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1.
Am J Physiol Heart Circ Physiol ; 321(3): H518-H531, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34328343

ABSTRACT

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.


Subject(s)
Anterior Cerebral Artery/physiology , Fingers/physiology , Movement , Oxygen Consumption , Prefrontal Cortex/physiology , Adult , Blood Flow Velocity , Female , Humans , Isometric Contraction , Male , Oxyhemoglobins/analysis , Prefrontal Cortex/blood supply , Prefrontal Cortex/metabolism , Reaction Time , Vasodilation
2.
BMC Neurosci ; 22(1): 10, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33588769

ABSTRACT

BACKGROUND: There is growing evidence for a positive correlation between measures of muscular strength and cognitive abilities. However, the neurophysiological correlates of this relationship are not well understood so far. The aim of this study was to investigate cortical hemodynamics [i.e., changes in concentrations of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb)] as a possible link between measures of muscular strength and cognitive performance. METHODS: In a cohort of younger adults (n = 39, 18-30 years), we assessed (i) handgrip strength by a handhold dynamometer, (ii) short-term working memory performance by using error rates and reaction times in the Sternberg task, and (iii) cortical hemodynamics of the prefrontal cortex (PFC) via functional near-infrared spectroscopy (fNIRS). RESULTS: We observed low to moderate negative correlations (rp = ~ - 0.38 to - 0.51; p < 0.05) between reaction time and levels of oxyHb in specific parts of the PFC. Furthermore, we noticed low to moderate positive correlations (rp = ~ 0.34 to 0.45; p < 0.05) between reaction times and levels of deoxyHb in distinct parts of the PFC. Additionally, higher levels of oxyHb (rp (35) = 0.401; p = 0.014) and lower levels of deoxyHb (rp (34) = - 0.338; p = 0.043) in specific parts of the PFC were linked to higher percentage of correct answers. We also found low to moderate correlations (p < 0.05) between measures of handgrip strength and levels of oxyHb (rp = ~ 0.35; p < 0.05) and levels of deoxyHb (rp = ~ - 0.25 to - 0.49; p < 0.05) in specific parts of the PFC. However, there was neither a correlation between cognitive performance and handgrip strength nor did cortical hemodynamics in the PFC mediate the relationship between handgrip strength and cognitive performance (p > 0.05). CONCLUSION: The present study provides evidence for a positive neurobehavioral relationship between cortical hemodynamics and cognitive performance. Our findings further imply that in younger adults higher levels of handgrip strength positively influence cortical hemodynamics although the latter did not necessarily culminate in better cognitive performance. Future research should examine whether the present findings can be generalized to other cohorts (e.g., older adults).


Subject(s)
Cognition/physiology , Hand Strength/physiology , Hemodynamics/physiology , Prefrontal Cortex/blood supply , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Male , Spectroscopy, Near-Infrared , Young Adult
3.
Mol Psychiatry ; 25(8): 1759-1776, 2020 08.
Article in English | MEDLINE | ID: mdl-30283033

ABSTRACT

Cocaine-induced vasoconstriction reduces blood flow, which can jeopardize neuronal function and in the prefrontal cortex (PFC) it may contribute to compulsive cocaine intake. Here, we used integrated optical imaging in a rat self-administration and a mouse noncontingent model, to investigate whether changes in the cerebrovascular system in the PFC contribute to cocaine self-administration, and whether they recover with detoxification. In both animal models, cocaine induced severe vasoconstriction and marked reductions in cerebral blood flow (CBF) in the PFC, which were exacerbated with chronic exposure and with escalation of cocaine intake. Though there was a significant proliferation of blood vessels in areas of vasoconstriction (angiogenesis), CBF remained reduced even after 1 month of detoxification. Treatment with Nifedipine (Ca2+ antagonist and vasodilator) prevented cocaine-induced CBF decreases and neuronal Ca2+ changes in the PFC, and decreased cocaine intake and blocked reinstatement of drug seeking. These findings provide support for the hypothesis that cocaine-induced CBF reductions lead to neuronal deficits that contribute to hypofrontality and to compulsive-like cocaine intake in addiction, and document that these deficits persist at least one month after detoxification. Our preliminary data showed that nifedipine might be beneficial in preventing cocaine-induced vascular toxicity and in reducing cocaine intake and preventing relapse.


