Effects on cerebral blood flow after single doses of the ß2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

AIMS: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, ß-adrenoceptor (ß-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant ß2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). METHODS: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, ß2-AR agonist clenbuterol (20-160 µg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a ß-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral ß2-AR responses. RESULTS: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 µg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 µg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of ß2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. CONCLUSIONS: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful ß2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Regional cerebral perfusion during the premonitory phase of triggered migraine: A double-blind randomized placebo-controlled functional imaging study using pseudo-continuous arterial spin labeling.

OBJECTIVE: To identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)-triggered migraine attacks. BACKGROUND: PS could provide insights into attack initiation and alterations in neuronal function prior to headache onset. METHODS: We undertook a functional imaging study using a double-blind placebo-controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine-like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty-three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo-continuous arterial spin labeling (3D pCASL). RESULTS: The primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p < 0.05 family-wise error-corrected) during NTG-induced PS. A separate region of interest analysis revealed significant CBF increases in the region of the hypothalamus (p = 0.006, effect size 0.77). Post hoc analyses revealed significant reductions in CBF over the occipital cortices in participants with a history of migraine with underlying aura (n = 14). CONCLUSIONS: We identified significant regional CBF changes associated with NTG-induced PS, consistent with other investigations and with novel findings, withstanding statistical comparison against placebo. These findings were not present in patients who continually took preventive medication. Additional findings were identified only in participants who experience migraine with aura. Understanding this biological and treatment-related heterogeneity is vital to evaluating functional imaging outcomes in migraine research.

Changes of regional cerebral blood flow after repeated transcranial direct current stimulation in healthy participants: a pilot study.

BACKGROUND: Transcranial direct current stimulation (tDCS) can potentially enhance brain function and cognition in healthy individuals as well as in patients with cognitive impairment. However, neural correlates of repeated tDCS remain relatively unexplored in a healthy population. PURPOSE: To assess the effects of repeated tDCS on regional cerebral blood flow (rCBF) in healthy volunteers in a pilot investigation. MATERIAL AND METHODS: Five healthy adults received bifrontal tDCS to the dorsolateral prefrontal cortex (F3-F4 montage, 1 mA intensity, 30 minutes/session, five sessions/week) over four weeks. All participants underwent brain single-photon emission computed tomography (SPECT) scans at baseline and one week after the last tDCS session. Changes in rCBF were examined using Statistical Parametric Mapping. RESULTS: Resting rCBF was significantly improved in the right superior frontal gyrus at the follow-up (P < 0.001). Adverse events were not reported and the stimulation was well-tolerated. CONCLUSION: Repeated tDCS may be effective for enhancing brain function in healthy participants. Larger sham-controlled studies should be performed to confirm our preliminary findings.

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder.

INTRODUCTION: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. METHODS: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. RESULTS: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. CONCLUSION: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

Regional cerebral blood flow in major depression treated with electroconvulsive therapy: an arterial spin labeling magnetic resonance study.

Until recently, regional cerebral blood flow (rCBF) in major depressive disorder (MDD) patients treated with electroconvulsive therapy (ECT) using arterial spin labeling (ASL) magnetic resonance imaging (MRI) have seldom been studied. We report here 10 patients with MDD treated by bilateral frontotemporal ECT. rCBF was assessed with ASL MRI pre- and post-ECT, and compared with patients treated by antidepressants. Compared to pre-ECT, rCBF significantly decreased in the bilateral frontal gyrus. Compared to medication, in patients treated with ECT, rCBF showed a significant decrease in the left amygdala, parahippocampal and olfactory gyrus, and right occipital, lingual, calcarine gyrus, and significantly increased in the bilateral frontal gyrus and right frontal gyrus. Compared with antidepressants, ECT altered rCBF, and showed potential to be a superior treatment for major depressive disorder.

Effects of a multicomponent day-care program on cerebral blood flow in patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is a prodromal phase of dementia and is considered an important period for intervention to prevent conversion to dementia. It has been well established that multicomponent day-care programs including exercise training, cognitive intervention and music therapy have beneficial effects on cognition, but the effects on cerebral blood flow (CBF) in MCI remain unknown. This study examined whether a multicomponent day-care program would have beneficial effects on the longitudinal changes of CBF in MCI patients. METHODS: Participants were 24 patients with MCI attending a day-care program; they underwent two 99 mTc-ethyl cysteinate dimer single photon emission computed tomography scans during the study period. We evaluated the association between the changes of regional cerebral blood flow and the attendance rate. RESULTS: There was a significant negative correlation between the reduction of regional CBF in the right parietal region and the attendance rate. We found no significant relation between the baseline CBF images and the attendance rate. CONCLUSIONS: Our results suggest that continuous participation in a multicomponent day-care program might prevent reduction in brain activity in patients with MCI.

