Young female participants show blunted placebo effects associated with blunted responses to a cue predicting a safe stimulus in the right dorsolateral prefrontal cortex.

Discrimination of cues predicting non-nociceptive/nociceptive stimuli is essential for predicting whether a non-painful or painful stimulus will be administered and for eliciting placebo/nocebo (pain reduction/pain enhancement) effects. Dysfunction of the neural system involved in placebo effects has been implicated in the pathology of chronic pain, while female sex is one of the important risk factors for development of chronic pain in young adults. The dorsolateral prefrontal cortex (dl-PFC) is suggested to be involved in placebo effects and is sensitive to sex and age. In this study, to examine the neural mechanisms by which sex and age alter placebo and nocebo effects, we analyzed cerebral hemodynamic activities in the dl-PFC in different sex and age groups during a differential conditioning task. During the training session, two different sounds were followed by low- and high-intensity electrical shocks. In the following recording session, electrical shocks, the intensity of which was mismatched to the sounds, were occasionally administered to elicit placebo and nocebo effects. In young female participants, both placebo effects and hemodynamic responses to the conditioned sounds in the right dl-PFC were significantly lower than those in elderly female participants, while there were no age differences in male participants. The hemodynamic responses to the sound paired with the safe stimulus in the right dl-PFC were significantly correlated with placebo effects, except in the young female group. These results suggest that blunted placebo effects in the young female participants are ascribed to blunted responses to the sound associated with the safe stimulus in the right dl-PFC, and that sex- and age-related factors may alter the responsiveness of the right dl-PFC to associative cues predicting a safe stimulus.

Time-course of physical properties of the psoas major muscle after exercise as assessed by MR elastography.

This study aimed to analyze the time-course of the physical properties of the psoas major muscle (PM) before and after exercise using magnetic resonance elastography (MRE). Muscle stiffness is one of the important properties associated with muscle function. However, there was no research on the stiffness of the PM after exercise. In this study, we investigated time-course changes of the shear modulus of the PM after exercise. Furthermore, T2 values and apparent diffusion coefficient (ADC), as the additional information associated with muscular physical properties, were also measured simultaneously. Healthy young male volunteers were recruited in this study (n = 9) and they were required to perform a hand-to-knee isometric and unilateral exercise (left side). At each time-point before and after exercise, a set of 3 types of MR scans to measure multiple physical properties of the PM [shear modulus (MRE), T2 values, and ADC] were repeatedly taken. On day 1, a single set MR scan was taken before exercise (pre-exercise MR scan), and 6 sets MR scans were taken (5.5 to 38.0 min after exercise). After about 10-min rest (46.0 to 56.0 min after exercise), 4 sets MR scans were taken (57.5 to 77.0 min after exercise). About 10-min rest was taken again (85.0-95.0 min after exercise), 4 sets MR scans were taken (96.5 to 116.0 min after exercise). On days 2 and 7, a single set MR scan (MRE, T2 value, and ADC) was taken on each experimental day. The data were analyzed as relative changes (%) of the given parameters to the pre-exercise values. The results indicated significant decreases in PM shear modulus up to about 30 min after exercise. Then, it gradually increased and showed significant increases at about 100 min after exercise compared to that before exercise. T2 values and ADC showed significant increases up to about 65 min after exercise compared to those before exercise, and then returned to the pre-exercise values. On days 2 and 7, all values showed no significant changes compared to the pre-exercise values. This study is the first to report the time-course of the physical properties of the PM after exercise.

Examination of the Prefrontal Cortex Hemodynamic Responses to the Fist-Edge-Palm Task in Naïve Subjects Using Functional Near-Infrared Spectroscopy.

The Fist-Edge-Palm (FEP) task, a manual hand task, has been used to detect frontal dysfunctions in clinical situations: its performance failures are observed in various prefrontal cortex (PFC)-related disorders, including schizophrenia. However, previous imaging studies reported that the performance of the FEP task activated motor-related areas, but not the PFC. Here, we aimed to investigate the relationships between the performance of the FEP task and PFC functions. Hemodynamic activity in the PFC, including the dorsolateral PFC (area 46) and frontal pole (area 10), was recorded. Healthy young subjects performed the FEP task as well as a palm tapping (PT) task (control task) three times. The subjects also completed a Wisconsin Card Sorting Test (WCST) and Schizotypal Personality Scale (STA) questionnaire. We found that hemodynamic activity (Oxy-Hb) in the PFC increased in the first trial of the FEP task but decreased considerably in the second and third trials compared to the PT task. The number of performance errors in the FEP task also decreased in the second and third trials. Error reduction (i.e., learning) in the FEP task between the first and second trials was negatively correlated with schizotypal trait and the number of perseveration errors in the WCST. Furthermore, changes in the PFC hemodynamic activity between the first and second trials were positively correlated with error reduction in the FEP task between the first and second trials, and negatively correlated with the number of perseveration errors in the WCST. These results suggest that learning in the FEP task requires PFC activation, which is negatively associated with perseveration errors in the WCST. The results further suggest that the FEP task, in conjunction with near-infrared spectroscopy, may be useful as a diagnostic method for various disorders with PFC dysfunction.

Impaired hemodynamic activity in the right dorsolateral prefrontal cortex is associated with impairment of placebo analgesia and clinical symptoms in postherpetic neuralgia.

The dorsolateral prefrontal cortex (dlPFC) is functionally linked to the descending pain modulation system and has been implicated in top down pain inhibition, including placebo analgesia. Therefore, functions of the dlPFC may be impaired in patients with chronic pain. Postherpetic neuralgia (PHN) is one of several syndromes with chronic neuropathic pain. In the present study, we investigated possible dysfunction of the dlPFC in chronic pain using patients with PHN. In a conditioning phase, heathy controls (n = 15) and patients with PHN (n = 7) were exposed to low (LF) and high (HF) frequency tones associated with noxious stimuli: weak (WS) and strong (SS) electrical stimulation, respectively. After the conditioning, cerebral hemodynamic activity was recorded from the bilateral dlPFC while the subjects were subjected to the cue tone-noxious electrical stimulation paradigm, in which incorrectly cued noxious stimuli were sometimes delivered to induce placebo and nocebo effects. The results indicated that hemodynamic responses to the LF tone in the right dlPFC was significantly lower in patients with PHN compared to the healthy controls. Furthermore, the same hemodynamic responses in the right dlPFC were correlated with placebo effects. In addition, clinical symptoms of PHN were negatively correlated to cerebral hemodynamic responses in the right dlPFC and magnitudes of the placebo effects. The results suggest that the right dlPFC, which is closely associated with the descending pain modulation system, is disturbed in PHN.