The contralateral effects of anticipated stimuli on brain activity measured by ERP and fMRI.

The present study examined the effects of unilateral stimulus presentation on the right hemisphere preponderance of the stimulus-preceding negativity (SPN) in the event-related potential (ERP) experiment, and aimed to elucidate whether unilateral stimulus presentation affected activations in the bilateral anterior insula in the functional magnetic resonance imaging (fMRI) experiment. Separate fMRI and ERP experiments were conducted using visual and auditory stimuli by manipulating the position of stimulus presentation (left side or right side) with the time estimation task. The ERP experiment revealed a significant right hemisphere preponderance during left stimulation and no laterality during the right stimulation. The fMRI experiment revealed that the left anterior insula was activated only in the right stimulation of auditory and visual stimuli whereas the right anterior insula was activated by both left and right stimulations. The visual condition retained a contralateral dominance, but the auditory condition showed a right hemisphere dominance in a localized area. The results of this study indicate that the SPN reflects perceptual anticipation, and also that the anterior insula is involved in its occurrence.

Relationship between Facial Color Changes and Psychological Problems Associated with Lower Back Pain.

Background and Objectives: The aim of this study was to determine whether a non-contact sensor that detects complexion changes can be used to assess the psychological state of patients with chronic lower back pain (LBP). Materials and Methods: Twenty-six patients with LBP (LBP group; mean age = 68.0 ± 13.9 years) and 18 control subjects without LBP (control group; mean age = 60.8 ± 16.1 years) were included in the study. All the subjects in the two groups wore headphones when asked LBP-related and LBP-unrelated questions. During questioning, the facial image of the subjects was captured using a video camera, and the complexion of the subjects was converted into red, green, and blue (RGB) values. RGB correlation coefficients (RGBCCs; range: 0-1) represent the difference in complexion between LBP-related and LBP-unrelated questions. A high RGBCC indicates that the brain is more activated by LBP-related questions than by LBP-unrelated questions. We also noted the scores of subjects on the Numerical Rating Scale (NRS), Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). Results: There were no significant differences in RGBCC between the control and LBP groups (0.64 versus 0.56, p = 0.08). In the LBP group, no correlation was observed between RGBCC and each examination item of NRS, JOABPEQ, and HADS. In contrast, a correlation was observed between RGBCC and the rumination subscale of PCS in the LBP group (Spearman's rank correlation coefficient = 0.40, p = 0.04). Conclusions: The complexion of patients with catastrophic thinking changes when the patients are asked LBP-related questions.

Effects of negativity bias on amygdala and anterior cingulate cortex activity in short and long emotional stimulation paradigms.

Recent functional studies have reported that amygdala and anterior cingulate cortex (ACC) dysfunction is a reproducible and good biomarker of major depressive disorder. When we use the activation of these regions as biomarkers of major depressive disorder, a short and simple stimulation paradigm could be preferable to reduce the burden on patients. However, negativity bias, which is the phenomenon by which negative stimuli are processed noticeably faster than positive stimuli, might affect the activation of these regions in the short and simple stimulation paradigm. Few studies have reported the relationship between the length of the stimulation paradigm and activation in the amygdala and ACC from the viewpoint of negativity bias. The purpose of this study was to assess the effects of negativity bias on the amygdala and ACC as a result of manipulating the stimulation paradigm (short-simple vs. long-complex conditions) on presenting pleasant and unpleasant pictures. Image analyses showed that the amygdala was activated during unpleasant picture presentation, regardless of the task length, but no activation was observed during pleasant picture presentation under the short-simple condition. The ACC was deactivated in both the short-simple and long-complex conditions. Region of interest analyses showed that the effect of negativity bias was prominent for the amygdala in the short-simple condition and for the ACC in the long-complex condition. In conclusion, the effects of negativity bias depend on neural regions, including the amygdala and ACC, and therefore, we should consider these effects while designing stimulation paradigms.

Voice, rhythm, and beep stimuli differently affect the right hemisphere preponderance and components of stimulus-preceding negativity.

The present study investigated whether auditory stimuli with different contents affect right laterality and the components of stimulus-preceding negativity (SPN). A time-estimation task was performed under voice, rhythm, beep, and control conditions. The SPN interval during which participants anticipated the stimulus was divided into quarters to define early and late SPNs. Early and late components of SPN were also extracted using a principal component analysis. The anticipation of voice sounds enhanced the early SPN and the early component, which reflected the anticipation of language processing. Beep sounds elicited the right hemisphere preponderance of the early component, the early SPN, and the late SPN. The rhythmic sound tended to attenuate the amplitude compared with the two other stimuli. These findings further substantiate the existence of separate early and late components of the SPN. In addition, they suggest that the early component reflects selective anticipatory attention toward differing types of auditory feedback.