Fasting prevents medetomidine-induced hyperglycaemia and alterations of neurovascular coupling in the somatosensory cortex of the rat during noxious stimulation.

Medetomidine and isoflurane are commonly used for general anaesthesia in fMRI studies, but they alter cerebral blood flow (CBF) regulation and neurovascular coupling (NVC). In addition, medetomidine induces hypoinsulinemia and hyperglycaemia, which also alter CBF regulation and NVC. Furthermore, sudden changes in arterial pressure induced by noxious stimulation may affect NVC differently under medetomidine and isoflurane anaesthesia, considering their different effects on vascular functions. The first objective of this study was to compare NVC under medetomidine and isoflurane anaesthesia during noxious stimulation. The second objective was to examine whether fasting may improve NVC by reducing medetomidine-induced hyperglycaemia. In male Wister rats, noxious electrical stimulation was applied to the sciatic nerve in fasted or non-fasted animals. CBF and local field potentials (LFP) were recorded in the somatosensory cortex to assess NVC (CBF/LFP ratio). The CBF/LFP ratio was increased by medetomidine compared with isoflurane (p = 0.004), but this effect was abolished by fasting (p = 0.8). Accordingly, medetomidine produced a threefold increase in blood glucose (p < 0.001), but this effect was also abolished by fasting (p = 0.3). This indicates that isoflurane and medetomidine anaesthesia alter NVC differently, but the undesirable glucose dependent effects of medetomidine on NVC can be prevented by fasting.

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle-aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99m Tc-HMPAO single-photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel-based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure.

PURPOSE: Previous work indicates that dynamic cerebral blood flow (CBF) regulation is impaired during hypercapnia; however, less is known about the impact of resting hypercapnia on regional CBF regulation during hypovolemia. Furthermore, there is disparity within the literature on whether differences between anterior and posterior CBF regulation exist during physiological stressors. We hypothesized: (a) lower-body negative pressure (LBNP)-induced reductions in cerebral blood velocity (surrogate for CBF) would be more pronounced during hypercapnia, indicating impaired CBF regulation; and (b) the anterior and posterior cerebral circulations will exhibit similar responses to LBNP. METHODS: In 12 healthy participants (6 females), heart rate (electrocardiogram), mean arterial pressure (MAP; finger photoplethosmography), partial pressure of end-tidal carbon dioxide (PETCO2), middle cerebral artery blood velocity (MCAv) and posterior cerebral artery blood velocity (PCAv; transcranial Doppler ultrasound) were measured. Cerebrovascular conductance (CVC) was calculated as MCAv or PCAv indexed to MAP. Two randomized incremental LBNP protocols were conducted (- 20, - 40, - 60 and - 80 mmHg; three-minute stages), during coached normocapnia (i.e., room air), and inspired 5% hypercapnia (~ + 7 mmHg PETCO2 in normoxia). RESULTS: The main findings were: (a) static CBF regulation in the MCA and PCA was similar during normocapnic and hypercapnic LBNP trials, (b) MCA and PCA CBV and CVC responded similarly to LBNP during normocapnia, but (c) PCAv and PCA CVC were reduced to a greater extent at - 60 mmHg LBNP (P = 0.029; P < 0.001) during hypercapnia. CONCLUSION: CBF regulation during hypovolemia was preserved in hypercapnia, and regional differences in cerebrovascular control may exist during superimposed hypovolemia and hypercapnia.

Possible neuroprotective effects of rasagiline in Alzheimer's disease: a SPECT study.

BACKGROUND: The current lack of effective treatments for Alzheimer's disease (AD) and the rapidly increasing burden of the disease highlight the urgent need to find new treatments. Despite accumulating evidence of the beneficial effects of rasagiline in neurodegenerative diseases such as Parkinson's disease, the effects of rasagiline on the brains of patients with AD have not been elucidated. PURPOSE: To examine the effects of rasagiline on regional cerebral flow (rCBF) in patients with AD using single photon emission computed tomography (SPECT). MATERIAL AND METHODS: Among 22 patients with AD, 11 patients received adjunctive rasagiline at 1 mg/day in conjunction with acetylcholinesterase inhibitors (AChEI); 11 patients were only treated with AChEI for about 1.6 years. All patients underwent brain technetium-99m hexamethylpropylene amine oxime SPECT scans and clinical assessments at baseline and follow-up visits. Annual percent changes in rCBF were compared between the groups in a voxel-wise manner. RESULTS: SPECT analysis revealed that the rasagiline-treated group showed more increased rCBF in the cingulate gyrus, inferior frontal gyrus, putamen, and thalamus compared to the comparison group (P < 0.005). CONCLUSION: We demonstrated that adjunctive rasagiline treatment may have beneficial effects on brain perfusion in patients with AD, suggesting potential neuroprotective effects.

