Publications by authors named "Georgia Wilson"

34 Publications

Modulatory effects of actual and imagined acupuncture on the functional connectivity of the periaqueductal grey and ventral tegmental area.

Psychosom Med 2021 Jul 21. Epub 2021 Jul 21.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA Martinos Brain Imaging Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Objective: Both acupuncture and guided imagery hold promise for treating pain. The mechanisms underlying these alternative interventions remain unclear. The reported study aimed to comparatively investigate the modulation effect of actual and imagined acupuncture on the functional connectivity of descending pain modulation system and reward network.

Methods: Twenty-four healthy participants (mean [SE], 25.21 [0.77] years of age; 66.67% female) completed a crossover study that included five sessions, a training session and four intervention sessions administered in randomized order. We investigated the modulation effect of real acupuncture, sham acupuncture, video-guided acupuncture imagery treatment (VGAIT) and VGAIT control on the resting state functional connectivity (rsFC) of periaqueductal gray (PAG) and ventral tegmental area (VTA). These are key regions of the descending pain modulatory system (DPMS) and dopaminergic reward system, respectively.

Results: Compared with sham acupuncture, real acupuncture produced decreased PAG-precuneus (Pcu) rsFC and increased VTA-amygdala/hippocampus rsFC. Heat pain threshold changes applied on the contralateral forearm were significantly associated with the decreased PAG-Pcu (r = 0.49, p = 0.016) and increased VTA-hippocampus rsFC (r = -0.77, p < 0.001).Compared to VGAIT control, VGAIT produced decreased PAG-paracentral lobule (PCL)/posterior cingulate cortex/Pcu, middle cingulate cortex (MCC), and medial prefrontal cortex rsFC, and decreased VTA-caudate and MCC rsFC.Direct comparison between real acupuncture and VGAIT showed that VGAIT decreased rsFC in PAG-PCL/MCC, VTA-caudate/anterior cingulate cortex/nucleus accumbens, and VTA-MCC.

Conclusions: Results suggest that both actual and imagined acupuncture can modulate key regions in DPMS and reward networks, but through different pathways. Identification of different pain-relief mechanisms may facilitate the development of new pain management methods.
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http://dx.doi.org/10.1097/PSY.0000000000000984DOI Listing
July 2021

An investigation of factors encouraging and deterring EC use: a thematic analysis of accounts from UK adults.

Psychol Health 2021 Jul 19:1-17. Epub 2021 Jul 19.

Public Health Institute, Liverpool John Moores University, Liverpool, UK.

Objective: This study aimed to explore E-cigarette (EC) accounts from a small sample of UK adults with varied smoking/EC experiences. This was to contribute to existing knowledge of adult perceptions and understand the factors that encourage or deter use to inform health messaging aimed at professionals, policy makers and the general public.

Design: Twelve participants, five men and seven women aged 23-55 years (mean age 32.43) with mixed smoking/EC backgrounds took part in face-to-face interviews, analysed using semantic-level inductive thematic analysis.

Results: The analysis identified three key themes. (1) relates to the understanding of the social representations of ECs. (2) captures the impact of varied EC related communication on perception. (3) conveys aspects of nicotine addiction and how this influences EC use.

Conclusion: ECs were generally perceived as more socially acceptable than cigarettes by non-smokers, although there were varying levels of acceptability depending on the type of EC device used. There was also unanimity concerning uncertainty surrounding the devices. Behavioural/sensory elements and personal enjoyment of ECs were consistent elements that encouraged or deterred use. Although non-smokers/vapers did not use the devices, they expressed similar apprehensions to those who did.
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http://dx.doi.org/10.1080/08870446.2021.1952583DOI Listing
July 2021

Mind-Body Exercise Modulates Locus Coeruleus and Ventral Tegmental Area Functional Connectivity in Individuals With Mild Cognitive Impairment.

Front Aging Neurosci 2021 14;13:646807. Epub 2021 Jun 14.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States.

Mild cognitive impairment (MCI) is a common global health problem. Recently, the potential of mind-body intervention for MCI has drawn the interest of investigators. This study aims to comparatively explore the modulation effect of Baduanjin, a popular mind-body exercise, and physical exercise on the cognitive function, as well as the norepinephrine and dopamine systems using the resting state functional connectivity (rsFC) method in patients with MCI. 69 patients were randomized to the Baduanjin, brisk walking, or healthy education control group for 6 months. The Montreal Cognitive Assessment (MoCA) and magnetic resonance imaging (MRI) scans were applied at baseline and at the end of the experiment. Results showed that (1) compared to the brisk walking, the Baduanjin significantly increased MoCA scores; (2) Baduanjin significantly increased the right locus coeruleus (LC) and left ventral tegmental area (VTA) rsFC with the right insula and right amygdala compared to that of the control group; and the right anterior cingulate cortex (ACC) compared to that of the brisk walking group; (3) the increased right LC-right insula rsFC and right LC-right ACC rsFC were significantly associated with the corresponding MoCA score after 6-months of intervention; (4) both exercise groups experienced an increased effective connectivity from the right ACC to the left VTA compared to the control group; and (5) Baduanjin group experienced an increase in gray matter volume in the right ACC compared to the control group. Our results suggest that Baduanjin can significantly modulate intrinsic functional connectivity and the influence of the norepinephrine (LC) and dopamine (VTA) systems. These findings may shed light on the mechanisms of mind-body intervention and aid the development of new treatments for MCI.
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http://dx.doi.org/10.3389/fnagi.2021.646807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236862PMC
June 2021

Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability.

