Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the u...Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.展开更多
Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network （DMN）, s...Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network （DMN）, since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network. Second, we review empirical studies of the anatomical and functional DMN, and anti-correlation between DMN and the task positive network in schizophrenia. Finally, we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN, review the role of DMN as a treatment biomarker for this disease, and consider the DMN effects of individualized therapies for schizophrenia.展开更多
Functional magnetic resonance imaging studies have shown that the insular cortex has a signif- icant role in pain identification and information integration, while the default mode network is associated with cognitive...Functional magnetic resonance imaging studies have shown that the insular cortex has a signif- icant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the defauk mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy sub- jects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the impor- tance of the interaction between these regions in pain processing.展开更多
AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patie...AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patients.METHODS:Eleven patients with HM(HM group)and 15 age-and sex-matched non-HM controls(non-HM group)were recruited.ALFFs were calculated and compared between HM group and non-HM group.Independent component analysis(ICA)was conducted to identify DMN,and comparisons between DMNs of two groups were performed.Region-of-interest(ROI)-based analysis was performed to explore functional connectivity(FC)between DMN regions.RESULTS:Significantly increased ALFFs in left inferior temporal gyrus(ITG),bilateral rectus gyrus(REC),bilateral middle temporal gyrus(MTG),left superior temporal gyrus(STG),and left angular gyrus(ANG)were detected in HM group compared with non-HM group(all P<0.01).HM group showed increased FC in the posterior cingulate gyrus(PCC)/precuneus(preCUN)and decreased FC in the left medial prefrontal cortex(mPFG)within DMN compared with nonHM group(all P<0.01).Compared with non-HM group,HM group showed higher FC between mPFG and bilateral middle frontal gyrus(MFG),ANG,and MTG(all P<0.01).In addition,HM patients showed higher FC between PCC/(preCUN)and the right cerebellum,superior frontal gyrus(SFG),left pre CUN,superior frontal gyrus(SFG),and medial orbital of the superior frontal gyrus(ORB supmed;all P<0.01).CONCLUSION:HM patients show different ALFFs and DMNs compared with non-HM subjects,which may imply the cognitive alterations related to HM.展开更多
The default mode network is associated with senior cognitive functions in humans. In this study, we performed independent component analysis of blood oxygenation signals from 14 heroin users and 13 matched normal cont...The default mode network is associated with senior cognitive functions in humans. In this study, we performed independent component analysis of blood oxygenation signals from 14 heroin users and 13 matched normal controls in the resting state through functional MRI scans. Results showed that the default mode network was significantly activated in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users, and an enhanced activation signal was observed in the right inferior parietal Iobule （P 〈 0.05, corrected for false discovery rate）. Experimental findings indicate that the default mode network is altered in heroin users.展开更多
Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic chang...Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.展开更多
Attentional issues may affect acquiring new information, task performance, and learning. Cortical network activities change during different functional brain states, including the default mode network (DMN) and attent...Attentional issues may affect acquiring new information, task performance, and learning. Cortical network activities change during different functional brain states, including the default mode network (DMN) and attention network. We investigated the neural mechanisms underlying attentional functions and correlations between DMN connectivity and attentional function using the Trail-Making Test (TMT)-A and -B. Electroencephalography recordings were performed by placing 19 scalp electrodes per the 10 - 20 system. The mean power level was calculated for each rest and task condition. Non-parametric Spearman’s rank correlation was used to examine the correlation in power levels between the rest and TMT conditions. The most significant correlations during TMT-A were observed in the high gamma wave, followed by theta and beta waves, indicating that most correlations were in the parietal lobe, followed by the frontal, central, and temporal lobes. The most significant correlations during TMT-B were observed in the beta wave, followed by the high and low gamma waves, indicating that most correlations were in the temporal lobe, followed by the parietal, frontal, and central lobes. Frontoparietal beta and gamma waves in the DMN may represent attentional functions.展开更多
