Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural ...changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.
Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, ...the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract‐based spatial statistical analyses of regional activity, patients showed decreased structural‐functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post‐central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small‐worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un‐evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.
The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, ...the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols 1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS) on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or “protocol” main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies.
•1Hz and continuous TBS can modulate the function of SMA network.•1Hz repetitive TMS increased the functional connectivity of paracentral gyrus.•Continuous TBS decreased the functional connectivity of IFG, SMA/MCC.•The two protocols show similar effective time (~10min) after the end of stimulation.
The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent ...(BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus.
Previous studies have implied a key role for the prefrontal cortex in the antidepressive effect of electroconvulsive therapy (ECT). However, there is still ubiquitous inconsistency across these ...studies, partly due to several confounding effects induced by the use of different samples. Studies with independent samples are necessary for validations to minimize confounding effects. In the current study, resting‐state magnetic resonance imaging of 84 participants was collected using two scanners and two types of scanning parameters. One sample consisted of 28 patients and 23 healthy controls, and the other sample consisted of 33 patients. The local activity (indexed by the amplitude of low‐frequency fluctuations) and functional connectivity were used to examine functional plasticity in the two independent samples before and after ECT. Both samples showed increased local activity of the dorsomedial prefrontal cortex (DMPFC) and enhanced connectivity of the DMPFC with the posterior cingulate cortex (PCC) following ECT. The enhanced connectivity between the DMPFC and PCC was positively associated with clinical improvement for both samples. These findings provide relatively strong evidence to support the functional plasticity of the dorsomedial prefrontal cortex and reorganization by ECT. The functional plasticity of the DMPFC‐PCC may underlie the antidepressive effect of ECT.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson's disease (PD). This study aimed to investigate the ...clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double‐blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta‐burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long‐lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA‐GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA‐GP pathway.
An accelerated continuous theta‐burst stimulation protocol significantly alleviates motor symptoms in Parkinson's disease. Symptom improvement can be observed as early as 1 week after the start of treatment, and maintained 8 weeks after the end of treatment. Gray matter volume in the globus pallidus (GP) increased after treatment, and the increment was positively correlated with symptom improvement as well as baseline supplementary motor area‐GP structural connectivity.
Traditional repetitive transcranial magnetic stimulation can only produce a significant but weak effect on the cortex while theta burst stimulation (TBS), a patterned accelerated form of stimulation, ...can produce a stronger poststimulation effect, which may improve decision‐making abilities. We designed a comparative assessment of the effect of intermittent TBS (iTBS), 20 Hz, in two risk decision‐making tasks on healthy controls. Participants were randomized and assigned to the iTBS (n = 29), 20 Hz (n = 29), or sham (n = 29) groups. The effects of the different methods of left dorsolateral prefrontal cortex stimulation on risk decision‐making functions were compared based on subjects’ performance in the Game of Dice Task (GDT) and Risky Gains Task (RGT). The main indicators were positive and negative feedback utilization rates of GDT and RGT. Both iTBS and 20 Hz stimulation resulted in significant improvements upon negative feedback in the GDT, with increases in safe options and reductions in risky options; iTBS stimulation increased subjects’ use of positive feedback in the GDT and RGT (all p < 0.05). Furthermore, the iTBS group had a stronger feedback risk reduction effect than the 20 Hz or sham group following RGT negative feedback (p < 0.05). Individuals would integrate positive and negative information more efficiently, leading to them making rational choices after excitatory transcranial magnetic stimulation. Moreover, iTBS has a stronger risk reduction effect following negative feedback than the 20Hz stimulation did. In summary, iTBS might have clinical value in decision promotion.
iTBS has a stronger decision promoting effect than 20 Hz, which can be used as an effective way to alter choice and presents an improvement on standard rTMS protocols.
Inter-hemispheric cooperation is a prominent feature of the human brain, and previous neuroimaging studies have revealed aberrant inter-hemispheric cooperation patterns in patients with major ...depressive disorder (MDD). Typically, inter-hemispheric cooperation is examined by calculating the functional connectivity (FC) between each voxel in one hemisphere and its anatomical (structurally homotopic) counterpart in the opposite hemisphere. However, bilateral hemispheres are actually asymmetric in anatomy.
In the present study, we utilized connectivity between functionally homotopic voxels (CFH) to investigate abnormal inter-hemispheric cooperation in 96 MDD patients compared to 173 age- and sex-matched healthy controls (HCs). In addition, we analyzed the spatial correlations between abnormal CFH and the density maps of 13 neurotransmitter receptors and transporters.
The CFH values in bilateral orbital frontal gyri and bilateral postcentral gyri were abnormally decreased in patients with MDD. Furthermore, these CFH abnormalities were correlated with clinical symptoms. In addition, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR.
drug effect; the cross-sectional research design precludes causal inferences; the neurotransmitter atlases selected were constructed from healthy individuals rather than MDD patients.
These findings characterized the abnormal inter-hemispheric cooperation in MDD using a novel method and the underlying neurotransmitter mechanism, which promotes our understanding of the pathophysiology of depression.
•Major depressive disorder (MDD) patients showed a decreased connectivity between functionally homotopic voxels (CFH) in the bilateral orbital frontal gyri and bilateral postcentral gyri, when compared with healthy controls.•At the molecular level, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR.•The CFH abnormalities were correlated with clinical symptoms.
The spontaneous activity of the blood oxygen level-dependent （BOLD） signal has been demonstrated as a promising way for understanding how the brain intrinsically organized. However, most of these ...studies focused solely on the spontaneous activity in gray matter （GM） and not on white matter （WM）. This is likely because low-frequency BOLD fluctuations （LFBFs） in GM are related to postsynaptic potential, while the physiological significance of fluctuations in WM is largely unknown 1 . Recently, there are increasing evidences implicating the neurobiological significance of LFBFs in WM 2-4. Here, we further investigated this issue from the perspective of energy consumption.
Abstract
Auditory verbal hallucinations (AVHs) are a core symptom of schizophrenia, and resistant to antipsychotic medication in a substantial proportion of patients. This study aimed to investigate ...the neural correlates of AVHs in schizophrenia patients and its response to a modified continuous theta-burst stimulation (cTBS) by transcranial magnetic stimulation. In a cross-sectional experiment, resting-state functional magnetic resonance images were collected from 31 AVH schizophrenia patients, 26 non-AVH schizophrenia patients, and 33 sex-/age-matched healthy controls (HCs). Functional connectivity strength (FCS) maps were compared among groups by 1-way analysis of variance (ANOVA). In a longitudinal experiment, 16 and 11 AVH patients received real and sham cTBS treatment for 15 days, respectively. Notably, this was not a randomized control trail. Changes in AVH and FCS were analyzed by 2-way ANOVA and 2-sample t-test, respectively. In the cross-sectional experiment, comparison of FCS maps identified 8 clusters among groups, but only one cluster (in left cerebellum) differed significantly in AVH patients compared to both HCs and non-AVH patients. In the longitudinal experiment, the real cTBS group showed a greater improvement in symptoms and a larger FCS decrease in left cerebellum than the sham group. Pearson’s correlation analysis indicated that baseline FCS of the overlapping cerebellum cluster (between the cross-sectional and longitudinal findings) was negatively correlated with symptom improvement in the real treatment group. These findings emphasize the role of the left cerebellum in both the pathophysiology and clinical treatment of AVHs in schizophrenia patients.
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