Proc Natl Acad Sci U S A 2021 May;118(19)

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129;

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain's descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.
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http://dx.doi.org/10.1073/pnas.2101273118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126770PMC
May 2021

Altered Extended Locus Coeruleus and Ventral Tegmental Area Networks in Boys with Autism Spectrum Disorders: A Resting-State Functional Connectivity Study.

Neuropsychiatr Dis Treat 2021 22;17:1207-1216. Epub 2021 Apr 22.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Introduction: Previous studies have suggested that cerebral projections of the norepinephrine (NE) and dopamine (DA) systems have important etiology and treatment implications for autism spectrum disorder (ASD).

Methods: We used functional magnetic resonance imaging to evaluate spontaneous resting state functional connectivity in boys aged 7-15 years with ASD (n=86) and age-, intelligence quotient-matched typically developing boys (TD, n=118). Specifically, we investigated functional connectivity of the locus coeruleus (LC) and ventral tegmental area (VTA), the main source projection of neurotransmitters NE and DA, respectively.

Results: 1) Both the LC and VTA showed reduced connectivity with the postcentral gyrus (PoCG) in boys with ASD, reflecting the potential roles of NE and DA in modulating the function of the somatosensory cortex in boys with ASD. 2) The VTA had increased connectivity with bilateral thalamus in ASD; this alteration was correlated with repetitive and restrictive features. 3) Altered functional connectivity of both the LC and VTA with brain regions such as the angular gyrus (AG), middle temporal gyrus visual area (MT/V5), and occipital face area (OFA) in ASD group.

Discussion: Our findings implicate the role of LC-NE and VTA-DA systems from the perspective of functional neuroimaging and may shed light on pharmacological studies targeting NE and DA for the treatment of autism in the future.
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http://dx.doi.org/10.2147/NDT.S301106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075355PMC
April 2021

How expectations of pain elicited by consciously and unconsciously perceived cues unfold over time.

Neuroimage 2021 07 21;235:117985. Epub 2021 Mar 21.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Electronic address:

Expectation can shape the perception of pain within a fraction of time, but little is known about how perceived expectation unfolds over time and modulates pain perception. Here, we combine magnetoencephalography (MEG) and machine learning approaches to track the neural dynamics of expectations of pain in healthy participants with both sexes. We found that the expectation of pain, as conditioned by facial cues, can be decoded from MEG as early as 150 ms and up to 1100 ms after cue onset, but decoding expectation elicited by unconsciously perceived cues requires more time and decays faster compared to consciously perceived ones. Also, results from temporal generalization suggest that neural dynamics of decoding cue-based expectation were predominately sustained during cue presentation but transient after cue presentation. Finally, although decoding expectation elicited by consciously perceived cues were based on a series of time-restricted brain regions during cue presentation, decoding relied on the medial prefrontal cortex and anterior cingulate cortex after cue presentation for both consciously and unconsciously perceived cues. These findings reveal the conscious and unconscious processing of expectation during pain anticipation and may shed light on enhancing clinical care by demonstrating the impact of expectation cues.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248481PMC
July 2021

Altered functional connectivity between hypothalamus and limbic system in fibromyalgia.

Mol Brain 2021 01 20;14(1):17. Epub 2021 Jan 20.

Center for Complementary and Integrative Medicine, Division of Rheumatology, Tufts Medical Center / Tufts University School of Medicine, Boston, MA, 02111, USA.

The hypothalamus links the nervous system to the endocrine system and plays a crucial role in maintaining the human body's homeostasis. This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in fibromyalgia patients. 24 Fibromyalgia patients and 24 matched healthy controls (HCs) were recruited. Resting state fMRI data were collected from the fibromyalgia patients and HC's. Fibromyalgia patients went through a second scan after 12 weeks of Tai Chi mind-body intervention. Data analysis showed that fibromyalgia patients displayed less medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to the functional connectivity in the HCs. After the Tai Chi mind-body intervention, fibromyalgia patients showed increased MH rsFC with the thalamus and amygdala accompanied by clinical improvement. Effective connectivity analysis showed disrupted MH and thalamus interaction in the fibromyalgia patients, which was altered by mind-body exercise. Our findings suggest that fibromyalgia is associated with altered functional connectivity within the diencephalon and limbic system. Elucidating the roles of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of a new biomarker and effective treatment methods for this prevalent disorder.Trial Registration ClinicalTrials.gov, NCT02407665. Registered: 3 April 2015, https://clinicaltrials.gov/ct2/show/NCT02407665?term=NCT02407665&draw=2&rank=1.
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http://dx.doi.org/10.1186/s13041-020-00705-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816461PMC
January 2021

Author Correction: Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain.

