Tatia M.C. Lee

BIS-guided anesthesia decreases postoperative delirium and cognitive decline.

Background: Previous clinical trials and animal experiments have suggested that long-lasting neurotoxicity of general anesthetics may lead to postoperative cognitive dysfunction (POCD). Brain function monitoring such as the bispectral index (BIS) facilitates anesthetic titration and has been shown to reduce anesthetic exposure. In a randomized controlled trial, we tested the effect of BIS monitoring on POCD in 921 elderly patients undergoing major noncardiac surgery. Methods: Patients were randomly assigned to receive either BIS-guided anesthesia or routine care. The BIS group had anesthesia adjusted to maintain a BIS value between 40 and 60 during maintenance of anesthesia. Routine care group had BIS measured but not revealed to attending anesthesiologists. Anesthesia was adjusted according to traditional clinical signs and hemodynamic parameters. A neuropsychology battery of tests was administered before and at 1 week and 3 months after surgery. Results were compared with matched control patients who did not have surgery during the same period. Delirium was measured using the confusion assessment method criteria. Results: The median (interquartile range) BIS values during the maintenance period of anesthesia were significantly lower in the control group, 36 (31 to 49), compared with the BIS-guided group, 53 (48 to 57), P<0.001. BIS-guided anesthesia reduced propofol delivery by 21% and that for volatile anesthetics by 30%. There were fewer patients with delirium in the BIS group compared with routine care (15.6% vs. 24.1%, P=0.01). Although cognitive performance was similar between groups at 1 week after surgery, patients in the BIS group had a lower rate of POCD at 3 months compared with routine care (10.2% vs. 14.7%; adjusted odds ratio 0.67; 95% confidence interval, 0.32-0.98; P=0.025). Conclusions: BIS-guided anesthesia reduced anesthetic exposure and decreased the risk of POCD at 3 months after surgery. For every 1000 elderly patients undergoing major surgery, anesthetic delivery titrated to a range of BIS between 40 and 60 would prevent 23 patients from POCD and 83 patients from delirium.

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.

Significance This study unmasks a previously unidentified functional role of adiponectin (a hormone secreted by adipocytes) in modulating hippocampal neurogenesis and alleviating depression-like behaviors. To our knowledge, this is the first report showing that adiponectin may be an essential factor that mediates the antidepressant effects of physical exercise on the brain by adiponectin receptor 1-mediated activation of AMP-activated protein kinase. Our results reveal a possible mechanism by which exercise increases hippocampal neurogenesis and also suggest a promising therapeutic treatment for depression. Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals

Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based morphometry in 30 lifetime heroin-dependent individuals who had abstained from drug use for 5 months, and 34 healthy participants. The DGM of the prefrontal, temporal and cingulate cortices significantly decreased in heroin addicts relative to the healthy group. Critically, partial correlation analysis, which controlled for age, education and gender factors as well as nicotine use and heroin abstinence duration, showed that the duration of heroin use negatively correlated with the DGM in heroin-dependent individuals. These results provide compelling evidence for structural abnormality in heroin-dependent individuals and further suggest that duration of heroin use is a critical factor leading to brain damage.

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress.

Distinct Neural Activity Associated with Focused-Attention Meditation and Loving-Kindness Meditation

This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing.

The contribution of neuropsychology to diagnostic assessment in epilepsy

Neuropsychology plays a vital role in the treatment of epilepsy, providing information on the effects of seizures on higher cortical functions through the measurement of behavioral abilities and disabilities. This is accomplished through the design, administration and interpretation of neuropsychological tests, including those used in functional neuroimaging or cortical mapping and in intracarotid anesthetic procedures. The objective of this paper is to define and summarize in some detail the role and methods of neuropsychologists in specialized epilepsy centers. Included are information and recommendations regarding basic ingredients of a thorough neuropsychological assessment in the epilepsy setting, as well as suggestions for an abbreviated alternative exam when needed, with emphasis on functions associated with specific brain regions. The paper is intended for novice and experienced neuropsychologists to enable them to develop or evaluate their current practices, and also for other clinicians, who seek a better understanding of the methodology underlying the neuropsychological input to their work.

