BACKGROUND: Through their action on the locus coeruleus, ␣ 2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this observational study was to map brain regions whose activity is modified by clonidine infusion so as to better understand its loci of action, especially in relation to sedation. METHODS: Six ASA I–II right-handed volunteers were recruited. Electroencephalogram (EEG) was monitored continuously. After a baseline H215O activation scan, clonidine infusion was started at a rate ranging from (...) 6 to 10 ␮g ⅐ kgϪ1 ⅐ h Ϫ1. A sequence of 11 similar scans was then performed at 8 min intervals. Plasma clonidine concentration was measured. Using statistical parametric mapping, we sought linear correlations between normalized regional cerebral blood flow (rCBF), an indicator of regional brain activity, and plasma clonidine concentration or spindle EEG activity. RESULTS: Clonidine induced clinical sedation and EEG patterns (spindles) comparable to early stage nonrapid eye movement sleep. A significant negative linear correlation between clonidine concentration and rCBF or spindle activity was observed in the thalamus, prefrontal, orbital and parietal association cortex, posterior cingulate cortex, and precuneus. CONCLUSIONS: The EEG patterns and decreases in rCBF of specific brain regions observed during clonidine-induced sedation are similar to those of early stage nonrapid eye movement sleep. Patterns of deactivated brain regions are also comparable to those observed during general anesthesia or vegetative state, reinforcing the hypothesis that alterations in the activity of a common network occur during these modified conscious states. (shrink)

Patients with schizophrenia have a higher risk of cardiovascular diseases and higher mortality from them than does the general population; however, the underlying mechanism remains unclear. Impaired cerebral autoregulation is associated with cerebrovascular diseases and their mortality. Increased or decreased cerebral blood flow in different brain regions has been reported in patients with schizophrenia, which implies impaired cerebral autoregulation. This study investigated the cerebral autoregulation in 21 patients with schizophrenia and 23 age- and sex-matched (...) healthy controls. None of the participants had a history of cardiovascular diseases, hypertension, or diabetes. All participants underwent 10-min blood pressure and cerebral blood flow recording through finger plethysmography and Doppler ultrasonography, respectively. Cerebral autoregulation was assessed by analyzing two autoregulation indices: the mean blood pressure and cerebral blood flow correlation coefficient (Mx), and the phase shift between the waveforms of blood pressure and cerebral blood flow determined using transfer function analysis. Compared with the controls, the patients had a significantly higher Mx (0.257 vs. 0.399, p = 0.036) and lower phase shift (44.3° vs. 38.7° in the 0.07–0.20 Hz frequency band, p = 0.019), which indicated impaired maintenance of constant cerebral blood flow and a delayed cerebrovascular autoregulatory response. Impaired cerebral autoregulation may be caused by schizophrenia and may not be an artifact of coexisting medical conditions. The mechanism underlying impaired cerebral autoregulation in schizophrenia and its probable role in the development of cerebrovascular diseases require further investigation. (shrink)

Concepts and experimental results taken frombehavioral pharmacology, functional brain imaging,brain physiology, and behavioral neuroscience, wereused to develop the hypothesis that behavioraltolerance can, in part, be attributed to cellulartolerance. It is argued that task specific activationof circumscribed neuronal populations gives rise tocorresponding increases in regional cerebral bloodflow such that neurons related to task performance areexposed to higher effective doses of blood-borne drugthan neuronal groups not highly activated by thebehavioral task. Through this cerebral hemodynamicregulatory mechanism cellular tolerance phenomena (...) canat least partially account for behavioral tolerance(i.e., tolerance conferred through drugged practice). (shrink)

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of (...) long-term meditators was significantly higher compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function. (shrink)

Brain mapping studies using dynamic imaging methods demonstrate areas regional cerebral blood flow (rCBF) decreases, as well as areas where increases, during performance of various experimental tasks. Task holds for both sets of cerebral blood flow changes (CBF), providing the opportunity to investigate areas that become and “activated” in the experimental condition relative to control state. Such data yield the intriguing observation that in areas in emotional processing, such as the amygdala, the posteromedial (...) cortex, and the ventral anterior cingulate cortex, although flow as expected during specific emotion-related tasks, flow decreases performance of some attentionally demanding, cognitive tasks. Conversely, in some of the areas that appear to subserve cognitive functions, as the dorsal anterior cingulate and the dorsolateral prefrontal cortices, increases while performing attentionally demanding cognitive tasks, but during some experimentally induced and pathological emotional Although the specific nature of such reciprocal patterns of regional remains unclear, they may reflect an important cross-modal interaction during mental operations. The possibility that neural activity is less in areas required in emotional processing during some higher cognitive processes holds implications for the mechanisms underlying interactions cognition and emotion. Furthermore, the possibility that neural in some cognitive-processing areas is suppressed during intense states suggests mechanisms by which extreme fear or severe may interfere with cognitive performance. (shrink)

