Search

Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs. A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD. BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the default mode network. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities. Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings. The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention. • Brain changes in BD-RELs are not affected by illness-related confounding factors. • This review summarizes resting-state fMRI changes in BD-RELs. • BD-RELs present alterations in cortical, limbic, striatal, and thalamic areas. • RELs of psychotic BD show fronto-occipital and fronto-thalamic-striatal changes. • Results are heterogeneous and need to be replicated in future studies. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder associated with brain alterations at rest. Amplitude of low-frequency fluctuations (ALFF) and its fractional version (fALFF) have been widely used to investigate alterations in spontaneous brain activity in schizophrenia. However, results are still inconsistent. Furthermore, while these measurements are similar, they showed some differences, and no meta-analysis has been yet performed to compare them in schizophrenia. Thus, we conducted systematic research in five databases and in the grey literature to find articles investigating fALFF and/or ALFF alterations in schizophrenia. Two separate meta-analyses were performed using the SDM-PSI software to identify fALFF and ALFF alterations separately. Then, a conjunction analysis was conducted to determine congruent results between the two approaches. We found that patients with schizophrenia showed altered fALFF activity in the left insula/putamen, the right paracentral lobule and the left middle occipital gyrus compared to healthy individuals. Patients with schizophrenia exhibited ALFF alterations in the bilateral putamen, the bilateral caudate nucleus, the bilateral inferior frontal gyrus, the right precuneus, the right precentral gyrus, the left postcentral gyrus, the right posterior cingulate gyrus, compared to healthy controls. ALFF increased activity in the left putamen was higher in drug-naïve patients and was correlated with positive symptoms. The conjunction analysis revealed a spatial convergence between fALFF and ALFF studies in the left putamen. This left putamen cluster is part of the associative striatum. Its alteration in schizophrenia provides additional support to the influential aberrant salience hypothesis of psychosis. [ABSTRACT FROM AUTHOR]

Borderline personality disorder (BPD) is a severe psychiatric disorder characterized by emotion dysregulation, impulsivity, and interpersonal disturbances. Several structural and functional neuroimaging abnormalities have been described in BPD. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) studies have recently suggested various connectivity alterations within and between large-scale brain networks in BPD. This review aimed at providing an updated summary of the evidence reported by the available rs-fMRI studies in BPD individuals. A search on PubMed, Scopus, and Web of Science was performed to identify rs-fMRI alterations in BPD. A total of 15 studies met our inclusion criteria. Overall, aberrant resting-state functional connectivity (rs-FC) within and between default mode network (DMN), salience network (SN), and central executive network (CEN) were observed in BPD compared to healthy controls, as well as selective functional impairments in bilateral amygdala, anterior and posterior cingulate cortex, hippocampus, and prefrontal cortex. The observational design, small sample size, prevalence of females, high rates of concurrent comorbidities and medications, and heterogeneity across imaging methodologies limit the generalizability of the results. The identification of altered patterns of rs-FC within and between selective brain networks, including DMN, SN, and CEN, could further our knowledge of the clinical symptoms of BPD, and therefore, future studies with multimodal methodologies and longitudinal designs are warranted to further explore the neural correlates of this disorder. • The functional neurobiological underpinnings of BPD are largely unknown. • This review summarizes fMRI studies exploring rs-FC in BPD. • fMRI studies show alterations in rs-FC within and between brain networks. • Results need to be replicated in larger and more homogeneous samples. • Further studies with a longitudinal design and multimodal imaging are warranted. [ABSTRACT FROM AUTHOR]

The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment. This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample t -test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity. Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score. Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide. • This is a multi-center study using rs-fmri data from the REST-meta-MDD Consortium. • This study investigated 213 first episode drug-naïve adult MDD patients. • Using ReHo and ALFF analyses for all rs-fmri data. • Finding brain areas with specific changes in MDD with suicidal ideation or attempt. • Providing a reliable imaging basis for identifying and preventing suicide. [ABSTRACT FROM AUTHOR]

