Regional Tissue Oxygenation Research Articles

Pressor-dependent regional tissue oxygenation changes after polytrauma

Journal of the American College of Surgeons 205(3):p S32, September 2007. | DOI: 10.1016/j.jamcollsurg.2007.06.073

Effects of the selective endothelin A (ETA) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage – preliminary results from a randomized clinical series

To study the effects of clazosentan, a new selective endothelin receptor subtype A antagonist, on cerebral perfusion and cerebral oxygenation following severe aneurysmal subarachnoid haemorrhage (aSAH). All 12 patients treated at our institution in the context of a phase IIa, multicenter, randomized trial on clazosentan's safety and efficacy in reducing the incidence of angiographic cerebral vasospasm were included in this substudy. The phase IIa study (n = 34) consisted of two parts: a double-blind, randomized Part A (clazosentan 0.2 mg/kg/h versus placebo) and an open-label Part B (clazosentan 0.4 mg/kg/h for 12 h followed by 0.2 mg/kg/h) for patients with established vasospasm. In parallel to the phase IIa study protocol, which included assessment of vasospasm by angiography and transcranial Doppler sonography, we determined regional cerebral blood flow (rCBF), cerebrovascular resistance, and regional tissue oxygenation. Cerebral perfusion was comparable between treatment groups during the early post-bleeding period (rCBF placebo, 22.6 +/- 3.5 ml/100 g/min versus rCBF clazosentan, 23.9 +/- 1.1 ml/100 g/min). By the time of control angiography (day 8 after aSAH), rCBF decreased by 50% in the placebo group (11.3 +/- 6.7 ml/ 100 g/min) while it remained stable in the clazosentan group (23.5 +/- 12.9 ml/100 g/min). During Part B of the study, all 3 patients who developed haemodynamically relevant vasospasm during placebo treatment, showed a sustained improvement in rCBF upon conversion to clazosentan. These preliminary data suggest that clazosentan reduces the extent of vasospasm-associated impairment of cerebral perfusion following aSAH. Furthermore, clazosentan may exert beneficial actions on overt vasospasm-associated hypoperfusion.

Effects of hypervolemia and hypertension on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation after subarachnoid hemorrhage*

Hypertensive, hypervolemic, hemodilution therapy (triple-H therapy) is a generally accepted treatment for cerebral vasospasm after subarachnoid hemorrhage. However, the particular role of the three components of triple-H therapy remains controversial. The aim of the study was to investigate the influence of the three arms of triple-H therapy on regional cerebral blood flow and brain tissue oxygenation. Animal research and clinical intervention study. Surgical intensive care unit of a university hospital. Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients with subarachnoid hemorrhage. First, we investigated the effect of the three components of triple-H therapy under physiologic conditions in an experimental pig model. In the next step we applied the same study protocol to patients following aneurysmal subarachnoid hemorrhage. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, cardiac output, regional cerebral blood flow, and brain tissue oxygenation were continuously recorded. Intrathoracic blood volume and central venous pressure were measured intermittently. Vasopressors and/or colloids and crystalloids were administered to stepwise establish the three components of triple-H therapy. In the animals, neither induced hypertension nor hypervolemia had an effect on intracranial pressure, brain tissue oxygenation, or regional cerebral blood flow. In the patient population, induction of hypertension (mean arterial pressure 143 +/- 10 mm Hg) resulted in a significant (p < .05) increase of regional cerebral blood flow and brain tissue oxygenation at all observation time points. In contrast, hypervolemia/hemodilution (intrathoracic blood volume index 1123 +/- 152 mL/m) induced only a slight increase of regional cerebral blood flow while brain tissue oxygenation did not improve. Finally, triple-H therapy failed to improve regional cerebral blood flow more than hypertension alone and was characterized by the drawback that the hypervolemia/hemodilution component reversed the effect of induced hypertension on brain tissue oxygenation. Vasopressor-induced elevation of mean arterial pressure caused a significant increase of regional cerebral blood flow and brain tissue oxygenation in all patients with subarachnoid hemorrhage. Volume expansion resulted in a slight effect on regional cerebral blood flow only but reversed the effect on brain tissue oxygenation. In view of the questionable benefit of hypervolemia on regional cerebral blood flow and the negative consequences on brain tissue oxygenation together with the increased risk of complications, hypervolemic therapy as a part of triple-H therapy should be applied with utmost caution.