We have previously shown that several brain areas are activated both during sequence learning at wake and during subsequent rapid-eye-movements (REM) sleep (Nat. Neurosci. 3 (2000) 831– 836), suggesting that REM sleep participates in the reprocessing of recent memory traces in humans. However, the nature of the reprocessed information remains open. Here, we show that regional cerebral reactivation during posttraining REM sleep is not merely related to the acquisition of basic visuomotor skills during prior practice of the serial (...) reaction time task, but rather to the implicit acquisition of the probabilistic rules that defined stimulus sequences. Moreover, functional connections between the reactivated cuneus and the striatum—the latter being critical for implicit sequence learning—are reinforced during REM sleep after practice on a probabilistic rather than on a random sequence of stimuli. Our results therefore support the hypothesis that REM sleep is deeply involved in the reprocessing and optimization of the high-order information contained in the material to be learned. In addition, we show that the level of acquisition of probabilistic rules attained prior to sleep is correlated to the increase in regional cerebral blood flow during subsequent REM sleep. This suggests that posttraining cerebral reactivation is modulated by the strength of the memory traces developed during the learning episode. Our data provide the first experimental evidence for a link between behavioral performance and cerebral reactivation during REM sleep. © 2003 Elsevier Inc. All rights reserved. (shrink)

The present study examined deep gray matter perfusion in neonates with congenital heart disease (CHD) with arterial spin labeling magnetic resonance imaging preoperatively. We found that neonates with cyanotic CHD showed lower right thalamus compared with controls and lower right basal ganglia perfusion compared with acyanotic CHD. When the CHD group was assessed as a whole, it showed slightly decreased left thalamus perfusion compared with controls. The results suggest that cardiac physiology plays a crucial part in changes in regional (...) cerebral perfusion. Perfusion with arterial spin labeling may be a useful marker of high risk for impaired cerebral blood flow auto-regulation and cerebral hypoperfusion in neonates with CHD. (shrink)

Aircraft with increasingly high performance were important to the war effort in World War II. Changes in technology allowed aircraft to reach faster speeds and to complete missions at higher altitudes. With these changes came new obstacles for pilots who had to tolerate these stresses. Of primary concern to the U.S. War Department was the loss of consciousness that often occurred with high-speed maneuvers and especially during pull-up after dive-bombing missions. In some cases, pilots would experience up to 9G of (...) force during rapid ascent, much more than the 6G threshold that typically leads to loss of consciousness. In 1941, a research team in Red Wing, MN, proposed experiments to elucidate the mechanism .. (shrink)

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography, brain imaging, genetics, and biochemistry are reviewed: Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. Studies of the absolute level of regional cerebral (...) blood flow show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index. High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory. (shrink)

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend (...) many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N= 20), recent SRC youth (N= 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p= 0.032), decreased functional connectivity between the caudate and each of the pallidum (p= 0.035) and thalamus (p= 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p< 0.038); no changes were observed in recovered asymptomatic youth (N= 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N= 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p= 0.011) and reduced activity in the cerebellum (p= 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p< 0.014), reduced activity of the pallidum (p= 0.002), increased CBF in the caudate (p= 0.005), and reduced diffusivity in the central corpus callosum (p< 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome. (shrink)