Nat Commun 2020 08 25;11(1):4347. Epub 2020 Aug 25.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-18191-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447812PMC
August 2020

Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain.

Nat Commun 2020 08 7;11(1):3948. Epub 2020 Aug 7.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.
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http://dx.doi.org/10.1038/s41467-020-17788-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414843PMC
August 2020

Imagined and Actual Acupuncture Effects on Chronic Low Back Pain: A Preliminary Study.

Neural Plast 2020 1;2020:8579743. Epub 2020 Jul 1.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, 02129 MA, USA.

Background: Research suggests that imagined experiences can produce brain responses similar to those produced by actual experiences. Shared brain responses that support both imagination and perception may underlie the functional nature of mental imagery. In a previous study, we combined acupuncture and imagery to develop a new treatment method, video-guided acupuncture imagery treatment (VGAIT). We found that VGAIT significantly increased pain thresholds in healthy subjects. The aim of this study is to extend our previous finding by investigating whether VGAIT can relieve symptoms in patients with chronic low back pain.

Methods: We first performed a single-arm study in which we administered video-guided acupuncture imagery treatment (VGAIT) on patients with chronic low back pain (cLBP) (Study 1, = 18, 12 females). We then compared our findings to those from a recently published study in which real or sham acupuncture treatment was applied on patients with cLBP (Study 2, = 50, 31 females) using a similar protocol. All patients in Studies 1 and 2 received 6 treatments over 4 weeks.

Results: All three treatments (VGAIT, real, and sham acupuncture) significantly reduced pain severity as measured by a low back pain bothersomeness score. VGAIT produced similar effects to real acupuncture ( = 0.97) and nonsignificantly greater pain bothersomeness relief compared to sham acupuncture ( = 0.14). Additional analysis showed that there was no significant difference on the sensations evoked by different treatment modalities.

Conclusion: These findings support VGAIT as a promising method for pain management.
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http://dx.doi.org/10.1155/2020/8579743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350074PMC
June 2021

Characterizing the analgesic effects of real and imagined acupuncture using functional and structure MRI.

Neuroimage 2020 11 17;221:117176. Epub 2020 Jul 17.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States. Electronic address:

Acupuncture and imagery interventions for pain management have a long history. The present study comparatively investigated whether acupuncture and video-guided acupuncture imagery treatment (VGAIT, watching a video of acupuncture on the participant's own body while imagining it being applied) could modulate brain regional connectivity to produce analgesic effects. The study also examined whether pre-intervention brain functional and structural features could be used to predict the magnitude of analgesic effects. Twenty-four healthy participants were recruited and received four different interventions (real acupuncture, sham acupuncture, VGAIT, and VGAIT control) in random order using a cross-over design. Pain thresholds and magnetic resonance imaging (MRI) data were collected before and after each intervention. We first compared the modulatory effects of real acupuncture and VGAIT on intra- and inter-regional intrinsic brain connectivity and found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, whereas VGAIT increased ReHo in basal ganglia (BG) (i.e., putamen) and FC between the BG subcortical network and default mode network. The altered ReHo and FC were associated with changes in pain threshold after real acupuncture and VGAIT, respectively. A multimodality fusion approach with pre-intervention ReHo and gray matter volume (GMV) as features was used to explore the brain profiles underlying individual variability of pain threshold changes by real acupuncture and VGAIT. Variability in acupuncture responses was associated with ReHo and GMV in BG, whereas VGAIT responses were associated with ReHo and GMV in the anterior insula. These results suggest that, through different pathways, both real acupuncture and VGAIT can modulate brain systems to produce analgesic effects.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738388PMC
November 2020

Acupuncture Treatment Modulates the Connectivity of Key Regions of the Descending Pain Modulation and Reward Systems in Patients with Chronic Low Back Pain.

J Clin Med 2020 Jun 3;9(6). Epub 2020 Jun 3.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Chronic low back pain (cLBP) is a common disorder with unsatisfactory treatment options. Acupuncture has emerged as a promising method for treating cLBP. However, the mechanism underlying acupuncture remains unclear. In this study, we investigated the modulation effects of acupuncture on resting state functional connectivity (rsFC) of the periaqueductal gray (PAG) and ventral tegmental area (VTA) in patients with cLBP. Seventy-nine cLBP patients were recruited and assigned to four weeks of real or sham acupuncture. Resting state functional magnetic resonance imaging data were collected before the first and after the last treatment. Fifty patients completed the study. We found remission of pain bothersomeness in all treatment groups after four weeks, with greater pain relief after real acupuncture compared to sham acupuncture. We also found that real acupuncture can increase VTA/PAG rsFC with the amygdala, and the increased rsFC was associated with decreased pain bothersomeness scores. Baseline PAG-amygdala rsFC could predict four-week treatment response. Our results suggest that acupuncture may simultaneously modulate the rsFC of key regions in the descending pain modulation (PAG) and reward systems (VTA), and the amygdala may be a key node linking the two systems to produce antinociceptive effects. Our findings highlight the potential of acupuncture for chronic low back pain management.
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http://dx.doi.org/10.3390/jcm9061719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356178PMC
June 2020

Potential Locations for Noninvasive Brain Stimulation in Treating Autism Spectrum Disorders-A Functional Connectivity Study.

