional experiences.

Blink before and after you think: Blinks occur prior to and following cognitive load indexed by pupillary responses

Pupil dilation and blinks provide complementary, mutually exclusive indices of information processing. Though each index is associated with cognitive load, the occurrence of a blink precludes the measurement of pupil diameter. These indices have generally been assessed in independent literatures. We examine the extent to which these measures are related on two cognitive tasks using a novel method that quantifies the proportion of trials on which blinks occur at each sample acquired during the trial. This measure allows cross-correlation of continuous pupil-dilation and blink waveforms. Results indicate that blinks occur during early sensory processing and following sustained information processing. Pupil dilation better reflects sustained information processing. Together these indices provide a rich picture of the time course of information processing, from early reactivity through sustained cognition, and after stimulus-related cognition ends.

Imaging brain and immune association accompanying cognitive appraisal of an acute stressor.

Acute stress elicits multiple responses in autonomic, endocrine, and immune systems. Cognitive appraisal is believed to be one important modulator of such stress responses. To investigate brain substrates of crosstalks between the homeostasis-maintaining systems accompanying appraisal of stressor controllability, we simultaneously recorded regional cerebral blood flow (rCBF) using 15O-water positron emission tomography, cardiovascular indices (heart rate (HR) and blood pressure (BP)), neuroendocrine indices (concentrations of epinephrine, norepinephrine, and adrenocorticotropic hormone (ACTH) in blood), and immune indices (proportions of subsets of lymphocytes (NK cells, helper T cells, cytotoxic T cells, and B cells) in blood), in 11 male subjects who performed a mental arithmetic task with either high controllability (HC) and low controllability (LC). The LC task resulted in less sense of control in subjects than the HC task. Significant increases of rCBF in the medial and lateral orbitofrontal cortices (OFC), and in the medial and lateral prefrontal cortices (MPFC, LPFC) were observed by subtracting the HC task from the LC task. More importantly, significant positive correlations between rCBF and HR, BP, and NK cells were commonly found in the OFC and MPFC during the LC tasks, but not during the HC tasks. The present results showed for the first time that the prefrontal neural network including the OFC and MPFC might be one pivotal region for bi-directional functional association between the brain and peripheral autonomic and immune activities accompanying appraisal of an acute stressor.

Brain and autonomic association accompanying stochastic decision-making

To examine the functional association between brain and autonomic activities accompanying decision-making, we simultaneously recorded regional cerebral blood flow using (15)O-water positron emission tomography and event-related brain potentials (ERPs) time-locked to feedback of reward and punishment, as well as cardiovascular parameters, during a stochastic decision-making task. We manipulated the uncertainty of outcomes in the task; specifically, we compared a condition with high predictability of reward/punishment (contingent-reward condition) and a condition with low predictability of reward/punishment (random-reward condition). The anterior cingulate cortex (ACC) was commonly activated in both conditions. Compared with the contingent-reward condition, the orbitofrontal and right dorsolateral prefrontal cortices and dorsal striatum were activated in the random-reward condition, where subjects had to continue to seek contingency between stimuli and reward/punishment. Activation of these brain regions correlated with a positive component of ERPs locked to feedback signals (feedback-related positivity), which showed an association with behavioral decision-making in the contingent-reward condition. Furthermore, cardiovascular responses were attenuated in the random-reward condition, where continuous attention and contingency monitoring were needed, and such attenuation of cardiovascular responses was mediated by vagal activity that was governed by the rostral ACC. These findings suggest that the prefrontal-striatal network provides a neural basis for decision-making and modulation over the peripheral autonomic activity accompanying decision-making.

Regulation of natural killer cell redistribution by prefrontal cortex during stochastic learning.

Acute stress elicits redistribution of lymphocyte subsets, especially natural killer (NK) cells, probably for preparatory defense against potential invasion of antigens in fight-flight situations. We previously reported that regulation of lymphocyte redistribution is based on the evaluation of the controllability of a stressor (Kimura, K., Ohira, H., Isowa, T., Matsunaga, M., Murashima, S. 2007. Regulation of lymphocytes redistribution via autonomic nervous activity during stochastic learning. Brain Behav. Immun. 21, 921-934; Ohira, H., Isowa, T., Nomura, M., Ichikawa, N., Kimura, K., Miyakoshi, M., Iidaka, T., Fukuyama, S., Nakajima, T., Yamada, J. 2008. Imaging brain and immune association accompanying cognitive appraisal of an acute stressor. Neuroimage 39, 500-514). Specifially, lymphocyte redistribution is somewhat attenuated when a stressor is uncontrollable, probably to save biological energy in a situation where appropriate coping is unclear. We infer that this phenomenon might reflect top-down regulation over peripheral immune function by higher-ordered brain regions. To investigate the neural basis of such a phenomenon, we simultaneously recorded regional cerebral blood flow using (15)O-water positron emission tomography and cardiovascular (blood pressure and heart rate), neuroendocrine (epinephrine, norepinephrine, and adrenocorticotropic hormone), and immune (proportions of NK cells and helper T cells in blood) indices in 16 male subjects who performed a stochastic learning task with manipulation of controllability (controllable vs. uncontrollable). Consistent with previous studies, the proportion of peripheral NK cells was attenuated in an uncontrollable stress condition. The dorsolateral prefrontal and orbitofrontal cortices were activated in the uncontrollable situation but not in the controllable condition, and additionally, these prefrontal brain regions significantly correlated with the degree of redistribution of NK cells in the uncontrollable condition. The results of the study suggest these brain regions are involved in both evaluation of the controllability of a stressor and regulation of immune function.