The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized, Controlled Trial

Our goal was to investigate the effect of placentofetal transfusion on cerebral oxygenation in preterm infants by near-infrared spectroscopy. A total of 39 preterm infants with a median gestational age of 30.4 weeks were randomly assigned to an experiment group (n = 15) and a control group (n = 24). The delivery of the infants in the experiment group was immediately followed by maternal administration of syntocinon, the infant was placed 15 cm below the placenta, and cord clamping was delayed by 60 to 90 seconds. The infants in the control group were delivered conventionally. At the ages of 4 and 24 hours, cerebral hemoglobin concentrations, cerebral blood volume, and regional tissue oxygenation were measured by near-infrared spectroscopy. Cerebral blood volume was not different between the 2 groups at the age of 4 hours (6.1 vs 5.8 mL/100 g of tissue) nor at the age of 24 hours (6.2 vs 6.2 mL/100 g of tissue). Mean regional tissue oxygenation of the experiment group was higher at the ages of 4 hours (69.9% vs 65.5%) and of 24 hours (71.3% vs 68.1%). Delayed clamping of the umbilical cord improves cerebral oxygenation in preterm infants in the first 24 hours.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation

β2 Adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats

Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats. Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)]. Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus. Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension.

Effects of Small Volume Resuscitation and the Additional Use of Norepinephrine on Regional and Local Brain Tissue Oxygenation in Severe Hemorrhage

Department of Anesthesiology, University of Regensburg, Germany Abstracts published in the Journal of Neurosurgical Anesthesiology have been reviewed by the organizations or JNA Affiliate Societies at whose meetings the abstracts have been accepted for presentation. These abstracts have not undergone review by the Editorial Board of the Journal of Neurosurgical Anesthesiology. 34th Annual Meeting of the Society of Neurosurgical Anesthesia and Critical Care, Chicago, Illinois, October 13th, 2006

Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in preterm infants undergoing critical care

To determine whether pulse oximetry-detected episodes of desaturation are associated with impairment of cerebral and somatic (renal) tissue oxygenation in mechanically ventilated preterm neonates. Observational cross-sectional study. Neonatal intensive care unit of a university-affiliated children's hospital. Ten mechanically ventilated preterm (gestational age 24-32 wks) infants. In addition to the traditional monitoring of hemodynamic variables that included pulse oximetry (Sao2), near-infrared spectroscopy (NIRS) was used to evaluate the cerebral and somatic (renal) tissue oxygen saturation (rSO2C and rSO2R, respectively). A total of 40 rSO2C and rSO2R measurements were simultaneously recorded: 20 during hypoxic events when the Sao2 was </=80% for >/=4 secs (cases) and generally ranged between 70% and 80%, and 20 measurements when the Sao2 was >/=85% (paired controls). Additionally, the fractional oxygen extraction (FOE) from the cerebral (FOEC) and renal (FOER) tissue was calculated. All the measurements were made under steady conditions during a 2-hr period. The rSO2C, rSO2R, FOEC, and FOER among the cases (Sao2 </= 80%) and controls (Sao2 >/= 85%) were compared using the paired Student's t-test. Both rSO2C and rSO2R during the desaturation episodes were lower than in the controls (51.6 +/- 6.3% vs. 66.2 +/- 10.2%, p < .0001 and 61.1 +/- 6.8% vs. 80.1 +/- 10.0%, p < .0001, respectively). The FOEC during the hypoxic episodes was comparable with control levels but increased in renal tissue. However, during two of the desaturation episodes (10%), the rSO2C and FOEC levels (which were <44% and >0.47, respectively) may reflect compromised tissue oxygen supply. In the majority of mechanically ventilated preterm neonates, the reduction in cerebral and renal tissue oxygenation associated with short periods of decreased arterial saturation to 70-80% does not significantly compromise oxygen utilization in the cerebral tissue but increases oxygen extraction in the renal tissue, which might cause ischemic tissue injury following a further reduction in oxygen delivery.