Subject(s)
Cocaine-Related Disorders/etiology , Cocaine/administration & dosage , Cocaine/pharmacology , Ischemia/chemically induced , Animals , Drug-Seeking Behavior/drug effects , Male , Mice , Nifedipine/pharmacology , Prefrontal Cortex/blood supply , Prefrontal Cortex/drug effects , Rats , Rats, Wistar , Self Administration
4.
Acta Neurochir (Wien) ; 163(2): 357-364, 2021 02.
Article in English | MEDLINE | ID: mdl-32929542

ABSTRACT

BACKGROUND: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. METHODS: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. RESULTS: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. CONCLUSIONS: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.


Subject(s)
Hemangioma, Cavernous, Central Nervous System/surgery , Prefrontal Cortex/blood supply , Radiosurgery/methods , Adolescent , Adult , Aged , Child , Female , Hemangioma, Cavernous, Central Nervous System/complications , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Veins/abnormalities , Veins/surgery , Vision Disorders/etiology , Young Adult
5.
Cell Mol Neurobiol ; 40(5): 829-843, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31865501

ABSTRACT

Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P4). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P4 treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P4 treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors.


Subject(s)
Carotid Artery, Common/drug effects , Carotid Stenosis/drug therapy , Neuroprotective Agents/therapeutic use , Nitric Oxide Synthase Type III/metabolism , Prefrontal Cortex/blood supply , Prefrontal Cortex/drug effects , Progesterone/analogs & derivatives , Receptors, Progesterone/metabolism , Animals , Carotid Artery, Common/pathology , DNA Fragmentation , Extracellular Signal-Regulated MAP Kinases/metabolism , Male , Neurons/drug effects , Neurons/pathology , Neuroprotective Agents/pharmacology , Prefrontal Cortex/pathology , Progesterone/chemistry , Progesterone/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Wistar , Signal Transduction
6.
Dev Sci ; 23(5): e12928, 2020 09.
Article in English | MEDLINE | ID: mdl-31802580

ABSTRACT

Infancy is marked by rapid neural and emotional development. The relation between brain function and emotion in infancy, however, is not well understood. Methods for measuring brain function predominantly rely on the BOLD signal; however, interpretation of the BOLD signal in infancy is challenging because the neuronal-hemodynamic relation is immature. Regional cerebral blood flow (rCBF) provides a context for the infant BOLD signal and can yield insight into the developmental maturity of brain regions that may support affective behaviors. This study aims to elucidate the relations among rCBF, age, and emotion in infancy. One hundred and seven mothers reported their infants' (infant age M ± SD = 6.14 ± 0.51 months) temperament. A subsample of infants completed MRI scans, 38 of whom produced usable perfusion MRI during natural sleep to quantify rCBF. Mother-infant dyads completed the repeated Still-Face Paradigm, from which infant affect reactivity and recovery to stress were quantified. We tested associations of infant age at scan, temperament factor scores, and observed affect reactivity and recovery with voxel-wise rCBF. Infant age was positively associated with CBF in nearly all voxels, with peaks located in sensory cortices and the ventral prefrontal cortex, supporting the formulation that rCBF is an indicator of tissue maturity. Temperamental Negative Affect and recovery of positive affect following a stressor were positively associated with rCBF in several cortical and subcortical limbic regions, including the orbitofrontal cortex and inferior frontal gyrus. This finding yields insight into the nature of affective neurodevelopment during infancy. Specifically, infants with relatively increased prefrontal cortex maturity may evidence a disposition toward greater negative affect and negative reactivity in their daily lives yet show better recovery of positive affect following a social stressor.


Subject(s)
Brain/physiology , Cerebrovascular Circulation/physiology , Emotions/physiology , Temperament/physiology , Brain/blood supply , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Mothers/psychology , Prefrontal Cortex/blood supply , Stress, Psychological/physiopathology
7.
Psychogeriatrics ; 20(3): 254-261, 2020 May.
Article in English | MEDLINE | ID: mdl-31881113

