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Short-term group cognitive behavior therapy contributes to recovery from mild depression: Evidence from functional and structural MRI
Author’s Accepted Manuscript Short-term group cognitive behavior therapy contributes to recovery from mild depression: evidence from functional and structural MRI Xue Du, Yu Mao, Qinglin Zhang, Qing Hua Luo, Jiang Qiu www.elsevier.com
PII: DOI: Reference:
S0925-4927(16)30108-1 http://dx.doi.org/10.1016/j.pscychresns.2016.04.010 PSYN10532
To appear in: Psychiatry Research: Neuroimaging Received date: 4 June 2015 Revised date: 8 January 2016 Accepted date: 17 April 2016 Cite this article as: Xue Du, Yu Mao, Qinglin Zhang, Qing Hua Luo and Jiang Qiu, Short-term group cognitive behavior therapy contributes to recovery from mild depression: evidence from functional and structural MRI, Psychiatry Research: Neuroimaging, http://dx.doi.org/10.1016/j.pscychresns.2016.04.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Short-term group cognitive behavior therapy contributes to recovery from mild depression: evidence from functional and structural MRI Xue Dua,b1, Yu Maoa,b,1, Qinglin Zhanga,b*,Qing Hua Luoc*, Jiang Qiua,b*
a
Key Laboratory of Cognition And Personality (SWU), Ministry of Education,
Chongqing 400715, China b
School of Psychology, Southwest University, Chongqing 400715, China
c
Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical
University, Chongqing,400016, China E-mail address:[email protected] [email protected] [email protected]
*Corresponding authors: Qinglin Zhang and Jiang Qiu, School of Psychology, Southwest University, Beibei, Chongqing 400715 China *Qinghua Luo, Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 China. Tel:+86 23 6836 7942 (China (023) 68367942).
Abstract We used the functional and structural magnetic resonance imaging to explore the neural correlates of response to group cognitive behavioral therapy (CBT) in mild depression. College students with mild depressive symptoms participated in our 1
The authors contributed equally to this work
4-week group CBT training. The behavioral results showed that depression symptoms decreased after participation in group CBT. After the training, the gray matter volume (GMV) in the right middle frontal gyrus (MFG) increased and amplitude of low-frequency fluctuations (ALFF) decreased. In addition, GMV in the left postcentral gyrus decreased after the group CBT. Moreover, the increase of percentage change in the right MFG was positively correlated with the decrease of the Beck Depression Inventory (BDI) score, while less decrease in percentage change in the left postcentral gyrus was significantly correlated with greater decrease of BDI score. Finally, after the training, functional connectivity between the right MFG and the insula decreased, while the connectivity between the left postcentral gyrus and the parahippocampal gyrus increased. These findings suggested that short-term participation in group CBT had an effective impact on mild depression. It contributed to decreasing negative bias (salience detection for negative stimuli).
Keywords: Gray matter volume; Amplitude of low-frequency fluctuation; Functional connectivity; Group cognitive behavioral therapy
1. Introduction Depression is a highly prevalent, clinically significant, and disorder (Kessler et al., 2003; Rush et al., 2003; Richards, 2011). Major depression disorder (MDD) is one of the most common psychiatric disorders. Moreover, many individuals experience sub-threshold depressive symptoms that do not meet criteria for full-blown MDD episodes (Furukawa et al., 2009). Previous studies pointed out that persistent
depressive symptoms below the threshold for a diagnosis of major depression could cause chronic illness and have a high risk of progression to more serious disorders (Cuijpers and Smit, 2004; Cuijpers et al., 2007). In fact, mild or sub-threshold depression is a state that has been postulated to represent the low end of a continuum of depressive severity. Although sub-threshold depressive states are quantitatively different from MDD, they may not be qualitatively different (Gotlib, 1984). Mild depression can be considered as a significant indicator of risk for MDD. A more precise understanding of mild depression, which is thought to be prodromal to MDD, might aid in the effort to prevent the onset of clinical depression through early diagnosis and intervention. According to the World Mental Health Survey, mild and sub-threshold cases are prevalent in every country, so the value of treating mild cases should be carefully considered (Demyttenaere et al., 2013). Given the importance of identifying biomarkers of depression, it must be a priority target for society and governments to recognize and treat mild cases of depression to forestall the development of a substantial proportion of future serious cases (Beddington et al., 2008; Sahakian et al., 2010; Collins et al., 2011). Cognitive behavior therapy (CBT) is a widely investigated and practiced psychotherapeutic approach that can effectively reduce rates of subsequent relapse and recurrence (Beck et al., 1979; Cuijpers et al., 2013). The premise of CBT derives from Beck’s Cognitive Theory of Depression, which posits that depression is state in which self-reinforcing dysfunctional negative schemata dominate every aspect of an individual’s information processing (Beck, 1967, 1976). Hence, the focus of CBT is on modifying negative cognition, also known as dysfunctional schemata (Beck, 1976). Generally, theoretical models of the action of CBT in depression implicate top-down mechanisms, because the mediation of depression-relevant cognition, affective bias,
and maladaptive information processing is emphasized in the intervention (Beck, 1979; Clak and Beck, 1999). Moreover, group intervention can be used as a therapeutic intervention, as well as a preventative measure (Corey, 2011), due to its cost-effectiveness and potential to facilitate peer support (Edelman et al., 1989; Burlingame et al., 2004). With the development of functional neuroimaging techniques, many investigators have begun to study the neural mechanisms underlying different forms of CBT. These studies identified showed certain brain regions as being involved in the process, including the anterior cingulate cortex (ACC) and the prefrontal gyrus (Fu et al., 2008; Dichter et al., 2010; Forbes et al., 2010; Ritchey et al., 2011). Although the results are promising, functional imaging studies of CBT are methodologically demanding and have varied dramatically with regard to paradigms and analytic methods (Bennett and Miller, 2010). In fact, structural neuroimaging approaches have more often been performed in clinical practice (Redlich et al., 2014). Until now, there have been few structural neuroimaging studies that examined changes that occurred after group CBT in mild depression. Therefore, we tried to combine the advantage of both functional and structural neuroimaging techniques to explore the neural correlates of response to CBT in mild depression. Additionally, a large number of reports found that different dependent measures of depression might have different reliabilities and sensitivities to change (Brown et al., 1995; Shafer, 2006). Thus, the choice of different assessment instruments might lead to different conclusions about the efficacy of the various therapies under investigation. In considering of our aim, we chose the Beck Depression Inventory (BDI) as a conservative means of measuring change in depressive symptomatology (Dobson, 1989). In this study, we predicted that (1) behavioral symptoms could be
reduced after group CBT, (2) the efficacy of CBT in mild depression might be reflected in associated changes in brain regions, such as the prefrontal gyrus, which has been related to cognitive and affective processing (Bush et al., 2000; De Lange et al., 2008; Kumari et al., 2009; Etkin et al., 2011; Ritchey et al., 2011). To some extent, this study might be the first one to combine functional and structural techniques to explore the neural correlates of response to CBT in mild depression. As such, it should provide potential suggestions for future clinical applications and early intervention in cases of mild depression. 2. Methods 2.1.Participants Twenty participants (mean age (SD) = 19.94 (1.06) years; 10 women, 10 men) were recruited from our ongoing project to examine the associations among brain-imaging findings, creativity and mental health. None of the participants in the present study met DSM-IV criteria for depression (American Psychiatric Association, 1994). Because of our focus on mild depression, the 21-item BDI was used as the assessment instrument in our study. According to the norm in China, the inclusion criteria for minor depression require at least 4 points on the BDI (Beck, 1967; Hongbo and Yanping, 1987). Participants who had a history of psychiatric or neurological disorders were also excluded. In total, four subjects were excluded from the training group: two had dropped out of the training, and two had excessive head motion in the scanner. Therefore, the data that were analyzed derived from 16 participants, including both pre- and post-training scans. Written informed consent was obtained from all participants before study. This study was approved by the Institutional Human Participants Review Board of Southwest University Imaging Center for Brain Research.