Quantitative tissue hemoglobin oxygen saturation measurement in decompensated heart failure

Summary Background This study determined if patients with acutely decompensated heart failure (HF) have abnormal regional tissue oxygenation when compared with stable outpatients and if values change with treatment. Methods We prospectively used differential absorption spectroscopy to measure the subcutaneous tissue hemoglobin oxygen saturation (S t O 2 ), both at presentation and discharge in patients admitted with acutely decompensated systolic HF. These values were compared with a convenience sample of stable HF patients to determine if admitted patients have different S t O 2 values that, after undergoing inpatient treatment, approach those of the stable HF population. Results Stable outpatients ( n = 45) had significantly higher S t O 2 values than inpatients ( n = 20), both at admission ( p p t O 2 values. Four inpatients died of HF related causes and 6 were readmitted with HF within 6 months. Conclusions Patients with acutely decompensated HF have significantly decreased tissue oxygenation that is lower than those found in the stable outpatient population and does not respond to inpatient treatment. Measurement of subcutaneous tissue hemoglobin oxygen saturation may enable clinicians to diagnose and treat HF more effectively.

Near infrared spectroscopy monitoring during pediatric aortic coarctation repair

Near infrared spectroscopy (NIRS) measures regional tissue oxygenation continuously and noninvasively and may allow assessment of changes in regional perfusion in real time. We used NIRS monitoring to track real-time changes in regional oxygenation (rSO2) above and below the aortic cross-clamp in patients undergoing aortic coarctation repair and routinely stored these data in an operative electronic data base. This allowed us to analyze the changes in rSO2 during aortic coarctation repair for three pediatric age groups (neonates, infants <1 year, and children >1 year). Two site [cerebral (rSO2-C) and somatic thoracodorsal (rSO2-S)] rSO2 monitoring was performed in patients undergoing aortic coarctation repair. Data for rSO2 were analyzed across sites and age groups before, during and after cross-clamp. Twenty-six patients were available for analysis (11 neonates, 5 infants and 10 children). The regional oxygenation below the cross clamp (rSO2-S) declined significantly in all three age groups, but the decrease in neonates and infants <1 year of age was significantly greater than in the older children. Monitoring rSO2-S provides real-time trend information of regional oxygenation below the aortic cross-clamp. The decline in rSO2-S during aortic cross-clamp was rapid and large in most neonates and young infants <1 year which suggests impairment of regional perfusion presumably because of a lack of adequate collateral circulation to the monitored regional tissue. In contrast, the rSO2-S changed only to a minor degree in most infants and children >1 year, possibly because they had time to develop a more adequate collateral circulation around incomplete aortic obstruction.

Regional cerebral saturation monitoring with near-infrared spectroscopy during selective antegrade cerebral perfusion: Diagnostic performance and relationship to postoperative stroke

To investigate whether regional cerebral tissue oxygen saturation monitoring during hypothermic selective antegrade cerebral perfusion in surgery involving the aortic arch can predict neurologic sequelae and to evaluate the diagnostic performance of near-infrared spectroscopy monitoring in this setting. Data from 46 consecutive patients were analyzed. Selective antegrade cerebral perfusion was established by perfusion of the right subclavian artery (with or without left carotid artery perfusion) or by separate concomitant perfusion of the innominate and the left carotid arteries. The bilateral regional cerebral tissue oxygen saturation index was monitored by using near-infrared spectroscopy equipment (INVOS 4100). Stroke was the primary clinical end point, along with the indices of diagnostic performance. Six patients died in the hospital, and 6 patients (13%) experienced a perioperative stroke. In patients with stroke, regional cerebral tissue oxygen saturation values were significantly lower during selective antegrade cerebral perfusion, and regional cerebral tissue oxygen saturation tended to be lower in the affected hemisphere. In receiver operating characteristic curve analysis, the area under the curve for relative regional cerebral tissue oxygen saturation values ranged from 0.72 to 0.87. During selective antegrade cerebral perfusion, regional cerebral tissue oxygen saturation between 76% and 86% of baseline had a sensitivity up to 83% and a specificity up to 94% in identifying individuals with stroke. The associated odds ratio for stroke was 5.6 (95% confidence interval, 0.5-144) to 21 (95% confidence interval, 1.8-566). Monitoring of regional cerebral tissue oxygen saturation by using near-infrared spectroscopy during selective antegrade cerebral perfusion allows detection of clinically important cerebral desaturation. It can help predict perioperative neurologic sequelae. Its performance as a diagnostic instrument is satisfying and supports its use as a noninvasive trend monitor of cerebral saturation.