Regional cerebral blood flow as predictor of response to occipital nerve block in cluster headache.

BACKGROUND: Cluster headache is an excruciating disorder with no cure. Greater occipital nerve blockades can transiently suppress attacks in approximately 50% of patients, however, its mechanism of action remains uncertain, and there are no reliable predictors of treatment response. To address this, we investigated the effect of occipital nerve blockade on regional cerebral blood flow (rCBF), an index of brain activity, and differences between treatment responders and non-responders. Finally, we compared baseline perfusion maps from patients to a matched group of healthy controls. METHODS: 21 male, treatment-naive patients were recruited while in a cluster headache bout. During a pain-free phase between headaches, patients underwent pseudo-continuous arterial spin labelled MRI assessments to provide quantitative indices of rCBF. MRIs were performed prior to and 7-to-21 days following treatment. Patients also recorded the frequency of their headache attacks in a daily paper diary. Neuropsychological assessment including anxiety, depression and quality of life measures was performed in a first, scanning free session for each patient. RESULTS: Following treatment, patients demonstrated relative rCBF reductions in posterior temporal gyrus, cerebellum and caudate, and rCBF increases in occipital cortex. Responders demonstrated relative rCBF increases, compared to non-responders, in medial prefrontal cortex and lateral occipital cortex at baseline, but relative reductions in cingulate and middle temporal cortices. rCBF was increased in patients compared to healthy controls in cerebellum and hippocampus, but reduced in orbitofrontal cortex, insula and middle temporal gyrus. CONCLUSIONS: We provide new mechanistic insights regarding the aetiology of cluster headache, the mechanisms of action of occipital nerve blockades and potential predictors of treatment response. Future investigation should determine whether observed effects are reproducible and extend to other headache disorders.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling.

BACKGROUND: Migraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine. METHODS: This study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated. RESULTS: In comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R. CONCLUSIONS: Our results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Changes in Regional Cerebral Perfusion Over Time in Idiopathic REM Sleep Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder is associated with increased risk of neurodegeneration, but the temporal evolution of regional perfusion, a marker of cerebral activity, has not been characterized. The objective of the current study was to study longitudinal regional perfusion in patients with idiopathic rapid eye movement sleep behavior disorder. METHODS: Thirty-seven patients and 23 controls underwent high-resolution single-photon emission computed tomography. After 17 months on average, scans were repeated for idiopathic rapid eye movement sleep behavior disorder patients. We compared regional cerebral blood flow between groups and over time. RESULTS: At baseline, patients showed lower relative regional perfusion in the anterior frontal and lateral parietotemporal cortex compared with controls. However, over time, patients showed an increase in relative regional perfusion in the anterior frontal, lateral parietal, and occipitotemporal cortex, reverting toward normal control levels. CONCLUSIONS: Patients with idiopathic rapid eye movement sleep behavior disorder showed significant areas of relative regional hypoperfusion, which disappeared over time to finally return to average levels, suggesting possible developing compensation in areas affected by neurodegeneration. © 2020 International Parkinson and Movement Disorder Society.

A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [-9; +10; +60] and L-LPM [-46; -12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76-100%) and specificity 88% (72-97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.

Cerebral perfusion abnormalities in patients with persistent postural-perceptual dizziness (PPPD): a SPECT study.

Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome with chronic dizziness interrupting daily life. Although the high levels of anxiety and functional changes in postural control strategy and multi-sensory information processing and integration may be underlying the pathophysiology, its neural mechanisms are poorly understood. The aim of this study was to examine the regional cerebral blood flow (rCBF) in patients with PPPD using single photon emission computed tomography (SPECT). A total of 25 patients with PPPD and 25 healthy controls participated in the study. All participants underwent brain SPECT and the patients completed the Dizziness Handicap Inventory. SPECT images were compared between the groups, and the correlation of rCBF and disease severity/duration was assessed in patients. Compared with controls, PPPD patients showed a significantly decreased rCBF in the insula and frontal lobe, mainly in the left posterior insula, bilateral superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and left medial orbital gyrus. Additionally, PPPD patients showed a significant rCBF increase in the bilateral cerebellum compared with controls. The results of our study suggest that the altered rCBF in the insular, frontal, and cerebellar cortices might be reflecting the process of maladaptation and the compensatory responses for the changes in PPPD.