Preparing for saliencies: Emotional expectations under probabilistically and aversively salient situations.

In humans, the expectation process in decision making has not been as thoroughly investigated as the evaluation process. The present study focused on the interaction between probabilistic saliency and motivational saliency during expectation and evaluation periods using stimulus-preceding negativity (SPN) and reward positivity (RewP). Twenty healthy participants performed a modified monetary-incentive delay task under reward-approach and punishment-avoidance conditions. Each condition was characterized by the likely outcome (reward only, punishment only) to manipulate motivational saliency. The task difficulty was regulated to control for probabilistic saliency, and the error trial was set as a probabilistically salient event (75% correct, 25% error). The results demonstrated that there was a larger SPN in the 25%-error trial than the 75%-correct trial and that it was left hemisphere predominant. Furthermore, there was an interaction between probabilistic and motivational saliency such that the SPN in the error trial was larger in the punishment-avoidance than in the reward-approach condition at Fz and at the right hemisphere. In contrast, RewP was only significantly different from zero in the 75%-correct trial in the reward-approach condition. These results confirm that the SPN increases with probabilistic saliency and that probabilistically salient events may intervene in the motivational saliency of the outcome; furthermore, that RewP reflects the weighted positive value of the outcome for reward but not the weighted negative value of the outcome for punishment. We discuss the interaction between probabilistic saliency and motivational saliency on SPN and its left hemisphere predominance based on the functions of the insular cortex.

Possible mechanisms of hypothermia after inhibition of the median or dorsal raphe nucleus of freely moving rats.

We previously reported that tetrodotoxin (TTX) perfusion into the median raphe nucleus (MRN), which contains the cell bodies of serotonin (5-HT) neurons, induced a considerable body temperature reduction under normal and low ambient temperatures (23 and 5°C, respectively) in freely moving rats but showed no such effect under high ambient temperature (35°C). In the present study, we aimed to determine the mechanism(s) of body temperature reduction after TTX perfusion into the MRN by measuring tail skin temperature (an index of heat loss), heart rate (an index of heat production), and locomotor activity (Act) under normal ambient temperature (23°C). We performed similar experiments in the dorsal raphe nucleus (DRN), another area containing cell bodies of 5-HT neurons, to compare any functional differences with the MRN. TTX perfusion into the MRN or DRN induced significant hypothermia (from 37.4±0.2 to 33.7±0.4°C or from 37.4±0.1 to 34.5±0.4°C, respectively; P<0.001) with increased tail skin temperature (from 26.1±0.8 to 31.1±1.3°C or from 26.3±0.9 to 31.7±0.4°C, respectively; P<0.001), but no change in heart rate. However, TTX perfusion into the MRN or DRN differentially affected Act. TTX perfusion into the MRN induced hyperactivity (from 10.7±4.6 to 67.6±25.1 counts/min; P<0.01), whereas perfusion into the DRN induced immobility. Thus, the 5-HT projections from the MRN and DRN may play similar roles in thermoregulation, both in the heat production system and in the heat loss system, but their roles in the regulation of Act might be distinct and opposite.

Source analysis of stimulus-preceding negativity constrained by functional magnetic resonance imaging.

The stimulus-preceding negativity (SPN) is an event-related potential (ERP) reflecting anticipation. The anterior insular cortex is assumed to be one of the physiological sources of the SPN. However, the precise neural substrates of the SPN have yet to be confirmed. We therefore performed separate functional magnetic resonance imaging (fMRI) and ERP studies using the same time estimation task, followed by fMRI-constrained ERP source analysis. Dipole locations were determined by the fMRI results, while the time courses of dipole activities were modeled by the ERP data. Analysis revealed that the right anterior insula was significantly activated before delivery of the feedback stimulus, whereas the left anterior insula was not, and that the SPN mainly arose from four groups of brain regions related to, respectively: (1) the salience network, (2) reward expectation, (3) perceptual anticipation, and (4) arousal. The results suggest that the SPN pertains to multiple brain functions with complex interactions.

Facial, verbal, and symbolic stimuli differently affect the right hemisphere preponderance of stimulus-preceding negativity.