Front Psychiatry 2020 7;11:388. Epub 2020 May 7.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Objectives: Noninvasive brain stimulation (NIBS) is an emerging tool for treating autism spectrum disorder (ASD). Exploring new stimulation targets may improve the efficacy of NIBS for ASD.

Materials And Methods: We first conducted a meta-analysis on 170 functional magnetic resonance imaging studies to identify ASD-associated brain regions. We then performed resting state functional connectivity analysis on 70 individuals with ASD to investigate brain surface regions correlated with these ASD-associated regions and identify potential NIBS targets for ASD.

Results: We found that the medial prefrontal cortex, angular gyrus, dorsal lateral prefrontal cortex, inferior frontal gyrus, superior parietal lobe, postcentral gyrus, precentral gyrus, middle temporal gyrus, superior temporal sulcus, lateral occipital cortex, and supplementary motor area/paracentral gyrus are potential locations for NIBS in ASD.

Conclusion: Our findings may shed light on the development of new NIBS targets for ASD.
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http://dx.doi.org/10.3389/fpsyt.2020.00388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221195PMC
May 2020

Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain.

Neuroimage 2020 09 18;218:116969. Epub 2020 May 18.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address:

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC)/and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415705PMC
September 2020

Locations for noninvasive brain stimulation in treating depressive disorders: A combination of meta-analysis and resting-state functional connectivity analysis.

Aust N Z J Psychiatry 2020 06 18;54(6):582-590. Epub 2020 May 18.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Objective: Many noninvasive brain stimulation techniques have been applied to treat depressive disorders. However, the target brain region in most noninvasive brain stimulation studies is the dorsolateral prefrontal cortex. Exploring new stimulation locations may improve the efficacy of noninvasive brain stimulation for depressive disorders. We aimed to explore potential noninvasive brain stimulation locations for depressive disorders through a meta-analysis and a functional connectivity approach.

Methods: We conducted a meta-analysis of 395 functional magnetic resonance imaging studies to identify depressive disorder-associated brain regions as regions of interest. Then, we ran resting-state functional connectivity analysis with three different pipelines in 40 depression patients to find brain surface regions correlated with these regions of interest. The 10-20 system coordinates corresponding to these brain surface regions were considered as potential locations for noninvasive brain stimulation.

Results: The 10-20 system coordinates corresponding to the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, medial prefrontal cortex, supplementary motor area, bilateral supramarginal gyrus, bilateral primary motor cortex, bilateral operculum, left angular gyrus and right middle temporal gyrus were identified as potential locations for noninvasive brain stimulation in depressive disorders. The coordinates were: posterior to F3, posterior to F4, superior to F3, posterior to F7, anterior to C4, P3, midpoint of F7-T3, posterior to F8, anterior to C3, midpoint of Fz-Cz, midpoint of Fz-Fp1, anterior to T4, midpoint of C3-P3, and anterior to C4.

Conclusion: Our study identified several potential noninvasive brain stimulation locations for depressive disorders, which may serve as a basis for future clinical investigations.
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http://dx.doi.org/10.1177/0004867420920372DOI Listing
June 2020

Structural and Functional Hippocampal Changes in Subjective Cognitive Decline From the Community.

Front Aging Neurosci 2020 17;12:64. Epub 2020 Mar 17.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.

Background: Recently, subjective cognitive decline (SCD) has been described as the earliest at-risk state of Alzheimer's disease (AD), and drawn attention of investigators. Studies suggested that SCD-community individuals may constitute a more vulnerable population than SCD-clinic patients, therefore, to investigate the early changes of the brain may provide guidance for treatment of the disease. We sought to investigate the changes of structure and functional connectivity alternation of the hippocampus in individuals with SCD recruited from the community using structural and resting-state functional MRI (fMRI).

Methods: Thirty-five SCD patients and 32 healthy controls were recruited. Resting-state fMRI data and high-resolution T1-weighted images were collected. Whole-brain voxel-based morphometry was used to examine the brain structural changes. We also used the hippocampal tail and the whole hippocampus as seeds to investigate functional connectivity alternation in SCD.

Results: Individuals with SCD showed significant gray matter volume decreases in the bilateral hippocampal tails and enlargement of the bilateral paracentral lobules. We also found that individuals with SCD showed decreased hippocampal tail resting-state functional connectivity (rsFC) with the right medial prefrontal cortex (mPFC) and the left temporoparietal junction (TPJ), and decreased whole hippocampus rsFC with the bilateral mPFC and TPJ. These brain region and FC showing significant differences also showed significantly correlation with Montreal Cognitive Assessment (MoCA) scores.