Computerized relaxation training has been suggested as an effective and easily accessible intervention for individuals with psychological distress. To better elucidate the neural mechanism that underpins the effects of relaxation training, we investigated whether a 10-session computerized relaxation training program changed prefrontal gamma-aminobutyric acid levels and cerebral blood flow in women with psychological distress. We specifically focused on women since they were reported to be more vulnerable to develop stress-related disorders than men. Nineteen women with psychological distress (...) but without a diagnosis of psychiatric disorders received the 10-day computerized relaxation training program that consisted of 30-min cognitive-relaxation training and 10-min breathing-relaxation training per day. At baseline and post-intervention, perceived stress levels, anxiety, fatigue, and sleep quality were assessed by self-report questionnaires. Brain magnetic resonance spectroscopy and arterial spin labeling scans were also performed before and after the intervention to evaluate GABA levels and relative CBF in the prefrontal region. Levels of perceived stress, anxiety, fatigue, and sleep quality improved following 10 sessions of computerized relaxation training, resulting in a significant relief in composite scores of stress-related symptoms. The prefrontal GABA levels decreased, while relative CBF increased after the intervention. In addition, a greater increase in relative prefrontal CBF was associated with better composite scores of stress-related symptoms following the intervention. The current findings suggest that computerized relaxation training may improve stress-related symptoms through modulating the prefrontal GABA levels and CBF in women with psychological distress. (shrink)

Pericytes, like vascular smooth muscle cells, are perivascular cells closely associated with blood vessels throughout the body. Pericytes are necessary for vascular development and homeostasis, with particularly critical roles in the brain, where they are involved in regulating cerebral blood flow and establishing the blood-brain barrier. A role for pericytes during neurovascular disease pathogenesis is less clear—while some studies associate decreased pericyte coverage with select neurovascular diseases, others suggest increased pericyte infiltration in response to hypoxia (...) or traumatic brain injury. Here, we used an endothelial loss-of-function Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)/Notch mediated mouse model of brain arteriovenous malformation (AVM) to investigate effects on pericytes during neurovascular disease pathogenesis. We tested the hypothesis that pericyte expansion, via morphological changes, and Platelet-derived growth factor B/Platelet-derived growth factor receptor β (Pdgf-B/Pdgfrβ)-dependent endothelial cell-pericyte communication are affected, during the pathogenesis of Rbpj mediated brain AVM in mice. Our data show that pericyte coverage of vascular endothelium expanded pathologically, to maintain coverage of vascular abnormalities in brain and retina, following endothelial deletion of Rbpj. In Rbpj-mutant brain, pericyte expansion was likely attributed to cytoplasmic process extension and not to increased pericyte proliferation. Despite expanding overall area of vessel coverage, pericytes from Rbpj-mutant brains showed decreased expression of Pdgfrβ, Neural (N)-cadherin, and cluster of differentiation (CD)146, as compared to controls, which likely affected Pdgf-B/Pdgfrβ-dependent communication and appositional associations between endothelial cells and pericytes in Rbpj-mutant brain microvessels. By contrast, and perhaps by compensatory mechanism, endothelial cells showed increased expression of N-cadherin. Our data identify cellular and molecular effects on brain pericytes, following endothelial deletion of Rbpj, and suggest pericytes as potential therapeutic targets for Rbpj/Notch related brain AVM. (shrink)

Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV) lateralization data, obtained with functional TransCranial Doppler (fTCD) ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralization (...) Index (LI) for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG) at two difficulty levels. In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG, and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training. CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated. The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques. (shrink)

ObjectiveTo investigate the instant impact of hemodialysis on the cerebral morphological measurements of patients with end-stage renal disease.Materials and methodsTwenty-five patients undergoing maintenance HD and twenty-eight age-, sex-, and education-matched healthy control were included. The HD group and HC group had 3D high-resolution structural magnetic resonance imaging scans twice and once, respectively. Both groups underwent neuropsychologic tests. The morphological measurements of structural MRI were measured using CAT12 and these measures were compared among three groups. The relationship between morphological measures (...) and clinical parameters and neuropsychological tests were investigated through multiple regression analysis.ResultsCompared to the HC group, the cortical thickness before HD significantly decreased in the bilateral temporal lobe and significantly decreased in the left superior temporal gyrus after HD. The cortical thickness significantly increased in the bilateral temporal lobe, frontal lobe and occipital lobe after HD compared to before HD. The sulcus depth in the bilateral insula, frontal lobe, and parietal lobe after HD significantly increased compared to before HD. No significant differences in sulcus depth between HD and HC were detected. After HD, the cortical thickness of the right parsopercularis was positively correlated with the number connection test-A. Cortical thickness in multiple regions were positively correlated with blood flow velocity and cortical thickness in the left parahippocampal gyrus was negatively correlated with ultrafiltration volume. Patients showed better performance in the digit symbol test and line tracing test after HD compared to before HD, but there were no significant differences in the comparison of neuropsychologic tests between patients and HC.ConclusionThe instant morphological changes were captured during a single hemodialysis in HD patients. There was an association between these instant changes in the brain and clinical parameters and neuropsychologic tests. This work implied the instant impact of a single hemodialysis impact on the brain in HD patients. (shrink)

BackgroundSonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography.Materials and methodsMontreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (...) (MCA), bilaterally, and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT).ResultsWorse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted.ConclusionThese treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement. (shrink)

Awareness is a personal experience, which is only accessible to the rest of world through interpretation. We set out to identify a neural correlate of visual awareness, using brief subliminal and supraliminal verbal stimuli while measuring cerebral blood flow distribution with H215O PET. Awareness of visual verbal stimuli differentially activated medial parietal association cortex (precuneus), which is a polymodal sensory cortex, and dorsolateral prefrontal cortex, which is thought to be primarily executive. Our results suggest participation of these (...) higher order perceptual and executive cortical structures in visual verbal awareness. (shrink)

While philosophers have, for centuries, pondered upon the relation between mind and brain, neuroscientists have only recently been able to explore the connection analytically — to peer inside the black box. This ability stems from recent advances in technology and emerging neuroimaging modalities. It is now possible not only to produce remarkably detailed images of the brain’s structure (i.e. anatomical imaging) but also to capture images of the physiology associated with mental processes (i.e. functional imaging). We are able to see (...) how specific regions of the brain ‘light up’ when activities such as reading this book are performed, and how our neurons and their elaborate cast of supporting cells organize and coordinate their tasks. As demonstrated in the other chapters of this book, the mapping of the human mind (mostly by measuring regional changes in blood flow, initially by positron emission tomography (PET) and recently by functional magnetic resonance imaging or (fMRI)) has provided insight into the functional neuroanatomy of neuropsychiatric diseases. Amazingly, the idea that regional cerebral blood flow (rCBF) is related intimately to brain function goes back more than a century. As is often the case in science, this idea was initially the result of unexpected observations. The Italian physiologist Angelo Mosso first expressed the idea while studying pulsations of the living human brain that keep pace with the heartbeat (Mosso, 1881). These brain pulsations can be observed on the surface of the fontanelles in newborn children. Mosso believed that they reflected blood flow to the brain. He observed similar pulsations in an adult with a post-traumatic skull defect over the frontal lobes. While studying this subject, a peasant named Bertino, Mosso observed a sudden increase in the magnitude of the ‘brain’s heart-beats’ when the church bells signalled 12 o’clock, the time for a required prayer. The changes in brain pulsations occurred independently of any change in pulsations in the forearm.. (shrink)

Thoracoabdominal normothermic regional perfusion (TA-NRP), a new method of controlled donation after circulatory death, seems to provide more and better organs for patients on organ transplant waiting lists compared to standard controlled donation after circulatory death. Despite its benefits, the ethical permissibility of TA-NRP is currently a highly debated issue. The recent statement published by the American College of Physicians (ACP) highlights the reasons for these debates. Critics’ main concern is that TA-NRP violates the Dead Donor Rule. This paper (...) presents an ethical analysis of the objections raised by the ACP against TA-NRP and argues that TA-NRP is not only morally permissible but also morally required where it is financially and technically feasible. To support this conclusion, the concepts of ‘resuscitation,’ ‘intention,’ ‘irreversibility,’ ‘permanence,’ ‘impossibility,’ and ‘respect’ in the context of TA-NRP are explored. Additionally, the ethical permissibility of this procedure is evaluated through the lenses of Utilitarianism, Kantianism, the core principles of bioethics, and the Doctrine of Double Effect. This ethical analysis demonstrates why the ACP’s objection lacks a solid moral foundation and conflates moral and legal considerations. This paper also argues that extra measures are needed to ensure the moral permissibility of TA-NRP, emphasizing the importance of informed consent, additional brain blood flow and activity monitoring, and a contingency plan to abort the organ procurement process if a sign of morally relevant brain activity is detected. (shrink)

