Sex differences in brain activity and connectivity in late-life depression

Functional Brain Networks of Trait and State Anxiety in Late-Life Depression

Neural response to stress differs by sex in young adulthood

Objective To explore the changes of rest-state functional MRI (fMRI) features in patients with Parkinson's disease. Methods Twelve patients with Parkinson's disease, collected in our hospital from September 2013 to March 2014, and 12 volunteers (controls) were recruited. The fMRI based on blood oxygen level dependent (BOLD) was performed at resting state; the differences of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were statistically analyzed; and the correlations of values of ALFF and ReHo with uniformed Parkinsonism rating scale (UPDRS) scores and Hoehn-Yahr (H-Y) grading were analyzed. Results PD patients exhibited increased ALFF values in the limbic lobe, the right parahippocampal gyrus and the right middle temporal pole, and reduced ALFF values in the left thalamus as compared with the controls. PD patients exhibited increased ReHo values in the superior medial frontal gyrus, the left middle frontal gyrus, brodmann area (BA) 9 and medial frontal gyrus, and reduced ReHo values in the left rolandic, the left superior temporal gyrus and insula lobe as compared with the controls. ALFF values were positively correlated with the UPDRS III scores in the right posterior cerebellum lobe and cerebellar tonsil. ALFF values and H-Y grading were negatively correlated on the left superior frontal gyrus. Negative correlation was noted between the ReHo values and UPDRS III scores in the right superior temporal gyrus and insular lobe. Positive correlation was noted between the ReHo values and H-Y grading in medial frontal gyrus, limbic lobe, anterior cingulate, medial orbitofrontal area, middle superior frontal gyrus, BA32, left superior frontal gyrus and BA10. Conclusion By resting-state fMRI, abnormal brain function in Parkinson's disease was noted; ReHo and ALFF showed abnormal changes in the connection of neuronal networks, and the compensatory response may lead to the increased brain function. Key words: Parkinson’s disease; Functional MR imaging; Regional homogeneity; Amplitude of low frequency fluctuation

Purpose: Sex differences in conduct disorder (CD) pathophysiology have yet to be resolved. In this study, we applied the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to compare spontaneous brain activity in male versus female adolescents diagnosed with CD in light of the gender paradox hypothesis.Materials and Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) examinations were conducted with 51 CD patients (35 males) and 53 age-matched healthy controls (HCs; 35 males). Pearson analysis was conducted to detect relationship between ALFF/fALFF values in gender-differentiated regions and clinical characteristics.Results: We observed that male CD patients showed significant increased ALFF in the bilateral superior temporal gyrus (STG)/insula, and significant decreased ALFF in the left anterior cingulate cortex (ACC), left middle frontal gyrus (BA8 andBA11), left middle temporal gyrus and left inferior/middle temporal gyrus relative to female CD patients. The fALFF in male CD patients was significantly increased in the right STG/insula, decreased in the right superior frontal gyrus, left middle frontal gyrus, right inferior frontal gyrus, and right postcentral gyrus relative to female CD patients. Considering the sex-by-diagnosis interactions in CD patients, the male CD patients had significantly higher fALFF in the left putamen, lower fALFF in the right postcentral gyrus relative to the female CD patients.Conclusion: The brain regions whose activity index values differed in relation to sex should be further explored in CD pathophysiology studies, particularly with respect to sex differences in clinical symptoms, emotional features, cognitive features, and prevalence rates in CD. The present findings are consistent with the gender paradox hypothesis.