Our conscious day-to-day self is often described as the “tip of the iceberg” of a much greater cognitive system. The edge of the water divides the phenomenal self from the sub/unconscious underlying it. Similar to a...Our conscious day-to-day self is often described as the “tip of the iceberg” of a much greater cognitive system. The edge of the water divides the phenomenal self from the sub/unconscious underlying it. Similar to an iceberg, the unconscious activity below the water vastly outweighs the conscious activity above it. What exactly lies beneath the surface of this murky water is a tantalizing topic of research and theory. The current research predominantly focuses on the physiology of the brain and the default mode network has been identified as an intrinsic mode of functioning. It is well known that autonomic nervous system sympathovagal balance orchestrated by the central autonomic network is strongly associated with modulation of cardiac, respiratory rate and other visceral physiological activity. In this article, we use existing research and a novel theory to tie together the default mode network, the autonomic nervous system, and non-neural physiology to describe a hypothesis on a greater biological system from which intrinsic brain activity may be founded. This hypothesis is that intrinsic brain activity and connectivities are significantly founded on activity of the body. We review how cardiorespiratory and other rhythms and electrical activity of the body may modulate and even underlie fundamental activity of the human brain and ultimately the mind. A more holistic biological system that could interface the brain and body via mechanisms such as neurovascular coupling would more accurately describe the nature of neural systems. Greater knowledge on the association and interface of brain and body via isomorphic physiologic counterparts to mind may carry profound implications in understanding intrinsic activity of the brain, consciousness, mind, and mental illness.展开更多
Background Successful aging （SA） and mild cognitive impairment （MCI） are heterogeneous groups of aging.To explore the heterogeneity,the functional connectivity was studied in these populations.Methods The present ...Background Successful aging （SA） and mild cognitive impairment （MCI） are heterogeneous groups of aging.To explore the heterogeneity,the functional connectivity was studied in these populations.Methods The present study utilized functional connectivity magnetic resonance imaging （fcMRI） to investigate default mode network （DMN） in 8 healthy subjects of SA,8 subjects of usual aging （UA）,and 8 MCI patients during verbal fluency tests （VFTs）.Functional connectivity （based seeds） of different groups was analyzed by using statistical test.Results Compared with SA and UA groups,MCI subjects exhibited decreased functional connectivity in the DMN regions,including the inferior parietal Iobule and left angular gyrus （t=3.53,P 〈0.001）.Compared with UA and MCI groups,the SA elderly exhibited increased functional connectivity in the precuneus （t=3.53,P〈0.001）.Conclusions These findings suggested that abnormalities of functional connectivity in DMN might be related with semantic memory impairment in aging.Left angular gyrus and precuneus might be the potential imaging-based biomarker for distinguishing heterogeneous process of elderly.展开更多
Emotion and executive control are often conceptualized as two distinct modes of human brain functioning.Little,however,is known about how the dynamic organization of large-scale functional brain networks that support ...Emotion and executive control are often conceptualized as two distinct modes of human brain functioning.Little,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their interactions.The amygdala and prefrontal systems have long been thought to play crucial roles in these processes.Recent advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their interactions.Here,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based approaches.In this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain networks.This model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.展开更多
The serotonin-transporter-linked polymorphic region(5-HTTLPR)is associated with mood disorders.This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced...The serotonin-transporter-linked polymorphic region(5-HTTLPR)is associated with mood disorders.This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced frontal cortical control.In Caucasians,the short form is associated with this effect,but in Han Chinese we recently found that the long form is involved.Serotonin receptors have rich expression in default mode network(DMN)regions and the recent studies have found an association between the short form of the 5-HTTLPR and DMN functional connectivity(FC)in Caucasians.The present study has investigated whether there may also be anethnic difference in this influence of 5-HTTLPR on the DMN.We recruited 233 young Han Chinese subjects and calculated the resting-state default-network FC.Our study found that the L carriers had decreased FC in the bilateral medial prefrontal cortex,right parahippocampal gyrus,left middle temporal gyrus,and increased FC in left precuneus(Pcu)compared to SS.The PCC-Pcu FC in L carriers was significantly negatively correlated with the depression scores.Our findings,therefore,suggest that there is also a difference between Caucasian and Han Chinese subjects in the association between the different forms of the5-HTTLPR and DMN functional connectivity.展开更多
