Longitudinal Functional Magnetic Resonance Imaging of Brain Activity, Connectivity, and Behavior in Breast Cancer Survivors Following Chemotherapy.

Chemotherapy related cognitive impairment (CRCI) is a type of memory and cognitive impairment induced by chemotherapy and has become a growing clinical problem. Breast cancer survivors (BCs) refer to patients from the moment of breast cancer diagnosis to the end of their lives. Managing Cancer and Living Meaningfully (CALM) is a convenient and easy-to-apply psychological intervention that has been proven to improve quality of life and alleviate CRCI in BCs. However, the underlying neurobiological mechanisms remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) has become an effective method for understanding the neurobiological mechanisms of brain networks in CRCI. The fractional amplitude of low-frequency fluctuations (fALFF) and ALFF have often been used in analyzing the power and intensity of spontaneous regional resting state neural activity. The recruited BCs were randomly divided into the CALM group and the care as usual (CAU) group. All BCs were evaluated by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) before and after CALM or CAU. The rs-fMRI imaging was acquired before and after CALM intervention in CALM group BCs. The BCs were defined as before CALM intervention (BCI) group and after CALM intervention (ACI) group. There were 32 BCs in CALM group and 35 BCs in CAU group completed the overall study. There were significant differences between the BCI group and the ACI group in the FACT-Cog-PCI scores. Compared with the BCI group, the ACI group showed lower fALFF signal in the left medial frontal gyrus and right sub-gyral and higher fALFF in the left occipital_sup and middle occipital gyrus. There was a significant positive correlation between hippocampal ALFF value and FACT-Cog-PCI scores. CALM intervention may have an effective function in alleviating CRCI of BCs. The altered local synchronization and regional brain activity may be correlated with the improved cognitive function of BCs who received the CALM intervention. The ALFF value of hippocampus seems to be an important factor in reflect cognitive function in BCs with CRCI and the neural network mechanism of CALM intervention deserves further exploration to promote its application.

The purpose of this study was to investigate changes in functional connectivity and regional brain activity between and within the default mode network (DMN), salience network (SN), and executive control network (ECN) among individuals with disorders of consciousness (DOC) in the conditions of minimally conscious state (MCS) and vegetative-state/unresponsive wakefulness syndrome (VS/UWS). Twenty-five VS/UWS patients, 14 MCS patients, and 30 healthy individuals as normal control, completed resting-state fMRI scans. ROI-wise functional connectivity and fractional amplitude of low-frequency fluctuation (fALFF) were implemented to examine group differences. All ROI-wise and fALFF analyses masks were identified from the triple-network model. ROI-wise analyses indicated significantly decreased functional connectivity between posterior cingulate cortex (DMN)-left anterior insula (SN), right anterior insula (SN)-left dorsolateral prefrontal cortex (ECN), and right anterior insula (SN)-right amygdala (SN) in VS/UWS patients compared to MCS patients. Moreover, fALFF were observed reduced in the triple-network across all DOC patients, and as the clinical manifestations of DOC deteriorated from MCS to VS/UWS, fALFF in dorsal DMN, anterior/posterior SN, and left ECN became significantly reduced. Moreover, a positive correlation between fALFF of the left ECN and Coma Recovery Scale-Revised (CRS-R) total scores was found across all DOC patients. These findings contribute to a better understanding of the underlying neural mechanism of functional connectivity and regional brain activity in DOC patients, and this triple-network model provides new connectivity pattern changes that may be integrated in future diagnostic tools based on the neural signatures of conscious states.