• Somatization symptoms are associated with emotional memory in adolescents with depressive disorders. • Somatization symptoms in adolescent depression are associated with the superior occipital gyrus and inferior temporal gyrus. • Superior occipital, middle occipital and inferior temporal gyrus may be the brain regions acting on the memory bias of adolescent depressive disorder patients. Studies have revealed that somatization symptoms are associated with emotional memory in adolescents with depressive disorders. This study investigated somatization symptoms and emotional memory among adolescents with depressive disorders using low-frequency amplitude fluctuations (ALFF). Participants were categorized into the somatization symptoms (FSS) group, non-FSS group and healthy control group (HC). The correctness of negative picture re-recognition was higher in the FFS and HC group than in the non-FSS group. The right superior occipital gyrus and right inferior temporal gyrus were significantly larger in the FSS group than those in the non-FSS and HC groups. Additionally, the ALFF in the superior occipital and inferior temporal gyrus were positively correlated with CSI score. Furthermore, the ALFF values in the temporal region positively correlated with correct negative image re-recognition. The negative image re-recognition rate was positively correlated with the ALFF in the left and right middle occipital gyri. These findings indicated that somatization symptoms in adolescent depression are associated with the superior occipital gyrus and inferior temporal gyrus. Notably, somatization symptoms play a role in memory bias within depressive disorders, with middle occipital and inferior temporal gyri potentially serving as significant brain regions. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have revealed hippocampal hyperactivity in schizophrenia. In the early stage of the illness, hyperactivity is present in the anterior hippocampus and is thought to spread to other regions as the illness progresses. However, there is limited evidence for changes in basal hippocampal function following the onset of psychosis. Resting state functional MRI signal amplitude may be a proxy measure for increased metabolism and disrupted oscillatory activity, both consequences of an excitation/inhibition imbalance underlying hippocampal hyperactivity. Here, we used fractional amplitude of low frequency fluctuations (fALFF) to test the hypothesis of progressive hippocampal hyperactivity in a two-year longitudinal case-control study. We found higher fALFF in the anterior and posterior hippocampus of individuals in the early stage of non-affective psychosis at study entry. Contrary to our hypothesis of progressive hippocampal dysfunction, we found evidence for normalization of fALFF over time in psychosis. Our findings support a model in which hippocampal fALFF is a marker of psychosis vulnerability or acute illness state rather than an enduring feature of the illness. [ABSTRACT FROM AUTHOR]

Early life maltreatment (ELM) has an impact on brain functions involved in parenting and is associated with impaired maternal sensitivity. Here, we investigated the influence of ELM on intrinsic neural function and its associations with maternal sensitivity in mothers without a current episode of a mental disorder. Twenty-seven mothers with ELM and 29 mothers without ELM were examined using resting-state functional magnetic resonance imaging, followed by Amplitude of Low Frequency Fluctuations, regional homogeneity and seed-based functional connectivity analyses. Videotaped interactions between mothers and their school-aged children were conducted to assess maternal sensitivity based on the Emotional Availability Scales. Regional and functional connectivity measures were used to investigate associations between intrinsic activity and emotional availability. Mothers with ELM showed reduced maternal sensitivity and lower intrinsic neural activity in the right superior frontal gyrus, the left precuneus, the left middle occipital gyrus, and the parietal cortex (left angular and right supramarginal gyrus) compared to mothers without ELM (p <.001, whole-brain). Amplitude of Low Frequency Fluctuations in the superior frontal gyrus was positively associated with maternal sensitivity across all participants (p =.002). The data suggest a behavioral and neural signature of ELM even in currently mentally healthy mothers. In particular, effects of ELM were found in distinct brain regions involved in social cognition and executive control. These ELM-related alterations may be associated with maternal behavior. • Early life maltreatment (ELM) affects behavior and neural activity in mothers. • Mothers with ELM show altered regional and network level intrinsic neural activity. • Mentalizing, mirror neuron and executive control networks are affected by ELM. • Intrinsic activity of superior frontal gyrus is associated with maternal sensitivity. [ABSTRACT FROM AUTHOR]