Using positron emission tomography (PET) and regional cerebral blood flow (rCBF) measurements, we investigated the cerebral correlates of consciousness in a sequence learning task through a novel application of the Process Dissociation Procedure, a behavioral paradigm that makes it possible to separately assess conscious and unconscious contributions to performance. Results show that the metabolic response in the anterior cingulate / mesial prefrontal cortex (ACC / MPFC) is exclusively and specifically correlated with the explicit component of (...) performance during recollection of a learned sequence. This suggests a significant role for the ACC / MPFC in the explicit processing of sequential material.  2003 Elsevier Science B.V. All rights reserved. (shrink)

IntroductionDeep brain stimulation is an effective treatment for advanced Parkinson’s disease with the targeting bilateral subthalamic nucleus or globus pallidus internus. So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.Materials and MethodsSeventeen patients with Parkinson’s disease who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson’s (...) Disease Rating Scale part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination, Frontal Assessment Battery, Geriatric Depression Scale, levodopa equivalent dose, and cerebral blood flow by single photon emission computed tomography. Patient backgrounds were compared between four cohorts with favorable and unfavorable postoperative outcome.ResultsSignificant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores.DiscussionUnilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms. (shrink)

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants (...) aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy. (shrink)

BackgroundExercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in (...) a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy dynamic monitoring in comparison with resistance exercise.MethodsA cross-over study design was adopted in this study, and 15 healthy young subjects were randomly divided into group A and group B according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min, and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model in different regions of interest, and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.ResultsThe activation differences of Task 1 and Task 2 in the right premotor cortex and the left PMC were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area, left dorsolateral prefrontal cortex, left and right PMC between baseline and Post-task 1. The differences in systolic pressure between the two groups at three time points among women were statistically significant.ConclusionIn this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases. (shrink)

PurposeTo explore the changes of cerebral blood flow and fractional anisotropy in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level.Materials and MethodsIn total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural (...) MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales.ResultsAfter rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract. The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus.ConclusionOur results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST. (shrink)

The potential anesthetic neurotoxicity on the neonate is an important focus of research investigation in the field of pediatric anesthesiology. It is essential to understand how these anesthetics may affect the development and growth of neonatal immature and vulnerable brains. Functional magnetic resonance imaging has suggested that using anesthetics result in reduced functional connectivity may consider as core sequence for the neurotoxicity and neurodegenerative changes in the developed brain. Anesthetics either directly impact the primary structures and functions of the brain (...) or indirectly alter the hemodynamic parameters that contribute to cerebral blood flow in neonatal patients. We hypothesis that anesthetic agents may either decrease the brain functional connectivity in neonatal patients or animals, which was observed by fMRI. This review will summarize the effect and mechanism of anesthesia on the rapid growth and development infant and neonate brain with fMRI through functional connectivity. It is possible to provide the new mechanism of neuronal injury induced by anesthetics and objective imaging evidence in animal developing brain. (shrink)

The blood oxygen level dependent effect that provides the contrast in functional magnetic resonance imaging has been demonstrated to affect the linewidth of spectral peaks as measured with magnetic resonance spectroscopy and through this, may be used as an indirect measure of cerebral blood flow related to neural activity. By acquiring MR-spectra interleaved with frames without water suppression, it may be possible to image the BOLD effect and associated metabolic changes simultaneously through changes in the linewidth (...) of the unsuppressed water peak. The purpose of this study was to implement this approach with the MEGA-PRESS sequence, widely considered to be the standard sequence for quantitative measurement of GABA at field strengths of 3 T and lower, to observe how changes in both glutamate and GABA levels may relate to changes due to the BOLD effect. MR-spectra and fMRI were acquired from the occipital cortex of 20 healthy participants whilst undergoing intrascanner visual stimulation in the form of a red and black radial checkerboard, alternating at 8 Hz, in 90 s blocks comprising 30 s of visual stimulation followed by 60 s of rest. Results show very strong agreement between the changes in the linewidth of the unsuppressed water signal and the canonical haemodynamic response function as well as a strong, negative, but not statistically significant, correlation with the Glx signal as measured from the OFF spectra in MEGA-PRESS pairs. Findings from this experiment suggest that the unsuppressed water signal provides a reliable measure of the BOLD effect and that correlations with associated changes in GABA and Glx levels may also be measured. However, discrepancies between metabolite levels as measured from the difference and OFF spectra raise questions regarding the reliability of the respective methods. (shrink)