Conclusion: Individuals with SCD recruited from the community is associated with structural and functional changes of the hippocampus, and these changes may serve as potential biomarkers of SCD.

Clinical Trial Registration: The Declaration of Helsinki, and the study was registered in http://www.chictr.org.cn. The Clinical Trial Registration Number was ChiCTR-IPR-16009144.
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http://dx.doi.org/10.3389/fnagi.2020.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090024PMC
March 2020

A thematic analysis of smokers' and non-smokers' accounts of E-cigarettes.

J Health Psychol 2020 Mar 4:1359105320909877. Epub 2020 Mar 4.

Manchester Metropolitan University, UK.

This study explored smokers' and non-smokers' accounts of E-cigarettes. A total of 51 UK-based participants, 20 men and 31 women, responded to open-ended questions online. Inductive thematic analysis identified that the factors that influence E-cigarette behaviour and opinion in adult smokers and non-smokers are related to and Participants presented varying accounts of E-cigarettes, suggesting that individual narratives regarding E-cigarettes are multi-faceted. This is important information for health professionals and policy makers tasked with advising on E-cigarette use.
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http://dx.doi.org/10.1177/1359105320909877DOI Listing
March 2020

Corrigendum to "Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain" [Neuroimage Clinical 23 (2019) 101885].

Neuroimage Clin 2020 12;25:102093. Epub 2019 Dec 12.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.nicl.2019.102093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042668PMC
December 2019

Corrigendum to 'Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain' Neuroimage Clinical, 23, 2019, 101885.

Neuroimage Clin 2019;24:102105. Epub 2019 Nov 29.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.nicl.2019.102105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978220PMC
November 2019

Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: An fMRI study.

Neuroimage Clin 2019 5;24:101971. Epub 2019 Aug 5.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 120 2nd Ave, Room 101, Charlestown, MA 02129, USA. Electronic address:

Background: Migraine is a common episodic neurological disorder. Literature has shown that transcutaneous auricular vagus nerve stimulation (taVNS) at 1 Hz can significantly relieve migraine symptoms. However, its underlying mechanism remains unclear. This study aims to investigate the neural pathways associated with taVNS treatment of migraine.

Methods: Twenty-nine patients with migraine were recruited from outpatient neurology clinics. Each patient attended two magnetic resonance imaging/functional magnetic resonance imaging (MRI/fMRI) scan sessions separated by one week. Each session included a pre-stimulation resting state fMRI scan, fMRI scans during real or sham 1 Hz taVNS (with block design), and a post-stimulation resting state fMRI scan.

Results: Twenty-six patients were included in the final analyses. Real taVNS evoked fMRI signal decreases in brain areas belonging to the default mode network (DMN) and brain stem areas including the locus coeruleus (LC), raphe nuclei, parabrachial nucleus, and solitary nucleus. Sham taVNS evoked fMRI signal decreases in brain areas belonging to the DMN. Compared to sham taVNS, real taVNS produced greater deactivation at the bilateral LC. Resting state functional connectivity (rsFC) analysis showed that after taVNS, LC rsFC with the right temporoparietal junction and left secondary somatosensory cortex (S2) significantly increased compared to sham taVNS. The increased rsFC of the left LC-left S2 was significantly negatively associated with the frequency of migraine attacks during the preceding month.

Conclusion: Our results suggest that taVNS at 1 Hz can significantly modulate activity/connectivity of brain regions associated with the vagus nerve central pathway and pain modulation system, which may shed light on the neural mechanisms underlying taVNS treatment of migraine.
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http://dx.doi.org/10.1016/j.nicl.2019.101971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239932PMC
September 2020

New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses.

Front Aging Neurosci 2019 27;11:228. Epub 2019 Aug 27.