The present study investigated whether the right hemisphere preponderance of stimulus-preceding negativity (SPN) was affected by different categories of visual feedback stimulus. A time estimation task was performed with facial, verbal, symbolic, and no-feedback conditions. A principal component analysis identified an early component of SPN in addition to a late component that was morphologically similar to the original SPN. Motivational scores in the verbal and facial conditions were higher than that in the symbolic condition. Significant right hemisphere preponderance of the late SPN was observed in the symbolic condition but not in the verbal condition, whereas right hemisphere preponderance of the early SPN was observed in the facial condition. The right hemisphere preponderance was influenced by the category of visual feedback stimulus through stimulus-related activation and the effect of the motivational level.

Waiting to perceive: reward or punishment?

Neurobiological accounts of the dopaminergic reward system and psychophysiological explanations of the error-related negativity (ERN) both emphasize the comparison of expected versus actual outcome for voluntary actions. The stimulus-preceding negativity (SPN) constitutes a valuable index of that expectation, in that it has high temporal resolution and its anatomical, cognitive and affective correlates have been reasonably well characterized. This review links established findings regarding the SPN to current research on the dorsal and ventral attention systems, somatic marker hypothesis, ERN, the reward system and relevant neurological and psychiatric findings. Special emphasis is given to the pre-feedback SPN and its origin within anterior insular cortex.

The role of the right anterior insular cortex in the right hemisphere preponderance of stimulus-preceding negativity (SPN): an fMRI study.

The stimulus-preceding negativity (SPN) is an event-related potential that reflects emotional and perceptual anticipation. The SPN is characterized by a right hemisphere preponderance in amplitude, and previous studies suggest that activity in the insular cortex might contribute to the amplitude of the SPN. Although the insula might contribute to the SPN's occurrence, the exact role of the insula in the pattern of SPN right hemisphere dominance remains unclear. In the present study, we manipulated task difficulty and brain activation was measured using event-related fMRI, to examine the relationship between insula functioning and the right hemisphere preponderance of the SPN. Twenty-three participants performed a time estimation task, in which they had to press a button when they thought a predetermined time had elapsed. Three seconds after pressing the button, a feedback stimulus was presented, informing subjects as to whether their response was correct, too early, or too late. There were four experimental conditions: easy, moderate, difficult, and no feedback. The fMRI results showed significantly increased activation in the bilateral insular cortex during the pre-feedback anticipation phase, in which the subjects prepare to pay attention to the occurrence of feedback stimuli. In addition, in the Difficult-Easy and Difficult-Moderate contrasts, significantly increased activations of the right anterior insula were demonstrated, suggesting the possibility that this area does underlie the SPN right hemisphere preponderance. Because the right anterior insula is related to awareness of viscerosensory information, the SPN right hemisphere preponderance might itself be related to the awareness of interoceptive information that precedes feedback stimuli.

Effect of chronic cold exposure on noradrenergic modulation in the preoptic area of thermoregulation in freely moving rats.

For this study, we compared the thermoregulatory involvement of noradrenaline (NA) in the medial preoptic area (mPOA) of non-cold acclimated rats to that of cold-acclimated rats. We quantified the release of NA in the mPOA during 3 h cold (5 degrees C) exposure in room-temperature-acclimated rats (RA group, kept at 23 degrees C for 2 weeks) and cold-acclimated rats (CA group, kept at 5 degrees C for 2 weeks). We concurrently monitored the core body temperature (Tc), heart rate (HR), and tail skin temperature (Tt). Cold exposure significantly increased Tc and HR, and decreased Tt in both groups. However, the cold-induced increase of the extracellular NA levels in mPOA was observed only in the RA group: not in the CA group. To elucidate these different results in NA levels further, and to evaluate participation of the mPOA in thermoregulation in the cold, we measured Tc, HR, and Tt during perfusion of alpha-adrenoceptor antagonist phenoxybenzamine during cold exposure (5 degrees C). This pharmacological procedure induced marked hypothermia, with decreases in HR only in the RA group; no changes were observed in Tc or any thermoregulatory parameter in the CA group. These results suggest that NA in the mPOA modulates heat production in response to acute cold stress in the RA group. However, this thermoregulatory action of NA in the mPOA was attenuated in the CA group.

Effects of monetary reward and punishment on stimulus-preceding negativity.

This study examined the effects of emotional valence on stimulus-preceding negativity (SPN) using reward and fine. A time estimation task under reward, punishment, combined, and control conditions was performed. Participants were rewarded for accurate responses in the reward condition, and were fined for incorrect estimations in the punishment condition. in the combined condition, correct responses were rewarded and incorrect responses were fined. In the control condition, neither a reward nor fine was used. Results showed a significant interaction of condition x hemisphere. The SPN at the left hemisphere was increased in the reward condition. For the punishment effect, although it evoked right hemisphere dominance, no conditional difference was apparent at the right hemisphere. These results suggest that the SPN is affected by positive emotion: The left hemisphere activation might represent a pleasant emotion accompanying monetary gain.