ABSTRACT

AIM: As our society ages, the number of people living with dementia also steadily increases. Some work has focused on masticatory behaviour as a form of daily health care that could help prevent cognitive impairment and dementia. However, it is not yet clear how masticatory behaviour influences various cognitive functions. Therefore, the purpose of this study was to examine the effect of masticatory behaviour on the decline of generalized attention, an important cognitive function. METHODS: Participants were 35 healthy, dentulous individuals without stomatognathic abnormalities (24 men, 11 women; mean age: 56.8 ± 4.8 years). All participants completed three interventions: mastication, foot-stepping, and none (control). Pre- and post-intervention measures of generalized attention were measured by using neuropsychological tests to examine general attention; the results were then compared. Simultaneously, during the generalized attention task, the functional activity of the prefrontal cortex was observed on functional near-infrared spectroscopy. RESULTS: Response time of generalized attention improved in both the masticatory and foot-stepping interventions. There was a transient increase in oxyhaemoglobin activity in the right and left prefrontal cortices in the masticatory intervention. CONCLUSIONS: Masticatory behaviour may be involved in a partial improvement of generalized attention and may induce prefrontal cortex activity in middle-aged and older adults.


Subject(s)
Aging/physiology , Attention/physiology , Cognition/physiology , Healthy Volunteers , Mastication/physiology , Prefrontal Cortex/physiology , Aged , Female , Humans , Male , Middle Aged , Oxygen/blood , Prefrontal Cortex/blood supply , Spectroscopy, Near-Infrared
8.
Brain Cogn ; 136: 103613, 2019 11.
Article in English | MEDLINE | ID: mdl-31561091

ABSTRACT

To investigate neural correlates of repetitive assembly tasks in ecologically-valid empirical settings, this study measured bilateral prefrontal (PFC) and motor activations when participants performed a carburetor assembly task using functional near-infrared spectroscopy (fNIRS). Participants worked for one hour at a typical (low-) pace and at an accelerated high-pace. Before and after the task, a test was conducted to assess motion stability and fine motor control. The behavioral data revealed decreased motion stability after the assembly work in both conditions, with a significantly higher reduction after the high-pace task. The fNIRS data also revealed reduced activations in bilateral prefrontal and motor regions in both conditions over time. However, the low-pace task led to significantly greater activity decreases compared with the high-pace. Activity decrease in prefrontal and motor regions within the low pace also significantly related to minimal motion stability impairment, suggesting that the brain activation decreases in this and, potentially, findings of higher alpha in past repetitive-task studies using EEG, may be a result of not fatigue but worker adaptation or increasing efficiency.


Subject(s)
Hemodynamics/physiology , Motor Skills/physiology , Prefrontal Cortex/blood supply , Adult , Brain Mapping , Female , Humans , Male , Prefrontal Cortex/physiology , Spectroscopy, Near-Infrared/methods , Young Adult
9.
Addict Biol ; 24(3): 485-497, 2019 05.
Article in English | MEDLINE | ID: mdl-29504647

ABSTRACT

Cocaine addiction is associated with dysfunction of the prefrontal cortex (PFC), which facilitates relapse and compulsive drug taking. To assess if cocaine's effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography and multi-wavelength laser speckle to measure vascularization and hemodynamics and used GCaMP6f to monitor intracellular Ca2+ levels ([Ca2+ ]in ) as a marker of neuronal activity. Rats were given short (1 hour; ShA) or long (6 hours; LgA) access cocaine self-administration. As expected, LgA but not ShA rats escalated cocaine intake. In naïve rats, acute cocaine decreased oxygenated hemoglobin, increased deoxygenated hemoglobin and reduced cerebral blood flow in PFC, likely due to cocaine-induced vasoconstriction. ShA rats showed enhanced hemodynamic response and slower recovery after cocaine, versus naïve. LgA rats showed a blunted hemodynamic response, but an enhanced PFC neuronal [Ca2+ ]in increase after cocaine challenge associated with drug intake. Both ShA and LgA groups had higher vessel density, indicative of angiogenesis, presumably to compensate for cocaine's vasoconstricting effects. Cocaine self-administration modified the PFC cerebrovascular responses enhancing it in ShA and attenuating it in LgA animals. In contrast, LgA but not ShA animals showed sensitized neuronal reactivity to acute cocaine in the PFC. The opposite changes in hemodynamics (decreased) and neuronal responses (enhanced) in LgA rats indicate that these constitute distinct effects and suggest that the neuronal and not the vascular effects are associated with escalation of cocaine intake in addiction whereas its vascular effect in PFC might contribute to cognitive deficits that increase vulnerability to relapse.