WHO II low grade glioma evolves inevitably to anaplastic transformation. Magnetic resonance imaging is a good non-invasive way to watch it, by hemodynamic and metabolic modifications, thanks to multinuclear spectroscopy 1H/31P. In this work we study a multi-scale minimal model of hemodynamics and metabolism applied to the study of gliomas. This mathematical analysis leads us to a fast-slow system. The control of the position of the stationary point brings to the concept of domain of viability. Starting from this system, the (...) equations bring to light the parameters that push glioma cells out of their domain of viability. Four fundamental factors are highlighted. The first two are cerebral blood flow and the rate of lactate transport through monocarboxylate transporters, which must be reduced in order to push glioma out of its domain of viability. Another factor is the intra arterial lactate, which must be increased. The last factor is pH, indeed a decrease of intra cellular pH could interfere with glioma growth. These reflections suggest that these four parameters could lead to new therapeutic strategies for the management of low grade gliomas. (shrink)

Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a (...) previously developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation Balloon model of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas. (shrink)

SignificanceElectrical burns can cause severe damage to the nervous system, resulting in autonomic dysfunction with reduced cerebral perfusion. However, few studies have investigated these consequences.AimTo elucidate changes in prefrontal cerebral hemodynamics using functional near-infrared spectroscopy (fNIRS) during the head-up tilt table test (HUT) for patients with electrical burns.ApproachWe recruited 17 patients with acute electrical burns within 1 week after their accidents and 10 healthy volunteers. The NIRS parameters acquired using an fNIRS device attached to the forehead were analyzed (...) in five distinct HUT phases.ResultsBased on their HUT response patterns, patients with electrical burns were classified into the group with abnormal HUT results (APG, n = 4) or normal HUT results (NPG, n = 13) and compared with the healthy control (HC, n = 10) participants. We found trends in hemodynamic changes during the HUT that distinguished HC, NPG, and APG. Reduced cerebral perfusion and decreased blood oxygenation during the HUT were found in both the NPG and APG groups. Patients with electrical burns had autonomic dysfunction compared to the HC participants.ConclusionsUsing fNIRS, we observed that acute-stage electrical burn injuries could affect cerebral perfusion. (shrink)

ObjectiveThe correlation between the performance of coordination movement and brain activity is still not fully understood. The current study aimed to identify activated brain regions and brain network connectivity changes for several coordinated finger movements with different difficulty levels and to correlate the brain hemodynamics and connectivity with kinematic performance.MethodsTwenty-one right-dominant-handed subjects were recruited and asked to complete circular motions of single and bilateral fingers in the same direction and in opposite directions on a plane. Kinematic data including radius and (...) angular velocity at each task and synchronized blood oxygen concentration data using functional near-infrared spectroscopy were recorded covering six brain regions including the prefrontal cortex, motor cortex, and occipital lobes. A general linear model was used to locate activated brain regions, and changes compared with baseline in blood oxygen concentration were used to evaluate the degree of brain region activation. Small-world properties, clustering coefficients, and efficiency were used to measure information interaction in brain activity during the movement.ResultIt was found that the radius error of the dominant hand was significantly lower than that of the non-dominant hand in both clockwise and counterclockwise movements. The fNIRS results confirmed that the contralateral brain region was activated during single finger movement and the dominant motor area was activated in IP movement, while both motor areas were activated simultaneously in AP movement. The Δhbo were weakly correlated with radius errors. Brain information interaction in IP movement was significantly larger than that from AP movement in the brain network in the right prefrontal cortex. Brain activity in the right motor cortex reduces motor performance, while the right prefrontal cortex region promotes it.ConclusionOur results suggest there was a significant correlation between motion performance and brain activation level, as well as between motion deviation and brain functional connectivity. The findings may provide a basis for further exploration of the operation of complex brain networks. (shrink)

In this paper, we report on an experiment with The Walking Dead (TWD), which is a narrative-driven adventure game with morally charged decisions set in a post-apocalyptic world filled with zombies. This study aimed to identify physiological markers of moral decisions and non-moral decisions using infrared thermal imaging (ITI). ITI is a non-invasive tool used to capture thermal variations due to blood flow in specific body regions that might be caused by sympathetic activity. Results show that moral decisions (...) seem to elicit a significant decrease in temperature in the chin region 20 seconds after participants are presented with a moral decision. However, given the small sample involved, and the lack of significance in other regions, future studies might be needed to confirm the results obtained in this work. (shrink)