Contrast Echocardiography: A Valid and Sensitive Imaging Method in the Investigation of Transmyocardial Laser-Revascularization in an Acute Ischemia Model

In an acute porcine myocardial ischemia model we examined the effect of transmyocardial laser-revascularization (TMLR) on the regional micro perfusion and oxygen supply. In clinical practice, contrast echocardiography is a reliable tool for the measurement of changes in regional blood flow in the ischemic myocardium. We compared contrast echocardiography with the laser Doppler measurement of micro perfusion and with the quantification of regional tissue oxygen tension using a Clark electrode. 22 pigs were randomised in the interventional group and 12 in the control group. Measurements with all three methods were performed before and after occlusion of the first diagonal branch of the left anterior descending coronary artery and, in the interventional group, after TMLR. We investigated not only the effects in the dependent ischemic myocardium, but also in two other myocardial areas, not involved in the coronary occlusion. There was a significant effect of TMLR on regional micro perfusion and local oxygen tension in the dependent ischemic myocardial area. Contrast echocardiography is a successful experimental tool to measure changes in regional myocardial perfusion which cannot be perceived using clinical imaging methods.

Monitoring Oxygen Delivery in the Critically Ill

An accurate assessment of regional tissue oxygen delivery (DO(2)) may help the intensivist to attenuate end-organ damage in critically ill patients. Transport of oxygen from the ambient air to the mitochondria occurs by convection and diffusion, and is tightly regulated by neural and humoral factors. This article reviews the basic principles of DO(2) and the abnormal oxygen supply-demand relationship seen in patients with shock. It also discusses approaches to monitoring DO(2), including clinical symptoms/signs, acid-base status, and gas exchange, which provide global assessment, as well as gastric tonometry, which may reflect regional DO(2). Some new experimental methods, such as near-infrared spectroscopy and positron emission tomography, are still in development but may in the future provide useful clinical devices for quantifying the adequacy of regional tissue oxygenation in critically ill patients.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation*

Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. Animal research and clinical intervention study. Surgical intensive care unit of a university hospital. Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.

Both Milrinone and Colforsin Daropate Attenuate the Sustained Pial Arteriolar Constriction Seen After Unclamping of an Abdominal Aortic Cross-Clamp in Rabbits

We previously reported that unclamping of an abdominal aortic cross-clamp causes initial dilation of pial arteries followed by sustained constriction. Both milrinone and colforsin daropate have a vasodilator action, and both have been used in such critical conditions as abdominal aortic aneurysmectomy. We measured cerebral pial arteriolar diameters using a rabbit closed cranial window preparation before (baseline) and 15 min after the start of an IV infusion of 0.9% saline (control group), milrinone, or colforsin daropate (0.05 and 0.5 microg . /kg(-1) . min(-1)) (pre-clamp), just after aortic clamping, 20 min after clamping, and at 0 to 60 min after unclamping. In the control group, a significant decrease in diameter persisted for at least 60 min after unclamping (maximum, -15% for large and -26% for small arterioles versus baseline). These values were significantly smaller after both doses of milrinone and the larger dose of colforsin daropate (-5% and -8%, 10% and 12%, and -2% and -5%, respectively vs baseline, at 60 min). In a second experiment, changes in regional cerebral blood flow and tissue oxygen tension reflected changes in vascular variables. Thus, sustained cerebral pial arteriolar constriction induced by aortic unclamping can be attenuated by IV milrinone or colforsin daropate.

Changes in oxyhemoglobin dissociation curve in intrabdominal organs during pig experimental orthotopic liver transplantation

