强迫症患者言语流畅性任务脑激活时间特征的近红外光谱成像研究

目的:探讨强迫症患者言语流畅性任务(VFT)下前额叶及颞叶激活的时间特征。方法:选取70例符合DSM-IV强迫症诊断标准的患者和70例正常对照,应用52通道的近红外光谱成像技术(NIRS)测评完成VFT时前额叶及颞叶血流的变化。比较两组完成任务时氧合血红蛋白(oxy-Hb)、脱氧血红蛋白(deoxy-Hb)及总血红蛋白(total-Hb)浓度达峰时间的差异。结果:与正常对照组相比,强迫症患者52个通道oxy-Hb、deoxy-Hb和total-Hb浓度的平均达峰时间明显延迟[(61±12)s vs.(52±11)s,(64±10)s vs.(58±10)s,(59±13)s vs.(51±13)s,均P<0.01]。强迫症组oxy-Hb和total-Hb在眶额叶、额极、前额下回、颞中回及颞上回等脑区达峰时间明显延迟(均P<0.05,FDR校正)。结论:强迫症患者执行言语流畅性任务时前额叶及颞叶皮质激活可能有延迟。     

A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder

Many neuropsychological studies demonstrate impairment of working memory in patients with major depressive disorder (MDD). However, there are not enough functional neuroimaging studies of MDD patients seeking for the underlying brain activity relevant to working memory function. The objective of this study is to evaluate prefrontal hemodynamic response related to working memory function in patients with MDD. Twenty-four subjects with MDD and 26 age- and gender-matched healthy subjects were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and superior temporal cortical surface areas during the execution of working memory task (WM; 2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of task-related changes in cerebral blood volumes in the cortical surface areas. MDD patients showed a smaller increase in lateral prefrontal and superior temporal cortex activation during the 2-back task and associated poorer task performance than healthy controls. The results coincided with previous findings in terms of working memory deficits and prefrontal cortex dysfunction in MDD patients, but contradicted with some previous fMRI studies that suggested increased cortical activity during the working memory task in patients with depression. The contradiction may, in part, be explained by a relatively low level of cognitive demand imposed on the subjects in the present study.     

Prefrontal hemodynamic response to verbal-fluency task and hyperventilation in bipolar disorder measured by multi-channel near-infrared spectroscopy

BACKGROUND: Many neuroimaging studies of patients with bipolar disorder have demonstrated functional hypofrontality (reduced activation of the frontal cortex), although this finding is still controversial. We previously found hypoactivation of the left prefrontal region in remitted subjects with bipolar disorder measured by one-channel near-infrared spectroscopy (NIRS). The aim of the present study was to clarify whether or not this finding was due to altered cerebral lateralization or caused by reduced cerebrovascular reactivity. METHODS: We enrolled nine remitted patients with bipolar disorder and nine normal controls. Hemodynamic responses in the prefrontal cortex during the verbal-fluency and hyperventilation tasks were monitored by 24-channel NIRS, which can measure oxygenated hemoglobin (OxyHb), deoxygenated hemoglobin, and total hemoglobin (TotalHb). RESULTS: The increases of OxyHb and TotalHb in the bipolar group were significantly smaller than that in the controls during the verbal-fluency task. The response of TotalHb during hyperventilation in the bipolar group was weaker than that in the controls. LIMITATIONS: The sample size was small. CONCLUSIONS: These findings suggest that the bilateral hypofrontality to a cognitive task is seen in remitted subjects with bipolar disorder, which may be related to vascular function as measured by the response to hyperventilation.     

Asymmetry of prefrontal cortex activities and catechol-O-methyltransferase Val158Met genotype in patients with panic disorder during a verbal fluency task: Near-infrared spectroscopy study

We examined the relationship between the catechol-O-methyltransferase (COMT) Val158Met genotype and frontal lobe function by using multi-channel near-infrared spectroscopy (NIRS). The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a verbal fluency task in the frontal region of 71 patients with panic disorder (PD). The activation of [oxy-Hb] on the right lateral prefrontal cortex was observed in the Met/Met genotype of the COMT gene polymorphism of PD patient groups in the analysis of NIRS, which seems to be related to the autonomic dysfunction in the pathogenesis of PD.     