Recently, we identified myeloid‐derived growth factor (MYDGF) as a blood flow‐induced angiocrine signal that promotes human and mouse hepatocyte proliferation and survival. Here, we review literature reporting changes in blood flow after partial organ resection in the liver, lung, and kidney, and we describe the angiocrine signals released by endothelial cells (ECs) upon blood flow alterations in these organs. While hepatocyte growth factor (HGF) and MYDGF are important angiocrine signals for liver regeneration, by now, (...) angiocrine signals have also been reported to stimulate hyperplasia and/or hypertrophy during the regeneration of lungs and kidneys. In addition, angiocrine signals play a critical role in tumor growth. Understanding the mechano‐elastic properties and flow‐mediated alterations in the organ‐specific microvasculature is crucial for therapeutic approaches to maintain organ health and initiate organ renewal. (shrink)

Neuroimaging has been to neuroethics what free will and determinism has been, albeit for much longer, to philosophy: pillars for scholarly inquiry and curiosity, and entries to dialogue, debate, and discovery. With interest piqued by reproducible measures of regional blood flow in the human brain under well-defined conditions such as existential problem solving, decision-making, and trust, this article meticulously documents emerging trends involving functional MRI studies. The article builds on that work and examines the hypothesis that almost (...) twenty years after the first wave of such studies, the focus on neuroimaging and its application to complex and profoundly personal human behaviors has not abated. Neuroimaging studies remain an unwavering source of energy for the field. It reviews some of the reasons that they have provoked so much attention in neuroethics and elsewhere, presenting a 2002–2008 update to the trends that documented for 1991–2001, comparing this second generation of data to the first. (shrink)

The articles by Bernat, Busch, Dudzinski et al., and Derse illustrate the difficulties with reconciling normothermic regional perfusion (NRP) with the dead donor rule (DDR) (Bernat forthcoming; Busch forthcoming; Dudzinski et al. forthcoming; Derse forthcoming). I appreciate their arguments because they help illuminate the issues that generate a dilemma: either reject NRP or the DDR. I am convinced that the dilemma is unavoidable because the procurement team is involved with determining and securing the death of the donor when circulation (...) restarts. Evidence for this is found in the reasons and recommendations given for blocking blood flow to the brain, both of which betray a lack of certainty over the donor’s vital status. The surgical activity in NRP therefore conflicts with the values the DDR protects: respect for the donor’s life and avoidance of conflict of interest. (shrink)

ObjectiveTo explore the effect of independently developed transcranial pulsed current stimulation on alleviating athlete’s mental fatigue.MethodsA total of 60 college athletes were randomly divided into the active stimulation group and the sham stimulation group. Subjective questionnaires, behavior test, and functional near-infrared spectroscopy test were conducted before and after the experiment. Two-way ANOVA with repeated measures was used to compare the differences in mental fatigue indexes before and after the two experimental conditions.ResultsAfter 7 days of exercise training, there was a significant (...) difference in the main effect of the time factor in all indexes of the two groups. The scores of rated perceived exertion scale, positive and negative affect schedule, critical flicker frequency, and reaction time, in the tPCS treatment group, were better than those in the sham stimulation group. After 7 days of exercise training, all the subjects had different degrees of athlete’s mental fatigue; the subjects in the active stimulation group have a good evaluation of the tPCS developed by the research group without adverse actions.ConclusiontPCS intervention can improve emotional state, reduce the subjective evaluation of fatigue, improve behavioral levels such as attention and reaction time and increase cerebral prefrontal blood flow and oxygen supply. (shrink)