The default mode network(DMN) is associated with the occurrence of mind-wandering or task-unrelated thought. In contrast, the frontal-parietal network(FPN) and visual network(VS) are involved in tasks with external st...The default mode network(DMN) is associated with the occurrence of mind-wandering or task-unrelated thought. In contrast, the frontal-parietal network(FPN) and visual network(VS) are involved in tasks with external stimuli. However, it is not clear how these functional network interactions support these two different processes– mind-wandering and on-task – especially with regard to individual variation in the mind-wandering experience. In this study, we investigated the functional connectivity and modular structure among the DMN, FPN, and VS. Our results showed that, compared to the on-task period, mindwandering was associated with increased DMN activity and increased DMN-VS connectivity. Moreover, mindwandering was accompanied by a large number of transitional nodes, which expressed a diversity of brain regions. Intriguingly, the functional connectivity of the FPN and VS was strongly correlated with individual behavioral performance. Our findings highlight the individual variation of mind-wandering, which implies the importance of other complementary large-scale brain networks.展开更多
Consensus of creativity research suggests that the measurement of both originality and valuableness is necessary when designing creativity tasks.However,few studies have emphasized valuableness when exploring underlyi...Consensus of creativity research suggests that the measurement of both originality and valuableness is necessary when designing creativity tasks.However,few studies have emphasized valuableness when exploring underlying neural substrates of creative thinking.The present study employs product-based creativity tasks that measure both originality and valuableness in an exploration of the dynamic relationship between the default mode(DMN),executive control(ECN),and salience(SN)networks through time windows.This methodology highlights relevance,or valuableness,in creativity evaluation as opposed to divergent thinking tasks solely measuring originality.The researchers identified seven brain regions belonging to the ECN,DMN,and SN as regions of interest(ROIs),as well as four representative seeds to analyze functional connectivity in 25 college student participants.Results showed that all of the identified ROIs were involved during the creative task.The insula,precuneus,and ventrolateral prefrontal cortex(vlPFC)remained active across all stages of product-based creative thinking.Moreover,the connectivity analyses revealed varied interaction patterns of DMN,ECN,and SN at different thinking stages.The integrated findings of the whole brain,ROI,and connectivity analyses suggest a trend that the DMN and SN(which relate to bottom-up thinking)attenuate as time proceeds,whereas the vlPFC(which relates to top-down thinking)gets stronger at later stages;these findings reflect the nature of our creativity tasks and decision-making of valuableness in later stages.Based on brain region activation throughout execution of the task,we propose that product-based creative process may include three stages:exploration and association,incubation and insight,and finally,evaluation and decision making.This model provides a thinking frame for further research and classroom instruction.展开更多
Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms.However,the neurobiological mechanisms underlying specific impairments are not fully understood.Advances in neuroimagi...Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms.However,the neurobiological mechanisms underlying specific impairments are not fully understood.Advances in neuroimaging techniques（such as diffusion tensor imaging and functional MRI）have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease.The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks.Using these powerful neuroimaging approaches,changes at the microstructural level can be detected through regional and global properties of neuronal networks.Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury,mainly focusing on structural and functional connectivity.Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury.These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae,as well as predicting outcome and prognosis.展开更多
OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic reso...OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent depression could be effectively treated with ta VNS.The changes in brain FC involving the basal ganglia,default mode,and sensorimotor networks provide insight into the effects of ta VNS treatment on recurrent depression.展开更多
Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated ...Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated that neurofeedback training alters the functional connectivity between brain regions in the task state and resting state, it is unclear how the regulation of the key hub of the default mode network (DMN) affects the topological properties of the resting-state brain network. The current study aimed to investigate what topological changes would occur in the large-scale intrinsic organization of the resting state after the real-time down-regulation of the posterior cingulate cortex (PCC). The results indicated that the down-regulation of the PCC in the DMN reduced the functional connectivity of the PCC with the nodes outside of the DMN and reduced functional connectivity between the superior medial frontal gyrus (SFGmed) and parahippocampal gyrus (PHG) in the experimental group. Moreover, the nodal graph properties of the SFGmed were reduced, while that of the PHG showed the opposite alteration after the down-regulation of the PCC. These findings possibly suggest that the regulation of the key hub of the DMN, the PCC, mainly changed the information transfer of the SFGmed and PHG.展开更多