2.2. The intervention The 4-week group CBT program was designed and led by two licensed psychologists. The group met for 90-min sessions for 4 consecutive weeks. Participants received a manual at the start of the training, as well as handouts and homework exercises at every session. The intervention incorporated the use of cognitive and behavioral techniques, including encouragement to express feelings and to provide group support. For example, the training emphasized how to identify and challenge maladaptive thoughts and beliefs. This included elements of basic cognitive skills, regulation of emotion, stress management, relaxation training, and group support. Elements of the group discussion specific to “disputing” of negative perceptions and the use of coping statements were included. The intervention’s brevity was determined from research suggesting the efficacy of short-term interventions (Ashton et al., 2009; Grilo et al., 2006). 2.3. Data acquisition Structural and functional magnetic resonance imaging (MRI) was acquired on a Siemens 3.0 T-Magnetom Sonata scanner (Siemens Medical, Erlangen, Germany). Subjects were equipped with a circularly polarized standard head coil; in addition, foam pads and headphones were used to reduce head motion and scanner noise. High-resolution T1-weighted anatomical images were acquired using a magnetization-prepared rapid gradient echo (MPRAGE) sequence: repetition time (TR) = 1900 ms; echo time (TE) = 2.52 ms; inversion time (TI) = 900 ms; flip angle (FA) = 9; field of view (FOV) = 256 × 256 mm2; resolution matrix = 256 × 256; slices = 176; thickness = 1 mm; voxel size = 1 × 1 × 1 mm. At the same slice locations as in the structural images, functional images were collected axially by using an
echo-planar imaging (EPI) sequence: TR=2000 ms; TE =30 ms; FA = 90°; FOV=220 × 220 mm2; resolution matrix = 64 × 64; slices = 20, thickness = 3 mm; voxel size = 3.4 × 3.4 × 4 mm. Before being scanned in a resting state, participants were instructed to keep their eyes closed but not to sleep. Instead, they were asked to relax their minds and remain motionless during the EPI data acquisition. The scan lasted for 488 s including 32 slices which were used to cover the whole brain. Each section contained 242 volumes. 2.4. Voxel-based morphometry (VBM) The MR images were processed using the SPM8 program (Wellcome Department of Cognitive Neurology, London, UK; www.fil.ion.ucl.ac.uk/spm) implemented in Matlab 7.8 (MathWorks Inc., Natick, MA, USA). Firstly, each MR image was displayed in SPM8 to monitor artifacts or anatomical abnormalities. To enhance registration, the reorientation of the images was manually set to the anterior commissure. Then, the New Segment Toolbox from SPM8 was used on every T1-weighted MR image to extract tissue maps corresponding to the gray matter volume (GMV), white matter volume (WMV), and cerebral spinal fluid in native space. After segmentation, we performed registration, normalization, and modulation by DARTEL in SPM8, which generates a more precise registration than the standard VBM procedure. For each voxel of GMV and WMV, Jacobian determinants were used for normalization to ensure that regional differences in the absolute amount of gray matter were conserved. The images were then resampled to 1.5-mm isotropic voxels in Montreal Neurological Institute (MNI) space. Finally, the warped modulated images of gray and white matter were smoothened through the convolution of an 8-mm full-width at half-maximum isotropic Gaussian kernel to increase their signal-to-noise ratio.