Activation of insular cortex and subcortical regions related to feedback stimuli in a time estimation task: an fMRI study.

We used functional magnetic resonance imaging to investigate brain activity related to motivational function of informative feedback stimuli in a time estimation task. In that task, subjects pressed a button as a response 3 s after a cue stimulus; a visual feedback stimulus was presented 2 s after the response. In a true feedback condition, subjects received true information (informative feedback) about their time-estimation performance. In the false feedback condition, the same visual signs were used, but they were presented randomly. Therefore, they were not related to actual performance. In the 20 subjects examined, higher hemodynamic responses were identified in the insular cortex, the thalamus, and the striatum by comparing the true feedback condition to the false feedback condition. The time estimation performance and subjective score on motivation were also markedly higher in the true feedback condition. The anterior insular cortex and striatal regions are known to be involved in motivational and reward processing. Therefore, the hemodynamic responses observed in this study suggest that the motivational function of the feedback information is a crucial factor for behavioral learning; it is considered that the informative feedback might serve as an implicit reward for humans.

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures.

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.

Different mechanisms involved in interhemispheric transfer of visuomotor information.

Twenty-one subjects underwent event-related fMRI while carrying out a simple visuomotor task in which they responded to stimuli flashed either onto the right visual field, onto the left visual field, or onto both visual fields at once. The aim of this study was to clarify areas of brain activity associated with crossed-uncrossed differences (CUD) and to investigate differences of the brain activity between CUD and redundancy gain. An intriguing brain activation related to CUD was found in the genu of the corpus callosum (CC). The sites of activation related to redundancy gain were the extrastriate cortex and the cingulate cortex. Our results suggested that CUD depended on the interhemispheric transfer via the CC, and that CUD and redundancy gain involved different brain mechanisms.

Effects of reward and stimulus modality on stimulus-preceding negativity.

The present study aimed to investigate the effect of reward and stimulus modality of feedback stimuli on the stimulus-preceding negativity. A time estimation task was performed, and (a) the motivational level (reward and no-reward) and (b) the stimulus modality (auditory and visual) of feedback stimuli were manipulated. The results demonstrated that the stimulus-preceding negativity was larger in the reward than in the no-reward condition, especially at the right frontal and the left occipito-temporal areas. Moreover, the stimulus-preceding negativity prior to visual feedback stimuli was larger over the occipital areas than in the auditory condition. In contrast, at the prefrontal areas, the amplitude prior to auditory feedback stimuli was larger than in the visual condition. Our results revealed that the prefeedback stimulus-preceding negativity was independently influenced by stimulus modality and motivation.

Neural correlates of phoneme-to-grapheme conversion.

In writing to dictation, one mode of language processing is based on the knowledge of how to convert speech sounds to the corresponding letters, namely, phoneme-to-grapheme conversion (phonological mode). Little is known about the neural substrates of the phoneme-to-grapheme conversion. Our study aims to clarify the neural substrates of phoneme-to-grapheme conversion in writing to dictation using functional magnetic resonance imaging. We employed Japanese as the stimulus language because in Japanese, one phoneme is represented by one grapheme (kana) and vice versa. Functional magnetic resonance imaging revealed that the left premotor, extending into Broca's area was activated. The present results suggested that the frontal region is required for the conversion of phonemes to graphemes in writing to dictation.

Effects of information and reward on stimulus-preceding negativity prior to feedback stimuli.

The purpose of the present study was to investigate the effects of informational and motivational level of feedback stimuli on the stimulus-preceding negativity (SPN). In the time estimation task, in which a visual stimulus was presented 3 s after a voluntary movement, (a) the information level (high information and low information) and (b) the motivation level (reward and no-reward) for feedback stimuli were manipulated. Under the high-information condition, subjects received feedback information about (1) correctness (correct or incorrect), (2) direction of error (under- or overestimate), and (3) degree of accuracy (accurate or less accurate) of their time estimation. In the low-information condition, however, they received information about the correctness only. In the reward condition, they received a monetary reward for accurate time estimations but received nothing in the no-reward condition. The results demonstrated a significant interaction of information by motivation level, showing that the SPN amplitude under the reward/high-information was larger than that in the no-reward/high-information condition. The results are discussed in terms of emotional anticipation, taking into consideration the result of self-report that subjects felt to be more motivated when they received precise information.