Subject(s)
Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Hemodynamics/drug effects , Neurons/drug effects , Prefrontal Cortex/drug effects , Anesthetics, Inhalation , Animals , Cerebrovascular Circulation/drug effects , Conditioning, Operant , Hemoglobins/metabolism , Isoflurane , Male , Neuroimaging/methods , Prefrontal Cortex/blood supply , Rats, Sprague-Dawley , Self Administration , Tomography, Optical Coherence , Vasoconstriction/drug effects
10.
Eur J Appl Physiol ; 119(8): 1819-1828, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31187281

ABSTRACT

PURPOSE: The aim was to compare changes in peripheral and cerebral oxygenation, as well as metabolic and performance responses during conditions of blood flow restriction (BFR, bilateral vascular occlusion at 0% vs. 45% of resting pulse elimination pressure) and systemic hypoxia (~ 400 m, FIO2 20.9% vs. ~ 3800 m normobaric hypoxia, FIO2 13.1 ± 0.1%) during repeated sprint tests to exhaustion (RST) between leg- and arm-cycling exercises. METHODS: Seven participants (26.6 ± 2.9 years old; 74.0 ± 13.1 kg; 1.76 ± 0.09 m) performed four sessions of RST (10-s maximal sprints with 20-s recovery until exhaustion) during both leg and arm cycling to measure power output and metabolic equivalents as well as oxygenation (near-infrared spectroscopy) of the muscle tissue and prefrontal cortex. RESULTS: Mean power output was lower in arms than legs (316 ± 118 vs. 543 ± 127 W; p < 0.001) and there were no differences between conditions for a given limb. Arms demonstrated greater changes in concentration of deoxyhemoglobin (∆[HHb], - 9.1 ± 6.1 vs. - 6.5 ± 5.6 µm) and total hemoglobin concentration (∆[tHb], 15.0 ± 10.8 vs. 11.9 ± 7.9 µm), as well as the absolute maximum tissue saturation index (TSI, 62.0 ± 8.3 vs. 59.3 ± 8.1%) than legs, respectively (p < 0.001), demonstrating a greater capacity for oxygen extraction. Further, there were greater changes in tissue blood volume [tHb] during BFR only compared to all other conditions (p < 0.01 for all). CONCLUSIONS: The combination of BFR and/or hypoxia led to increased changes in [HHb] and [tHb] likely due to greater vascular resistance, to which arms were more responsive than legs.


Subject(s)
High-Intensity Interval Training/methods , Hypoxia/physiopathology , Muscle, Skeletal/blood supply , Oxygen Consumption , Prefrontal Cortex/blood supply , Reperfusion/adverse effects , Adult , Female , High-Intensity Interval Training/adverse effects , Humans , Male , Muscle, Skeletal/physiology , Oxyhemoglobins/metabolism
11.
J Sports Sci ; 37(16): 1805-1815, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30897031

ABSTRACT

The purpose of this study was to examine CHO ingestion on a cognitive task using a field-simulated time-trial (TT) under hypoxia in well-trained triathletes. Ten male triathletes (age: 22.1 ± 1.1 years; VO2max: 59.4 ± 1.4 ml/kg/min) participated in this double-blind/crossover/counter-balanced design study. Participants completed 3 TT trials: 1) normoxic placebo (NPLA; FiO2 = 20.9%), 2) hypoxic placebo (HPLA; FiO2 = 16.3%), and 3) hypoxic CHO (HCHO; 6% CHO provided as 2 ml/kg/15 min; FiO2 = 16.3%). During the TT, physiological responses (SpO2, HR, RPE, and blood glucose/lactate), cognitive performance, and cerebral haemodynamics were measured. Hypoxia reduced TT performance by ~3.5-4% (p < 0.05), but CHO did not affect TT performance under hypoxia. For the cognitive task, CHO slightly preserved exercise-induced cognitive reaction speed but did not affect response accuracy during hypoxic exercise. However, CHO did not preserve the decreased Hb-Diff (cerebral blood flow, CBF) and increased HHb in the prefrontal lobe (p < 0.05) during hypoxic exercise, and CHO failed to preserve hypoxia-suppressed prefrontal CBF and tissue oxygen saturation. In conclusion, the present study demonstrates that CHO is effective in sustaining reaction speed for a cognitive task but not promoting TT performance during hypoxic exercise, which would be important for strategy-/decision-making when athletes compete at moderate high-altitude.