Very late-onset schizophrenia-like psychosis (VLOSLP) is a subtype of schizophrenia spectrum disorders in which individuals experience psychotic symptoms for the first time after the age of 60. The incidence of VLOSLP shows a linear relationship with increasing age. However, no studies have reported alterations in spontaneous brain activity among VLOSLP patients and their correlation with cognitive function and clinical symptoms. To explore VLOSLP brain activity and correlations with cognitive function and clinical symptoms using resting-state functional magnetic resonance imaging. This study included 33 VLOSLP patients and 34 healthy controls. The cognitive assessment utilized the Mini Mental State Examination, Montreal Cognitive Assessment, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Clinical characteristic acquisition was performed via the Positive and Negative Syndrome Scale (PANSS). All participants were scanned via resting-state functional magnetic resonance imaging, and the data were processed using amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity, and voxel-mirrored homotopic connectivity (VMHC). The VLOSLP group presented decreased ALFF values in the left cuneus, right precuneus, right precentral gyrus, and left paracentral lobule; increased fALFF values in the left caudate nucleus; decreased fALFF values in the right calcarine fissure and surrounding cortex (CAL) and right precuneus; increased regional homogeneity values in the right putamen; and decreased VMHC values in the bilateral CAL, bilateral superior temporal gyrus, and bilateral cuneus. In the VLOSLP group, ALFF values in the right precuneus were negatively correlated with Mini Mental State Examination score and PANSS positive subscale score, and VMHC values in the bilateral CAL were negatively correlated with the RBANS total score, RBANS delayed memory score, and PANSS positive subscale score. The changes of brain activity in VLOSLP are concentrated in the right precuneus and bilateral CAL regions, which may be associated with cognitive impairment and clinically positive symptoms.

Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.

ObjectiveDysphagia after cerebral infarction (DYS) has been detected in several brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we used two rs-fMRI measures to investigate the changes in brain function activity in DYS and their correlations with dysphagia severity.MethodIn this study, a total of 22 patients with DYS were compared with 30 patients without dysphagia (non-DYS) and matched for baseline characteristics. Then, rs-fMRI scans were performed in both groups, and regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) values were calculated in both groups. The two-sample t-test was used to compare ReHo and fALFF between the groups. Pearson's correlation analysis was used to determine the correlations between the ReHo and fALFF of the abnormal brain regions and the scores of the Functional Oral Intake Scale (FOIS), the Standardized Bedside Swallowing Assessment (SSA), the Videofluoroscopic Swallowing Study (VFSS), and the Penetration-Aspiration Scale (PAS).ResultsCompared with the non-DYS group, the DYS group showed decreased ReHo values in the left thalamus, the left parietal lobe, and the right temporal lobe and significantly decreased fALFF values in the right middle temporal gyrus and the inferior parietal lobule. In the DYS group, the ReHo of the right temporal lobe was positively correlated with the SSA score and the PAS score (r = 0.704, p < 0.001 and r = 0.707, p < 0.001, respectively) but negatively correlated with the VFSS score (r = −0.741, p < 0.001). The ReHo of the left parietal lobe was positively correlated with SSA and PAS (r = 0.621, p = 0.002 and r = 0.682, p < 0.001, respectively) but negatively correlated with VFSS (r = −0.679, p = 0.001).ConclusionThe changes in the brain function activity of these regions are related to dysphagia severity. The DYS group with high ReHo values in the right temporal and left parietal lobes had severe dysphagia.

Managing Cancer and Living Meaningfully (CALM) intervention's impact on chemotherapy-related cognitive impairment (CRCI) in breast cancer survivors (BCs) was investigated through resting-state functional magnetic resonance imaging (rs-fMRI) to elucidate the underlying neural mechanisms involved. 68 BCs were randomly assigned to either the CALM group (33 patients) or the care-as-usual (CAU) group (35 patients). Cognitive function was assessed before and after the intervention in both groups using the Mini Mental State Examination (MMSE) scale. Pre- and post-intervention rs-fMRI data were also collected for regional homogeneity (ReHo) and functional connectivity (FC) analyses in the CALM group. A total of 68 BCs were randomly assigned to either the CALM group (n = 33) or the care-as-usual (CAU) group (n = 35). Cognitive function was evaluated pre- and post-intervention using the Mini-Mental State Examination (MMSE). In the CALM group, rs-fMRI data were acquired before and after the intervention to assess alterations in regional homogeneity (ReHo) and functional connectivity (FC). CALM intervention demonstrated a greater enhancement in cognitive function compared to CAU (P = 0.004). Following CALM, ReHo exhibited an increase in bilateral occipital and temporal regions, including the superior, middle, and inferior occipital gyri, lingual gyrus, as well as the middle and superior temporal gyri, while a decrease was observed in frontal and cingulate regions, including the bilateral middle, medial, and dorsolateral superior frontal gyri, anterior cingulate and paracingulate gyri, precuneus, posterior cingulate, and left angular gyrus. FC analysis revealed diminished connectivity between the middle frontal gyrus and occipital/calcarine regions, whereas connectivity strengthened with the left anterior cingulate/paracingulate and right orbital frontal regions. ΔMMSE exhibited a positive correlation with ReHo in the left middle frontal gyrus (r = 0.355, P = 0.042) and a reduction in middle frontal-occipital FC (left calcarine: r = 0.353, P = 0.044; right/left middle occipital: r = 0.388/0.423, P = 0.029/0.014). CALM intervention mitigates CRCI in BCs, with the middle frontal gyrus may play a critical.