Abstract A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with ...Abstract A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network （DMN）, its function has been associated with memory processing, and it has been referred to as the parietal memory network （PMN）. Independent component analysis （ICA） is the most common data-driven method used to extract PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determi- nation in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high model order across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.展开更多
Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during th...Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during the recovery sleep remains unclear. In the current study, we performed sleep deprivation experiments on ten adult rats, and recorded the local field potentials from default mode network(DMN) regions during sleep before and after sleep deprivation. The DMN dynamics was assessed with the configurations of coactive micropatterns(CAMPs) using our previously proposed CAMP method. Our analysis revealed that the effects of sleep deprivation on DMN dynamics in the slow-wave sleep(SWS) state and the rapid eye-movement sleep(REM)state were disparate. Dynamic configurations of DMN activity in the SWS state were significantly impaired after sleep deprivation, with increased occurrence of low-activity CAMP and reorganized transition structure across three CAMPs. Moreover,enhanced functional connectivity and improved efficiencies in all CAMP networks were observed during the SWS state in the recovery sleep. However, there were no significant alterations in either DMN dynamics or CAMP network structures in the REM sleep state after sleep deprivation. Our results described the alterations of DMN dynamics in different sleep states after sleep deprivation, and illustrated the differential effects of sleep deprivation on two sleep states. These findings demonstrated the underlying neural mechanisms of the effects of sleep deprivation on DMN activity during sleep and increased our understanding of the physiological roles of the DMN in maintain sleep homeostasis after sleep deprivation.展开更多
To explore the brain default mode network(DMN)in patients with motor aphasia resulting from cerebral infarction,we used resting state functional magnetic resonance imaging(fMRI)to investigate the possible neural mecha...To explore the brain default mode network(DMN)in patients with motor aphasia resulting from cerebral infarction,we used resting state functional magnetic resonance imaging(fMRI)to investigate the possible neural mechanism.Thirteen patients with motor aphasia resulting from cerebral infarction and ten matched controls were selected in this study.All subjects were examined using resting state fMRI.We chose the posterior cingulate cortex as the region of interest and then used functional connectivity analysis to calculate the DMN functional connectivity and analyze differences in the functional connectivity between the two groups.Compared with normal controls,aphasia patient group showed a significantly decreased functional connectivity in bilateral medial frontal gyrus,superior frontal gyrus,middle frontal gyrus,middle temporal gyrus,precuneus and cuneus.The aphasia patient group showed increased functional connectivity mainly in bilateral medial frontal gyrus,middle frontal gyrus,inferior frontal gyrus,precentral gyrus,insula.The DMN in cerebral infarction motor aphasia patients showed significantly decreased functional connectivity in the resting state.The DMN most likely plays an important role in motor aphasia resulting from cerebral infarction.Furthermore,functional connectivity in the brain regions surrounding the left and right Broca’s areas was significantly enhanced due to compensatory mechanisms.This may be helpful for the recovery of language function in cerebral infarction patients with motor aphasia.展开更多
Recently,in collaboration with a total of 25major depressive disorder(MDD)research groups from 17distinct institutes,Yan ChaoGan’s(严超赣)lab published a scientific paper in PNAS(2019,116(18):9078—9083).MDD,often re...Recently,in collaboration with a total of 25major depressive disorder(MDD)research groups from 17distinct institutes,Yan ChaoGan’s(严超赣)lab published a scientific paper in PNAS(2019,116(18):9078—9083).MDD,often referred to as depression,is a psychiatric disorder with high recurrence rate,high suicide and disability rate,which causes an extremely heavy social and economic burden each year.展开更多
文摘Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.
基金supported by the National Natural Science Foundation of China(81271484,81471361,30900486,and 81371480)the National Basic Research Development Program(973 Program)of China(2012CB517904)the Nation Sponsored Study Abroad Program from China Scholarship Council(201506370095)
文摘Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network （DMN）, since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network. Second, we review empirical studies of the anatomical and functional DMN, and anti-correlation between DMN and the task positive network in schizophrenia. Finally, we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN, review the role of DMN as a treatment biomarker for this disease, and consider the DMN effects of individualized therapies for schizophrenia.