Synchronous activity of two people's prefrontal cortices during a cooperative task measured by simultaneous near-infrared spectroscopy

The brain activity during cooperation as a form of social process is studied. We investigate the relationship between coinstantaneous brain-activation signals of multiple participants and their cooperative-task performance. A wearable near-infrared spectroscopy (NIRS) system is used for simultaneously measuring the brain activities of two participants. Each pair of participants perform a cooperative task, and their relative changes in cerebral blood are measured with the NIRS system. As for the task, the participants are told to count 10 s in their mind after an auditory cue and press a button. They are also told to adjust the timing of their button presses to make them as synchronized as possible. Certain information, namely, the "intertime interval" between the two button presses of each participant pair and which of the participants was the faster, is fed back to the participants by a beep sound after each trial. When the spatiotemporal covariance between the activation patterns of the prefrontal cortices of each participant is higher, the intertime interval between their button-press times was shorter. This result suggests that the synchronized activation patterns of the two participants' brains are associated with their performance when they interact in a cooperative task.     

Load-dependent brain activation assessed by time-domain functional near-infrared spectroscopy during a working memory task with graded levels of difficulty

We evaluated frontal brain activation during a mixed attentional/working memory task with graded levels of difficulty in a group of 19 healthy subjects, by means of time-domain functional near-infrared spectroscopy (fNIRS). Brain activation was assessed, and load-related oxy- and deoxy-hemoglobin changes were studied. Generalized linear model (GLM) was applied to the data to explore the metabolic processes occurring during the mental effort and, possibly, their involvement in short-term memorization. GLM was applied to the data twice: for modeling the task as a whole and for specifically investigating brain activation at each cognitive load. This twofold employment of GLM allowed (1) the extraction and isolation of different information from the same signals, obtained through the modeling of different cognitive categories (sustained attention and working memory), and (2) the evaluation of model fitness, by inspection and comparison of residuals (i.e., unmodeled part of the signal) obtained in the two different cases. Results attest to the presence of a persistent attentional-related metabolic activity, superimposed to a task-related mnemonic contribution. Some hemispherical differences have also been highlighted frontally: deoxy-hemoglobin changes manifested a strong right lateralization, whereas modifications in oxy- and total hemoglobin showed a medial localization. The present work successfully explored the capability of fNIRS to detect the two neurophysiological categories under investigation and distinguish their activation patterns.     

Multiple-time replicability of near-infrared spectroscopy recording during prefrontal activation task in healthy men

Near-infrared spectroscopy (NIRS) has the potential for clinical application in neuropsychiatry because it enables non-invasive and convenient measurement of hemodynamic response to cognitive activation. Using 24-channel NIRS in 12 healthy men, we examined the replicability of oxy- and deoxy-hemoglobin concentration ([oxyHb], [deoxyHb]) changes in the prefrontal cortex during the category fluency task over four repeated sessions (each 1-week apart). Multiple methods were employed to evaluate the replicability of magnitude, location, and time course of the NIRS signals ([oxyHb], [deoxyHb]). Task performances did not differ significantly across sessions, nor were they significantly correlated with NIRS signals. Repeated measures ANOVA and variance component analysis indicated high replicability of magnitude for both NIRS measures, whereas the effect sizes of between-session differences in [oxyHb] were not negligible. The number and spatial location of significantly activated channels were sufficiently replicable for both measures, except that the across-session overlap of significantly activated channels was weak in [deoxyHb]. The time course of the activation was acceptably replicable in both measures. Taken together, these findings suggest there is considerable replicability of multiple-time measurements of prefrontal hemodynamics during cognitive activation in men. Further studies using different conditions or assessing sensitivity to longitudinal changes following interventions are necessary.     

Reduced prefrontal activation during Tower of London in first-episode schizophrenia: A multi-channel near-infrared spectroscopy study

Cognitive impairments are considered as a core feature of schizophrenia and have been reported in associated with dysfunction of the prefrontal cortex (PFC). The Tower of London (TOL) task is a widely used neuropsychological test to assess the planning ability and the PFC function. In the present study, we examined functional changes in the PFC of 40 first-episode schizophrenia patients and 40 age- and gender-matched healthy controls by means of multi-channel Near-infrared spectroscopy (NIRS) during performance of the TOL task. NIRS is a noninvasive optical method that can measure relative changes in oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin in cortical tissue. Compared to the healthy controls, schizophrenia patients exhibited a significant decreased activation in the left PFC and poorer TOL performance. The results confirm the functional deficits of the PFC and impaired planning ability in first-episode schizophrenia patients and suggest that NIRS may be a useful clinical tool for evaluating PFC activation in psychiatric disorders.     