Liver transplantation has become a gold standard treatment for irreversible liver disease. Conventional measures of oxygenation are inadequate to understand the dynamics of regional oxygen metabolism during liver transplantation because they represent global markers of tissue dysoxia. Therefore, the addition of an assessment of the hemoglobin O(2) binding capacity can give a better insight into systemic and regional tissue oxygenation and can reflect a more accurate estimation of oxygen release to the tissues than can the hemoglobin, the PaO(2) and SaO(2) alone. This prospective study was designed to evaluate possible alterations in the oxyhemoglobin dissociation curve of vital end organs (small bowel, liver, and kidney) in an experimental liver transplantation model. Fifteen pigs with body weights ranging from 25 to 30 kg were used for the study. Five healthy pigs underwent a sham operation under general anesthesia (group A-control). Ten pigs underwent orthotopic liver transplantation (OLT). Five of them were healthy (group B), whereas the other five were in acute liver failure, which had been surgically induced (group C). Systemic arterial blood pressure, cardiac index, and pulmonary and systemic vascular resistance indexes were measured. Venous blood gas analysis was also performed from pulmonary artery, superior mesenteric, hepatic, and renal veins at well-defined timepoints during the course of the OLT. A statistically significant (P < 0.05) decrease of P(50) in groups B and C compared with group A was observed 30 minutes after reperfusion in the systemic circulation, hepatic, and renal veins. This coincided with a decrease in animal temperature 30 minutes after reperfusion. Regarding group C, after reperfusion of the newly transplanted liver there was a significant increase of P(50) in the small bowel in comparison to baseline values. In conclusion, these changes in P(50) may suggest the occurrence of abnormal tissue oxygenation after reperfusion.

Correlation between continuously monitored regional cerebral blood flow and brain tissue oxygenation

Department of Klinik für Anästhesiologie und Operative Intensivm, Universitätsklinikum Bonn, Bonn, Germany

Noninvasive assessment of cardiac output

Improved outcome from shock depends on early detection and correction of circulatory abnormalities. Global cardiac output and oxygen delivery must be adequate and distributed appropriately to meet metabolic demands to prevent the development of multiple organ system dysfunction, prolonged morbidity, and death. Circulatory assessment using standard monitors gives incomplete and sometimes misleading information. This article focuses on the available and emerging technologies that emphasize assessment of blood flow and regional tissue oxygenation.

Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen

The purpose of this study was to investigate the relationship between continuously monitored regional cerebral blood flow (CBF) and brain tissue oxygen (PtiO2). Continuous advanced multimodal neuromonitoring including monitoring of PtiO2 (Licox, GMS) and CBF (QFlow, Hemedex) was performed in eight patients after severe subarachnoid haemorrhage (n=5) and traumatic brain injury (n=3) for an average of 9.6 days. Parameters were measured using a flexible polarographic PtiO2-probe and a thermal diffusion CBF-microprobe. Regarding the whole monitoring period in all patients, the data indicated a significant correlation between CBF and PtiO2 (r=0.36). In 72% of 400 analysed intervals of 30 minutes duration with PtiO2 changes larger than 5 mmHg, a strong correlation between CBF and PtiO2 existed (r>0.6). In 19% of intervals a still statistically significant correlation was observed (0.3<r<0.6). During the remaining 9% no correlation was found (r<0.3). Regarding the clinical stability of the monitoring devices, the CBF monitoring system allowed monitoring of CBF in 64% of the time when PtiO2 monitoring was possible only. Phases of non-monitoring were mostly due to fever of the patient, when the system does not allow monitoring to avoid overheating of the cerebral tissue. This study suggests a correlation between CBF and PtiO2. The level of PtiO2 seems to be predominately determined by regional CBF, since changes in PtiO2 were correlated in 90% of episodes to simultaneous changes of CBF.

Near-infrared spectroscopy in psychiatry

Near-infrared spectroscopy (NIRS) is a noninvasive optical method for in vivo measurement of regional brain tissue oxygenation. Light from the near-infrared spectrum can penetrate the skull and is mainly absorbed by oxyhaemoglobin (O(2)Hb) and desoxyhaemoglobin (HHb). From the amount of reflected near-infrared light in relation to the amount absorbed by brain tissue, regional changes in O(2)Hb and HHb concentrations can be calculated spectrophotometrically. It has been shown that NIRS is not only able to measure massive disturbances in cerebral blood circulation due to serious neurological diseases, but that it also is sensitive enough to assess task-specific patterns of activation in healthy subjects during circumscribed cognitive processes. Preliminary investigations indicate altered regional brain tissue oxygenation in psychiatric patients during cognitive activation tasks. The NIRS outmatches other functional imaging methods in that it has no side effects and is well tolerated by psychiatric patients. Furthermore, it can be applied quickly and easily. Thus, NIRS is a potential screening method in psychiatric settings, provided that robust parameters of reliable diagnostic and/or prognostic value can be developed for individual psychiatric illnesses. However, this will depend on broader application of the method combined with established neurophysiological procedures and functional imaging techniques in psychiatric research.