This study aimed to explore the changes in brain functional activity before and after acceptance and commitment therapy (ACT) treatment in patients with major depressive disorder (MDD) and the correlation between brain functional changes and clinical symptoms. We recruited 12 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for MDD. Patients underwent clinical assessments and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after ACT intervention. The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) maps were obtained after data preprocessing, and the ALFF/fALFF values of patients were extracted and compared. Pearson correlation analysis was used to analyze the correlation between fALFF/ALFF values and clinical symptoms. A total of nine MDD patients completed the study. The results showed that, following treatment, there was an improvement in psychological flexibility, along with a reduction in depressive symptoms. Additionally, MDD patients exhibited increased ALFF in the left inferior frontal gyrus and triangle, as well as increased fALFF in the left medial superior frontal gyrus following symptom remission. Pearson correlation analysis showed that fALFF of the left medial superior frontal gyrus at baseline was negatively correlated with the rate of Acceptance and Action Questionnaire, Second Edition (AAQ-II), change (r = -0.76, P < 0.05). We observed alterations in spontaneous activity in regions of the prefrontal cortex in MDD patients following ACT, providing preliminary relevant insights into understanding the neural mechanisms underlying the treatment of MDD by ACT.

BackgroundPrevious autism research has hypothesized that abnormalities of functional connectivity in autism spectrum disorder (ASD) may vary with the spatial distance between two brain regions. Although several resting-state functional magnetic resonance imaging (rsfMRI) studies have extensively examined long-range (or distant) connectivity in the adult ASD brain, short-range (or local) connectivity has been investigated in less depth. Furthermore, the possible relationship between functional connectivity and brain activity level during the resting state remains unclear.MethodsWe acquired rsfMRI data from 50 adults with high-functioning ASD and 50 matched controls to examine the properties of spontaneous brain activity using measures of local and distant connectivity together with a measure of the amplitude of brain activity, known as fractional amplitude of low-frequency fluctuation (fALFF). The two connectivity measures were calculated using a common graph-theoretic framework. We also examined the spatial overlaps between these measures and possible relationships of these disrupted functional measures with autistic traits assessed by the Autism-Spectrum Quotient (AQ).ResultsCompared to the controls, participants with ASD exhibited local over-connectivity in the right superior frontal gyrus and middle frontal gyrus, accompanied by local under-connectivity in the bilateral fusiform gyri (FG) and right middle temporal gyrus (MTG). On the other hand, we did not find any significant alterations in distant connectivity. Participants with ASD also exhibited reduced fALFF in the right middle occipital gyrus, lingual gyrus, and FG. Further conjunction and spatial overlap analyses confirmed that the spatial pattern of reduced fALFF substantially overlapped with that of local under-connectivity, demonstrating the co-occurrence of disrupted connectivity and spontaneous activity level in the right inferior occipital gyrus, posterior MTG (pMTG), and FG. Finally, within the ASD group, disrupted local connectivity in the right pMTG significantly correlated with the “social interaction” subscale score of the AQ.ConclusionsThese findings revealed local functional disruptions in the occipital and temporal regions, especially the right FG and pMTG, in the form of co-occurrence of spontaneous brain activity level and local connectivity, which may underline social and communicative dysfunctions in adult ASD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0026-z) contains supplementary material, which is available to authorized users.