Author Affiliations: UC San Francisco; University of Southern California; UC San Francisco University of Southern California Mayo Clinic, Rochester Mayo Clinic, Rochester; UC Berkeley; U Pennsylvania; USC; UC Davis; Brigham and Women's Hospital/Harvard Medical School Indiana University Washington University St. Louis University of Pennsylvania; Prevent Alzheimer's Disease 2020 (Chair) Siemens; Alzheimer's Association University of Pittsburgh Washington University St. Louis Cornell University; Albert Einstein College of Medicine of Yeshiva University; AD Drug Discovery Foundation; Acumen Pharmaceuticals; Washington University St. Louis; Northwestern University; National Institute of Mental Health; Brown University; Eli Lilly (Chair); BWH/HMS (Chair); University of Washington (Chair); Mayo Clinic, Rochester (Core PI) University of Southern California; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC Davis (Core PI); UC Davis; UC San Diego; Mayo Clinic, Rochester (Core PI); Mayo Clinic, Rochester; University of London; UCLA School of Medicine; UCSF MRI; UC Davis; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; UC Berkeley (Core PI); University of Michigan; University of Utah; Banner Alzheimer's Institute; Banner Alzheimer's Institute; University of Pittsburgh; UC Berkeley; Washington University St. Louis; Washington University St. Louis; Washington University St. Louis; Washington University St. Louis; UPenn School of Medicine; UPenn School of Medicine; UPenn School of Medicine; UPenn School of Medicine; UPenn School of Medicine; USC (Core PI); USC; USC; Indiana University; Indiana University; UC Irvine; Indiana University; Indiana University; Indiana University; Indiana University; UC San Francisco; UC San Diego; Prevent Alzheimer's Disease 2020; UC San Diego; National Institute on Aging; UC San Francisco; Brown University; National Institute of Mental Health; Cornell University; Johns Hopkins University; Richard Frank Consulting; Prevent Alzheimer's Disease 2020; National Institute on Aging; Oregon Health & Science University; University of Southern California; University of California - San Diego; University of Michigan; Mayo Clinic, Rochester; Baylor College of Medicine; Columbia University Medical Center; Washington University, St. Louis; University of Alabama - Birmingham; Mount Sinai School of Medicine; Rush University Medical Center; Wien Center; Johns Hopkins University; New York University; Duke University Medical Center; University of Pennsylvania; University of Kentucky; University of Pittsburgh; University of Rochester Medical Center; University of California, Irvine; University of Texas Southwestern Medical School; Emory University; University of Kansas, Medical Center; University of California, Los Angeles; Mayo Clinic, Jacksonville; Indiana University; Yale University School of Medicine; McGill Univ., Montreal-Jewish General Hospital; Sunnybrook Health Sciences, Ontario; U.B.C. Clinic for AD & Related Disorders; Cognitive Neurology - St. Joseph's, Ontario; Cleveland Clinic Lou Ruvo Center for Brain Health; Northwestern University; Premiere Research Inst (Palm Beach Neurology); Georgetown University Medical Center; Brigham and Women's Hospital; Stanford University; Banner Sun Health Research Institute; Boston University; Howard University; Case Western Reserve University; University of California, Davis - Sacramento; Neurological Care of CNY; Parkwood Hospital; University of Wisconsin; University of California, Irvine - BIC; Banner Alzheimer's Institute; Dent Neurologic Institute; Ohio State University; Albany Medical College; Hartford Hospital, Olin Neuropsychiatry Research Center; Dartmouth-Hitchcock Medical Center; Wake Forest University Health Sciences; Rhode Island Hospital; Butler Hospital; UC San Francisco; Medical University South Carolina; St. Joseph's Health Care; Nathan Kline Institute; University of Iowa College of Medicine; Cornell University; University of South Florida: USF Health Byrd Alzheimer's Institute; University of California, San Francisco; University of Southern California; UC San Francisco; University of Southern California; Mayo Clinic, Rochester; Brigham and Women's Hospital/ Harvard Medical School; UC Davis; Mayo Clinic, Rochester; UC Berkeley; Washington University St. Louis; Indiana University; Perelman School of Medicine, UPenn; USC; Perelman School of Medicine, University of Pennsylvania; UC San Francisco; Rehabilitation Institute of Chicago, Feinberg School of Medicine, Northwestern University; BWH/HMS (Chair); University of Washington (Chair); Core PI; Mayo Clinic, Rochester (Core PI); University of Southern California; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Diego; UC San Francisco; UC San Francisco; UC San Francisco; UC Davis (Core PI); UC San Diego; Mayo Clinic, Rochester (Core PI); Mayo Clinic, Rochester; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic; UC Berkeley (Core PI); University of Michigan; University of Utah; Banner Alzheimer's Institute; Banner Alzheimer's Institute; UC Berkeley; Washington University St. Louis; Washington University St. Louis; Washington University St. Louis; Perelman School of Medicine, UPenn; Perelman School of Medicine, UPenn; Perelman School of Medicine, UPenn; Perelman School of Medicine, UPenn; Perelman School of Medicine, UPenn; USC (Core PI); USC; USC; Indiana University; Indiana University; UC Irvine; Indiana University; Indiana University; Indiana University; Indiana University; UC San Francisco; Department of Defense (retired); University of Southern California; University of California, San Diego; Columbia University Medical Center; Rush University Medical Center; Wien Center; Duke University Medical Center; University of Rochester Medical Center; University of California, Irvine; Medical University South Carolina; Premiere Research Inst (Palm Beach Neurology); University of California, San Francisco; Georgetown University Medical Center; Brigham and Women's Hospital; Banner Sun Health Research Institute; Howard University; University of Wisconsin; University of Washington; Stanford University; Cornell University.

Background: Non-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.

Objective: To explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.

Methods: The meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.

Results: We found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.

Conclusion: Our results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.
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http://dx.doi.org/10.3389/fnagi.2019.00228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736566PMC
August 2019

Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: A multiple mode MRI study.