基金supported by the Science and Technology Foundation of Guangdong Province of China,No.2012B031800305
文摘Functional magnetic resonance imaging studies have shown that the insular cortex has a signif- icant role in pain identification and information integration, while the default mode network is associated with cognitive and memory-related aspects of pain perception. However, changes in the functional connectivity between the defauk mode network and insula during pain remain unclear. This study used 3.0 T functional magnetic resonance imaging scans in 12 healthy sub- jects aged 24.8 ± 3.3 years to compare the differences in the functional activity and connectivity of the insula and default mode network between the baseline and pain condition induced by intramuscular injection of hypertonic saline. Compared with the baseline, the insula was more functionally connected with the medial prefrontal and lateral temporal cortices, whereas there was lower connectivity with the posterior cingulate cortex, precuneus and inferior parietal lobule in the pain condition. In addition, compared with baseline, the anterior cingulate cortex exhibited greater connectivity with the posterior insula, but lower connectivity with the anterior insula, during the pain condition. These data indicate that experimental low back pain led to dysfunction in the connectivity between the insula and default mode network resulting from an impairment of the regions of the brain related to cognition and emotion, suggesting the impor- tance of the interaction between these regions in pain processing.
基金Supported by the National Natural Science Foundation of China(No.81870685)Beijing Natural Science Foundation(No.7172173)Key Laboratory of Myopia,Ministry of Health(Fudan University)(No.EENTM-15-01)。
文摘AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patients.METHODS:Eleven patients with HM(HM group)and 15 age-and sex-matched non-HM controls(non-HM group)were recruited.ALFFs were calculated and compared between HM group and non-HM group.Independent component analysis(ICA)was conducted to identify DMN,and comparisons between DMNs of two groups were performed.Region-of-interest(ROI)-based analysis was performed to explore functional connectivity(FC)between DMN regions.RESULTS:Significantly increased ALFFs in left inferior temporal gyrus(ITG),bilateral rectus gyrus(REC),bilateral middle temporal gyrus(MTG),left superior temporal gyrus(STG),and left angular gyrus(ANG)were detected in HM group compared with non-HM group(all P<0.01).HM group showed increased FC in the posterior cingulate gyrus(PCC)/precuneus(preCUN)and decreased FC in the left medial prefrontal cortex(mPFG)within DMN compared with nonHM group(all P<0.01).Compared with non-HM group,HM group showed higher FC between mPFG and bilateral middle frontal gyrus(MFG),ANG,and MTG(all P<0.01).In addition,HM patients showed higher FC between PCC/(preCUN)and the right cerebellum,superior frontal gyrus(SFG),left pre CUN,superior frontal gyrus(SFG),and medial orbital of the superior frontal gyrus(ORB supmed;all P<0.01).CONCLUSION:HM patients show different ALFFs and DMNs compared with non-HM subjects,which may imply the cognitive alterations related to HM.
基金sponsored by a grant from the National Natural Science Foundation of China,No.30973084-C160801,C010604the Natural Science Foundation of Anhui Province,No.11040606M167
文摘The default mode network is associated with senior cognitive functions in humans. In this study, we performed independent component analysis of blood oxygenation signals from 14 heroin users and 13 matched normal controls in the resting state through functional MRI scans. Results showed that the default mode network was significantly activated in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users, and an enhanced activation signal was observed in the right inferior parietal Iobule （P 〈 0.05, corrected for false discovery rate）. Experimental findings indicate that the default mode network is altered in heroin users.
基金supported by the National Natural Science Foundation of China,Nos.82271963(to HJL),81771806(to HJL),61936013(to HJL),82001914(to ZCT),81871511(to HZ)National Key R&D Program of China,No.2021YFA1301603(to ZCT)the Natural Science Foundation of Beijing,No.7212051(to HJL).
文摘Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.
文摘Attentional issues may affect acquiring new information, task performance, and learning. Cortical network activities change during different functional brain states, including the default mode network (DMN) and attention network. We investigated the neural mechanisms underlying attentional functions and correlations between DMN connectivity and attentional function using the Trail-Making Test (TMT)-A and -B. Electroencephalography recordings were performed by placing 19 scalp electrodes per the 10 - 20 system. The mean power level was calculated for each rest and task condition. Non-parametric Spearman’s rank correlation was used to examine the correlation in power levels between the rest and TMT conditions. The most significant correlations during TMT-A were observed in the high gamma wave, followed by theta and beta waves, indicating that most correlations were in the parietal lobe, followed by the frontal, central, and temporal lobes. The most significant correlations during TMT-B were observed in the beta wave, followed by the high and low gamma waves, indicating that most correlations were in the temporal lobe, followed by the parietal, frontal, and central lobes. Frontoparietal beta and gamma waves in the DMN may represent attentional functions.