Regional cerebral blood flow correlates eating abnormalities in frontotemporal dementia.

BACKGROUND: Eating abnormalities are one of the core symptoms of frontotemporal dementia (FTD), especially for behavioral variant FTD (bvFTD), and semantic variant primary progressive aphasia (svPPA). METHODS: A group of FTD patients (43 bvFTD, 29 svPPA) underwent single-photon emission CT (SPECT) to measure the region cerebral blood flow (rCBF). The Cambridge Behavioral Inventory (CBI) was used to measure the eating abnormalities. A whole-brain voxel-based correlation between eating abnormalities and rCBF was investigated. RESULTS: In bvFTD, the sweet preference was correlated with decreased rCBF in the bilateral gyrus rectus and temporal pole, and eating the same food was correlated with the left ventral anterior cingulate cortex. In svPPA, decreased rCBF in the left inferior temporal gyrus was correlated with eating the same food. CONCLUSIONS: These findings showed that either different symptoms in the same subtype or the same symptom in different subtypes of FTD may be correlated with different regions, indicating different neural mechanisms behind them.

Extracranial-intracranial bypass approach to cerebral revascularization: a historical perspective.

While the majority of cerebral revascularization advancements were made in the last century, it is worth noting the humble beginnings of vascular surgery throughout history to appreciate its progression and application to neurovascular pathology in the modern era. Nearly 5000 years of basic human inquiry into the vasculature and its role in neurological disease has resulted in the complex neurosurgical procedures used today to save and improve lives. This paper explores the story of the extracranial-intracranial approach to cerebral revascularization.

Decreased prefrontal oxygenation elicited by stimulation of limb mechanosensitive afferents during cycling exercise.

Our laboratory reported using near-infrared spectroscopy that feedback from limb mechanoafferents may decrease prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) during the late period of voluntary and passive cycling. To test the hypothesis that the decreased Oxy-Hb of the prefrontal cortex would be augmented depending on the extent of limb mechanoafferent input, the prefrontal Oxy-Hb response was measured during motor-driven one- and two-legged passive cycling for 1 min at various revolutions of pedal movement in 19 subjects. Furthermore, we examined whether calculated tissue oxygenation index (TOI) decreased during passive cycling as the Oxy-Hb did, simultaneously assessing blood flows of extracranial cutaneous tissue and the common and internal carotid arteries (CCA and ICA) with laser and ultrasound Doppler flowmetry. Minute ventilation and cardiac output increased and peripheral resistance decreased during passive cycling, depending on both revolutions of pedal movement and number of limbs, whereas mean arterial blood pressure did not change. Passive cycling did not change end-tidal CO2, suggesting absence of a hypocapnic change. Prefrontal Oxy-Hb decreased during passive cycling, being in proportion to revolution of pedal movement but not number of cycling limbs. In addition, prefrontal TOI decreased during passive cycling as Oxy-Hb did, whereas blood flows of forehead cutaneous tissue, CCA, and ICA did not change significantly. Thus, a decrease in Oxy-Hb reflected a decrease in tissue blood flow of the intracerebral vasculature but not the extracerebral compartment. It is likely that feedback from mechanoafferents decreased regional cerebral blood flow of the prefrontal cortex in relation to the revolutions of pedal movement.

Pattern of cerebral hypoperfusion according to the clinical staging in dementia with Lewy bodies.

This study aimed to detect different patterns of cerebral hypoperfusion in DLB according to clinical staging. Thirty-three patients with DLB were recruited by clinical dementia rating (CDR) stage. Compared with control, cerebral hypoperfusion was mainly observed in the lingual gyrus, the cuneus, the occipital gyrus in CDR 0.5 group; the fusiform gyrus, the middle temporal gyrus, and the posterior cingulate in CDR 1; and the lingual gyrus, the cuneus, the hippocampus, the fusiform gyrus, and the inferior frontal gyrus in CDR 2. Our findings suggest that cerebral hypoperfusion spreads to the frontal cortex and temporal lobes as disease progresses.

An increase in prefrontal oxygenation at the start of voluntary cycling exercise was observed independently of exercise effort and muscle mass.

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.