fMRI of patients with social anxiety disorder during a social situation task

Previous functional neuroimaging studies found that the amygdala and other limbic regions may play a substantial role in social anxiety disorder (SAD). However, more widely distributed large-scale brain systems may be involved in cognitive processing in SAD patients when confronted with social situations. We employed functional MRI (fMRI) to investigate local brain activation of patients with SAD (n=6) and healthy controls (HC, n=9) during cognitive work. During fMRI scanning, subjects performed a social situation task using a block design paradigm in which the task and control trials were performed by turn. The patients with SAD showed higher anxiety levels during scanning in all social situations. The HC group showed greater common activation in the posterior cingulate cortex (PCC), cuneus, occipital gyrus, and cerebellum. Although the patients with SAD showed activation patterns similar to that of the HC group, they showed comparatively significant decreased activation in the left cerebellum, left precuneus, and bilateral PCC. The present study demonstrates that SAD may involve dysfunction of a broad neuronal network including the limbic system, parieto-posterior cortex and cerebellum. The findings contribute to previous findings that revealed abnormal activities of emotion-related regions including the amygdala and insular cortex during facial perception in SAD.     

Mapping of calf muscle oxygenation and haemoglobin content during dynamic plantar flexion exercise by multi-channel time-resolved near-infrared spectroscopy

A compact and fast multi-channel time-resolved near-infrared spectroscopy system for tissue oximetry was developed. It employs semiconductor laser and fibre optics for delivery of optical signals. Photons are collected by eight 1 mm fibres and detected by a multianode photomultiplier. A time-correlated single photon counting board is used for the parallel acquisition of time-resolved reflectance curves. Estimate of the reduced scattering coefficient is achieved by fitting with a standard model of diffusion theory, while the modified Lambert-Beer law is used to assess the absorption coefficient. In vivo measurements were performed on five healthy volunteers to monitor spatial changes in calf muscle (medial and lateral gastrocnemius; MG, LG) oxygen saturation (SmO2) and total haemoglobin concentration (tHb) during dynamic plantar flexion exercise performed at 50% of the maximal voluntary contraction. At rest SmO2 was 73.0 +/- 0.9 and 70.5 +/- 1.7% in MG and LG, respectively (P = 0.045). At the end of the exercise, SmO2 decreased (69.1 +/- 1.8 and 63.8 +/- 2.1% in MG and LG, respectively; P < 0.01). The LG desaturation was greater than the MG desaturation (P < 0.02). These results strengthen the role of time-resolved near-infrared spectroscopy as a powerful tool for investigating the spatial and temporal features of muscle SmO2 and tHb.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Angiotensin-related genes in patients with panic disorder.

Enhanced respiratory variability and decreased heart rate variability have repeatedly been observed in patients with panic disorder. Prompted by the notion that angiotensin may be involved in the control of respiration, heart rate variability, and anxiety-like behavior, we investigated the putative association between polymorphisms in three angiotensin-related genes and panic disorder-angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II (ANG II) receptor type 1 (ATr1) in 72 patients with panic disorder and 504 controls. Allele and genotype distribution of the ATr1 A1166C allele and the AGT M235T did not differ between patients and controls. With respect to the ACE I/D polymorphism, the I allele was found to be more frequent in male (chi(2) = 8.042, df = 1, P = 0.005), but not female, panic disorder patients than in controls. The results of this investigation provide preliminary evidence for the suggestion that angiotensin-related genes may be associated with panic disorder in men.     

Frontal EEG asymmetry and symptom response to cognitive behavioral therapy in patients with social anxiety disorder

Although previous studies have shown that socially anxious individuals exhibit greater relative right frontal electroencephalogram (EEG) activity at rest, no studies have investigated whether improvements in symptoms as a result of treatment are associated with concomitant changes in resting brain activity. Regional EEG activity was measured at rest in 23 patients with social anxiety disorder (SAD) before and after cognitive behavioral therapy (CBT). Results indicated that patients shifted significantly from greater relative right to greater relative left resting frontal brain activity from pre- to posttreatment. Greater left frontal EEG activity at pretreatment predicted greater reduction in social anxiety from pre- to posttreatment and lower posttreatment social anxiety after accounting for pretreatment symptoms. These relations were specific to the frontal alpha EEG asymmetry metric. These preliminary findings suggest that resting frontal EEG asymmetry may be a predictor of symptom change and endstate functioning in SAD patients who undergo efficacious psychological treatment.     