Feeling bad about screwing up: emotion regulation and action monitoring in the anterior cingulate cortex

This study examined neural features of emotional responses to errors. We specifically examined whether directed emotion regulation of negative emotion associated with error modulates action-monitoring functions of anterior cingulate cortex, including conflict monitoring, error processing, and error prevention. Seventeen healthy adults performed a continuous performance task during assessment by fMRI. In each block, participants were asked either to increase or decrease their negative emotional responses or to react naturally after error commission. Emotion regulation instructions were associated with modulation of rostral and dorsal anterior activity and of their effective connectivity following errors and conflict. Cingulate activity and connectivity predicted subsequent errors. These data may suggest that responses to errors are affected by emotion and that aspects of emotion and cognition are inextricably linked, even during a nominally cognitive task.

Eyeblink Activity as an Index of Cognitive Processing: Temporal Distribution of Eyeblinks as an Indicator of Expectancy in Semantic Priming

Eyeblink activity was examined as a psychophysiological index of cognitive processing during a typical semantic priming task. To examine the expectancy-induced effects, the proportion of semantically related pairs was controlled. 8 undergraduates engaged in a lexical decision task for target words. Each condition differed in target type (Semantically Related with prime vs Unrelated vs Nonword) and proportion of Semantically Related pairs (High vs Low). As a result, the temporal distribution of blinks was clearly influenced by the semantic priming effect. The peak of blink bursts, which is correlated with the end of cognitive processing, occurred the fastest in the semantically Related and High proportion condition. While blink latency showed larger individual differences, the temporal distribution of blinks was suggested as a more efficient index of cognitive processing.

Subjective and model-estimated reward prediction: Association with the feedback-related negativity (FRN) and reward prediction error in a reinforcement learning task

In this study, we examined whether the feedback-related negativity (FRN) is associated with both subjective and objective (model-estimated) reward prediction errors (RPE) per trial in a reinforcement learning task in healthy adults (n=25). The level of RPE was assessed by 1) subjective ratings per trial and by 2) a computational model of reinforcement learning. As results, model-estimated RPE was highly correlated with subjective RPE (r=.82), and the grand-averaged ERP waves based on the trials with high and low model-estimated RPE showed the significant difference only in the time period of the FRN component (p<.05). Regardless of the time course of learning, FRN was associated with both subjective and model-estimated RPEs within subject (r=.47, p<.001; r=.40, p<.05) and between subjects (r=.33, p<.05; r=.41, p<.005) only in the Learnable condition where the internal reward prediction varied enough with a behavior-reward contingency.

Polymorphism of the serotonin transporter gene modulates brain and physiological responses to acute stress in Japanese men

A short (S) variant, compared to a long (L) variant, of the promoter region of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been related to emotional hyper-reactivity. We tested whether the 5HTTLPR could modulate acute stress responses in the brain and, the cardiovascular and neuroendocrine systems. Ten Japanese male participants carrying double copies of the S alleles and 10 Japanese males carrying S and L alleles conducted a mental arithmetic task, and their regional cerebral blood flow by 15O positron emission tomography and cardiovascular and neuroendocrine parameters were measured. During the acute stress task, the participants with the SS alleles showed stronger reactivity in blood pressure and secretion of epinephrine, compared to the participants with the SL and LL alleles. Furthermore, the SS carriers showed greater activation in stress-related brain regions such as the hypothalamus, cerebellum, midbrain, and pulvinar compared to the SL and LL carriers during the acute stress task. The present findings indicated that the S allele of the 5HTTLPR is associated with greater brain and physiological reactivity to acute stress in Japanese men.

Neural and sympathetic activity associated with exploration in decision-making: further evidence for involvement of insula

We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition) and a condition with high uncertainty of gain/loss (random-reward condition). Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET), and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.