K L Kahlbaum published in 1874 the first recorded description of catatonia. Akinetic catatonia is now defined as a neuropsychiatric syndrome principally characterised by akinesia, mutism, stupor, and catalepsy. 1 Even if some advances have been made in the recognition of catatonia, in particular by the development of different rating scales, 1 the pathophysiology of this syndrome is not clearly established. A right handed 14 year old girl presented with akinetic catatonia during an episode of depression in the context of (...) a bipolar type I disorder. Her catatonic status was characterised by akinesia with brief episodic spontaneous stereotyped movements, mutism, no spontaneous oral intake, catalepsy, waxy flexibility, and stupor with brief occasional eye contacts. This corresponded to a total score of 19 on the Northoff Catatonia Scale.1 Electroencephalogram performed one day after onset of symptoms showed diffuse theta activity with sporadic diffuse delta activity. Cerebral magnetic resonance imaging was normal. Brain positron emission tomographies (PET) were obtained on a CTI-Siemens HR+ tomograph. A first PET (PET1) using (18F(- fluorodeoxyglucose (FDG) was performed on day 2 in a drug free state. Thereafter, intramuscular injection of 2 mg of lorazepam induced rapid clinical remission of the akinetic phase. Oral lorazepam was then given (3.75 mg/day) during five days. On day 8, a second PET with FDG was performed while the patient was treated by olanzapine (15 mg/day) and presented hyperactivity, logorrhoea, and disinhibition characterised by uncontrolled social interactions and physical contacts. Neuropsychological testing performed some days after remission revealed no apraxia or language disturbances but dysfunction of executive tasks manifested in the revised Wisconsin card sorting, the Tower of London, Stroop, and Trailmaking tests. Voxel based analyses comparing patient’s cerebral glucose metabolism with that of 29 right handed healthy controls (16 women and 13 men, mean age 32) were performed using Statistical Parametric Mapping (SPM99) (Wellcome Department of Cognitive Neurology, London, UK).. (shrink)

Modern readers view ancient theories of blood flow through the lens of circulation. Since the nineteenth century, scholarly work on the ancient understanding of the vascular system has run the gamut from attempting to prove that an ancient author had in fact, to some extent or another, pre-empted Harvey's discovery of the circulation of the blood or towards attempting, often with some empathetic embarrassment, to explain the failure on the part of an ancient author to notice something (...) that seems so obvious to the modern eye. Thus C.R.S. Harris's 1973 book The Heart and Vascular System in Ancient Greek Medicine, which remains the standard on the topic, opens with a sentence in which he marvels at how the otherwise admirable ancient Greek physicians could have ‘failed entirely to arrive at any conception of the circulation of the blood’. This modern vantage point has had an unfortunate effect. In the case of Aristotle in particular, understanding of his cardiovascular system has been diminished by a tendency to define it in contradistinction to our own modern understanding of circulation. By deliberately uncoupling from the framework of modern physiology, this paper will offer a richer and more accurate picture of his views. (shrink)

This article combines in-depth interviews and Karen Barad's work on materiality to think about the ways in which the materiality of blood might be understood in relation to sociality and blood-borne virus prevention among BDSM (bondage and domination, dominance and submission and sadomasochism) body modification practitioners in Sydney, Australia. In doing so, it confronts questions of how the materiality of blood can be theorized in ways that neither presume a fixed, a priori ontological status or essence, nor (...) exclude it from an active role in the production of realities. In taking account of both its co-constitutive role in practice, and its figurative power (as flow) in understanding the mind/body, discourse/materiality conjunctions at work in BDSM body modification practice, we aim to illuminate further the imbrication of materiality and meaning, and generate a more complex and fruitful account of blood for the purposes of blood-borne virus prevention and education. (shrink)

The concept of locally specialized functions dominates research on higher brain function and its disorders. Locally specialized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psychological studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that (...) activate synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our understanding of cognitive coordination, its neural basis, and its relevance to psychopathology. Key Words: attention; cerebral cortex; cognitive coordination; cognitive neuropsychiatry; cognitive neuropsychology; context disorganization; Gamma rhythms; Gestalt theory; glutamate; grouping; memory; NMDA-receptors; PCP-psychosis; perceptual organization; schizophrenia. (shrink)

Experiential and behavioural aspects of emotions can be measured readily but developing a contactless measure of emotions’ physiological aspects has been a major challenge. We hypothesised that different emotion-evoking films can produce distinctive facial blood flow patterns that can serve as physiological signatures of discrete emotions. To test this hypothesis, we created a new Transdermal Optical Imaging system that uses a conventional video camera to capture facial blood flows in a contactless manner. Using this and deep machine (...) learning, we analysed videos of the faces of people as they viewed film clips that elicited joy, sadness, disgust, fear or a neutral state. We found that each of these elicited a distinct blood flow pattern in the facial epidermis, and that Transdermal Optical Imaging is an effective contactless and inexpensive tool to the reveal physiological correlates of discrete emotions. (shrink)