Subject(s)
Bicycling/physiology , Cognition/physiology , Dietary Carbohydrates/administration & dosage , Physical Endurance/physiology , Beverages , Cerebrovascular Circulation , Cross-Over Studies , Decision Making , Double-Blind Method , Exercise Test , Hemodynamics , Humans , Hypoxia , Male , Oxygen/blood , Prefrontal Cortex/blood supply , Reaction Time , Young Adult
12.
Clin Oral Investig ; 23(3): 1181-1196, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29967973

ABSTRACT

OBJECTIVES: Neuropsychological associations can be considerable in occlusal dysesthesia (OD) patients who routinely complain of persistent occlusal discomfort, and somatization effects in the superior medial prefrontal cortex and the temporal and parietal regions are also present. However, the relationship between physical activity, i.e., chewing, prefrontal cognitive demand, and psychiatric states in OD patients remains unclear. We investigated this relationship in this study. MATERIALS AND METHODS: OD patients (n = 15) and healthy control (n = 15; HC) subjects were enrolled in this study. Occlusal contact, chewing activities of the masticatory muscles, prefrontal activities, and psychiatric states such as depression and somatization, of the participants were evaluated. Functional near-infrared spectroscopy was used to determine prefrontal hemodynamics and the Symptom Checklist-90-R was used to score the psychiatric states. RESULTS: We observed a significant association between prefrontal deactivation during chewing and somatization subscales in OD patients. Further, there were no significant differences with regard to the occlusal state and chewing physical activities between the OD patients and HC subjects. CONCLUSIONS: Chewing-related prefrontal deactivation may be associated with somatization severity in OD patients. CLINICAL RELEVANCE: fNIRS is a functional imaging method that uses the principal of neuro-vascular couplings. It is applicable for evaluation of psychiatric state based on prefrontal cortex blood flow in patients with psychiatric disorders.


Subject(s)
Cerebrovascular Circulation , Mastication , Paresthesia/physiopathology , Prefrontal Cortex/physiopathology , Hemodynamics , Humans , Prefrontal Cortex/blood supply , Spectroscopy, Near-Infrared
13.
Int J Mol Sci ; 20(6)2019 Mar 21.
Article in English | MEDLINE | ID: mdl-30901926

ABSTRACT

Schizophrenia is a chronic mental disease, affecting around 1% of the general population. Schizophrenia is characterized by productive, negative, affective, and disorganization symptoms, and cognitive deficits. Cognitive deficits prevail in most of the schizophrenia patients and are one of the most disabling symptoms. They usually occur before the acute episode of the disease and tend to become chronic with no satisfactory treatment from antipsychotic drugs. Because of their early manifestation in patients' lives, cognitive deficits are suggested to be the primary symptom of schizophrenia. The pathogenesis of cognitive deficits in schizophrenia is not fully understood. They are linked with hypofrontality, which is a decrease in blood flow and glucose metabolism in the prefrontal lobe of schizophrenia-suffering patients. Hypofrontality is linked with disturbances of the corticolimbothalamic circuit, important for cognition and memory in humans. The circuit consists of a group of neuroanatomic structures and hypothetically any disturbance in them may result in cognitive deficits. We present a translational preclinical model of understanding how antipsychotic medication may decrease the N-methyl-D-aspartic acid (NMDA) receptors' activity and produce dysfunctions in the corticolimbothalamic circuit and hypofrontality. From several pharmacological experiments on rats, including mainly our own recent findings, we collected data that suggest that antipsychotic medication may maintain and escalate hypofrontality in schizophrenia, decreasing NMDA receptor activity in the corticolimbothalamic circuit in the human brain. We discuss our findings within the literature of the subject.