Background: The clinical and epidemiological features of bipolar disorder (BD) between females and males have many differences. The association between brain function and gender in BD is unknown. This research aimed to investigate the association between brain function and gender in BD by using amplitude of low-frequency fluctuations (ALFFs).Methods: Ninety-eight patients (49 females and 49 males) with BD and 171 matched healthy controls (HCs, 89 females and 82 males) were recruited for resting-state functional magnetic resonance imaging. ALFF was used to estimate brain function.Results: A main effect of diagnosis in ALFF was observed in the dorsal lateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), caudate and occipital lobe. A main effect of gender in ALFF was found in the right VPFC, DLPFC, thalamus, and occipital lobe. A main effect of diagnosis gender interaction in ALFF was observed in the left DLPFC. Analyses of two-sample t-test indicated that male patients with BD had increased ALFF in the right hippocampus, right amygdala, left caudate, and left DLPFC, and decreased ALFF in the occipital lobe compared with male HC. Female patients with BD demonstrated increased ALFF in the right VPFC and right DLPFC compared with female HC. Male patients with BD exhibited increased ALFF in the right VPFC and left DLPFC and decreased ALFF in the occipital lobe compared with female patients with BD.Limitations: This study did not consider the effect of medications and emotional states on brain activity.Conclusions: Results suggested gender differences in the dysfunctions of the cortico-limbic neural system in BD. [ABSTRACT FROM AUTHOR]

• Machine learning approach for PD investigation. • Multi-frequency based machine learning in PD. • Frequency specificities of ALFF maps in PD. The application of resting state functional MRI (RS-fMRI) in Parkinson's disease (PD) was widely performed using standard statistical tests, however, the machine learning (ML) approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t -test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107–0.0286 Hz; Slow-4: 0.0286–0.0821 Hz; conventional: 0.01–0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right inferior parietal lobe (IPL) and supramarginal gyrus (SMG), was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the ML approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information. [ABSTRACT FROM AUTHOR]

Reduced cerebral blood flow (CBF), an indicator of neurovascular processes and metabolic demands, is a common finding in Alzheimer's disease. However, little is known about what contributes to CBF deficits in individuals with mild cognitive impairment (MCI). We examine regional CBF differences in 17 MCI compared with 21 age-matched cognitively healthy older adults. Next, we examined associations between CBF, white matter lesion (WML) volume, amplitude of low-frequency fluctuations, and cortical thickness to better understand whether altered CBF was detectable before other markers and the potential mechanistic underpinnings of CBF deficits in MCI. MCI had significantly reduced CBF, whereas cortical thickness and amplitude of low-frequency fluctuation were not affected. Reduced CBF was associated with the WML volume but not associated with other measures. Given the presumed vascular etiology of WML and relative worsening of vascular health in MCI, it may suggest CBF deficits result from early vascular as opposed to metabolic deficits in MCI. These findings may support vascular mechanisms as an underlying component of cognitive impairment. • Reduced CBF was observed in MCI, whereas thickness and ALFF were minimally affected. • CBF reductions are related to increased WML volume in MCI but not related to others. • Early changes in vascular health may affect CBF deficits in MCI. • Our findings may support a vascular etiology to early degenerative changes in MCI. [ABSTRACT FROM AUTHOR]

Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n = 42) and healthy comparison subjects (HCS, n = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness. [ABSTRACT FROM AUTHOR]

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron. • Brain iron and amplitude of low-frequency fluctuations are coupled in infants. • R2 * -ALFF coupling increases with age in DMN in early infancy. • Iron accumulation was observed across the entire brain in early infancy. [ABSTRACT FROM AUTHOR]

