UNASSIGNED: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson\'s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.
UNASSIGNED: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.
UNASSIGNED: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

UNASSIGNED: Whether alteration in regional brain volumes can be detected in Type A alcoholics both at baseline and after a long follow-up remains to be confirmed. Therefore, we examined volume alterations at baseline, and longitudinal changes in a small follow-up subsample.
UNASSIGNED: In total of 26 patients and 24 healthy controls were assessed at baseline using magnetic resonance imaging and voxel-based morphometry, among which 17 patients and 6 controls were re-evaluated 7 years later. At baseline, regional cerebral volumes of patients were compared to controls. At follow-up, three groups were compared: abstainers (n = 11, more than 2 years of abstinence), relapsers (n = 6, <2 years of abstinence), and controls (n = 6).
UNASSIGNED: The cross-sectional analyses detected, at both times, higher caudate nuclei volumes bilaterally in relapsers compared to abstainers. In abstainers, the longitudinal analysis indicated recovery of normal gray matter volumes in the middle and inferior frontal gyrus, and in the middle cingulate, while white matter volumes recovery was detected in the corpus callosum and in anterior and superior white matter specific regions.
UNASSIGNED: Overall, the present investigation revealed larger caudate nuclei in the relapser AUD patient group both at baseline and at follow-up in the cross-sectional analyses. This finding suggest that a higher caudate volume could be a candidate risk factor of relapse. In patients with specific type A alcohol-dependence, we showed that long-term recovery in fronto-striato-limbic GM and WM volumes occurs during long-term abstinence. These results support the crucial role of frontal circuitry in AUD.

UNASSIGNED: This study explored the structural imaging changes in patients with subcortical ischemic vascular disease (SIVD)-vascular cognitive impairment no dementia (VCIND) and the correlation between the changes in gray matter volume and the field of cognitive impairment to provide new targets for early diagnosis and treatment.
UNASSIGNED: Our study included 15 patients with SIVD-normal cognitive impairment (SIVD-NCI), 63 with SIVD-VCIND, 26 with SIVD-vascular dementia (SIVD-VD), and 14 normal controls (NC). T1-weighted images of all participants were collected, and DPABI and SPM12 software were used to process the gray matter of the four groups based on voxels. Fisher\'s exact test, one-way ANOVA and Kruskal-Wallis H test were used to evaluate all clinical and demographic data and compare the characteristics of diencephalic gray matter atrophy in each group. Finally, the region of interest (ROI) of the SIVD-VCIND was extracted, and Pearson correlation analysis was performed between the ROI and the results of the neuropsychological scale.
UNASSIGNED: Compared to the NC, changes in gray matter atrophy were observed in the bilateral orbitofrontal gyrus, right middle temporal gyrus, superior temporal gyrus, and precuneus in the SIVD-VCIND. Gray matter atrophy was observed in the left cerebellar region 6, cerebellar crural region 1, bilateral thalamus, right precuneus, and calcarine in the SIVD-VD. Compared with the SIVD-VCIND, gray matter atrophy changes were observed in the bilateral thalamus in the SIVD-VD (p < 0.05, family-wise error corrected). In the SIVD-VCIND, the total gray matter volume, bilateral medial orbital superior frontal gyrus, right superior temporal gyrus, middle temporal gyrus, and precuneus were positively correlated with Boston Naming Test score, whereas the total gray matter volume, right superior temporal gyrus, and middle temporal gyrus were positively correlated with overall cognition.
UNASSIGNED: Structural magnetic resonance imaging can detect extensive and subtle structural changes in the gray matter of patients with SIVD-VCIND and SIVD-VD, providing valuable evidences to explain the pathogenesis of subcortical vascular cognitive impairment and contributing to the early diagnosis of SIVD-VCIND and early warning of SIVD-VD.

UNASSIGNED: Pediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children\'s cognitive function, brain structure and brain function were not yet fully illustrated.
UNASSIGNED: Full Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls.
UNASSIGNED: (1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index.
UNASSIGNED: Multiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index.