Subject(s)
Antipsychotic Agents/chemistry , Prefrontal Cortex/blood supply , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Receptors, N-Methyl-D-Aspartate/chemistry , Animals , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacology , Cognition/drug effects , Cognition Disorders/etiology , Cognition Disorders/metabolism , Gene Expression Regulation/drug effects , Glutamates/metabolism , Humans , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Schizophrenia/etiology , Schizophrenia/metabolism , Signal Transduction/drug effects , Synaptic Transmission/drug effects
14.
Neuroimage ; 181: 132-141, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29981482

ABSTRACT

Cerebrovascular reactivity (CVR) is a measure of vascular response to a vasoactive stimulus, and can be used to assess the health of the brain vasculature. In this current study we used different analyses of BOLD fMRI responses to CO2 to provide a number of metrics including ramp and step CVR, speed of response and transfer function analysis (TFA). 51 healthy control volunteers between the ages of 18-85 (26 males) were recruited and scanned at 3T field strength. Atlases reflecting voxel-wise means and standard deviations were compiled to assess possible differences in these metrics between four age cohorts. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm, and monitoring end-tidal partial pressures of CO2 (PETCO2) and O2 (PETO2). No significant differences were found for resting PETCO2 values between cohorts. Ramp CVR decreased significantly with age in white matter frontal regions comprising the ACA-MCA watershed area, a finding that may be indicative of age related changes. Similarly, TFA showed that gain was reduced in the left white matter ACA-MCA watershed area as well as the posterior and anterior cingulate cortex, and superior frontal gyrus in the oldest compared to youngest cohort. These findings, detailing changes in cerebrovascular regulation in the healthy aging brain should prove useful in mapping areas of dysregulated blood flow in individuals with vascular risk factors especially those at risk for developing vascular dementia.


Subject(s)
Aging/physiology , Carbon Dioxide/pharmacology , Cerebral Cortex/physiology , Frontal Lobe/physiology , Functional Neuroimaging/methods , Neurovascular Coupling/physiology , White Matter/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Cerebral Cortex/blood supply , Cerebral Cortex/diagnostic imaging , Female , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Gyrus Cinguli/blood supply , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiology , Humans , Hypercapnia/chemically induced , Hypercapnia/diagnostic imaging , Hypercapnia/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , White Matter/blood supply , White Matter/diagnostic imaging , Young Adult
15.
Am J Physiol Regul Integr Comp Physiol ; 314(2): R252-R264, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29141949

ABSTRACT

Impaired microvascular insulin signaling may develop before overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex), and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase Cß (PKCß). Juvenile Ossabaw miniature swine (3.5 mo of age) were divided into two groups: lean control ( n = 6) and obese ( n = 6). Obesity was induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 10 wk. Juvenile obesity was characterized by excess body mass, hyperglycemia, physical inactivity (accelerometer), and marked lipid accumulation in the skeletal muscle, with no evidence of overt atherosclerotic lesions in athero-prone regions, such as the abdominal aorta. Endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) vasomotor responses in the brachial and carotid arteries (wire myography), as well as in the skeletal muscle resistance and 2A pial arterioles (pressure myography) were unaltered, but insulin-induced microvascular vasodilation was impaired in the obese group. Blunted insulin-stimulated vasodilation, which was reversed with acute PKCß inhibition (LY333-531), occurred alongside decreased tissue perfusion, as well as reduced insulin-stimulated Akt signaling in the prefrontal cortex, but not the triceps. In the early stages of juvenile obesity development, the microvasculature and prefrontal cortex exhibit impaired insulin signaling. Such adaptations may underscore vascular and neurological derangements associated with juvenile obesity.


Subject(s)
Insulin Resistance , Insulin/blood , Microvessels/metabolism , Muscle, Skeletal/blood supply , Pediatric Obesity/metabolism , Prefrontal Cortex/blood supply , Vasodilation , Age Factors , Animals , Disease Models, Animal , Disease Progression , Female , Male , Microvessels/drug effects , Microvessels/physiopathology , Pediatric Obesity/physiopathology , Phosphorylation , Protein Kinase C beta/antagonists & inhibitors , Protein Kinase C beta/metabolism , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Swine , Swine, Miniature , Time Factors , Vasodilation/drug effects
16.
Hum Psychopharmacol ; 33(2): e2655, 2018 03.
Article in English | MEDLINE | ID: mdl-29532516

ABSTRACT

OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18 F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy. RESULTS: Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness. CONCLUSIONS: Physiological "coupling" between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.