The resulting maps representing the GMV of each participant in the pre- and post-MRI experiments were then forwarded to the group paired t analysis as described below. In the whole-brain analysis, using a paired t-test, we investigated regions that showed increased GMV following group training. We also applied explicit masking using the population-specific masking toolbox in SPM8 in order to restrict the search volume within gray matter and white matter (http://www.cs.ucl.ac.uk/staff/g.ridgway/masking/). This approach was used instead of absolute or relative threshold masking in order to reduce the risk of false negatives caused by overly restrictive masking, in which potentially interesting voxels are excluded from the statistical analysis (Ridgway et al., 2009). In this computation, the cluster-level statistical threshold was set at p < 0.05, and corrected using non-stationary cluster correction (Hayasaka et al., 2004) with an underlying voxel level of p < 0.001. 2.5. Amplitude of low frequency fluctuation analysis The processing of resting-state image data for the pre- and post-training was performed using the DPARSF, data-processing assistant software for the resting state (http://www.restfmri.net/forum/DPARSF) (Yan and Zang, 2010). Both toolboxes were based on the SPM8 software package. To control for the signal equilibrium and the participants’ adaptation to their immediate environment, the first 10 volumes of the functional images were discarded. Then the remaining 232 images were corrected by slice timing and realigned to middle image volume to correct head motion. After that, all realigned images were spatially normalized to the MNI template and resampled into 3 × 3 × 3 mm3. Finally, the images were smoothed with an 8-mm FWHM Gaussian kernel. The smoothed data were linearly detrended and filtered using a band
pass filter (0.01-0.08 Hz) to reduce the very low-frequency drift and high-frequency respiratory or cardiac noise (Biswal et al., 1995; Lowe et al., 1998). We used the amplitude of low frequency fluctuation (ALFF) for detecting regional signals of change in spontaneous activity. In our study, all the individual data were transformed to Z scores by subtracting the global mean value and then dividing by the standard deviation. Finally, the Z maps were transformed to MNI space, and all the maps obtained before and after training were compared using two-tailed paired sample t-tests. 2.6.Functional connectivity ALFF can only provide information about synchronous regional cerebral activity, while functional connectivity analysis can examine the cross-correlations between spatially remote regions, which ensures the integrity of distributed brain networks. Therefore, we performed the functional connectivity by using a seed voxel correlation approach in the Resting-State fMRI Data Analysis Toolkit (REST) software package (Song et al., 2011). Before the functional connectivity analysis, we regressed out the time courses for the various covariates (global signal, white matter, cerebrospinal fluid, and six motion parameters for head movement) in order to cancel out the potential impact of physiological artifacts. We used the clusters that were significantly different in the structural results between pre- and post-training scans as seed regions. All the Z-transformed correlation coefficients [Z(r)] were calculated between the average time course in each seed and the whole brain based on a voxel-wise basis. We used a two-tailed paired sample t-test to look for areas with statistically significant differences in functional connectivity with seeds between pre- and post-training scans. 3. Results 3.1 Behavioral data
Before training, the mean (± SD) of the BDI was 9.81+5.32; after the course of training, it was reduced by approximately 43%, BDI = 5.56+5.66. There was a significant difference between the pre- and post-training scores (t (15) = 3.29, p=0.005), indicating that symptom severity decreased significantly after the training. BDI scores showed no significant gender differences (t (15) = 0.10, p = 0.92). Fig. 1 shows the trend of BDI reduction after 4 weeks of training. INSERT FIGURE 1 ABOUT HERE 3.2 VBM results To explore the structural correlates of response to CBT in mild depression, we initially used a paired sample t-test to investigate whether there were any significant differences in GMV before and after training. The whole-brain analysis indicated that after 4 weeks of training, the GMV of the right middle frontal gyrus (MFG, MNI=33, 43, 14) significantly increased, while the left postcentral gyrus (MNI=-62, -18, 30) significantly decreased. To examine whether the GMV changes were correlated with behavioral changes, we first we calculated the percentage changes of the GMV using the formula [(GMV at follow-up - GMV at baseline)/GMV at baseline × 100] in each subject. After that, we performed a correlation analysis in SPSS. We found that the increase of percentage change in the right MFG was positively correlated with the decrease of the BDI score (r=0.52, p<0.05). Smaller decrease in the percentage change in the left postcentral gyrus was significantly correlated with greater decrease in the BDI score (r=0.55, p<0.05). INSERT FIGURE 2 3 ABOUT HERE 3.3 ALFF results We tested whether the significantly changed areas identified by VBM were also greatly altered in functional neuroimaging by examining the ALFF (0.01–0.08 Hz) of
blood oxygenation level-dependent (BOLD) signals in the significant areas identified by VBM. At first, we extracted the raw signal of the right MFG and the left postcentral gyrus, respectively. Then, we performed a paired sample t-test in SPSS. The ALFF maps from those significant coordinates were produced by using an 8-mm radius sphere at a peak activation voxel in the REST. The results showed that only the maps of ALFF in the right MFG significantly decreased after the training (t (15) = -2.36, p<0.05). No significant change was detected in the left postcentral gyrus (t (15) = 0.63, p = 0.54). Furthermore, we carried out a voxel-wise ALFF analysis in whole brain and found some regional changes in addition to the MFG, such as the superior frontal gyrus, medial frontal gyrus, inferior frontal gyrus, and inferior temporal gyrus. Unfortunately, all these regions were so small that they were not significant after correction for multiple comparisons. 3.4 Functional connectivity results The significantly changed areas identified by VBM, the right MFG and the left postcentral gyrus, were set as the regions of interest (ROIs) in the functional connectivity analysis. Connectivity maps were compared across pre- and post-training conditions by using a paired sample t-test. We found that the pre-training scan showed significantly greater activation in the right insula than was observed post-training (MNI=33, 12, 9), which indicated that the connectivity between the right MFG and the insula decreased after training, whereas the left postcentral gyrus showed a significant enhancement with the left parahippocampal gyrus（MNI=-24, -15, -30） after training. INSERT FIGURE 4 ABOUT HERE 4
Discussion
In the present study, we used both functional and structural neuroimaging techniques to explore the neural correlates of response to CBT in mild depression. We found that (1) subjects showed significantly increased GMV and decreased ALFF in the right MFG, accompanied by decreased GMV in the left postcentral gyrus, after 4 weeks of group counseling with CBT. (2) Further correlation analysis suggested the increase of percentage change in the right MFG was positively correlated with the decrease of the BDI score. In addition, smaller decrease of percentage change in the left postcentral gyrus was significantly correlated with greater decrease of BDI score. (3) Functional connectivity results revealed that the connectivity between the right MFG and the insula decreased after the training. Meanwhile, the connectivity between the left postcentral gyrus and the parahippocampal gyrus increased. We would discuss the implications of these results as follows. Firstly, we found increased GMV and decreased ALFF in the right MFG after the training. According to a voxel-based meta-analysis result, sadness consistently activated the MFG (Vytal and Hamann, 2010). We know that everyone at some point in their lives has felt depression or sadness. Moreover, unremitting feelings of sadness constitute an important symptom of depression (DSM-IV). In fact, a key neuropsychological impairment in depression is a mood-congruent processing bias in which ambiguous or positive events are experienced as negative (Beck, 1979). For example, patients have been found to show a negative bias, tending to misperceive happy faces as being neutral and neutral faces as being sad (Persad and Polivy, 1993). Meanwhile, depressed patients have been reported to show exaggerated activity in the MFG when responding to sad words (Elliott et al., 2002). Several recent studies have indicated that “the larger the volume, the better the function” premise does not always hold true (Kanai and Rees, 2011; Takeuchi et al., 2011). Therefore, we speculate that
the increased GMV in the MFG in our study might be reflective of the decreased function in this region. Liu et al. (2014) found that compared with healthy controls, treatment-naive depressed patients showed increased ALFF in the frontal cortex. Additionally, Guo et al. (2012) found higher ALFF in the frontal gyrus in treatment-resistant depressed patients relative to treatment-responsive depressed patients. To some extent, the results support the unifying opinion that negative biases in information processing for depression and anxiety are the explicit targets for psychological treatments, such as CBT (Beck, 1979). Also, we found that the functional connectivity between the right middle frontal gyrus (part of dorsal anterior cingulate cortex, dACC) and insula was decreased after training. The insula and the dACC are two prominent nodes in the salience network (SN), which is critical in detecting the salience of internal and external stimuli (Seeley et al., 2007; Bressler and Menon, 2010; Menon, 2011). For example, Damasio (2000) found that the SN circuitry was implicated in self-generated emotional processing. Previous studies showed that some forms of pathology subsequently resulted after the SN went into overdrive (Paulus and Stein, 2006; Stein et al., 2007). According to the neutral mechanisms of the cognitive model of depression, depressed mood state may result from a cognitive bias towards negative information and away from positive information (Disner et al., 2011). Therefore, our results, to some extent, provide neuroimaging evidence to support that CBT could decrease the salience detection for negative stimuli. Finally, our results showed that the connectivity between the left postcentral gyrus and the parahippocampal gyrus was increased after training. Distinct activity in the parahippocampus gyrus has been shown to recognize items previously encountered and those falsely believed to have been encountered (Cabeza et al., 2001).