Brain Behav Immun 2019 Nov 28;82:253-263. Epub 2019 Aug 28.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

Objectives: Knee osteoarthritis (KOA) is a common degenerative joint disease with no satisfactory intervention. Recently, both physical and mindfulness exercises have received considerable attention for their implications in KOA pain management, and the dorsolateral prefrontal cortex (DLPFC) has displayed a critical role in pain modulation. This study aimed to comparatively investigate the modulation effects of different exercises using multidisciplinary measurements.

Methods: 140 KOA patients were randomized into Tai Chi, Baduanjin, stationary cycling, or health education control groups for 12 weeks. Knee Injury and Osteoarthritis Outcome Score (KOOS), resting state functional magnetic resonance imaging (fMRI), structural MRI, and serum biomarkers were measured at baseline and at the end of the study.

Results: We found: 1) increased KOOS pain subscores (pain reduction) and serum programmed cell death protein 1 (PD-1) levels in the three exercise groups compared to the control group; 2) decreased resting state functional connectivity (rsFC) of the DLPFC-supplementary motor area (SMA) and increased rsFC between the DLPFC and anterior cingulate cortex in all exercise groups compared to the control group; 3) significant associations between DLPFC-SMA rsFC with KOOS pain subscores and serum PD-1 levels at baseline; 4) significantly increased grey matter volume in the SMA in the Tai Chi and stationary cycling groups, and a trend toward significant increase in the Baduanjin group compared to the control group; 5) significant DLPFC rsFC differences among different exercise groups; and 6) that baseline DLPFC-SMA rsFC can predict the effect of mind-body exercise on pain improvement in KOA.

Conclusion: Our results suggest that different exercises can modulate both common and unique DLPFC (cognitive control) pathways, and altered DLPFC-SMA rsFC is associated with serum biomarker levels. Our findings also highlight the potentials of neuroimaging biomarkers in predicting the therapeutic effect of mind-body exercises on KOA pain.
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http://dx.doi.org/10.1016/j.bbi.2019.08.193DOI Listing
November 2019

Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study.

Br J Anaesth 2019 Oct 5;123(4):506-518. Epub 2019 Aug 5.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.

Background: Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis.

Methods: We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis.

Results: Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups.

Conclusions: Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain.

Clinical Trial Registration: ChiCTR-IOR-16009308.
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http://dx.doi.org/10.1016/j.bja.2019.06.017DOI Listing
October 2019

Identifying inter-individual differences in pain threshold using brain connectome: a test-retest reproducible study.

Neuroimage 2019 11 23;202:116049. Epub 2019 Jul 23.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address:

Individuals are unique in terms of brain and behavior. Some are very sensitive to pain, while others have a high tolerance. However, how inter-individual intrinsic differences in the brain are related to pain is unknown. Here, we performed longitudinal test-retest analyses to investigate pain threshold variability among individuals using a resting-state fMRI brain connectome. Twenty-four healthy subjects who received four MRI sessions separated by at least 7 days were included in the data analysis. Subjects' pain thresholds were measured using two modalities of experimental pain (heat and pressure) on two different locations (heat pain: leg and arm; pressure pain: leg and thumbnail). Behavioral results showed strong inter-individual variability and strong within-individual stability in pain threshold. Resting state fMRI data analyses showed that functional connectivity profiles can accurately identify subjects across four sessions, indicating that an individual's connectivity profile may be intrinsic and unique. By using multivariate pattern analyses, we found that connectivity profiles could be used to predict an individual's pain threshold at both within-session and between-session levels, with the most predictive contribution from medial-frontal and frontal-parietal networks. These results demonstrate the potential of using a resting-state fMRI brain connectome to build a 'neural trait' for characterizing an individual's pain-related behavior, and such a 'neural trait' may eventually be used to personalize clinical assessments.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819259PMC
November 2019

Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain.

Neuroimage Clin 2019 28;23:101885. Epub 2019 May 28.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address:

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.
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http://dx.doi.org/10.1016/j.nicl.2019.101885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551557PMC
June 2020

Mind-body exercise improves cognitive function and modulates the function and structure of the hippocampus and anterior cingulate cortex in patients with mild cognitive impairment.

Neuroimage Clin 2019 22;23:101834. Epub 2019 Apr 22.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States of America. Electronic address:

Mild cognitive impairment (MCI) is a common neurological disorder. This study aims to investigate the modulation effect of Baduanjin (a popular mind-body exercise) on MCI. 69 patients were randomized to Baduanjin, brisk walking, or an education control group for 24 weeks. The Montreal Cognitive Assessment (MoCA) and Magnetic Resonance Imaging scans were applied at baseline and at the end of the experiment. Compared to the brisk walking and control groups, the Baduanjin group experienced significantly increased MoCA scores. Amplitude of low-frequency fluctuations (ALFF) analysis showed significantly decreased ALFF values in the right hippocampus (classic low-freqency band, 0.01-0.08 Hz) in the Baduanjin group compared to the brisk walking group and increased ALFF values in the bilateral anterior cingulate cortex (ACC, slow-5 band, 0.01-0.027 Hz) in the Baduanjin group compared to the control group. Further, ALFF value changes in the right hippocampus and bilateral ACC were significantly associated with corresponding MoCA score changes across all groups. We also found increased gray matter volume in the Baduanjin group in the right hippocampus compared to the brisk walking group and in the bilateral ACC compared to the control group. In addition, there was an increased resting state functional connectivity between the hippocampus and right angular gyrus in the Baduanjin group compared to the control group. Our results demonstrate the potential of Baduanjin for the treatment of MCI.
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http://dx.doi.org/10.1016/j.nicl.2019.101834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535682PMC
March 2020

Abnormal thalamocortical network dynamics in migraine.