Hallucinations characterize schizophrenia, with approximately 59% of patients reporting auditory hallucinations and 27% reporting visual hallucinations. Prior neuroimaging studies suggest that hallucinations are linked to disrupted communication across distributed (sensory, salience-monitoring and subcortical) networks. Yet, our understanding of the neurophysiological mechanisms that underlie auditory and visual hallucinations in schizophrenia remains limited. This study integrates two resting-state functional magnetic resonance imaging (fMRI) analysis methods - amplitudes of low-frequency fluctuations (ALFF) and functional network connectivity (FNC) - to explore the hypotheses that (1) abnormal FNC between salience and sensory (visual/auditory) networks underlies hallucinations in schizophrenia, and (2) disrupted hippocampal oscillations (as measured by hippocampal ALFF) beget changes in FNC linked to hallucinations. Our first hypothesis was supported by the finding that schizophrenia patients reporting hallucinations have higher FNC between the salience network and an associative auditory network relative to healthy controls. Hippocampal ALFF was negatively associated with FNC between primary auditory cortex and the salience network in healthy subjects, but was positively associated with FNC between these networks in patients reporting hallucinations. These findings provide indirect support favoring our second hypothesis. We suggest future studies integrate fMRI with electroencephalogram (EEG) and/or magnetoencephalogram (MEG) methods to directly probe the temporal relation between altered hippocampal oscillations and changes in cross-network functional communication. [ABSTRACT FROM AUTHOR]

Objective: This paper studies the fatigue caused by prolonged watching of three-dimensional television (3DTV) by applying the amplitude of low frequency fluctuation (ALFF) and the community partitioning algorithm in brain functional network techniques to resting-state functional magnetic resonance imaging (fMRI). In this study, two specific frequency bands (Slow5: 0.01–0.027 Hz and Slow4: 0.027–0.073 Hz) were analyzed to investigate the change of brain spontaneous activity after one-hour watching of 3DTV. Meanwhile, the changes of brain modular organization were analyzed to discuss the physiological mechanism of brain fatigue during long period of watching 3DTV. Methods: Valid data of resting state fMRI from 20 dextromanual subjects were adopted before and after 1 h watching of 3DTV/2DTV. Then, ALFF was processed using SPM8 and REST software to analyze the variation of resting-state fMRI induced by watching 2D/3DTV. Community partitioning algorithm was used to evaluate the change of brain modular organization. Results: While watching 2DTV does not significantly change the brain spontaneous activity, watching 3DTV makes significant differences on middle frontal gyrus (BA9/BA10), right inferior occipital gyrus (BA18/19), right inferior temporal gyrus (BA20/37) and cingulate cortex (BA32). The result shows that dorsal stream was activated after watching 3DTV through analyzed modularity and community, which verifies that watching 3DTV requires the brain visual pathway to process stereoscopic display. Meanwhile, the result further reflects that the neural circuit, including visual conducting pathway, temporal lobe and basal ganglia loop, is closely related to brain fatigue caused by long period of watching 3DTV. The study has shown the potential risk of 3DTV to viewers’ health, especially on vision and recognition functions. The basal ganglia neurons play crucial roles in the physiological mechanism of brain fatigue. Therefore, prolonged 3DTV watching should be avoided particularly for physically developing teenagers. This research suggested that the ALFF technique and brain modular organization is able to reveal intrinsic changes caused by visual fatigue and provided a foundation for 3DTV fatigue assessment. [ABSTRACT FROM AUTHOR]

Objective The study aimed to investigate the functional alterations of spontaneous brain activity in patients with spastic paraplegia type 4 (SPG4), and the relationship with the severity of spasticity. Methods Twelve patients with SPG4 and ten healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to characterize regional neural function, and functional connectivity (FC) was used to evaluate the functional integration of the brain network. Results Compared to healthy controls, patients with SPG4 exhibited significantly decreased ReHo values in the medial superior frontal gyrus. ALFF values were lower in left insula and higher in right precentral and superior frontal gyrus of the patient group. Increased ALFF values in the right precentral gyrus negatively correlated with Spastic Paraplegia Rating Scale (SPRS) scores in the patients. The connectivity study showed that the SPG4 patients had one increased FC between the left middle frontal gyrus to the left middle orbitofrontal gyrus, and pairs of decreased FC. Conclusions Our findings confirm that the baseline regional neural activity and interregional connectivity are altered in many brain regions in patients with SPG4, and certain changes are correlated with disease severity, providing potential diagnostic markers for SPG4. [ABSTRACT FROM AUTHOR]