A variety of studies demonstrated that depressed patients had a tendency to selectively recall negative material which were congruent with their mood (Matt et al., 1992; Howe and Malone, 2011). For example, Joormann et al. (2009) found that compared with non-depressed controls, depressed patients falsely recalled more negative words and showed a poorer baseline recall of true words. Therefore, it was speculated that the increased functional connectivity between the left postcentral gyrus and the parahippocampus gyrus might be associated with an enhanced ability of memory recognition, especially for distinguishing the false item. Notwithstanding the potential implications of this study, its main limitations should be acknowledged. First, the absence of a control group and a clinical depression group limit the interpretation of our results. Subjects in our study were all healthy, with only mild emotional disturbance, making them clearly different from clinically depressed patients. Thus, further studies are needed to compare neural activity among patients with depressive disorders, ranging from mild, to moderate, to severe, and normal controls. Second, because the sample size was relatively small, future studies must replicate the findings in larger numbers of participants. Third, expanded studies of the functions of particular brain regions, task paradigms, and brain lesions are needed in the future. 5
Conclusions In summary, in this study, both functional and structural neuroimaging
techniques were used to explore the neural correlates of response to CBT in mild depression. Participation in group CBT was associated with increased GMV and decreased ALFF in the right middle frontal gyrus, findings that were was related to negative bias, and to decreased GMV in the left postcentral gyrus. Finally, the decreased functional connectivity between the right middle frontal gyrus and the
insula showed that CBT could decrease the salience detection for negative stimuli after the training. Moreover, the increased connectivity between the left postcentral gyrus and the parahippocampal gyrus might be associated with the increased ability to distinguish falsely remembered items from previously encountered items. All these results indicated that a short-term psychotherapy training has effects on both the functional and the structural brain. More extensive studies might lead to new insights into neural plasticity and clinical applications of group CBT. Acknowledgments This research was supported by the National Natural Science Foundation of China (31271087; 31470981; 31571137; 31500885), National Outstanding Young People Plan, the Program for the Top Young Talents by Chongqing, the Fundamental Research Funds for the Central Universities (SWU1509383), Natural Science Foundation of Chongqing （cstc2015jcyjA10106), General Financial Grant from the China Postdoctoral Science Foundation (2015M572423), a Joint-PhD scholarship (No. 201506990037) of the China Scholarship Council (CSC) to study at Texas Tech University, Innovative Research Project for Postgraduate Student of Chongqing (CYB2015060). The authors declare no competing interests. References American Psychiatric Association, 1994. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. APA, Washington, DC. Ashton, K., Drerup, M., Windover, A., Heinberg, L., 2009. Brief, four-session group CBT reduces binge eating behaviors among bariatric surgery candidates. Surgery for Obesity and Related Diseases 5, 257-262. Beck, A.T., 1967. Depression: Clinical, Experimental, and Theoretical Aspects. University of Pennsylvania Press, Philadelphia. Beck, A.T., 1976. Cognitive Therapy and the Emotional Disorders. International Universities Press, New York. Beck, A.T., Rush, A.J., Shaw, B.F., Emery, G., 1979. Cognitive Therapy of Depression. Guilford Press, New York. Beddington, J., Cooper, C.L., Field, J., Goswami, U., Huppert, F.A., Jenkins, R., Jones, H.S., Kirkwood, T.B., Sahakian, B.J., Thomas, S.M., 2008. The mental wealth of nations. Nature 455, 1057-1060. Bennett, C.M., Miller, M.B., 2010. How reliable are the results from functional magnetic resonance imaging? Annals of the New York Academy of Sciences 1191, 133-155.
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Figure Legends
Fig. 1. Demonstration of depressive symptoms change after 4 weeks of group CBT. After 4 weeks of training, there were significant reductions of Beck Depression Inventory (BDI) scores in mild depression.
Fig. 2. A: Increased gray matter volume (GMV) in the right middle frontal gyrus after 4 weeks of group CBT (displayed at pcorrected < 0.05). B: After 4 weeks of group CBT, we found that the increase of the percentage change in the right middle frontal gyrus was positively correlated with the decrease of the BDI score. C: Significantly decreased amplitude of low-frequency fluctuation (ALFF) in the right middle frontal gyrus after the training.
Fig. 3. A: Decreased gray matter volume (GMV) in the left postcentral gyrus activity after 4 weeks of group CBT (displayed at pcorrected < 0.05). B: After 4 weeks of group CBT, we found that a smaller decrease in percentage change in the left postcentral was significantly correlated with a greater decrease of BDI score.
Fig. 4. Resting functional connectivity results. A: Significantly decreased connectivity was found between the right middle frontal gyrus and the insula after training. B: Connectivity between the left postcentral gyrus and the parahippocampal gyrus increased.
