Effects of inter-stimulus and inter-trial intervals on somatosensory gating.

AIM OF THE STUDY: Sensory gating is a human higher cognitive function that serves to suppress excessive sensory information and prevent brain overactivity. To elucidate this function, a paired-pulse stimulation paradigm has been used while recording electroencephalography (EEG), and evaluated as an amplitude ratio of responses to a second stimulus (S2) over responses to the first stimulus (S1). The present study investigated the effects of the inter-stimulus interval (ISI) and inter-trial interval (ITI) on somatosensory gating using somatosensory-evoked potentials (SEPs). METHODS: In Experiment 1, ISI was set at five conditions: 200, 400, 600, 800, and 1000 ms. In Experiment 2, ITI was set at four conditions: 1, 2, 4, and 8 s. RESULTS: ISI affected the S2/S1 amplitude ratios of P22 and N27 at C3' and N30 at Fz, and these S2/S1 amplitude ratios decreased the most under the 200 and 400-ms conditions. ITI affected the S2/S1 amplitude ratios of P22, N27, and N60 at C3', and especially, the somatosensory gating did not work under the 1-s condition. These results suggest that not all SEP components are modulated in the same manner with changing ISI and ITI. The effects of ISI and ITI independently affected the somatosensory gating. CONCLUSIONS: Based on our findings, preferable parameters are 200-400 ms for ISI and 4 s or longer for ITI to evaluate the functional mechanisms on somatosensory gating in SEPs.

Observations of cold-induced vasodilation in persons with spinal cord injuries.

STUDY DESIGN: Acute experimental study. OBJECTIVES: Cold-induced vasodilation is a local mechanism of protection against frostbite in non-injured persons. We assessed whether an increase in skin blood flow (SkBF) during local cooling (LC) was observed in individuals with spinal cord injuries (SCIs) and if the response patterns differed between region levels or sites. SETTING: Laboratory of Wakayama Medical University and the affiliated clinics, Japan. METHODS: A local cooler device (diameter 4 cm) was placed on the chest (sensate) and right thigh (non-sensate) in persons with cervical (SCIC; n = 9) and thoracolumbar SCIs (SCITL; n = 9). After the surface temperature under the device was controlled at 33 °C for 10 min (baseline), LC (-0.045 °C/s) was applied and the skin temperature was maintained at 15 and 8 °C for 15 min of each stage. SkBF (laser Doppler flowmetry) was monitored using a 1-mm needle-type probe inserted into its center. RESULTS: The percent change in SkBF (%ΔSkBF) on the chest remained unchanged until the end of 15 °C stage; thereafter, it increased to a level at least 70% greater than the baseline during the 8 °C stage in both groups. The %ΔSkBF on the thigh in both SCIC and SCITL notably increased from 8 and 6 min respectively, during the 8°C stage, compared to 1 min before the stage; however, it did not exceed the baseline level. CONCLUSIONS: An increase in SkBF during LC was observed both in the sensate and non-sensate areas in SCIs, although the magnitude was larger in the sensate area.

Quantification of catecholamine neurotransmitters released from cutaneous vasoconstrictor nerve endings in men with cervical spinal cord injury.

Control of cutaneous circulation is critically important to maintain thermoregulation, especially in individuals with cervical spinal cord injury (CSCI) who have no or less central thermoregulatory drive. However, the peripheral vasoconstrictor mechanism and capability have not been fully investigated after CSCI. Post- and presynaptic sensitivities of the cutaneous vasoconstrictor system were investigated in 8 CSCI and 7 sedentary able-bodied (AB) men using an intradermal microdialysis technique. Eight doses of norepinephrine (NE, 10-8 to 10-1 M) and five doses of tyramine (TY, 10-8, 10-5 to 10-2 M) were administered into the anterior right and left thigh, respectively. Endogenous catecholamines, noradrenaline, and dopamine, collected at the TY site, were determined by high-performance liquid chromatography with electrochemical detection. Regardless of vasoconstrictor agents, cutaneous vascular conductance decreased dose-dependently and responsiveness was similar between the groups (NE: Group P = 0.255, Dose P = 0.014; TY: Group P = 0.468, Dose P < 0.001), whereas the highest dose of each drug induced cutaneous vasodilation. Administration of TY promoted the release of noradrenaline and dopamine in both groups. Notably, the amount of noradrenaline released was similar between the groups (P = 0.819), although the concentration of dopamine was significantly greater in individuals with CSCI than in AB individuals (P = 0.004). These results suggest that both vasoconstrictor responsiveness and neural functions are maintained after CSCI, and dopamine in the skin is likely to induce cutaneous vasodilation.

Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

Effects of whole body skin cooling on human cognitive processing: a study using SEPs and ERPs.

The present study investigated the effect of whole body skin cooling on somatosensory ascending processing by utilizing somatosensory-evoked potentials (SEPs) and motor execution, as well as inhibitory processing by event-related potentials (ERPs). Fourteen healthy participants wearing a water-perfused suit performed two sessions (sessions 1 and 2) consisting of SEPs and ERPs with somatosensory Go/No-go paradigms under two conditions (cold stress and control) on different days. In session 2, under the cold stress condition, whole body skin cooling was achieved by circulating 20°C water through the suit for 40 min, whereas 34°C water was perfused in the other sessions. The mean skin temperature decreased from 35.0 ± 0.5°C (session 1) to 30.4 ± 0.9°C (session 2) during whole body skin cooling, but the internal temperature was maintained. Whole body skin cooling delayed the peak latencies of N20, P25, and P45 components at C4' of SEPs (all: P < 0.05). Moreover, the peak latencies of P14, N18, and P22 components at Fz of SEPs and the Go-P300 component of ERPs were delayed (all: P < 0.05). In contrast, the peak amplitudes of all individual components of SEPs as well as N140 and P300 of ERPs remained unchanged. These results suggest that passive whole body skin cooling delays neural activities on somatosensory processing and higher cognitive function.

Differences in serum IL-6 response after 1 °C rise in core body temperature in individuals with spinal cord injury and cervical spinal cord injury during local heat stress.

OBJECTIVES: Passive rise in core body temperature achieved by head-out hot water immersion (HHWI) results in acute increases in serum interleukin (IL)-6 but no change in plasma adrenaline in patients with cervical spinal cord injury (CSCI). The purpose of the present study was to determine the mechanism of heat stress-induced increase in serum IL-6. SETTING: A cross-sectional study. METHODS: The study subjects were nine with CSCI, ten with thoracic and lumbar spinal cord injury (TLSCI) and eight able-bodied (AB) subjects. Time since injury was 16.1 ± 3.4 years in TLSCI and 16.4 ± 4.1 years in CSCI. Subjects were subjected to lower-body heat stress (LBH) by wearing a hot water-perfused suit until 1 °C increase in core temperature. The levels of serum IL-6, plasma adrenaline, tumour necrosis factor (TNF)-α, C-reactive protein (CRP), and counts of blood cells were measured at normothermia and after LBH. RESULTS: Serum IL-6 concentrations increased significantly immediately after LBH in all the three groups. ΔIL-6% was lower in CSCI subjects compared with AB subjects. Plasma adrenaline concentrations significantly increased after LBH in AB and TLSCI subjects, but did not change throughout the study in CSCI subjects. Cardiac output and heart rate increased at the end of LBH in all three groups. CONCLUSIONS: Under a similar increase in core temperature, ΔIL-6% was lower in the CSCI group compared with the AB group. These findings suggest that the observed rise in IL-6 during hyperthermia is mediated, at least in part, by plasma adrenaline.

A comparison of static and dynamic cerebral autoregulation during mild whole-body cold stress in individuals with and without cervical spinal cord injury: a pilot study.

STUDY DESIGN: Experimental study. OBJECTIVES: To characterize static and dynamic cerebral autoregulation (CA) of individuals with cervical spinal cord injury (SCI) compared to able-bodied controls in response to moderate increases in mean arterial pressure (MAP) caused by mild whole-body cold stress. SETTING: Japan METHODS: Five men with complete autonomic cervical SCI (sustained > 5 y) and six age-matched able-bodied men participated in hemodynamic, temperature, catecholamine and respiratory measurements for 60 min during three consecutive stages: baseline (10 min; 33 °C water through a thin-tubed whole-body suit), mild cold stress (20 min; 25 °C water), and post-cold recovery (30 min; 33 °C water). Static CA was determined as the ratio between mean changes in middle cerebral artery blood velocity and MAP, dynamic CA as transfer function coherence, gain, and phase between spontaneous changes in MAP to middle cerebral artery blood velocity. RESULTS: MAP increased in both groups during cold and post-cold recovery (mean differences: 5-10 mm Hg; main effect of time: p = 0.001). Static CA was not different between the able-bodied vs. the cervical SCI group (mean (95% confidence interval (CI)) of between-group difference: -4 (-11 to 3) and -2 (-5 to 1) cm/s/mm Hg for cold (p = 0.22) and post-cold (p = 0.24), respectively). At baseline, transfer function phase was shorter in the cervical SCI group (mean (95% CI) of between-group difference: 0.6 (0.2 to 1.0) rad; p = 0.006), while between-group differences in changes in phase were not different in response to the cold stress (interaction term: p = 0.06). CONCLUSIONS: This pilot study suggests that static CA is similar between individuals with cervical SCI and able-bodied controls in response to moderate increases in MAP, while dynamic CA may be impaired in cervical SCI because of disturbed sympathetic control.