Several studies with resting-state magnetic resonance imaging (rs-fMRI) have examined functional impairments and plasticity within language network in patients with post-stroke aphasia (PSA). However, there is still ubiquitous inconsistency across these studies, partly due to restricted to very small sample size and the absence of validation with follow-up data. In the current study, we aimed at providing relatively strong evidence to support functional impairments and its reorganization in PSA. Here, the amplitude of low frequency fluctuations (ALFF) and functional connectivity were used to assess functional alterations of PSA with moderate sample size at baseline (thirty-five PSA patients and thirty-five healthy controls). Functional abnormalities at baseline were observed whether improved among sixteen follow-up patients. Compared with controls, PSA at baseline presented decreased ALFF in the left inferior frontal gyrus (IFG) and decreased functional connectivity of the left IFG with the bilateral supplementary motor area (SMA) and right superior temporal gyrus (STG). The decreased ALFF in IFG, decreased IFG-SMA and IFG-STG connectivity were enhanced among follow-up patients and was synchronized with language-performance improvement. Our results revealed reduced intrinsic neural activity and inter-connections within language network in PSA, which would be normalized synchronously as the improvement of language performance. [ABSTRACT FROM AUTHOR]

• Sour exposure induced decreased amplitude of low-frequency fluctuation (ALFF), namely reduced neural activation in the somatosensory cortex in the left post-central gyrus. • Sweet exposure led to increased neural activation (ALFF) in the bilateral putamen involved in reward processing. • In contrast to sweet taste, sour exposure showed increased brain activation in the right superior frontal gyrus, which has been linked to functioning in high-order cognitive control. Taste perception has been deeply explored from the behavioural level to delineating neural mechanisms. However, most previous studies about the neural underpinnings of taste perception have focused on task-related brain activation. Notably, evidence indicates that task-induced brain activation often involves interference from irrelevant task materials and only accounts for a small fraction of the brain's energy consumption. Investigation of the resting-state spontaneous brain activity would bring us a comprehensive understanding of the neural mechanism of taste perception. Here we acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from twenty-two participants immediately after they received sweet, sour and tasteless gustatory stimulation. Our results showed that, in contrast to the tasteless condition, the sour exposure induced decreased amplitude of low-frequency fluctuation (ALFF) in the somatosensory cortex in the left post-central gyrus, and the sweet exposure led to increased ALFF in the bilateral putamen involved in reward processing. Moreover, in contrast to the sweet stimulation condition, the sour stimulation condition showed increased ALFF in the right superior frontal gyrus, which has been linked to functioning in high-order cognitive control. Altogether, our data indicate that taste exposure may affect the spontaneous functional activity in brain regions, including the somatosensory areas, reward processing areas and high-order cognitive functioning areas. Our findings may contribute to a further understanding the neural network and mechanisms after taste exposure. [ABSTRACT FROM AUTHOR]