Excessive exercise may also lead to exercise addiction (EXA), which is harmful to people\'s physical and mental health. Behavioral and neuroimaging studies have demonstrated that addictive disorders are essentially motivational problems. However, little is known about the neuropsychological mechanism of EXA and the effects of motivation on EXA.
We investigated 130 regularly exercised participants with EXA symptoms to explore the neurobiological basis of EXA and its association with motivation. The correlation between EXA and gray matter volume (GMV) was evaluated by whole-brain regression analysis based on voxel-based morphometry. Then, regional brain function was extracted and the relationship between brain structure-function-EXA was analyzed. Finally, mediation analysis was performed to further detect the relationship between the brain, motivation, and EXA.
Whole-brain correlation analyses showed that the GMV of the right orbitofrontal cortex (OFC) was negatively correlated with EXA. The function of the right OFC played an indirect role in EXA and affected EXA via the GMV of the OFC. Importantly, the GMV of the right OFC played a mediating role in the relationship between ability motivation and EXA. These results remain significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence, total intracranial volume, and head motion.
The results should be interpreted carefully because only the people with EXA symptoms were included.
This study provided evidence for the underlying neuropsychological mechanism of the important role of the right OFC in EXA and revealed that there may be a decrease in executive control function in EXA.

UNASSIGNED: Type 2 diabetes mellitus (T2DM) is an important risk factors for mild cognitive impairment (MCI). Structural magnetic resonance imaging (sMRI) is an effective and widely used method to investigate brain pathomorphological injury in neural diseases. In present study, we aimed to determine the brain regional alterations that correlated to the incidence of MCI in T2DM patients.
UNASSIGNED: Eighteen T2DM patients with and without MCI (DMCI/T2DM) respectively, and eighteen age/gender-matched healthy controls (HC) were recruited. Brain MRI imagines of all the individuals were subjected to automatic quantified brain sub-structure volume segmentation and measurement by Dr. brain ™ software. The relative volume of total gray matter (TGM), total white matter (TWM), and 68 pairs (left and right) of brain sub-structures were compared between the three groups. Cognitive function correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted in the MCI-related brain regions in T2DM patients, and we utilized a machine learning method to classify the three group of subjects.
UNASSIGNED: 10 and 27 brain sub-structures with significant relative volumetric alterations were observed in T2DM patients without MCI and T2DM patients with MCI, respectively (p < 0.05). Compared with T2DM patients without MCI, eight critical regions include right anterior orbital gyrus, right calcarine and cerebrum, left cuneus, left entorhinal area, left frontal operculum, right medial orbital gyrus, right occipital pole, left temporal pole had significant lower volumetric ratio in T2DM patients with MCI (p < 0.05). Among them, the decrease of volumetric ratio in several regions had a positive correlation with Montreal Cognitive Assessment (MoCA) scores and Mini-Mental State Examination (MMSE) scores. The classification results conducted based on these regions as features by random forest algorithm yielded good accuracies of T2DM/HC 69.4%, DMCI/HC 72.2% and T2DM/DMCI 69.4%.
UNASSIGNED: Certain brain regional structural lesions occurred in patients with T2DM, and this condition was more serious in T2DM patients combined with MCI. A systematic way of segmenting and measuring the whole brain has a potential clinical value for predicting the presence of MCI for T2DM patients.

BACKGROUND: Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer\'s disease (AD) subtype research. However, how the two measures affect the definition of AD subtypes remains unclear.
METHODS: A total of 180 AD patients from the ADNI database were used to identify AD subgroups. The subtypes were identified via a data-driven strategy based on the density features and CT features, respectively. Then, the similarity between the two features in AD subtype definition was analyzed.
RESULTS: Four distinct subtypes were discovered by both density and CT features: diffuse atrophy AD, minimal atrophy AD (MAD), left temporal dominant atrophy AD (LTAD), and occipital sparing AD. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2.
CONCLUSIONS: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. Meanwhile, the influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition. This study provides a valuable reference for selecting features in future studies of AD subtypes.