Subject(s)
Cetirizine/pharmacology , Cognition/drug effects , Diphenhydramine/pharmacology , Hemodynamics/drug effects , Histamine H1 Antagonists/pharmacology , Prefrontal Cortex/drug effects , Brain Mapping , Cross-Over Studies , Double-Blind Method , Female , Fluorodeoxyglucose F18/pharmacokinetics , Glucose/metabolism , Healthy Volunteers , Humans , Image Processing, Computer-Assisted , Male , Neuropsychological Tests , Positron-Emission Tomography , Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Spectroscopy, Near-Infrared , Time Factors
17.
Eur J Appl Physiol ; 118(8): 1689-1702, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29855789

ABSTRACT

PURPOSE: We have reported using near-infrared spectroscopy that an increase in prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) at the start of cycling exercise has relation to central command, defined as a feedforward signal descending from higher brain centers. The final output of central command evokes the exercise effort-dependent cardiovascular responses. If the prefrontal cortex may output the final signal of central command toward the autonomic nervous system, the prefrontal oxygenation should increase depending on exercise effort. To test the hypothesis, we investigated the effects of exercise intensity and muscle mass on prefrontal oxygenation in 13 subjects. METHODS: The subjects performed one- or two-legged cycling at various relative intensities for 1 min. The prefrontal Oxy-Hb and cardiovascular variables were simultaneously measured during exercise. RESULTS: The increase in cardiac output and the decrease in total peripheral resistance at the start of one- and two-legged cycling were augmented in proportion to exercise intensity and muscle mass recruitment. The prefrontal Oxy-Hb increased at the start of voluntary cycling, while such increase was not developed during passive cycling. Mental imagery of cycling also increased the prefrontal Oxy-Hb, concomitantly with peripheral muscle vasodilatation. However, the increase in prefrontal Oxy-Hb at the start of voluntary cycling seemed independent of exercise intensity and muscle mass recruitment. CONCLUSIONS: It is likely that the increased prefrontal activity at the start of cycling exercise is not representative of the final output signal of central command itself toward the autonomic nervous system but may trigger neuronal activity in the caudal brain responsible for the generation of central command.


Subject(s)
Exercise/physiology , Muscle, Skeletal/physiology , Oxygen Consumption , Prefrontal Cortex/blood supply , Adult , Autonomic Nervous System/physiology , Female , Humans , Male , Muscle, Skeletal/innervation , Oxyhemoglobins/metabolism , Prefrontal Cortex/physiology , Random Allocation
18.
Eur J Appl Physiol ; 118(11): 2417-2427, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30167957

ABSTRACT

PURPOSE: To compare prefrontal cortex oxygenation in recreationally-active women using oral contraceptives (WomenOC; n = 8) to women with a natural menstrual cycle (WomenNC; n = 8) during incremental exercise to exhaustion. METHODS: Participants performed incremental cycling to exhaustion to determine lactate threshold 1 (LT1) and 2 (LT2) and peak oxygen uptake (VO2peak). Prefrontal cortex oxygenation was monitored via near-infrared spectroscopy through concentration changes in oxy-haemoglobin (Δ[HbO2]), deoxy-haemoglobin (Δ[HHb]), total-haemoglobin (Δ[tHb]) and tissue saturation index (TSI). RESULTS: 17ß-oestradiol and progesterone were lower in WomenOC (35 ± 26; 318 ± 127 pmol·L-1, respectively) than WomenNC (261 ± 156; 858 ± 541 pmol·L-1, respectively). There were no differences in full blood examination results or serum nitric oxide (p > 0.05). However, WomenOC presented lower concentrations in ferric-reducing ability of plasma (- 8%; effect size; ES - 0.52 ± 0.61), bilirubin (- 32%; ES - 0.56 ± 0.62) and uric acid (- 17%; ES - 0.53 ± 0.61). Cardiopulmonary parameters were similar between groups during cycling, including VO2peak (p = 0.99). While there was a significant effect of time on all parameters measured by near-infrared spectroscopy during incremental cycling, there was no effect of OC at LT1, LT2 or exhaustion calculated as a change from baseline (TSI; p = 0.096, Δ[HbO2]; p = 0.143, Δ[HHb]; p = 0.085 and Δ[tHb]; p = 0.226). The change in TSI from LT1 to LT2 was significantly different between groups (WomenNC; mean difference + 2.06%, WomenOC; mean difference - 1.73%; p = 0.003). CONCLUSION: Prefrontal tissue oxygenation declined at a lower relative exercise intensity in WomenOC as compared to WomenNC, however, this did not influence VO2peak. The results provide the first evidence for variance in the cerebral oxygenation response to exercise, which may be associated with female sex hormones.