• Frontal and temporal lobe ALFF is associated with negative symptoms severity in schizophrenia. • Regional ALFF is differentially associated with negative symptom domains in schizophrenia. • Understanding underlying neuropathology of negative symptoms may aid its unmet therapeutic need. This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Huntington's Disease (HD) is characterized by motor, cognitive and psychiatric dysfunction. Functional MRI (fMRI) provides new insight into the pathologic mechanism underlying the cognitive symptoms. Previous fMRI studies of HD focused on functional synchronization of various brain areas by measuring functional connectivity, a method that is unable to identify regional intrinsic neural activity changes in the brain. To fill in this gap, we utilized amplitude of low frequency fluctuations (ALFF).Objective: To investigate alterations in regional brain activity and their association with clinical characteristics in the early stages of HD.Methods: Ten early stage HD patients and 20 age- and sex-matched healthy controls were scanned to obtain imaging data. HD patients were assessed with the Unified Huntington's Disease Rating Scale, Mini-Mental State Exam (MMSE), Stroop test, Symbol Digit Modalities Test (SDMT), Verbal Fluency Test and Beck Depression Index.Results: Gray matter volume (GMV) reduction was detected in bilateral striatum and left calcarine cortex in the HD group. After correcting for GMV, HD patients demonstrated significantly decreased ALFF in the right precuneus and angular gyrus, and increased ALFF in bilateral inferior temporal gyrus (ITG) and left superior frontal gyrus. Increased mean values of ALFF in the left ITG were correlated with worse performance in SDMT, and decreased mean values of ALFF in the precuneus were correlated with worse performance in the Stroop test and SDMT.Conclusions: Our results suggest that intrinsic brain activity alterations in the precuneus and cortico-striatal circuit may be the mechanism underlying impaired cognition in early HD. [ABSTRACT FROM AUTHOR]

Background The psychological profile of patients with borderline personality disorder (BPD), with impulsivity and emotional dysregulation as core symptoms, has guided the search for abnormalities in specific brain areas such as the hippocampal-amygdala complex and the frontomedial cortex. However, whole-brain imaging studies so far have delivered highly heterogeneous results involving different brain locations. Methods Functional resting-state and diffusion magnetic resonance imaging data were acquired in patients with BPD and in an equal number of matched control subjects ( n = 60 for resting and n = 43 for diffusion). While mean diffusivity and fractional anisotropy brain images were generated from diffusion data, amplitude of low-frequency fluctuations and global brain connectivity images were used for the first time to evaluate BPD-related brain abnormalities from resting functional acquisitions. Results Whole-brain analyses using a p = .05 corrected threshold showed a convergence of alterations in BPD patients in genual and perigenual structures, with frontal white matter fractional anisotropy abnormalities partially encircling areas of increased mean diffusivity and global brain connectivity. Additionally, a cluster of enlarged amplitude of low-frequency fluctuations (high resting activity) was found involving part of the left hippocampus and amygdala. In turn, this cluster showed increased resting functional connectivity with the anterior cingulate. Conclusions With a multimodal approach and without using a priori selected regions, we prove that structural and functional abnormality in BPD involves both temporolimbic and frontomedial structures as well as their connectivity. These structures have been previously related to behavioral and clinical symptoms in patients with BPD. [ABSTRACT FROM AUTHOR]

Previous neuroimaging studies have suggested that individuals at risk for schizophrenia exhibit structural and functional brain abnormalities. However, few studies focus on resting state baseline activity in individuals with genetic high-risk for schizophrenia (HR). We examined cerebral spontaneous neural activity in HR by measuring the amplitude of low frequency fluctuations (ALFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance signal during resting state. Using a 3T MRI scanner, 28 non-psychotic young adult participants with at least one parent with schizophrenia and 44 matched unrelated healthy comparison subjects (HC) were scanned during the resting-state. The ALFF of the BOLD signal for each participant was calculated, and these values were then compared between-groups using voxel-based analysis of the ALFF maps. The HR group showed significantly increased ALFF compared to the HC group in the striatum, including the left caudate nucleus extending to the putamen and the right caudate nucleus. There was also increased ALFF in HR relative to controls in the left medial temporal region including hippocampus, parahippocampal gyrus and the fusiform gyrus, as well as regions including the left lateral thalamus, bilateral ventral and dorsal anterior cingulate cortex, bilateral calcarine sulcus and precuneus. There was significantly decreased ALFF in the HR group relative to controls in the left inferior parietal lobule/postcentral gyrus. Our findings suggest that altered intrinsic neuronal activity in cortico-striato-thalamic networks may represent genetic vulnerability for the development of schizophrenia. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that neurological changes are important findings of tinnitus patients. Previous studies on tinnitus have indicated that patients with pulsatile tinnitus (PT) often show altered baseline brain activity in the resting state. This study used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in spontaneous brain activity among patients with unilateral pulsatile tinnitus in the early stage of disease (less than forty-eight months) and determined the relationship of these changes with clinical data. The PT patients (n = 34) and matched normal control subjects (n = 34) were enrolled in this study. Spontaneous brain activity was revealed by the regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values. Compared with normal controls, the patients with PT had significantly increased ReHo and ALFF in the posterior cingulate cortex, right inferior parietal lobule (IPL) and right cerebellum posterior lobe. The PT group showed increased ReHo in the posterior cingulate cortex (PCC), precuneus, right IPL, right superior frontal gyrus, some occipital areas and part of the right cerebellum posterior lobe. For ALFF, the increased clusters were in the PCC and precuneus and in some areas of the cerebellum posterior lobe, bilateral IPL and inferior frontal gyrus (IFG). Increased PT duration was correlated with increased ALFF in the bilateral inferior frontal gyrus (IFG) and precuneus. An increased THI score was correlated with ReHo and ALFF values in the precuneus. Taken together, the combined study of ReHo and ALFF measurements may yield a more comprehensive neurological pathophysiology framework for PT patients in the early stage of the disease. [ABSTRACT FROM AUTHOR]