Highlights
Short-term of group CBT was an effective treatment for mild depression Group CBT increased GMV and decreased ALFF in the right middle frontal gyrus Group CBT decreased the GMV in the left postcentral gyrus Group CBT decreased salience detection for negative stimuli
PII: DOI: Reference:
S0925-4927(16)30108-1 http://dx.doi.org/10.1016/j.pscychresns.2016.04.010 PSYN10532
To appear in: Psychiatry Research: Neuroimaging Received date: 4 June 2015 Revised date: 8 January 2016 Accepted date: 17 April 2016 Cite this article as: Xue Du, Yu Mao, Qinglin Zhang, Qing Hua Luo and Jiang Qiu, Short-term group cognitive behavior therapy contributes to recovery from mild depression: evidence from functional and structural MRI, Psychiatry Research: Neuroimaging, http://dx.doi.org/10.1016/j.pscychresns.2016.04.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Short-term group cognitive behavior therapy contributes to recovery from mild depression: evidence from functional and structural MRI Xue Dua,b1, Yu Maoa,b,1, Qinglin Zhanga,b*,Qing Hua Luoc*, Jiang Qiua,b*
a
Key Laboratory of Cognition And Personality (SWU), Ministry of Education,
Chongqing 400715, China b
School of Psychology, Southwest University, Chongqing 400715, China
c
Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical
University, Chongqing,400016, China E-mail address:[email protected] [email protected] [email protected]
*Corresponding authors: Qinglin Zhang and Jiang Qiu, School of Psychology, Southwest University, Beibei, Chongqing 400715 China *Qinghua Luo, Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 China. Tel:+86 23 6836 7942 (China (023) 68367942).
Abstract We used the functional and structural magnetic resonance imaging to explore the neural correlates of response to group cognitive behavioral therapy (CBT) in mild depression. College students with mild depressive symptoms participated in our 1
The authors contributed equally to this work
4-week group CBT training. The behavioral results showed that depression symptoms decreased after participation in group CBT. After the training, the gray matter volume (GMV) in the right middle frontal gyrus (MFG) increased and amplitude of low-frequency fluctuations (ALFF) decreased. In addition, GMV in the left postcentral gyrus decreased after the group CBT. Moreover, the increase of percentage change in the right MFG was positively correlated with the decrease of the Beck Depression Inventory (BDI) score, while less decrease in percentage change in the left postcentral gyrus was significantly correlated with greater decrease of BDI score. Finally, after the training, functional connectivity between the right MFG and the insula decreased, while the connectivity between the left postcentral gyrus and the parahippocampal gyrus increased. These findings suggested that short-term participation in group CBT had an effective impact on mild depression. It contributed to decreasing negative bias (salience detection for negative stimuli).
Keywords: Gray matter volume; Amplitude of low-frequency fluctuation; Functional connectivity; Group cognitive behavioral therapy
1. Introduction Depression is a highly prevalent, clinically significant, and disorder (Kessler et al., 2003; Rush et al., 2003; Richards, 2011). Major depression disorder (MDD) is one of the most common psychiatric disorders. Moreover, many individuals experience sub-threshold depressive symptoms that do not meet criteria for full-blown MDD episodes (Furukawa et al., 2009). Previous studies pointed out that persistent
depressive symptoms below the threshold for a diagnosis of major depression could cause chronic illness and have a high risk of progression to more serious disorders (Cuijpers and Smit, 2004; Cuijpers et al., 2007). In fact, mild or sub-threshold depression is a state that has been postulated to represent the low end of a continuum of depressive severity. Although sub-threshold depressive states are quantitatively different from MDD, they may not be qualitatively different (Gotlib, 1984). Mild depression can be considered as a significant indicator of risk for MDD. A more precise understanding of mild depression, which is thought to be prodromal to MDD, might aid in the effort to prevent the onset of clinical depression through early diagnosis and intervention. According to the World Mental Health Survey, mild and sub-threshold cases are prevalent in every country, so the value of treating mild cases should be carefully considered (Demyttenaere et al., 2013). Given the importance of identifying biomarkers of depression, it must be a priority target for society and governments to recognize and treat mild cases of depression to forestall the development of a substantial proportion of future serious cases (Beddington et al., 2008; Sahakian et al., 2010; Collins et al., 2011). Cognitive behavior therapy (CBT) is a widely investigated and practiced psychotherapeutic approach that can effectively reduce rates of subsequent relapse and recurrence (Beck et al., 1979; Cuijpers et al., 2013). The premise of CBT derives from Beck’s Cognitive Theory of Depression, which posits that depression is state in which self-reinforcing dysfunctional negative schemata dominate every aspect of an individual’s information processing (Beck, 1967, 1976). Hence, the focus of CBT is on modifying negative cognition, also known as dysfunctional schemata (Beck, 1976). Generally, theoretical models of the action of CBT in depression implicate top-down mechanisms, because the mediation of depression-relevant cognition, affective bias,
and maladaptive information processing is emphasized in the intervention (Beck, 1979; Clak and Beck, 1999). Moreover, group intervention can be used as a therapeutic intervention, as well as a preventative measure (Corey, 2011), due to its cost-effectiveness and potential to facilitate peer support (Edelman et al., 1989; Burlingame et al., 2004). With the development of functional neuroimaging techniques, many investigators have begun to study the neural mechanisms underlying different forms of CBT. These studies identified showed certain brain regions as being involved in the process, including the anterior cingulate cortex (ACC) and the prefrontal gyrus (Fu et al., 2008; Dichter et al., 2010; Forbes et al., 2010; Ritchey et al., 2011). Although the results are promising, functional imaging studies of CBT are methodologically demanding and have varied dramatically with regard to paradigms and analytic methods (Bennett and Miller, 2010). In fact, structural neuroimaging approaches have more often been performed in clinical practice (Redlich et al., 2014). Until now, there have been few structural neuroimaging studies that examined changes that occurred after group CBT in mild depression. Therefore, we tried to combine the advantage of both functional and structural neuroimaging techniques to explore the neural correlates of response to CBT in mild depression. Additionally, a large number of reports found that different dependent measures of depression might have different reliabilities and sensitivities to change (Brown et al., 1995; Shafer, 2006). Thus, the choice of different assessment instruments might lead to different conclusions about the efficacy of the various therapies under investigation. In considering of our aim, we chose the Beck Depression Inventory (BDI) as a conservative means of measuring change in depressive symptomatology (Dobson, 1989). In this study, we predicted that (1) behavioral symptoms could be
reduced after group CBT, (2) the efficacy of CBT in mild depression might be reflected in associated changes in brain regions, such as the prefrontal gyrus, which has been related to cognitive and affective processing (Bush et al., 2000; De Lange et al., 2008; Kumari et al., 2009; Etkin et al., 2011; Ritchey et al., 2011). To some extent, this study might be the first one to combine functional and structural techniques to explore the neural correlates of response to CBT in mild depression. As such, it should provide potential suggestions for future clinical applications and early intervention in cases of mild depression. 2. Methods 2.1.Participants Twenty participants (mean age (SD) = 19.94 (1.06) years; 10 women, 10 men) were recruited from our ongoing project to examine the associations among brain-imaging findings, creativity and mental health. None of the participants in the present study met DSM-IV criteria for depression (American Psychiatric Association, 1994). Because of our focus on mild depression, the 21-item BDI was used as the assessment instrument in our study. According to the norm in China, the inclusion criteria for minor depression require at least 4 points on the BDI (Beck, 1967; Hongbo and Yanping, 1987). Participants who had a history of psychiatric or neurological disorders were also excluded. In total, four subjects were excluded from the training group: two had dropped out of the training, and two had excessive head motion in the scanner. Therefore, the data that were analyzed derived from 16 participants, including both pre- and post-training scans. Written informed consent was obtained from all participants before study. This study was approved by the Institutional Human Participants Review Board of Southwest University Imaging Center for Brain Research.