文摘Our conscious day-to-day self is often described as the “tip of the iceberg” of a much greater cognitive system. The edge of the water divides the phenomenal self from the sub/unconscious underlying it. Similar to an iceberg, the unconscious activity below the water vastly outweighs the conscious activity above it. What exactly lies beneath the surface of this murky water is a tantalizing topic of research and theory. The current research predominantly focuses on the physiology of the brain and the default mode network has been identified as an intrinsic mode of functioning. It is well known that autonomic nervous system sympathovagal balance orchestrated by the central autonomic network is strongly associated with modulation of cardiac, respiratory rate and other visceral physiological activity. In this article, we use existing research and a novel theory to tie together the default mode network, the autonomic nervous system, and non-neural physiology to describe a hypothesis on a greater biological system from which intrinsic brain activity may be founded. This hypothesis is that intrinsic brain activity and connectivities are significantly founded on activity of the body. We review how cardiorespiratory and other rhythms and electrical activity of the body may modulate and even underlie fundamental activity of the human brain and ultimately the mind. A more holistic biological system that could interface the brain and body via mechanisms such as neurovascular coupling would more accurately describe the nature of neural systems. Greater knowledge on the association and interface of brain and body via isomorphic physiologic counterparts to mind may carry profound implications in understanding intrinsic activity of the brain, consciousness, mind, and mental illness.
基金The work was supported by grants from the National Natural Science Foundation of China （No.30770769）,the ＂973＂ Project （No.2011CB707803）,and the PCSIRT Project （No.IRT0910）.
文摘Background Successful aging （SA） and mild cognitive impairment （MCI） are heterogeneous groups of aging.To explore the heterogeneity,the functional connectivity was studied in these populations.Methods The present study utilized functional connectivity magnetic resonance imaging （fcMRI） to investigate default mode network （DMN） in 8 healthy subjects of SA,8 subjects of usual aging （UA）,and 8 MCI patients during verbal fluency tests （VFTs）.Functional connectivity （based seeds） of different groups was analyzed by using statistical test.Results Compared with SA and UA groups,MCI subjects exhibited decreased functional connectivity in the DMN regions,including the inferior parietal Iobule and left angular gyrus （t=3.53,P 〈0.001）.Compared with UA and MCI groups,the SA elderly exhibited increased functional connectivity in the precuneus （t=3.53,P〈0.001）.Conclusions These findings suggested that abnormalities of functional connectivity in DMN might be related with semantic memory impairment in aging.Left angular gyrus and precuneus might be the potential imaging-based biomarker for distinguishing heterogeneous process of elderly.
基金supported by the National Natural Science Foundation of China(31920103009,32371104,and 32130045)the Major Project of National Social Science Foundation(20&ZD153)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2023SHIBS0003).
文摘Emotion and executive control are often conceptualized as two distinct modes of human brain functioning.Little,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their interactions.The amygdala and prefrontal systems have long been thought to play crucial roles in these processes.Recent advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their interactions.Here,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based approaches.In this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain networks.This model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.
基金supported by the National Key Basic Research Program of China(2011CB707800)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB02030300)+1 种基金the National Natural Science Foundation of China(91132301 and 91232718)the Beijing Nova Program(2010B06)
文摘The serotonin-transporter-linked polymorphic region(5-HTTLPR)is associated with mood disorders.This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced frontal cortical control.In Caucasians,the short form is associated with this effect,but in Han Chinese we recently found that the long form is involved.Serotonin receptors have rich expression in default mode network(DMN)regions and the recent studies have found an association between the short form of the 5-HTTLPR and DMN functional connectivity(FC)in Caucasians.The present study has investigated whether there may also be anethnic difference in this influence of 5-HTTLPR on the DMN.We recruited 233 young Han Chinese subjects and calculated the resting-state default-network FC.Our study found that the L carriers had decreased FC in the bilateral medial prefrontal cortex,right parahippocampal gyrus,left middle temporal gyrus,and increased FC in left precuneus(Pcu)compared to SS.The PCC-Pcu FC in L carriers was significantly negatively correlated with the depression scores.Our findings,therefore,suggest that there is also a difference between Caucasian and Han Chinese subjects in the association between the different forms of the5-HTTLPR and DMN functional connectivity.