Subject(s)
Contraceptives, Oral, Hormonal/therapeutic use , Estradiol/blood , Oxygen Consumption/drug effects , Oxygen/blood , Prefrontal Cortex/drug effects , Progesterone/blood , Adolescent , Adult , Contraceptives, Oral, Hormonal/administration & dosage , Female , Humans , Oxygen Consumption/physiology , Oxyhemoglobins/metabolism , Prefrontal Cortex/blood supply , Prefrontal Cortex/metabolism , Spectroscopy, Near-Infrared , Young Adult
19.
Adv Exp Med Biol ; 1072: 111-117, 2018.
Article in English | MEDLINE | ID: mdl-30178332

ABSTRACT

The development of underwater Near-Infrared Spectroscopy (uNIRS) has enabled the measurement of tissue oxygenation within the swim environment. Unique physiological responses, such as the diving reflex, have been shown to occur during synchronized swimming and demonstrate an innate oxygen-conserving reflex. However, the prevalence of a sudden loss of consciousness ('hypoxic blackout') is an ongoing concern in this swim population. The purpose of this study was to investigate the reported low tissue oxygen conditions experienced in elite level synchronized swimmers (SyncS) during swim routines. Changes in peripheral muscle and brain oxygenation (Tissue Saturation Index (TSI %)) were continuously recorded during simulated synchronized swim routines. Six elite female synchronized swimmers were assessed; age 29.0 ± 4.4 years; height 168.4 ± 7.1 cm; weight 53.2 ± 3.2 kg; quadriceps skin fold; 10.2 ± 0.8 mm; ΔTSI (%) between the vastus lateralis (VL) and prefrontal cortex (PFC) were analyzed using paired (two-tailed) t-tests. The level of significance for analysis was set at p < 0.05. Significant difference (p = 0.001) was found in ΔTSI (%) between the VL and PFC. During dynamic leg kicking exercise, the initial effect of each leg kicking sequence is a rapid drop in TSI (%). This is consistent with an initial constriction (drop in blood flow in the muscle) accompanied by an increase in oxygen consumption. Cerebral oxygenation (PFC) remained largely unchanged during both maximal breath-hold and during vigorous exercise, presumably due to protective mechanisms in the brain in this population. We conclude that uNIRS is able to provide novel insights into SyncS hemodynamic responses and could be used to inform on the safety of new routines.


Subject(s)
Athletes , Prefrontal Cortex/blood supply , Quadriceps Muscle/blood supply , Spectroscopy, Near-Infrared/methods , Swimming/physiology , Adult , Breath Holding , Female , Hemodynamics/physiology , Humans , Oxygen Consumption/physiology
20.
Adv Exp Med Biol ; 1072: 119-125, 2018.
Article in English | MEDLINE | ID: mdl-30178333

ABSTRACT

Measurements of cerebral and muscle oxygenation (StO2) and perfusion ([tHb]) with functional near-infrared spectroscopy (fNIRS) and near infrared spectroscopy (NIRS), respectively, can be influenced by changes in systemic physiology. The aim of our study was to apply the oblique subspace projections signal decomposition (OSPSD) to find the contribution from systemic physiology, i.e. heart rate (HR), electrocardiography (ECG)-derived respiration (EDR) and partial pressure of carbon dioxide (pCO2) to StO2 and [tHb] signals measured on the prefrontal cortex (PFC) and calf muscle. OSPSD was applied to two datasets (n1 = 42, n2 = 79 measurements) from two fNIRS/NIRS speech studies. We found that (i) all StO2 and [tHb] signals contained components related to changes in systemic physiology, (ii) the contribution from systemic physiology varied strongly between subjects, and (iii) changes in systemic physiology generally influenced fNIRS signals on the left and right PFC to a similar degree.


Subject(s)
Muscle, Skeletal/blood supply , Physiological Phenomena/physiology , Prefrontal Cortex/blood supply , Signal Processing, Computer-Assisted , Spectroscopy, Near-Infrared/methods , Adolescent , Adult , Datasets as Topic , Female , Heart Rate/physiology , Humans , Male , Oxygen Consumption/physiology , Respiration
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