2.2. The intervention The 4-week group CBT program was designed and led by two licensed psychologists. The group met for 90-min sessions for 4 consecutive weeks. Participants received a manual at the start of the training, as well as handouts and homework exercises at every session. The intervention incorporated the use of cognitive and behavioral techniques, including encouragement to express feelings and to provide group support. For example, the training emphasized how to identify and challenge maladaptive thoughts and beliefs. This included elements of basic cognitive skills, regulation of emotion, stress management, relaxation training, and group support. Elements of the group discussion specific to “disputing” of negative perceptions and the use of coping statements were included. The intervention’s brevity was determined from research suggesting the efficacy of short-term interventions (Ashton et al., 2009; Grilo et al., 2006). 2.3. Data acquisition Structural and functional magnetic resonance imaging (MRI) was acquired on a Siemens 3.0 T-Magnetom Sonata scanner (Siemens Medical, Erlangen, Germany). Subjects were equipped with a circularly polarized standard head coil; in addition, foam pads and headphones were used to reduce head motion and scanner noise. High-resolution T1-weighted anatomical images were acquired using a magnetization-prepared rapid gradient echo (MPRAGE) sequence: repetition time (TR) = 1900 ms; echo time (TE) = 2.52 ms; inversion time (TI) = 900 ms; flip angle (FA) = 9; field of view (FOV) = 256 × 256 mm2; resolution matrix = 256 × 256; slices = 176; thickness = 1 mm; voxel size = 1 × 1 × 1 mm. At the same slice locations as in the structural images, functional images were collected axially by using an
echo-planar imaging (EPI) sequence: TR=2000 ms; TE =30 ms; FA = 90°; FOV=220 × 220 mm2; resolution matrix = 64 × 64; slices = 20, thickness = 3 mm; voxel size = 3.4 × 3.4 × 4 mm. Before being scanned in a resting state, participants were instructed to keep their eyes closed but not to sleep. Instead, they were asked to relax their minds and remain motionless during the EPI data acquisition. The scan lasted for 488 s including 32 slices which were used to cover the whole brain. Each section contained 242 volumes. 2.4. Voxel-based morphometry (VBM) The MR images were processed using the SPM8 program (Wellcome Department of Cognitive Neurology, London, UK; www.fil.ion.ucl.ac.uk/spm) implemented in Matlab 7.8 (MathWorks Inc., Natick, MA, USA). Firstly, each MR image was displayed in SPM8 to monitor artifacts or anatomical abnormalities. To enhance registration, the reorientation of the images was manually set to the anterior commissure. Then, the New Segment Toolbox from SPM8 was used on every T1-weighted MR image to extract tissue maps corresponding to the gray matter volume (GMV), white matter volume (WMV), and cerebral spinal fluid in native space. After segmentation, we performed registration, normalization, and modulation by DARTEL in SPM8, which generates a more precise registration than the standard VBM procedure. For each voxel of GMV and WMV, Jacobian determinants were used for normalization to ensure that regional differences in the absolute amount of gray matter were conserved. The images were then resampled to 1.5-mm isotropic voxels in Montreal Neurological Institute (MNI) space. Finally, the warped modulated images of gray and white matter were smoothened through the convolution of an 8-mm full-width at half-maximum isotropic Gaussian kernel to increase their signal-to-noise ratio.