Objective: To observe the characteristics of brain fMRI during olfactory stimulation in patients with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS), compare the differences of brain functional activation areas between patients with NMOSD and MS, and explore the characteristics of olfactory-related brain networks of NMOSD and MS.Methods: Nineteen patients with NMOSD and 16 patients with MS who met the diagnostic criteria were recruited, and 19 healthy controls matched by sex and age were recruited. The olfactory function of all participants was assessed using the visual analog scale (VAS). Olfactory stimulation was alternately performed using a volatile body (lavender and rose solution) and the difference in brain activation was evaluated by task-taste fMRI scanning simultaneously.Results: Activation intensity was weaker in the NMOSD group than in the healthy controls, including the left rectus, right superior temporal gyrus, and left cuneus. The activation intensity was stronger for the NMOSD than the controls in the left insula and left middle frontal gyrus (P < 0.05). Activation intensity was weaker in the MS group than the healthy controls in the bilateral hippocampus, right parahippocampal gyrus, right insula, left rectus gyrus, and right precentral gyrus, and stronger in the left paracentral lobule among the MS than the controls (P < 0.05). Compared with the MS group, activation intensity in the NMOSD group was weaker in the right superior temporal gyrus and left paracentral lobule, while it was stronger among the NMOSD group in the bilateral insula, bilateral hippocampus, bilateral parahippocampal gyrus, left inferior orbital gyrus, left superior temporal gyrus, left putamen, and left middle frontal gyrus (P < 0.05).Conclusion: Olfactory-related brain networks are altered in both patients, and there are differences between their olfactory-related brain networks. It may provide a new reference index for the clinical differentiation and disease evaluation of NMOSD and MS. Moreover, further studies are needed.

ObjectivePrevious reports have demonstrated significant brain activity changes in bilateral blindness, whereas brain activity changes in late monocular blindness (MB) at rest are not well studied. Our study aimed to investigate spontaneous brain activity in patients with late middle-aged MB using the amplitude of low-frequency fluctuation (ALFF) method and their relationship with clinical features.MethodsA total of 32 patients with MB (25 males and 7 females) and 32 healthy control (HC) subjects (25 males and 7 females), similar in age, sex, and education, were recruited for the study. All subjects were performed with resting-state functional magnetic resonance imaging scanning. The ALFF method was applied to evaluate spontaneous brain activity. The relationships between the ALFF signal values in different brain regions and clinical features in MB patients were investigated using correlation analysis.ResultsCompared with HCs, the MB patients had marked lower ALFF values in the left cerebellum anterior lobe, right parahippocampal gyrus, right cuneus, left precentral gyrus, and left paracentral lobule, but higher ALFF values in the right middle frontal gyrus, left middle frontal gyrus, and left supramarginal gyrus. However, there was no linear correlation between the mean ALFF signal values in brain regions and clinical manifestations in MB patients.ConclusionThere were abnormal spontaneous activities in many brain regions including vision and vision-related regions, which might indicate the neuropathologic mechanisms of vision loss in the MB patients. Meanwhile, these brain activity changes might be used as a useful clinical indicator for MB.

BackgroundStatic changes in local brain activity in patients suffering from amyotrophic lateral sclerosis (ALS) have been studied. However, the dynamic characteristics of local brain activity are poorly understood. Whether dynamic alterations could differentiate patients with ALS from healthy controls (HCs) remains unclear.MethodsA total of 54 patients with ALS (mean age = 48.71 years, male/female = 36/18) and 54 (mean age = 48.30 years, male/female = 36/18) HCs underwent magnetic resonance imaging scans. To depict static alterations in cortical activity, amplitude of low-frequency fluctuations (ALFF) which measures the total power of regional activity was computed. Dynamic ALFF (d-ALFF) from all subjects was calculated using a sliding-window approach. Statistical differences in ALFF and d-ALFF between both groups were used as features to explore whether they could differentiate ALS from HC through support vector machine method.ResultsIn contrast with HCs, patients with ALS displayed increased ALFF in the right inferior temporal gyrus and bilateral frontal gyrus and decreased ALFF in the left middle occipital gyrus and left precentral gyrus. Furthermore, patients with ALS demonstrated lower d-ALFF in widespread regions, including the right lingual gyrus, left superior temporal gyrus, bilateral precentral gyrus, and left paracentral lobule by comparison with HCs. In addition, the ALFF in the left superior orbitofrontal gyrus had a tendency of correlation with ALSFRS-R score and disease progression rate. The classification performance in distinguishing ALS was higher with both features of ALFF and d-ALFF than that with a single approach.ConclusionsDecreased dynamic brain activity in the precentral gyrus, paracentral gyrus, lingual gyrus, and temporal regions was found in the ALS group. The combined ALFF and d-ALFF could distinguish ALS from HCs with a higher accuracy than ALFF and d-ALFF alone. These findings may provide important evidence for understanding the neuropathology underlying ALS.

Lumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past. In this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms. The results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively. LDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.

Apathy is a prevalent psychiatric condition after stroke, affecting approximately 30% of stroke survivors. It is associated with slower recovery and an increased risk of depression. Understanding the pathophysiological mechanisms of post stroke apathy (PSA) is crucial for developing targeted rehabilitation strategies. In this study, we recruited a total of 18 PSA patients, 18 post-stroke non-apathy (NPSA) patients, and 18 healthy controls (HCs). Apathy was measured using the Apathy Evaluation Scale (AES). Resting-state functional magnetic resonance imaging (rs-fMRI) was utilized to investigate spontaneous brain activity. We estimated the amplitude of low-frequency fluctuation (ALFF) across three different frequency bands (typical band: 0.01-0.08 Hz; slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz) and the fractional amplitude of low-frequency fluctuation (fALFF). Band-specific ALFF differences among the three groups were analyzed. Significant differences were found in the typical band within the left lingual gyrus, right fusiform gyrus, right superior temporal gyrus (STG), and left insula. In the slow-4 band, significant differences were observed in the left middle frontal gyrus (MFG) and right STG. In the slow-5 band, significant differences were identified in the left calcarine cortex and right insula. For fALFF values, significant differences were found in the left lingual gyrus and right thalamus. Moreover, positive correlations were observed between AES scores and the ALFF values in the right STG (r = 0.490, p = 0.002) in the typical band, left MFG (r = 0.478, p = 0.003) and right STG (r = 0.451, p = 0.006) in the slow-4 band, and fALFF values of the right thalamus (r = 0.614, p < 0.001). This study is the first to investigate the neural correlates of PSA using voxel-level analysis and different ALFF banding methods. Our findings indicate that PSA involves cortical and subcortical areas, including the left MFG, right STG, and right thalamus. These results may help elucidate the neural mechanisms underlying PSA and could serve as potential neuroimaging indicators for early diagnosis and intervention.

Sex differences in brain activation to emotional stimuli: A meta-analysis of neuroimaging studies

Objective To explore the features of resting state brain activity of hypertension and hypertension co-morbid depression by resting state functional magnetic resonance imaging (fMRI) technology based on the amplitude of low frequency fluctuation (ALFF). Methods Thirty patients with hypertension co-morbid depression group (HD), 30 patients with hypertension group (H), and 30 normal controls group (NC) were selected. The demographic data and clinical features of all groups were collected. All participants underwent the fMRI and the resting state data of whole brain were analyzed by ALFF method. Results Four clusters with statistically significant differences in one-way analysis of variance in ALFF between the three groups including the left cerebellum, right thalamus, left superior temporal gyrus, and left superior medial frontal gyrus (F=14.99, 15.90, 11.52, 12.64, all P<0.05, AlphaSim corrected). Group H showed more decreased ALFF in right thalamus than group NC (MNI coordinates (x, y, z): 6,-15, 12; F=-3.96) . Compared group HD with group NC, decreased ALFF was found in left cerebellum (MNI coordinates (x, y, z):-48,-63,-27; F=-4.87) , right thalamus (MNI coordinates (x, y, z): 6,-15, 9;F=-5.20) and increased ALFF in left superior medial frontal gyrus (MNI coordinates (x, y, z):-24, 36, 42, F=5.08) . Compared group HD with group H, decreased ALFF was found in the left superior temporal gyrus (MNI coordinates (x, y, z):-54,-12, 12; F=-4.32) , increased ALFF in right superior frontal gyrus (MNI coordinates (x, y, z): 18, 36, 48; F=3.99) and left superior frontal gyrus (MNI coordinates (x, y, z):-15, 48, 42; F=3.57; all P<0.05, AlphaSim corrected). Conclusion Abnormal resting-state brain activity emerge in regulatory areas in patients with hypertension co-morbid depression, which is more seriously than ones with hypertension, and early positive and effective control of blood pressure may alleviate damage to brain function. Key words: Hypertension; Depressive disorder; Magnetic resonance imaging; Comorbidity; Amplitude of low frequency fluctuation