Objective The objectives of this study were, first, to explore differences in brain activity between normal people and idiopathic restless legs syndrome (RLS) patients during asymptomatic periods; and, second, to determine whether administering repetitive transcranial magnetic stimulation (rTMS) to specific cortical regions would reverse any observed differences in brain activity and alleviate patient symptoms. Methods Fifteen idiopathic RLS patients (nine drug-naive patients) and 14 gender- and age-matched healthy controls were enrolled. Resting-state functional magnetic resonance imaging was used to measure the amplitude of low-frequency fluctuations (ALFF) in spontaneous brain activity during asymptomatic periods. Seven patients received high-frequency (5 Hz) rTMS directed toward the leg area of the primary motor cortex. Scores on the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF values were measured before and after treatment. Results Compared with healthy controls, RLS patients showed lower ALFF in the sensorimotor and visual processing regions, and higher ALFF in the insula, parahippocampal and hippocampal gyri, left posterior parietal areas, and brainstem. These results were largely conserved when only drug-naive patients were considered. After rTMS treatment, ALFF in several sensorimotor and visual regions were significantly elevated and IRLSSG Rating Scale scores decreased, indicating improved RLS symptoms. Conclusions High-frequency rTMS delivered to the leg area of the primary motor cortex may raise functional activity in the sensorimotor and occipital regions, leading to improve symptoms in RLS patients. These results provide novel insight into RLS pathophysiology and suggest a potential mechanism for rTMS therapy in idiopathic RLS patients. [ABSTRACT FROM AUTHOR]

Background Visual hallucinations are an important non-motor complication of Parkinson's disease (PD) and carry a negative prognosis. Their biological basis is uncertain, but may relate to the activity of resting state networks in brain. We therefore aimed to investigate functional activity of brain in patients with visual hallucinations (PDVH) in resting state compared to patients without hallucinations (PDnonVH) and a healthy control group (HC). Methods Resting state functional MRI was acquired and the primary analysis compared the amplitude of low-frequency fluctuations (ALFF) across groups. This informed a secondary analysis, in the PD groups only, comparing functional connectivity between a ‘seed’ region in the occipital lobe and the rest of the brain. Results Individuals with PDVH showed lower ALFF in bilateral lingual gyrus and cuneus and greater ALFF in temporo-parietal regions, medial temporal gyrus and cerebellum than PDnonVH and HC. PDnonVH also had lower ALFF in occipitoparietal region and greater ALFF in medial temporal gyrus, temporo-parietal and cerebellum regions than HC. Functional connectivity analysis revealed that, although both PD groups had lower occipital functional connectivity relative to the HC group, occipital – corticostriatal connectivity was significantly higher in those with PDVH compared with PDnonVH. Conclusion Our study reveals widespread hemodynamic alterations in PD. However, within a functionally abnormal occipital lobe, those with PDVH have even lower ALFF than non-hallucinators, but have higher occipital functional connectivity with cortical-striatal regions. These findings suggest disruption of pathways underpinning both primary visual perceptual and intrinsic visual integration may contribute to visual hallucinations in PD. [ABSTRACT FROM AUTHOR]