BackgroundTo investigate the alterations in spontaneous brain activity and the similarities and differences between monocular deprivation amblyopia and binocular deprivation amblyopia.MethodsTwenty children with binocular deprivation amblyopia, 26 children with monocular deprivation amblyopia and 20 healthy controls underwent resting-state functional magnetic resonance imaging. The evaluation of altered spontaneous brain activity was conducted using fractional amplitude of low-frequency fluctuations (fALFF). One-way analysis of variance was employed to analyze fALFF values among the three groups. Additionally, the relationship between fALFF values and best corrected visual acuity (BCVA) was analyzed via correlation analysis.ResultsCompared to healthy controls, children with binocular deprivation amblyopia presented increased fALFF values in the left medial superior frontal gyrus, left middle frontal gyrus, left anterior cingulate cortex, left postcentral gyrus and bilateral precentral gyrus, and decreased fALFF values in the right fusiform gyrus. Compared to healthy controls, children with monocular deprivation amblyopia presented increased fALFF values in the right lingual gyrus, right superior frontal gyrus, right middle frontal gyrus, left superior temporal gyrus, triangular part of the left inferior frontal gyrus and bilateral middle temporal gyrus, and decreased fALFF values in the right precuneus. Compared with monocular deprivation amblyopia, fALFF values of binocular deprivation amblyopia were decreased in the triangular part of the left inferior frontal gyrus, right lingual gyrus and right cuneus, and increased in the left precentral gyrus and left postcentral gyrus. No significant correlations were found between the fALFF values of identified regions and the BCVA of amblyopic eyes for either type of amblyopia.ConclusionsChildren with deprivation amblyopia presented alterations in spontaneous activity in multiple brain regions, and these alterations differed between monocular amblyopia and binocular amblyopia. These abnormal spontaneous activities may reflect dysfunctions and compensation related to amblyopia.

Spontaneous neural activity alterations in temporomandibular disorders: A cross-sectional and longitudinal resting-state functional magnetic resonance imaging study

Aim: To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load. Methods: In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for by individually calibrating the number of items presented at each load. Results: An interaction between group and WM load was observed during stimulus encoding. At lower loads, greater activity in the right anterior cingulate and right precuneus was observed in MCI subjects. As the load increased to higher levels, reduced activation in these regions and greater deactivation in the posterior cingulate-medial precuneus were observed in MCI compared to control subjects. Stronger expression of load-related patterns of activation and deactivation in MCI subjects was associated with greater clinical severity and a more abnormal pattern of performance variability. Conclusion: Patterns of overactivation, underactivation and deactivation during successful encoding in MCI subjects were dependent on WM load. This type of graded cognitive challenge may operate like a ‘memory stress test’ in MCI and may be a useful biomarker of disease at the predementia stage.

It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis.

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory impairment. Previous studies have largely focused on alterations of static brain activity occurring in patients with AD. Few studies to date have explored the characteristics of dynamic brain activity in cognitive impairment, and their predictive ability in AD patients.MethodsOne hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (HC) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) and the dynamic fraction amplitude of low-frequency fluctuation (dfALFF) were used to assess the temporal variability of local brain activity in patients with AD or mild cognitive impairment (MCI). Pearson’s correlation coefficients were calculated between the metrics and subjects’ behavioral scores.ResultsThe results of analysis of variance indicated that the AD, MCI, and HC groups showed significant variability of dALFF in the cerebellar posterior and middle temporal lobes. In AD patients, these brain regions had high dALFF variability. Significant dfALFF variability was found between the three groups in the left calcarine cortex and white matter. The AD group showed lower dfALFF than the MCI group in the left calcarine cortex.ConclusionsCompared to HC, AD patients were found to have increased dALFF variability in the cerebellar posterior and temporal lobes. This abnormal pattern may diminish the capacity of the cerebellum and temporal lobes to participate in the cerebrocerebellar circuits and default mode network (DMN), which regulate cognition and emotion in AD. The findings above indicate that the analysis of dALFF and dfALFF based on functional magnetic resonance imaging data may give a new insight into the neurophysiological mechanisms of AD.

Mild cognitive impairment (MCI) reversion refers to patients with MCI who revert from MCI to a normal cognitive state. Exploring the underlying neuromechanism of MCI reverters may contribute to providing new insights into the pathogenesis of Alzheimer’s disease and developing therapeutic interventions. Information on patients with MCI and healthy controls (HCs) was collected from the Alzheimer’s Disease Neuroimaging Initiative database. We redefined MCI reverters as patients with MCI whose logical memory scores changed from MCI to normal levels using the logical memory criteria. We explored intrinsic brain activity alterations in MCI reverters from voxel, regional, and whole-brain levels by comparing resting-state functional magnetic resonance imaging metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) between MCI reverters and HCs. Finally, partial correlation analyses were conducted between cognitive scale scores and resting-state functional magnetic resonance imaging metrics of brain regions, revealing significant group differences. Thirty-two patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative database were identified as reverters. Thirty-seven age-, sex-, and education-matched healthy individuals were also enrolled. At the voxel level, compared with the HCs, MCI reverters had increased ALFF, fALFF, and PerAF in the frontal gyrus (including the bilateral orbital inferior frontal gyrus and left middle frontal gyrus), increased PerAF in the left fusiform gyrus, and decreased ALFF and fALFF in the right inferior cerebellum. Regarding regional and whole-brain levels, MCI reverters showed increased ReHo in the left fusiform gyrus and right median cingulate and paracingulate gyri; increased DC in the left inferior temporal gyrus and left medial superior frontal; decreased DC in the right inferior cerebellum and bilateral insular gyrus relative to HCs. Furthermore, significant correlations were found between cognitive performance and neuroimaging changes. These findings suggest that MCI reverters show significant intrinsic brain activity changes compared with HCs, potentially related to the cognitive reversion of patients with MCI. These results enhance our understanding of the underlying neuromechanism of MCI reverters and may contribute to further exploration of Alzheimer’s disease.

