Kouich Takamoto

Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats.

BackgroundEarly life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior.ResultsThree-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test.ConclusionRearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the beam walking test and tended to be positively correlated with activity in the center arena in the open field test. The results suggest that rearing in the enriched environment augmented parvalbumin-positive specific neurons in the basolateral amygdala, which induced behavioral plasticity that was reflected by a decrease in anxiety-like behavior in anxiogenic situations.

Effects of acupuncture on the brain hemodynamics

Acupuncture therapy has been applied to various psychiatric diseases and chronic pain since acupuncture stimulation might affect brain activity. From this point of view, we investigated the effects of acupuncture on autonomic nervous system and brain hemodynamics in human subjects using ECGs, EEGs and near-infrared spectroscopy (NIRS). Our previous studies reported that changes in parasympathetic nervous activity were correlated with number of de-qi sensations during acupuncture manipulation. Furthermore, these autonomic changes were correlated with EEG spectral changes. These results are consistent with the suggestion that autonomic changes induced by needle manipulation inducing specific de-qi sensations might be mediated through the central nervous system, especially through the forebrain as shown in EEG changes, and are beneficial to relieve chronic pain by inhibiting sympathetic nervous activity. The NIRS results indicated that acupuncture stimulation with de-qi sensation significantly decreased activity in the supplementary motor complex (SMC) and dorsomedial prefrontal cortex (DMPFC). Based on these results, we review that hyperactivity in the SMC is associated with dystonia and chronic pain, and that in the DMPFC is associated with various psychiatric diseases with socio-emotional disturbances such as schizophrenia, attention deficit hyperactive disorder, etc. These findings along with the previous studies suggest that acupuncture with de-qi sensation might be effective to treat the various diseases in which hyperactivity in the SMA and DMPFC is suspected of playing a role.

Significant correlation between autonomic nervous activity and cerebral hemodynamics during thermotherapy on the neck

Although local thermotherapy reduces mental stress and neck stiffness, its physiological mechanisms are still not fully understood. We speculated that local thermotherapy exerts its effect, in addition to its direct peripheral effects, through the central nervous system that is involved in controlling stress responses. In the present study, we investigated the effects of a heat- and steam-generating (HSG) sheet on cerebral hemodynamics and autonomic nervous activity using near-infrared spectroscopy (NIRS) and the electrocardiograms (ECGs). Thirteen healthy young female subjects participated in this study. HSG or simple (control) sheets were repeatedly applied to the neck for 120 s with 180 s intervals of rest between applications. During the experiment, brain hemodynamic responses (changes in Oxy-Hb, Deoxy-Hb, and Total-Hb) and autonomic nervous activity based on heart rate variability (HRV) were monitored. Subjective perception of neck stiffness and fatigue was significantly improved after application of the HSG sheet. NIRS findings indicated that the application of HSG sheets decreased Oxy-Hb concentration in the anterior-dorsal region of the medial prefrontal cortex (adMPFC), while increasing parasympathetic nervous activity and decreasing sympathetic nervous activity. Furthermore, changes in Oxy-Hb in the adMPFC were significantly and negatively correlated with those in parasympathetic nervous activity during application of the HSG sheet. These findings suggest that application of the HSG sheet to the neck region induced mental relaxation and ameliorated neck stiffness by modifying activity of the adMPFC.

Cerebral functional imaging using near-infrared spectroscopy during repeated performances of motor rehabilitation tasks tested on healthy subjects

To investigate the relationship between the frontal and sensorimotor cortices and motor learning, hemodynamic responses were recorded from the frontal and sensorimotor cortices using functional near infrared spectroscopy (NIRS) while healthy subjects performed motor learning tasks used in rehabilitation medicine. Whole-head NIRS recordings indicated that response latencies in the anterior dorsomedial prefrontal cortex (aDMPFC) were shorter than in other frontal and parietal areas. Furthermore, the increment rate of the hemodynamic responses in the aDMPFC across the eight repeated trials significantly correlated with those in the other areas, as well as with the improvement rate of task performance across the 8 repeated trials. In the second experiment, to dissociate scalp- and brain-derived hemodynamic responses, hemodynamic responses were recorded from the head over the aDMPFC using a multi-distance probe arrangement. Six probes (a single source probe and 5 detectors) were linearly placed 6 mm apart from each of the neighboring probes. Using independent component analyses of hemodynamic signals from the 5 source-detector pairs, we dissociated scalp- and brain-derived components of the hemodynamic responses. Hemodynamic responses corrected for scalp-derived responses over the aDMPFC significantly increased across the 8 trials and correlated with task performance. In the third experiment, subjects were required to perform the same task with and without transcranial direct current stimulation (tDCS) of the aDMPFC before the task. The tDCS significantly improved task performance. These results indicate that the aDMPFC is crucial for improved performance in repetitive motor learning.

Effects of compression at myofascial trigger points in patients with acute low back pain: A randomized controlled trial.

Although there is some evidence that massage therapy, especially compression at myofascial trigger points (MTrPs), is effective for sub‐acute and chronic low back pain, the effectiveness of massage therapy with compression at MTrPs for acute low back pain has not been studied.

Thermotherapy to the facial region in and around the eyelids altered prefrontal hemodynamic responses and autonomic nervous activity during mental arithmetic

To investigate neural mechanisms of local thermotherapy to reduce mental stress, participants were required to perform mental arithmetic after treatment by a heat- and steam-generating sheet on the facial eyelid region while hemodynamic activity and ECGs were monitored. The results indicated that thermotherapy decreased hemodynamic activity in the anterior dorsomedial prefrontal cortex (aDMPFC) involved in sympathetic activity. Consistently, thermotherapy increased parasympathetic activity while it decreased sympathetic activity. Furthermore, thermotherapy increased hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC) during mental arithmetic. These hemodynamic responses in the DLPFC during mental arithmetic were negatively correlated with that in the aDMPFC during thermotherapy. The results suggest that thermotherapy in the facial eyelid region is useful to ameliorate mental fatigue through its effects on the prefrontal cortex.