Effect of increases in cardiac contractility on cerebral blood flow in humans.

The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine [first a low dose (5 µg·kg-1·min-1) and then a high dose (15 µg·kg-1·min-1)] for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA, and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output, and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low- and high-dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low- and high-dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect overperfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion attributable to dobutamine administration does not cause cerebral overperfusion or an associated risk of cerebral vascular damage.NEW & NOTEWORTHY A dobutamine-induced increase in cardiac contractility did not increase internal carotid artery blood flow despite an increase in cardiac output and arterial blood pressure. In contrast, external carotid artery blood flow and conductance increased. This external cerebral blood flow response may assist with protecting from overperfusion of intracranial blood flow.

Effects of face/head and whole body cooling during passive heat stress on human somatosensory processing.

We herein investigated the effects of face/head and whole body cooling during passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs) at C4' and Fz electrodes. Fourteen healthy subjects received a median nerve stimulation at the left wrist. SEPs were recorded at normothermic baseline (Rest), when esophageal temperature had increased by ~1.2°C (heat stress: HS) during passive heating, face/head cooling during passive heating (face/head cooling: FHC), and after HS (whole body cooling: WBC). The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Latency indicated speed of the subcortical and cortical somatosensory processing, while amplitude reflected the strength of neural activity. Blood flow in the internal and common carotid arteries (ICA and CCA, respectively) and psychological comfort were recorded in each session. Increases in esophageal temperature due to HS significantly decreased the amplitude of N60, psychological comfort, and ICA blood flow in the HS session, and also shortened the latencies of SEPs (all, P < 0.05). While esophageal temperature remained elevated, FHC recovered the peak amplitude of N60, psychological comfort, and ICA blood flow toward preheat baseline levels as well as WBC. However, the latencies of SEPs did not recover in the FHC and WBC sessions. These results suggest that impaired neural activity in cortical somatosensory processing during passive HS was recovered by FHC, whereas conduction velocity in the ascending somatosensory input was accelerated by increases in body temperature.

Effects of aerobic exercise under different thermal conditions on human somatosensory processing.

The present study aimed to investigate the effects of aerobic exercise on human somatosensory processing recorded by somatosensory evoked potentials (SEPs) under temperate [TEMP, 20°C and 40% relative humidity (RH)] and hot (HOT, 35°C and 30% RH) environments. Fifteen healthy subjects performed 4 × 15-min bouts of a moderate cycling exercise [mean power output: 156.5 ± 7.7 (SE) W], with a 10-min rest period and received a posterior tibial nerve stimulation at the left ankle before and after each exercise bout; SEPs were recorded in five sessions; 1st (pre), 2nd (post-1st exercise bout), 3rd (post-2nd exercise bout), 4th (post-3rd exercise bout), and 5th (post-4th exercise bout). The peak latencies and amplitudes of the P37, N50, P60, and N70 components at Cz were evaluated. The latencies of P37, N50, P60, and N70 were significantly shorter with the repetition of aerobic exercise, and these shortened latencies were significantly greater in the HOT condition than in the TEMP condition (P37: 3rd, P < 0.05, and 5th, P < 0.01; P60: 4th, P < 0.05, and 5th, P < 0.01; N70: 4th, P < 0.05, and 5th, P < 0.001). No significant differences were observed in the amplitudes of any SEP component under either thermal condition. These results suggest that the conduction velocity of the ascending somatosensory input was accelerated by increases in body temperature, and aerobic exercise did not alter the strength of neural activity in cortical somatosensory processing.

The effect of elevations in internal temperature on event-related potentials during a simple cognitive task in humans.