The resulting maps representing the GMV of each participant in the pre- and post-MRI experiments were then forwarded to the group paired t analysis as described below. In the whole-brain analysis, using a paired t-test, we investigated regions that showed increased GMV following group training. We also applied explicit masking using the population-specific masking toolbox in SPM8 in order to restrict the search volume within gray matter and white matter (http://www.cs.ucl.ac.uk/staff/g.ridgway/masking/). This approach was used instead of absolute or relative threshold masking in order to reduce the risk of false negatives caused by overly restrictive masking, in which potentially interesting voxels are excluded from the statistical analysis (Ridgway et al., 2009). In this computation, the cluster-level statistical threshold was set at p < 0.05, and corrected using non-stationary cluster correction (Hayasaka et al., 2004) with an underlying voxel level of p < 0.001. 2.5. Amplitude of low frequency fluctuation analysis The processing of resting-state image data for the pre- and post-training was performed using the DPARSF, data-processing assistant software for the resting state (http://www.restfmri.net/forum/DPARSF) (Yan and Zang, 2010). Both toolboxes were based on the SPM8 software package. To control for the signal equilibrium and the participants’ adaptation to their immediate environment, the first 10 volumes of the functional images were discarded. Then the remaining 232 images were corrected by slice timing and realigned to middle image volume to correct head motion. After that, all realigned images were spatially normalized to the MNI template and resampled into 3 × 3 × 3 mm3. Finally, the images were smoothed with an 8-mm FWHM Gaussian kernel. The smoothed data were linearly detrended and filtered using a band
pass filter (0.01-0.08 Hz) to reduce the very low-frequency drift and high-frequency respiratory or cardiac noise (Biswal et al., 1995; Lowe et al., 1998). We used the amplitude of low frequency fluctuation (ALFF) for detecting regional signals of change in spontaneous activity. In our study, all the individual data were transformed to Z scores by subtracting the global mean value and then dividing by the standard deviation. Finally, the Z maps were transformed to MNI space, and all the maps obtained before and after training were compared using two-tailed paired sample t-tests. 2.6.Functional connectivity ALFF can only provide information about synchronous regional cerebral activity, while functional connectivity analysis can examine the cross-correlations between spatially remote regions, which ensures the integrity of distributed brain networks. Therefore, we performed the functional connectivity by using a seed voxel correlation approach in the Resting-State fMRI Data Analysis Toolkit (REST) software package (Song et al., 2011). Before the functional connectivity analysis, we regressed out the time courses for the various covariates (global signal, white matter, cerebrospinal fluid, and six motion parameters for head movement) in order to cancel out the potential impact of physiological artifacts. We used the clusters that were significantly different in the structural results between pre- and post-training scans as seed regions. All the Z-transformed correlation coefficients [Z(r)] were calculated between the average time course in each seed and the whole brain based on a voxel-wise basis. We used a two-tailed paired sample t-test to look for areas with statistically significant differences in functional connectivity with seeds between pre- and post-training scans. 3. Results 3.1 Behavioral data
Before training, the mean (± SD) of the BDI was 9.81+5.32; after the course of training, it was reduced by approximately 43%, BDI = 5.56+5.66. There was a significant difference between the pre- and post-training scores (t (15) = 3.29, p=0.005), indicating that symptom severity decreased significantly after the training. BDI scores showed no significant gender differences (t (15) = 0.10, p = 0.92). Fig. 1 shows the trend of BDI reduction after 4 weeks of training. INSERT FIGURE 1 ABOUT HERE 3.2 VBM results To explore the structural correlates of response to CBT in mild depression, we initially used a paired sample t-test to investigate whether there were any significant differences in GMV before and after training. The whole-brain analysis indicated that after 4 weeks of training, the GMV of the right middle frontal gyrus (MFG, MNI=33, 43, 14) significantly increased, while the left postcentral gyrus (MNI=-62, -18, 30) significantly decreased. To examine whether the GMV changes were correlated with behavioral changes, we first we calculated the percentage changes of the GMV using the formula [(GMV at follow-up - GMV at baseline)/GMV at baseline × 100] in each subject. After that, we performed a correlation analysis in SPSS. We found that the increase of percentage change in the right MFG was positively correlated with the decrease of the BDI score (r=0.52, p<0.05). Smaller decrease in the percentage change in the left postcentral gyrus was significantly correlated with greater decrease in the BDI score (r=0.55, p<0.05). INSERT FIGURE 2 3 ABOUT HERE 3.3 ALFF results We tested whether the significantly changed areas identified by VBM were also greatly altered in functional neuroimaging by examining the ALFF (0.01–0.08 Hz) of
blood oxygenation level-dependent (BOLD) signals in the significant areas identified by VBM. At first, we extracted the raw signal of the right MFG and the left postcentral gyrus, respectively. Then, we performed a paired sample t-test in SPSS. The ALFF maps from those significant coordinates were produced by using an 8-mm radius sphere at a peak activation voxel in the REST. The results showed that only the maps of ALFF in the right MFG significantly decreased after the training (t (15) = -2.36, p<0.05). No significant change was detected in the left postcentral gyrus (t (15) = 0.63, p = 0.54). Furthermore, we carried out a voxel-wise ALFF analysis in whole brain and found some regional changes in addition to the MFG, such as the superior frontal gyrus, medial frontal gyrus, inferior frontal gyrus, and inferior temporal gyrus. Unfortunately, all these regions were so small that they were not significant after correction for multiple comparisons. 3.4 Functional connectivity results The significantly changed areas identified by VBM, the right MFG and the left postcentral gyrus, were set as the regions of interest (ROIs) in the functional connectivity analysis. Connectivity maps were compared across pre- and post-training conditions by using a paired sample t-test. We found that the pre-training scan showed significantly greater activation in the right insula than was observed post-training (MNI=33, 12, 9), which indicated that the connectivity between the right MFG and the insula decreased after training, whereas the left postcentral gyrus showed a significant enhancement with the left parahippocampal gyrus（MNI=-24, -15, -30） after training. INSERT FIGURE 4 ABOUT HERE 4
Discussion
In the present study, we used both functional and structural neuroimaging techniques to explore the neural correlates of response to CBT in mild depression. We found that (1) subjects showed significantly increased GMV and decreased ALFF in the right MFG, accompanied by decreased GMV in the left postcentral gyrus, after 4 weeks of group counseling with CBT. (2) Further correlation analysis suggested the increase of percentage change in the right MFG was positively correlated with the decrease of the BDI score. In addition, smaller decrease of percentage change in the left postcentral gyrus was significantly correlated with greater decrease of BDI score. (3) Functional connectivity results revealed that the connectivity between the right MFG and the insula decreased after the training. Meanwhile, the connectivity between the left postcentral gyrus and the parahippocampal gyrus increased. We would discuss the implications of these results as follows. Firstly, we found increased GMV and decreased ALFF in the right MFG after the training. According to a voxel-based meta-analysis result, sadness consistently activated the MFG (Vytal and Hamann, 2010). We know that everyone at some point in their lives has felt depression or sadness. Moreover, unremitting feelings of sadness constitute an important symptom of depression (DSM-IV). In fact, a key neuropsychological impairment in depression is a mood-congruent processing bias in which ambiguous or positive events are experienced as negative (Beck, 1979). For example, patients have been found to show a negative bias, tending to misperceive happy faces as being neutral and neutral faces as being sad (Persad and Polivy, 1993). Meanwhile, depressed patients have been reported to show exaggerated activity in the MFG when responding to sad words (Elliott et al., 2002). Several recent studies have indicated that “the larger the volume, the better the function” premise does not always hold true (Kanai and Rees, 2011; Takeuchi et al., 2011). Therefore, we speculate that
the increased GMV in the MFG in our study might be reflective of the decreased function in this region. Liu et al. (2014) found that compared with healthy controls, treatment-naive depressed patients showed increased ALFF in the frontal cortex. Additionally, Guo et al. (2012) found higher ALFF in the frontal gyrus in treatment-resistant depressed patients relative to treatment-responsive depressed patients. To some extent, the results support the unifying opinion that negative biases in information processing for depression and anxiety are the explicit targets for psychological treatments, such as CBT (Beck, 1979). Also, we found that the functional connectivity between the right middle frontal gyrus (part of dorsal anterior cingulate cortex, dACC) and insula was decreased after training. The insula and the dACC are two prominent nodes in the salience network (SN), which is critical in detecting the salience of internal and external stimuli (Seeley et al., 2007; Bressler and Menon, 2010; Menon, 2011). For example, Damasio (2000) found that the SN circuitry was implicated in self-generated emotional processing. Previous studies showed that some forms of pathology subsequently resulted after the SN went into overdrive (Paulus and Stein, 2006; Stein et al., 2007). According to the neutral mechanisms of the cognitive model of depression, depressed mood state may result from a cognitive bias towards negative information and away from positive information (Disner et al., 2011). Therefore, our results, to some extent, provide neuroimaging evidence to support that CBT could decrease the salience detection for negative stimuli. Finally, our results showed that the connectivity between the left postcentral gyrus and the parahippocampal gyrus was increased after training. Distinct activity in the parahippocampus gyrus has been shown to recognize items previously encountered and those falsely believed to have been encountered (Cabeza et al., 2001).
