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.

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.

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.

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.

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.

[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases].

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.