The effect of hyperthermia on cognitive function remains equivocal, perhaps because of methodological discrepancy. Using electroencephalographic event-related potentials (ERPs), we tested the hypothesis that a passive heat stress impairs cognitive processing. Thirteen volunteers performed repeated auditory oddball paradigms under two thermal conditions, normothermic time control and heat stress, on different days. For the heat stress trial, these paradigms were performed at preheat stress (i.e., normothermic) baseline, when esophageal temperature had increased by ∼0.8°C, when esophageal temperature had increased by ∼2.0°C, and during cooling following the heat stress. The reaction time and ERPs were recorded in each session. For the time control trial, subjects performed the auditory oddball paradigms at approximately the same time interval as they did in the heat stress trial. The peak latency and amplitude of an indicator of auditory processing (N100) were not altered regardless of thermal conditions. An indicator of stimulus classification/evaluation time (latency of P300) and the reaction time were shortened during heat stress; moreover an indicator of cognitive processing (the amplitude of P300) was significantly reduced during severe heat stress (8.3 ± 1.3 µV) relative to the baseline (12.2 ± 1.0 µV, P < 0.01). No changes in these indexes occurred during the time control trial. During subsequent whole body cooling, the amplitude of P300 remained reduced, and the reaction time and latency of P300 remained shortened. These results suggest that excessive elevations in internal temperature reduce cognitive processing but promote classification time.

The role of cardiac sympathetic innervation and skin thermoreceptors on cardiac responses during heat stress.

The mechanism(s) for the changes in cardiac function during heat stress remain unknown. This study tested two unique hypotheses. First, sympathetic innervation to the heart is required for increases in cardiac systolic function during heat stress. This was accomplished by comparing responses during heat stress between paraplegics versus tetraplegics, with tetraplegics having reduced/absent cardiac sympathetic innervation. Second, stimulation of skin thermoreceptors contributes to cardiovascular adjustments that occur during heat stress in humans. This was accomplished by comparing responses during leg only heating between paraplegic versus able-bodied individuals. Nine healthy able-bodied, nine paraplegics, and eight tetraplegics participated in this study. Lower body (i.e., nonsensed area for para/tetraplegics) was heated until esophageal temperature had increased by ~1.0°C. Echocardiographic indexes of diastolic and systolic function were performed before and at the end of heat stress. The heat stress increased cardiac output in all groups, but the magnitude of this increase was attenuated in the tetraplegics relative to the able-bodied (1.3 ± 0.4 vs. 2.3 ± 1.0 l/min; P < 0.05). Diastolic function was maintained in all groups. Indexes of left atrial and ventricular systolic function were enhanced in the able-bodied, but did not change in tetraplegics, while these changes in paraplegics were attenuated relative to the able-bodied. These data suggest that the cardiac sympathetic innervation is required to achieve normal increases in cardiac systolic function during heat stress but not required to maintain diastolic function during this exposure. Second, elevated systolic function during heat stress primarily occurs as a result of increases in internal temperature, although stimulation of skin thermoreceptors may contribute.

Effects of passive heat stress on human somatosensory processing.

Herein, we investigated the effects of passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs). Fifteen healthy subjects received a median nerve stimulation at the left wrist under two thermal conditions: Heat Stress and normothermic Time Control. The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Under the Heat Stress condition, SEPs were recorded at normothermic baseline (1st), early in heat stress (2nd), when esophageal temperature had increased by ~1.0°C (3rd) and ~2.0°C (4th), and after heat stress (5th). In the Time Control condition, SEPs were measured at the same time intervals as those in the Heat Stress condition. The peak latencies and amplitudes of SEPs did not change early in heat stress. However, the latencies of P14, N20, and N60 at C4' and P14, N18, and P22 at Fz were significantly shorter in the 4th session than in the 1st session. Furthermore, the peak amplitudes of P25 and N60 at C4', and P22 and N30 at Fz decreased with increases in body temperature. On the other hand, under the Time Control condition, no significant differences were observed in the amplitudes or latencies of any component of SEPs. These results suggested that the conduction velocity of the ascending somatosensory input was accelerated by increases in body temperature, and hyperthermia impaired the neural activity of cortical somatosensory processing.

Blood flow in internal carotid and vertebral arteries during graded lower body negative pressure in humans.