Adverse childhood experiences (ACEs) can affect later-life health outcomes via brain structural differences. However, there is no sufficient empirical evidence about whether brain morphological differences remain until old ages.
We examined the association between ACEs and brain volumes among older individuals.
Residents aged 65-84 years in Tokamachi City, Japan, were randomly recruited, and 491 participants were included in the analysis.
ACEs were assessed with a self-reported questionnaire. The volumes of seven brain regions of interests were evaluated via structural magnetic resonance imaging.
In total, 143 (27.1%) participants experienced one ACE and 33 (6.7%) two or more ACEs. Participants with two or more ACEs had a larger anterior cingulate cortex volume (B = 0.346, 95% confidence interval [CI] = 0.04 to 0.66) and smaller hippocampal (B = -0.287, 95% CI = -0.58 to 0.001) and amygdala (B = -0.313, 95% CI = -0.59 to -0.03) volumes. Interestingly, we observed a distinct association between deprivation and threat. That is, deprivation was associated with a smaller amygdala volume (B = -0.164, 95% CI = -0.32 to -0.01) and threat with a larger anterior cingulate cortex volume (B = 0.401, 95% CI = 0.11 to 0.70).
ACEs were associated with the volumes of brain regions such as anterior cingulate cortex, hippocampus, and amygdala, which are responsible for emotion and self-regulation in older population. The effect of ACEs on the amygdala was commonly driven by deprivation experiences and that on the anterior cingulate cortex by threat.

Medial temporal lobe (MTL) atrophy is a key feature of Alzheimer\'s disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subregions with up-to-date approaches and using longitudinal designs to assess atrophy more sensitively. Age-related trajectories were estimated using the best-fitted polynomials in 209 CU adults (aged 19-85). Changes related to AD were investigated among amyloid-negative (Aβ-) (n = 46) and amyloid-positive (Aβ+) (n = 14) CU, Aβ+ patients with mild cognitive impairment (MCI) (n = 33) and AD (n = 31). Nineteen MCI-to-AD converters were also compared with 34 non-converters. Relationships with cognitive functioning were evaluated in 63 Aβ+ MCI and AD patients. All participants were followed up to 47 months. MTL subregions, namely, the anterior and posterior hippocampus (aHPC/pHPC), entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 [as perirhinal cortex (PRC) substructures], and parahippocampal cortex (PHC), were segmented from a T1-weighted MRI using a new longitudinal pipeline (LASHiS). Statistical analyses were performed using mixed models. Adult lifespan models highlighted both linear (PRC, BA35, BA36, PHC) and nonlinear (HPC, aHPC, pHPC, ERC) trajectories. Group comparisons showed reduced baseline volumes and steeper volume declines over time for most of the MTL subregions in Aβ+ MCI and AD patients compared to Aβ- CU, but no differences between Aβ- and Aβ+ CU or between Aβ+ MCI and AD patients (except in ERC). Over time, MCI-to-AD converters exhibited a greater volume decline than non-converters in HPC, aHPC, and pHPC. Most of the MTL subregions were related to episodic memory performances but not to executive functioning or speed processing. Overall, these results emphasize the benefits of studying MTL subregions to distinguish age-related changes from AD. Interestingly, MTL subregions are unequally vulnerable to aging, and those displaying non-linear age-trajectories, while not damaged in preclinical AD (Aβ+ CU), were particularly affected from the prodromal stage (Aβ+ MCI). This volume decline in hippocampal substructures might also provide information regarding the conversion from MCI to AD-dementia. All together, these findings provide new insights into MTL alterations, which are crucial for AD-biomarkers definition.

Previous studies have found that the striatum and the cerebellum played important roles in nicotine dependence, respectively. In heavy smokers, however, the effect of resting-state functional connectivity of cerebellum-striatum circuits in nicotine dependence remained unknown. This study aimed to explore the role of the circuit between the striatum and the cerebellum in addiction in heavy smokers using structural and functional magnetic resonance imaging. The grey matter volume differences and the resting-state functional connectivity differences in cerebellum-striatum circuits were investigated between 23 heavy smokers and 23 healthy controls. The cigarette dependence in heavy smokers and healthy controls were evaluated by using Fagerström Test. Then, we applied mediation analysis to test whether the resting-state functional connectivity between the striatum and the cerebellum mediates the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Compared with healthy controls, the heavy smokers\' grey matter volumes decreased significantly in the cerebrum (bilateral), and increased significantly in the caudate (bilateral). Seed-based resting-state functional connectivity analysis showed significantly higher resting-state functional connectivity among the bilateral caudate, the left cerebellum, and the right middle temporal gyrus in heavy smokers. The cerebellum-striatum resting-state functional connectivity fully mediated the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Heavy smokers showed abnormal interactions and functional connectivity between the striatum and the cerebellum, which were associated with the striatum morphometry and nicotine dependence. Such findings could provide new insights into the neural correlates of nicotine dependence in heavy smokers.