Sleep quality in patients with panic disorder: Relationship to nocturnal panic attacks

Summary Question of the Study Insomnia complaints are common in patients with panic disorder. Polysomnographic studies have confirmed patients' poorer sleep quality. The present study investigates subjective sleep quality and its relationship to nocturnal panic attacks.
Patients and Methods Fifty-four outpatients with panic disorder were included. During the course of diagnostic and therapeutic procedures, the patients completed several questionnaires assessing sleep quality, nocturnal panic attacks and panic symptomatology.
Results As expected, sleep quality was markedly reduced in the sample. In addition to ­insomnia complaints, restless legs symptoms and parasomnias were reported more often. Patients with nocturnal panic attacks reported lower sleep quality than the other patients, a finding that was not influenced by course or duration of the panic disorder.
Conclusions We suggest that assessment and specialized treatment of comorbid sleep disorders is very helpful for this patient group, especially for patients who suffer from nocturnal panic attacks.     

Decreased cerebral haemodynamic response to cognitive and physiological tasks in mood disorders as shown by near-infrared spectroscopy

BACKGROUND: Hypofrontality has been demonstrated in mood disorders by functional brain imaging methods such as positron emission tomography. However, the neurobiological basis of hypofrontality has not been well clarified. Near-infrared spectroscopy (NIRS) is a non-invasive technique for continuous monitoring of alterations in oxygenated (oxyHb) and deoxygenated (deoxyHb) haemoglobin using near-infrared light, which penetrates biological tissues. METHODS: We used NIRS during cognitive and physiological tasks to investigate alterations of haemoglobin oxygenation in the frontal region of euthymic patients with mood disorders (major depressive disorder (MD) and bipolar disorder (BP)) and in controls. RESULTS: The increase of oxyHb during a verbal fluency task was significantly less in the MD and the BP groups than in the controls. The MD group showed a significantly smaller decrease of oxyHb during hyperventilation than the controls. The BP group also showed a similar trend. CONCLUSIONS: These findings suggest that the hypofrontality in mood disorders may be associated with a poor response in the cerebral blood vessels to neuronal and chemical stimuli.     

Panic disorder and bipolar disorder: anxiety sensitivity as a potential mediator of panic during manic states

BACKGROUND: Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. METHODS: We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder (n=110) or major depressive disorder (n=92). RESULTS: Current mood state was significantly associated with ASI score (Chi-square=21.2, df=4, p=0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores (p<0.04). Current mixed state tended toward a similar association (p<0.10). LIMITATIONS: Conclusions are limited by the study's cross-sectional nature and relatively small sample size. CONCLUSIONS: These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder.     

beta-adrenoceptor affinity as a biological predictor of treatment response to paroxetine in patients with acute panic disorder

BACKGROUND: Few studies have reported on the functional differences of the beta-adrenoceptor between treatment responders and non-responders in panic disorder (PD). The aim of this study was to compare the nature of the beta-adrenoceptor function and clinical variables between treatment responders and non-responders to paroxetine treatment in acute PD patients. METHOD: Paroxetine was administered to all of the panic patients for 12 weeks. The lymphocyte beta-adrenoceptor density (Bmax), affinity (1/Kd), and sensitivity (cAMP ratio) were measured in 22 untreated outpatients with acute PD and 22 age, sex and BMI matched control subjects. Psychological assessments were conducted using the HAM-A, and HAM-D, STAI-S and STAI-T, Anxiety sensitivity index (ASI), and Acute panic inventory (API). RESULTS: A significantly higher Kd was observed in the panic patients before treatment as compared with the control subjects, but there was no significant difference in Kd between the panic patients and control subjects after the treatment. Among the 22 patients, the 11 treatment responders (50%) showed a significantly higher Kd and lower mean scores of HAM-D, STAI-S, STAI-T, and ASI at baseline, compared with the non-responders. Logistic regression revealed that the pretreatment Kd and HAM-D were significantly reliable predictors for treatment response (p<0.05). CONCLUSION: The beta-adrenoceptor affinity (1/Kd) was decreased and adaptively normalized after treatment with paroxetine in the acute panic patients. In addition, a low pretreatment beta-adrenoceptor affinity (1/Kd) was found to predict the treatment response and can be suggested as a biological predictor of treatment response in acute PD.