A variety of studies demonstrated that depressed patients had a tendency to selectively recall negative material which were congruent with their mood (Matt et al., 1992; Howe and Malone, 2011). For example, Joormann et al. (2009) found that compared with non-depressed controls, depressed patients falsely recalled more negative words and showed a poorer baseline recall of true words. Therefore, it was speculated that the increased functional connectivity between the left postcentral gyrus and the parahippocampus gyrus might be associated with an enhanced ability of memory recognition, especially for distinguishing the false item. Notwithstanding the potential implications of this study, its main limitations should be acknowledged. First, the absence of a control group and a clinical depression group limit the interpretation of our results. Subjects in our study were all healthy, with only mild emotional disturbance, making them clearly different from clinically depressed patients. Thus, further studies are needed to compare neural activity among patients with depressive disorders, ranging from mild, to moderate, to severe, and normal controls. Second, because the sample size was relatively small, future studies must replicate the findings in larger numbers of participants. Third, expanded studies of the functions of particular brain regions, task paradigms, and brain lesions are needed in the future. 5
Conclusions In summary, in this study, both functional and structural neuroimaging
techniques were used to explore the neural correlates of response to CBT in mild depression. Participation in group CBT was associated with increased GMV and decreased ALFF in the right middle frontal gyrus, findings that were was related to negative bias, and to decreased GMV in the left postcentral gyrus. Finally, the decreased functional connectivity between the right middle frontal gyrus and the
insula showed that CBT could decrease the salience detection for negative stimuli after the training. Moreover, the increased connectivity between the left postcentral gyrus and the parahippocampal gyrus might be associated with the increased ability to distinguish falsely remembered items from previously encountered items. All these results indicated that a short-term psychotherapy training has effects on both the functional and the structural brain. More extensive studies might lead to new insights into neural plasticity and clinical applications of group CBT. Acknowledgments This research was supported by the National Natural Science Foundation of China (31271087; 31470981; 31571137; 31500885), National Outstanding Young People Plan, the Program for the Top Young Talents by Chongqing, the Fundamental Research Funds for the Central Universities (SWU1509383), Natural Science Foundation of Chongqing （cstc2015jcyjA10106), General Financial Grant from the China Postdoctoral Science Foundation (2015M572423), a Joint-PhD scholarship (No. 201506990037) of the China Scholarship Council (CSC) to study at Texas Tech University, Innovative Research Project for Postgraduate Student of Chongqing (CYB2015060). The authors declare no competing interests. References American Psychiatric Association, 1994. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. APA, Washington, DC. Ashton, K., Drerup, M., Windover, A., Heinberg, L., 2009. Brief, four-session group CBT reduces binge eating behaviors among bariatric surgery candidates. Surgery for Obesity and Related Diseases 5, 257-262. Beck, A.T., 1967. Depression: Clinical, Experimental, and Theoretical Aspects. University of Pennsylvania Press, Philadelphia. Beck, A.T., 1976. Cognitive Therapy and the Emotional Disorders. International Universities Press, New York. Beck, A.T., Rush, A.J., Shaw, B.F., Emery, G., 1979. Cognitive Therapy of Depression. Guilford Press, New York. Beddington, J., Cooper, C.L., Field, J., Goswami, U., Huppert, F.A., Jenkins, R., Jones, H.S., Kirkwood, T.B., Sahakian, B.J., Thomas, S.M., 2008. The mental wealth of nations. Nature 455, 1057-1060. Bennett, C.M., Miller, M.B., 2010. How reliable are the results from functional magnetic resonance imaging? Annals of the New York Academy of Sciences 1191, 133-155.
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Figure Legends
Fig. 1. Demonstration of depressive symptoms change after 4 weeks of group CBT. After 4 weeks of training, there were significant reductions of Beck Depression Inventory (BDI) scores in mild depression.
Fig. 2. A: Increased gray matter volume (GMV) in the right middle frontal gyrus after 4 weeks of group CBT (displayed at pcorrected < 0.05). B: After 4 weeks of group CBT, we found that the increase of the percentage change in the right middle frontal gyrus was positively correlated with the decrease of the BDI score. C: Significantly decreased amplitude of low-frequency fluctuation (ALFF) in the right middle frontal gyrus after the training.
Fig. 3. A: Decreased gray matter volume (GMV) in the left postcentral gyrus activity after 4 weeks of group CBT (displayed at pcorrected < 0.05). B: After 4 weeks of group CBT, we found that a smaller decrease in percentage change in the left postcentral was significantly correlated with a greater decrease of BDI score.
Fig. 4. Resting functional connectivity results. A: Significantly decreased connectivity was found between the right middle frontal gyrus and the insula after training. B: Connectivity between the left postcentral gyrus and the parahippocampal gyrus increased.
Highlights
Short-term of group CBT was an effective treatment for mild depression Group CBT increased GMV and decreased ALFF in the right middle frontal gyrus Group CBT decreased the GMV in the left postcentral gyrus Group CBT decreased salience detection for negative stimuli