Neurology 2019 06 10;92(23):e2706-e2716. Epub 2019 May 10.

From the Department of Psychiatry (Y.T., N.M., J.P., G.W., J.K.), Massachusetts General Hospital and Harvard Medical School, Charlestown; The Mind Research Network (Z.F., V.C.), Albuquerque, NM; Acupuncture and Tuina School/3rd Teaching Hospital (F.Z., L.L., Z.L., F.L.), Chengdu University of Traditional Chinese Medicine, Chengdu; Traditional Chinese Medicine School (Y.G.), Ningxia Medical University, Yinchuan; and The Acupuncture and Tuina School (M.L.), Hunan University of Chinese Medicine, Changsha, China.

Objective: To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.

Methods: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.

Results: Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.

Conclusion: Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.
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http://dx.doi.org/10.1212/WNL.0000000000007607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556096PMC
June 2019

Treating Depression With Tai Chi: State of the Art and Future Perspectives.

Front Psychiatry 2019 12;10:237. Epub 2019 Apr 12.

Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, United States.

Major depressive disorder (MDD) is one of the most prevalent mental illnesses in America. Current treatments for MDD are unsatisfactory given high non-response rates, high relapse rates, and undesirable side effects. Accumulating evidence suggests that Tai Chi, a popular mind-body intervention that originated as a martial art, can significantly regulate emotion and relieve the symptoms of mood disorders. In addition, the availability of instructional videos and the development of more simplified and less structured Tai Chi has made it a promising low-intensity mind-body exercise. In this article, we first examine a number of clinical trials that implemented Tai Chi as a treatment for depression. Then, we explore several mechanisms by which Tai Chi may alleviate depressive symptoms, hypothesizing that the intervention may modulate the activity and connectivity of key brain regions involved in mood regulation, reduce neuro-inflammatory sensitization, modulate the autonomic nervous system, and regulate hippocampal neurogenesis. Finally, we discuss common challenges of the intervention and possible ways to address them. Specifically, we pose developing a simplified and tailored Tai Chi protocol for patients with depression, comparatively investigating Tai Chi with other mind-body interventions such as yoga and Baduanjin, and developing new mind-body interventions that merge the advantages of multiple mind-body exercises.
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http://dx.doi.org/10.3389/fpsyt.2019.00237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474282PMC
April 2019

Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study.

Br J Anaesth 2019 Aug 1;123(2):e303-e311. Epub 2019 Apr 1.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Radiology, Martinos Center for Biomedical Imaging, Charlestown, MA, USA. Electronic address:

Background: Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes.

Methods: We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres.

Results: ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre.

Conclusions: Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.
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http://dx.doi.org/10.1016/j.bja.2019.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676015PMC
August 2019

Visual network alterations in brain functional connectivity in chronic low back pain: A resting state functional connectivity and machine learning study.

Neuroimage Clin 2019 14;22:101775. Epub 2019 Mar 14.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Chronic low back pain (cLBP) is associated with widespread functional and structural changes in the brain. This study aims to investigate the resting state functional connectivity (rsFC) changes of visual networks in cLBP patients and the feasibility of distinguishing cLBP patients from healthy controls using machine learning methods. cLBP (n = 90) and control individuals (n = 74) were enrolled and underwent resting-state BOLD fMRI scans. Primary, dorsal, and ventral visual networks derived from independent component analysis were used as regions of interest to compare resting state functional connectivity changes between the cLBP patients and healthy controls. We then applied a support vector machine classifier to distinguish the cLBP patients and control individuals. These results were further verified in a new cohort of subjects. We found that the functional connectivity between the primary visual network and the somatosensory/motor areas were significantly enhanced in cLBP patients. The rsFC between the primary visual network and S1 was negatively associated with duration of cLBP. In addition, we found that the rsFC of the visual network could achieve a classification accuracy of 79.3% in distinguishing cLBP patients from HCs, and these results were further validated in an independent cohort of subjects (accuracy = 66.7%). Our results demonstrate significant changes in the rsFC of the visual networks in cLBP patients. We speculate these alterations may represent an adaptation/self-adjustment mechanism and cross-model interaction between the visual, somatosensory, motor, attention, and salient networks in response to cLBP. Elucidating the role of the visual networks in cLBP may shed light on the pathophysiology and development of the disorder.
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http://dx.doi.org/10.1016/j.nicl.2019.101775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444301PMC
January 2020
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