Increased gray matter volume in the right angular and posterior parahippocampal gyri in loving-kindness meditators

Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice. These regions are important for affective regulation associated with empathic response, anxiety and mood. At the same time, gray matter volume in the left temporal lobe in the LKM experts appeared to be greater, an observation that has also been reported in previous MRI meditation studies on meditation styles other than LKM. Overall, the findings of our study suggest that experience in LKM may influence brain structures associated with affective regulation.

Neural correlates of attention biases of people with major depressive disorder: a voxel-based morphometric study.

BACKGROUND Patients with major depressive disorder are found to show selective attention biases towards mood-congruent information. Although previous studies have identified various structural changes in the brains of these patients, it remains unclear whether the structural abnormalities are associated with these attention biases. In this study, we used voxel-based morphometry (VBM) to explore the structural correlates of attention biases towards depression-related stimuli. METHOD Seventeen female patients with major depressive disorder and 17 female healthy controls, matched on age and intelligence, underwent magnetic resonance imaging (MRI). They also performed positive-priming (PP) and negative-priming (NP) tasks involving neutral and negative words that assessed selective attention biases. The reaction time (RT) to a target word that had been attended to or ignored in a preceding trial was measured on the PP and NP tasks respectively. The structural differences between the two groups were correlated with the indexes of attention biases towards the negative words. RESULTS The enhanced facilitation of attention to stimuli in the PP task by the negative valence was only found in the depressed patients, not in the healthy controls. Such attention biases towards negative stimuli were found to be associated with reduced gray-matter concentration (GMC) in the right superior frontal gyrus, the right anterior cingulate gyrus and the right fusiform gyrus. No differential effect in inhibition of attention towards negative stimuli in the NP task was found between the depressed patients and the healthy controls. CONCLUSIONS Specific structural abnormalities in depression are associated with their attention biases towards mood-congruent information.

Age-related differences in neural activities during risk taking as revealed by functional MRI

Previous research has clearly documented that risky decision making is different in young and older adults. Yet, there has been a relative dearth of research that seeks to understand such age-related changes in the neural activities associated with risk taking. To address this research issue, 21 men (12 young men, mean age 29.9 ± 6.2 years and 9 older men, mean age 65.2 ± 4.2 years) performed a risky-gains task while their brain activities were monitored by an fMRI scanner. The older adults, relative to their younger peers, presented with contralateral prefrontal activity, particularly at the orbitofrontal cortex. Furthermore, stronger activation of the right insula was observed for the older-aged participants compared to the younger-aged adults. The findings of this study are consistent with the a priori speculations established in accordance with the HAROLD model as well as previous findings. Findings of this study suggest that when making risky decisions, there may be possible neuropsychological mechanisms underlying the change in impulsive and risk-taking behaviors during the course of natural ageing.

Gray matter reduction associated with emotion regulation in female outpatients with major depressive disorder: A voxel-based morphometry study

OBJECTIVE Though emotion dysregulation is the key feature in major depressive disorder, and structural changes in brain areas of depressed patients have been found, it is unknown how these regional volume alterations correlate with the ability to regulate emotion in the depressed population. METHOD We examined the gray matter concentration (GMC) and volume (GMV) in 17 depressed patients and 17 healthy volunteers using a voxel-based morphometry (VBM) study. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented. Statistical comparisons were performed using the general linear model. The identified volumetric alterations in the depressed participants were correlated with their performance on an emotion regulation task that involved reduction of positive or negative emotions to emotional pictures that were selected according to their individual ratings. RESULTS The depressed participants showed specific difficulty in regulating negative emotion, though not positive emotion, which was associated with reduced GMV and concentration in the anterior cingulate cortex (ACC) and the inferior orbitofrontal cortex (OFC). Decreased GMC in the superior temporal cortex was also found in people with major depressive disorder. CONCLUSIONS Abnormal structures in the ACC and OFC and the dysregulation of negative emotion may relate to the pathology of major depressive disorder.