Objective: To explore the characteristics of altered brain functional activity in patients with chronic cough using resting-state functional magnetic resonance imaging (fMRI). Methods: This was a prospective study. From January 2016 to January 2019, a total of 20 patients with refractory chronic cough [10 males and 10 females, (39.3±8.2) years], 19 patients with somatic cough syndrome [14 males and 5 females, (34.5±9.2) years], and 29 healthy controls [19 males and 10 females, (38.3±12.1) years] were recruited from the chronic cough outpatient clinic of the First Affiliated Hospital of Guangzhou Medical University for analysis. All participants underwent resting-state fMRI, as well as assessment of cough severity, and capsaicin cough challenge. The amplitude of low-frequency fluctuations (ALFF) was used to assess brain functional activity. First, differences in brain activity between patients with refractory chronic cough and healthy controls were compared. Subsequently, brain regions showing significant differences were selected as seed points, and seed-based whole-brain functional connectivity (FC) analyses were performed to examine group differences. Cough severity was evaluated using the visual analog scale (VAS), and cough sensitivity was defined as the capsaicin concentration that elicited five coughs (C5), expressed as lgC5. One-way analysis of variance (ANOVA) was used to compare the differences in lung function among groups. The Kruskal-Wallis test was applied to compare the differences in cough symptom scores (VAS) and capsaicin cough sensitivity (lgC5) among groups. The fMRI data were statistically analyzed using Rest 1.8 software, and two independent-sample t-tests were conducted for each group. Results: Patients with refractory chronic cough exhibited significantly higher ALFF values in the right cerebellar region 8 (0.96±0.14 vs. 0.72±0.15, t=5.46, P<0.001) and the right cerebellar region Crus2 (0.87±0.11 vs. 0.68±0.11, t=6.25, P<0.001) than healthy controls. Patients with somatic cough syndrome had significantly higher ALFF values in the rectus frontal muscle than healthy controls (1.19±0.26 vs. 0.90±0.16, t=4.92, P<0.001). With the right cerebellar region 8 as the seed point, the analysis of the whole brain FC showed that patients with refractory chronic cough had higher FC values in the left cerebellar region 8 (0.60±0.18 vs. 0.35±0.15, t=5.47, P<0.001), cerebellar vermis (0.85±0.17 vs. 0.69±0.16, t=5.26, P<0.001), and claustrum (0.33±0.13 vs. 0.14±0.10, t=6.02, P<0.001). With the right cerebellar region Crus2 as the seed point, the analysis of the whole brain FC showed that patients with refractory chronic had higher FC values in the right middle temporal gyrus, thalamus (0.31±0.17 vs. 0.10±0.11, t=5.57, P<0.001), right dorsolateral superior frontal gyrus (0.35±0.16 vs. 0.1±0.13, t=6.20, P<0.001) and right posterior central gyrus (0.41±0.19 vs. 0.17±0.17, t=4.52, P<0.001). In the correlation analysis, there was a moderate positive correlation (r=0.57, P=0.001) between the ALFF values of the right cerebellar region 8 and Crus2 regions in patients with refractory chronic cough. Conclusions: Enhanced FC in multiple brain regions was found in patients with refractory chronic cough and patients with somatic cough syndrome, suggesting central sensitization in these patients. The different active brain regions in patients with refractory chronic cough and patients with somatic cough syndrome indicate different central hypersensitivity mechanisms among different causes of chronic cough.