NEW FINDINGS: What is the central question of this study? Recently, the heterogeneity of the cerebral arterial circulation has been argued. Orthostatic tolerance may be associated with an orthostatic stress-induced change in blood flow in vertebral arteries rather than in internal carotid arteries, because vertebral arteries supply blood to the medulla oblongata, which is the location of important cardiac, vasomotor and respiratory control centres. What is the main finding and its importance? The effect of graded orthostatic stress on vertebral artery blood flow is different from that on internal carotid artery blood flow. This response allows for the possibility that orthostatic tolerance may be associated with haemodynamic changes in posterior rather than anterior cerebral blood flow. Recently, the heterogeneity of the cerebral arterial circulation has been argued, but the characteristics of vertebral artery (VA) and internal carotid artery (ICA) blood flow during graded orthostatic stress remain unknown. We hypothesized that the change in blood flow in VA is not similar to that in ICA blood flow during graded orthostatic stress. We measured blood flows in both ICA and VA during graded lower body negative pressure (LBNP; -20, -35 and -50 mmHg) by using two colour-coded ultrasound systems. The effect of graded orthostatic stress on the VA blood flow was different from that on the ICA blood flow (LBNP × artery, P = 0.006). The change in ICA blood flow was associated with the level of LBNP (r = 0.287, P = 0.029), and a reduction in ICA blood flow from pre-LBNP was observed during -50 mmHg LBNP (from 411 ± 35 to 311 ± 40 ml min(-1) , P = 0.044) without symptoms of presyncope. In contrast, VA blood flow was unchanged during graded LBNP compared with the baseline (P = 0.597) relative to the reduction in ICA blood flow and thus there was no relationship between VA blood flow and the level of LBNP (r = 0.167, P = 0.219). These findings suggest that the change in ICA blood flow is due to the level of LBNP during graded orthostatic stress, but the change in VA blood flow is different from that in ICA blood flow across the different levels of LBNP. These findings provide the possibility that posterior cerebral blood flow decreases only during severe orthostatic stress and is therefore more likely to be linked with orthostatic tolerance.

Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques.

RATIONALE: We previously showed that early calcification of atherosclerotic plaques associates with macrophage accumulation. Chronic renal disease and mineral imbalance accelerate calcification and the subsequent release of matrix vesicles (MVs), precursors of microcalcification. OBJECTIVE: We tested the hypothesis that macrophage-derived MVs contribute directly to microcalcification. METHODS AND RESULTS: Macrophages associated with regions of calcified vesicular structures in human carotid plaques (n=136 patients). In vitro, macrophages released MVs with high calcification and aggregation potential. MVs expressed exosomal markers (CD9 and TSG101) and contained S100A9 and annexin V. Silencing S100A9 in vitro and genetic deficiency in S100A9-/- mice reduced MV calcification, whereas stimulation with S100A9 increased calcification potential. Externalization of phosphatidylserine after Ca/P stimulation and interaction of S100A9 and annexin V indicated that a phosphatidylserine-annexin V-S100A9 membrane complex facilitates hydroxyapatite nucleation within the macrophage-derived MV membrane. CONCLUSIONS: Our results support the novel concept that macrophages release calcifying MVs enriched in S100A9 and annexin V, which contribute to accelerated microcalcification in chronic renal disease.

Effects of acute hypoxia on cerebrovascular responses to carbon dioxide.

In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO2 tension-mediated regulation of cerebral blood flow to help maintain cerebral O2 homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O2); (2) hypoxia (12% O2); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO2 was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady-state cerebrovascular CO2 reactivity and dCA. During normoxia, the addition of CO2 increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCA Vmean), while reducing dCA (change in phase = -0.73 ± 0.22 rad, P = 0.005). During acute hypoxia, internal carotid artery blood flow and MCA Vmean remained unchanged, but cerebrovascular CO2 reactivity (internal carotid artery, P = 0.003; MCA Vmean, P = 0.031) and CO2-mediated effects on dCA (P = 0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO2 tension-mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O2 homeostasis during acute periods of hypoxia.

Do changes in cerebral blood flow modulate the amplitudes of P300 during cognitive task?

A single session of aerobic or resistance training transiently enhances cognitive function, making it a valuable strategy for dementia prevention in the older people. Despite its acknowledged benefits, the precise mechanism behind exercise-induced cognitive improvement remains controversial. In the present study, we investigated the impact of altered cerebral blood flow (CBF) on brain neural activity originating from motor executive and inhibitory processing using electroencephalographic event-related potentials (EEG-ERPs). Sixteen healthy subjects participated in four sessions, with EEG-ERPs measured during somatosensory Go/No-go tasks. The sessions were conducted under four distinct respiratory conditions presented in random order: normal breathing (NB) and rapid breathing (RB) with room air, normal breathing with hypercapnic gas (5% CO2, 21% O2, and balanced N2) (NB+Gas), and rapid breathing with the same gas (RB+Gas). Changes in CBF were evaluated based on the middle cerebral artery mean blood velocity (MCA Vmean) using transcranial Doppler. PETCO2 was decreased under the RB condition but increased under the NB+Gas condition, thereby decreasing and increasing MCA Vmean, respectively. Under the NB+Gas condition, MCA Vmean significantly increased, but it had no effect on either the executive or inhibitory function. In contrast, the reduction in MCA Vmean induced by RB decreased the peak amplitudes of Go-P300 and No-go-P300. However, even under the RB+Gas condition while MCA Vmean increased, the peak amplitudes of both also decreased. These findings suggest that neither increases nor decreases in CBF affected cognitive function.