基金supported by grants from the National Natural Science Foundation of China (31571111)the Chongqing Research Program of Basic Research and Frontier Technology (cstc2017jcyjAX0110)the Fundamental Research Funds for the Central Universities (SWU1609109)
文摘The default mode network(DMN) is associated with the occurrence of mind-wandering or task-unrelated thought. In contrast, the frontal-parietal network(FPN) and visual network(VS) are involved in tasks with external stimuli. However, it is not clear how these functional network interactions support these two different processes– mind-wandering and on-task – especially with regard to individual variation in the mind-wandering experience. In this study, we investigated the functional connectivity and modular structure among the DMN, FPN, and VS. Our results showed that, compared to the on-task period, mindwandering was associated with increased DMN activity and increased DMN-VS connectivity. Moreover, mindwandering was accompanied by a large number of transitional nodes, which expressed a diversity of brain regions. Intriguingly, the functional connectivity of the FPN and VS was strongly correlated with individual behavioral performance. Our findings highlight the individual variation of mind-wandering, which implies the importance of other complementary large-scale brain networks.
文摘Consensus of creativity research suggests that the measurement of both originality and valuableness is necessary when designing creativity tasks.However,few studies have emphasized valuableness when exploring underlying neural substrates of creative thinking.The present study employs product-based creativity tasks that measure both originality and valuableness in an exploration of the dynamic relationship between the default mode(DMN),executive control(ECN),and salience(SN)networks through time windows.This methodology highlights relevance,or valuableness,in creativity evaluation as opposed to divergent thinking tasks solely measuring originality.The researchers identified seven brain regions belonging to the ECN,DMN,and SN as regions of interest(ROIs),as well as four representative seeds to analyze functional connectivity in 25 college student participants.Results showed that all of the identified ROIs were involved during the creative task.The insula,precuneus,and ventrolateral prefrontal cortex(vlPFC)remained active across all stages of product-based creative thinking.Moreover,the connectivity analyses revealed varied interaction patterns of DMN,ECN,and SN at different thinking stages.The integrated findings of the whole brain,ROI,and connectivity analyses suggest a trend that the DMN and SN(which relate to bottom-up thinking)attenuate as time proceeds,whereas the vlPFC(which relates to top-down thinking)gets stronger at later stages;these findings reflect the nature of our creativity tasks and decision-making of valuableness in later stages.Based on brain region activation throughout execution of the task,we propose that product-based creative process may include three stages:exploration and association,incubation and insight,and finally,evaluation and decision making.This model provides a thinking frame for further research and classroom instruction.
基金supported by a grant from the Medical Scientific Research Programs of Nanjing Military Command,No.14MS122
文摘Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms.However,the neurobiological mechanisms underlying specific impairments are not fully understood.Advances in neuroimaging techniques（such as diffusion tensor imaging and functional MRI）have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease.The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks.Using these powerful neuroimaging approaches,changes at the microstructural level can be detected through regional and global properties of neuronal networks.Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury,mainly focusing on structural and functional connectivity.Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury.These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae,as well as predicting outcome and prognosis.
基金Supported by the National Natural Science Foundation of China:Neuroimaging Study of Transcutaneous Auricular Vagus Nerve Stimulation in Treatment of Refractory Depression Based on Emotion Cognition Circuit(No.81774433)Prediction of Curative Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Depression based on MRI and Machine Learning Technology(No.82174282)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences:Study on the Mechanism and Efficacy Prediction of Transcutaneous Auricular Vagus Nerve Stimulation in the Treatment of Depression based on MRI Brain Imaging and Intestinal Flora(No.CI2021A03316)。
文摘OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent depression could be effectively treated with ta VNS.The changes in brain FC involving the basal ganglia,default mode,and sensorimotor networks provide insight into the effects of ta VNS treatment on recurrent depression.
文摘Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated that neurofeedback training alters the functional connectivity between brain regions in the task state and resting state, it is unclear how the regulation of the key hub of the default mode network (DMN) affects the topological properties of the resting-state brain network. The current study aimed to investigate what topological changes would occur in the large-scale intrinsic organization of the resting state after the real-time down-regulation of the posterior cingulate cortex (PCC). The results indicated that the down-regulation of the PCC in the DMN reduced the functional connectivity of the PCC with the nodes outside of the DMN and reduced functional connectivity between the superior medial frontal gyrus (SFGmed) and parahippocampal gyrus (PHG) in the experimental group. Moreover, the nodal graph properties of the SFGmed were reduced, while that of the PHG showed the opposite alteration after the down-regulation of the PCC. These findings possibly suggest that the regulation of the key hub of the DMN, the PCC, mainly changed the information transfer of the SFGmed and PHG.