Effects of Acupuncture Needling with Specific Sensation on Cerebral Hemodynamics and Autonomic Nervous Activity in Humans

Effective therapeutic factors in acupuncture therapy include specific stimulation points, called acupoints, and specific sensations, called de-qi, that are induced by needling manipulation. Human neuroimaging studies have reported that acupuncture stimulation with de-qi sensations induced specific activity patterns in the brain and modulated autonomic nervous activity. However, acupoints and nonacupoints have been reported to induce de-qi sensations. Thus, it remains unclear whether these physiological responses induced by acupuncture and associated with therapeutic efficacy are related to specific stimulation sites (acupoints) or unique de-qi sensations. This review focuses on the cerebral hemodynamic responses and autonomic nervous activity changes induced by acupuncture stimulation at acupoints and nonacupoints with and without de-qi sensations. We argue that the specific sensations induced by acupuncture are more important than the specific stimulation sites for inducing cerebral hemodynamic and autonomic responses and that autonomic responses during acupuncture, which might be important for therapeutic efficacy, might be mediated though the brain activity changes exemplified by the cerebral hemodynamic responses during acupuncture.

Compression at Myofascial Trigger Point on Chronic Neck Pain Provides Pain Relief through the Prefrontal Cortex and Autonomic Nervous System: A Pilot Study

Compression at myofascial trigger points (MTrPs), known as “ischemic compression,” has been reported to provide immediate relief of musculoskeletal pain and reduce the sympathetic activity that exacerbates chronic pain. We conducted a pilot study to investigate the possible involvement of the prefrontal cortex in pain relief obtained by MTrP compression in the present study, and analyzed the relationships among prefrontal hemodynamic activity, activity of the autonomic nervous system, and subjective pain in patients with chronic neck pain, with and without MTrP compression. Twenty-one female subjects with chronic neck pain were randomly assigned to two groups: MTrP compression (n = 11) or Non-MTrP compression (n = 10). Compression for 30 s was conducted 4 times. During the experiment, prefrontal hemodynamic activity [changes in Oxy-hemoglobin (Hb), Deoxy-Hb, and Total-Hb concentrations] and autonomic activity based on heart rate variability (HRV) were monitored by using near infrared spectroscopy (NIRS) and electrocardiography (ECG), respectively. The results indicated that MTrP compression significantly reduced subjective pain compared with Non-MTrP compression. The spectral frequency-domain analyses of HRV indicated that a low frequency (LF) component of HRV was decreased, and a high frequency (HF) component of HRV was increased during MTrP compression, while LF/HF ratio was decreased during MTrP compression. In addition, prefrontal hemodynamic activity was significantly decreased during MTrP compression compared with Non-MTrP compression. Furthermore, changes in autonomic activity were significantly correlated with changes in subjective pain and prefrontal hemodynamic activity. Along with previous studies indicating a role for sympathetic activity in the exacerbation of chronic pain, the present results suggest that MTrP compression in the neck region alters the activity of the autonomic nervous system via the prefrontal cortex to reduce subjective pain.

Effects of heat steam-generating sheets on the face regions on cerebral hemodynamics, autonomic nervous activity, and facial expression in fatigued subjects

The circadian rhythm of QT interval variability is still unclear, although it is known that QT interval prolongation is a predictor of sudden cardiac death. The aim of present study is to establish a dynamical model between RR interval variability and QT interval variability, and to identify its dynamical parameters in 24-hr circadian rhythms. A linear mathematical dynamical model is established between RR-interval variability and QT-interval variability. The model parameters can be identified using system identification technique. Simulated data show that the mathematical model fit well to the dynamics of QT-interval variability. Eight-young healthy subjects are recruited in the study. The results show that dynamics between RR variability and QT variability is individual-specific,and their dynamical parameters express distinct circadian rhythms. The results suggest that the circadian properties of QT interval dynamics may play a prominent role in sudden cardiac death prevention.

Effects of rearing-conditioning in environmental enrichment on parvalbumin-positive neurons in the amygdala

Emotional disorders are quite often accompanied with various psychiatric diseases and stress disorders, and it is an urgent problem to overcome these disorders for many peoples. Mice and rats exhibit profound emotional disorders such as elevated anxiety after having a status epilepticus (SE) by pilocarpine injection, however, its precise mechanism is not yet clarified. In order to know the pathogenic origin of the emotional disorders, we studied the changes in behavior and brain structures of mice after inducing SE with various conditions. In the present study, we used well-established behavior tests for anxiety, including a light and dark preference tests, an open field test, and an elevated plus maze test. Marked facilitation of anxiety-like behavior were observed in the mice which induced SE for 4.5 h as early as 4-6 days after SE. This emotional change was very stable and still observed 8 months after SE. It is known that SE induced mossy fiber sprouting of granule cells in dentate gyrus as well as a loss of parvalbumin-positive inter neurons in the cerebral cortex and hippocampus. Since mossy fiber sprouting was not observed on 6 days after SE by immunohistochemistry with antineuropeptide Y antibody, the sprouting was unlikely to be a pathogenic change for the emotional disorder. The mice in which SE was terminated at 1 hour by a phenobarbital administration also exhibited marked facilitation of anxiety-like behaviors 2 days after SE, however, this change was reversible and the mice showed a normal behavior 6 days after SE. These results suggested that there were at least two different mechanisms for the appearance of emotional disorder after pilocarpine-induced SE, one was reversible and another was irreversible, and the duration of SE was critical for the selection of mechanisms.