Synesthesia has specific cognitive processing during Go/No-go paradigms.

Grapheme-color synesthesia is a consistent and automatic perception of non-physical color when presented with a grapheme. Many previous studies focused on the synesthetic visual system, but other cognitive functions in grapheme-color synesthetes have remained unclear. Therefore, the objective of the present study was to investigate the characteristics of cognitive processing for motor execution and inhibition during Go/No-go paradigms in grapheme-color synesthesia using event-related potentials (ERPs). Six grapheme-color synesthetes and 24 non-synesthetes performed visual, auditory, and somatosensory Go/No-go paradigms. Omission errors were higher in grapheme-color synesthetes than non-synesthetes. Group-trial interactions (i.e., synesthetes-non-synesthetes × Go-No-go) were observed for the latency of the visual N2 component and amplitude of the somatosensory N2 component. Latencies of auditory and somatosensory P3 components were shorter in grapheme-color synesthetes than non-synesthetes. These findings suggest that grapheme-color synesthetes have specific cognitive processing in motor execution and inhibition as well as synesthetic color perception. Our data advance understanding of cognitive processing in grapheme-color synesthesia.

Effects of hypocapnia and hypercapnia on human somatosensory processing.

The present study investigated the effects of hypocapnia and hypercapnia on human somatosensory processing by utilizing somatosensory evoked magnetic fields (SEFs) with magnetoencephalography (MEG). Thirteen volunteers participated in two experiments separately to measure respiratory and cardiovascular data and SEFs. Both experiments consisted of a combination of normal and rapid respiratory rhythms and two inspiratory gas conditions (air and a hypercapnic gas); normal breathing with air (NB), rapid breathing with air (RB), normal breathing with the hypercapnic gas (NB+Gas), and rapid breathing with gas (RB+Gas). Partial pressures of end-tidal CO2 (PETCO2) increased during inhaling the hypercapnic gas and decreased during RB, but the RB+Gas condition continued to cause elevated PETCO2 compared with the baseline. Subsequently, middle cerebral artery blood (MCA) velocity using transcranial Doppler changed as well, while mean MCA velocity increased under the RB+Gas condition. The peak amplitude of the M60 component in SEFs was also significantly larger under with-gas than without-gas conditions, irrespective of the respiratory frequency. These results suggest that there is a close relationship between cerebral blood flow and neural activity of the M60 component in SEFs. This study provides evidence to further understanding on one of the neural mechanisms of hypercapnia.

Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice.

Medial-to-intimal migration of SMCs is critical to atherosclerotic plaque formation and remodeling of injured arteries. Considerable amounts of the shed soluble form of the LDL receptor relative LR11 (sLR11) produced by intimal SMCs enhance SMC migration in vitro via upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. Here, we show that circulating sLR11 is a novel marker of carotid intima-media thickness (IMT) and that targeted disruption of the LR11 gene greatly reduces intimal thickening of arteries through attenuation of Ang II-induced migration of SMCs. Serum concentrations of sLR11 were positively correlated with IMT in dyslipidemic subjects, and multivariable regression analysis suggested sLR11 levels as an index of IMT, independent of classical atherosclerosis risk factors. In Lr11-/- mice, femoral artery intimal thickness after cuff placement was decreased, and Ang II-stimulated migration and attachment of SMCs from these mice were largely abolished. In isolated murine SMCs, sLR11 caused membrane ruffle formation via activation of focal adhesion kinase/ERK/Rac1 accompanied by complex formation between uPAR and integrin alphavbeta3, a process accelerated by Ang II. Overproduction of sLR11 decreased the sensitivity of Ang II-induced activation pathways to inhibition by an Ang II type 1 receptor blocker in mice. Thus, we demonstrate a requirement for sLR11 in Ang II-induced SMC migration and propose what we believe is a novel role for sLR11 as a biomarker of carotid IMT.