基金supported by the National Basic Research(973)Program(2015CB351702)the National Natural Science Foundation of China(81571756,81270023,81278412,81171409,81000583,81471740,81220108014)+2 种基金Beijing Nova Program(XXJH2015B079 to Z.Y.)the Outstanding Young Investigator Award of Institute of Psychology,Chinese Academy of Sciences(to Z.Y.)the Key Research Program and the Hundred Talents Program of the Chinese Academy of Sciences(KSZD-EW-TZ-002 to X.N.Z)
文摘Abstract A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network （DMN）, its function has been associated with memory processing, and it has been referred to as the parietal memory network （PMN）. Independent component analysis （ICA） is the most common data-driven method used to extract PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determi- nation in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high model order across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.
基金supported by the MOST 2030 Brain Project (Grant No.2022ZD0208500)the National Natural Science Foundation of China(Grant Nos. 31771149, 81861128001, and 61933003)partly supported by the CAMS Innovation Fund for Medical Sciences (CIFMS)(Grant No.2019-I2M-5-039)。
文摘Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during the recovery sleep remains unclear. In the current study, we performed sleep deprivation experiments on ten adult rats, and recorded the local field potentials from default mode network(DMN) regions during sleep before and after sleep deprivation. The DMN dynamics was assessed with the configurations of coactive micropatterns(CAMPs) using our previously proposed CAMP method. Our analysis revealed that the effects of sleep deprivation on DMN dynamics in the slow-wave sleep(SWS) state and the rapid eye-movement sleep(REM)state were disparate. Dynamic configurations of DMN activity in the SWS state were significantly impaired after sleep deprivation, with increased occurrence of low-activity CAMP and reorganized transition structure across three CAMPs. Moreover,enhanced functional connectivity and improved efficiencies in all CAMP networks were observed during the SWS state in the recovery sleep. However, there were no significant alterations in either DMN dynamics or CAMP network structures in the REM sleep state after sleep deprivation. Our results described the alterations of DMN dynamics in different sleep states after sleep deprivation, and illustrated the differential effects of sleep deprivation on two sleep states. These findings demonstrated the underlying neural mechanisms of the effects of sleep deprivation on DMN activity during sleep and increased our understanding of the physiological roles of the DMN in maintain sleep homeostasis after sleep deprivation.
文摘To explore the brain default mode network(DMN)in patients with motor aphasia resulting from cerebral infarction,we used resting state functional magnetic resonance imaging(fMRI)to investigate the possible neural mechanism.Thirteen patients with motor aphasia resulting from cerebral infarction and ten matched controls were selected in this study.All subjects were examined using resting state fMRI.We chose the posterior cingulate cortex as the region of interest and then used functional connectivity analysis to calculate the DMN functional connectivity and analyze differences in the functional connectivity between the two groups.Compared with normal controls,aphasia patient group showed a significantly decreased functional connectivity in bilateral medial frontal gyrus,superior frontal gyrus,middle frontal gyrus,middle temporal gyrus,precuneus and cuneus.The aphasia patient group showed increased functional connectivity mainly in bilateral medial frontal gyrus,middle frontal gyrus,inferior frontal gyrus,precentral gyrus,insula.The DMN in cerebral infarction motor aphasia patients showed significantly decreased functional connectivity in the resting state.The DMN most likely plays an important role in motor aphasia resulting from cerebral infarction.Furthermore,functional connectivity in the brain regions surrounding the left and right Broca’s areas was significantly enhanced due to compensatory mechanisms.This may be helpful for the recovery of language function in cerebral infarction patients with motor aphasia.
文摘Recently,in collaboration with a total of 25major depressive disorder(MDD)research groups from 17distinct institutes,Yan ChaoGan’s(严超赣)lab published a scientific paper in PNAS(2019,116(18):9078—9083).MDD,often referred to as depression,is a psychiatric disorder with high recurrence rate,high suicide and disability rate,which causes an extremely heavy social and economic burden each year.