Intrinsic Brain Activity Mediates the Relationship Between Depressive Symptoms and Subjective Cognitive Complaints in Young Adults in Higher Education: A Resting-State fMRI Study Based on Amplitude of Low-frequency Fluctuation.

Sex Differences in Functional Brain Activation during a Lexical Visual Field Task

We aimed to investigate sex-dependent alterations in resting-state relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling in patients with schizophrenia. Resting-state functional magnetic resonance imaging and three-dimensional pseudo-continuous arterial spin labeling imaging were performed to obtain resting-state amplitude of low-frequency fluctuations and relative cerebral blood flow in 95 schizophrenia patients and 99 healthy controls. Sex differences in relative cerebral blood flow and amplitude of low-frequency fluctuations were compared in both groups. Diagnostic group differences in relative cerebral blood flow, amplitude of low-frequency fluctuations and relative cerebral blood flow-amplitude of low-frequency fluctuations coupling were compared in male and female subjects, respectively. In both healthy controls and schizophrenia patients, the males had higher relative cerebral blood flow in anterior brain regions and lower relative cerebral blood flow in posterior brain regions than did the females. Compared with multiple regions exhibiting sex differences in relative cerebral blood flow, only the left middle frontal gyrus had a significant sex difference in amplitude of low-frequency fluctuations. In the females, schizophrenia patients exhibited increased relative cerebral blood flow and amplitude of low-frequency fluctuations in the basal ganglia, thalamus and hippocampus and reduced relative cerebral blood flow and amplitude of low-frequency fluctuations in the frontal, parietal and occipital regions compared with those of healthy controls. However, there were fewer brain regions with diagnostic group differences in the males than in the females. Brain regions with diagnostic group differences in relative cerebral blood flow and amplitude of low-frequency fluctuations only partially overlapped. Only the female patients exhibited increased relative cerebral blood flow-amplitude of low-frequency fluctuations couplings compared with those of healthy females. The alterations in the relative cerebral blood flow and amplitude of low-frequency fluctuations in schizophrenia are sex-specific, which should be considered in future neuroimaging studies. The relative cerebral blood flow and amplitude of low-frequency fluctuations have different sensitivity in detecting changes in neuronal activity in schizophrenia and can provide complementary information.

The degree to which sex differences exist in the brain is a current topic of debate. In the present discussion paper, we reviewed eight functional magnetic resonance imaging (fMRI) papers to determine whether there are sex differences in brain activity during long-term memory retrieval. The objectives were: 1) to compare the experimental parameters in studies reporting significant versus null long-term memory sex differences, and 2) to identify whether specific brain regions were associated with sex differences during long-term memory. The following experimental parameters were extracted from each paper: the number of participants, the average age of participants, stimulus type(s), whether or not performance was matched, whether or not sex differences were reported, the type of between-subject statistical test used, and the contrast(s) employed. The particular experimental parameters employed in each study did not appear to determine whether sex differences were observed, as there were sex differences in all eight studies. An activation likelihood estimation (ALE) meta-analysis was conducted to identify brain regions activated to a greater degree by females than males or males than females. This ALE meta-analysis revealed sex differences (male > female) in the lateral prefrontal cortex, visual processing regions, parahippocampal cortex, and the cerebellum. This constitutes compelling evidence that there are substantial sex differences in brain activity during long-term memory retrieval. More broadly, the present findings question the widespread practice of collapsing across sex in the field of cognitive neuroscience.