Highlights: [•] Resting-state BOLD amplitude predicts individual variability. [•] Resting-state functional connectivity predicts executive performance. [•] Resting-state functional connectivity predicts more individual variability. [Copyright &y& Elsevier]

Abstract: Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01–0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. [Copyright &y& Elsevier]

Abstract: Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r =−0.436, p =0.040) and the left caudate (r =−0.542, p =0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO. [Copyright &y& Elsevier]

Abstract: The purpose of this study is to investigate whether spontaneous brain activity amplitude alteration occurs in RRMS by comparing appropriately processed fMRI data from subjects with RRMS and healthy controls. Resting-state fMRIs collected from thirty-five RRMS patients and thirty-five ageand sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, T2 lesion volume were further explored. Our results showed that RRMS patients showed no regions with decreased ALFF, while showed significantly increased ALFF in the bilateral thalami, right insula (BA 13)/ right superior temporal gyrus (BA 22). The correlation between the EDSS and ALFF in the right insula/ right superior temporal gyrus was significant. From this study, we demonstrate that increased resting state amplitudes occur in the brain of patients with RRMS, specifically in areas with extensive cortical connections. We hypothesize that this is an adaptive phenomenon, reflecting either ongoing cortical plasticity in the resting-state, or increased neuronal activity related to coordination of remapped cortical functions. [Copyright &y& Elsevier]

Neuroimaging studies often either look at functional activation in response to an explicit task, or functional connectivity (i.e., interregional correlations) during resting-state. Few studies have looked at the intensity of brain activity or its relationship with age, behavior, and language. The current study investigated both intensity (i.e., the Amplitude of Low-Frequency Fluctuations, ALFF) and the functional connectivity of spontaneous brain activity during rest and their relationship with age and language. A life-span sample of individuals (N = 152) completed a battery of neuropsychological tests to assess basic cognitive functions and resting-state functional MRI data to assess spontaneous brain activity. Focusing on an extend language network, the mean ALFF and total degree were calculated for this network. We found that increased age was associated with more intense activity (i.e., higher ALFF) but lower within-network connectivity. Additionally, these increases in activity within the language network during resting-state were related to worse language ability, particularly in younger adults, supporting a dedifferentiation account of cognition. Our results support the utility of using resting-state data as an indicator of cognition and support the role of ALFF as a potential biomarker in characterizing the relationships between resting-state brain activity, age, and cognition. • Increased age was associated with higher ALFF but lower connectivity. • Increased ALFF in the language network related to worse language ability. • These results support a dedifferentiation account of cognition. • Resting-state ALFF can link brain activity, age, and cognition. [ABSTRACT FROM AUTHOR]

Abstract: The resting state amplitude of low frequency fluctuations (ALFF) in functional magnetic resonance imaging has been shown to be reliable in healthy subjects, and to correlate with antipsychotic treatment response in antipsychotic–naïve schizophrenia patients. We found moderate to high test-retest stability of ALFF in chronically treated schizophrenia patients assessed twice over a median interval of 2.5months. [Copyright &y& Elsevier]

• The reduction of ReHo in the DMN is correlated with function. • The reduction in ALFF in the DMN is correlated with cognitive function. • The SMA may be related to cognitive impairment in patients with MDD. • The correlations between the SMA and cognitive function need clarification. Major depressive disorder (MDD) is characterized by heterogeneous clinical performance and neurocognitive impairment. It is important to explore the correlation between global functioning and regional homogeneity (ReHo)/amplitude of low-frequency fluctuation (ALFF) values in MDD patients. 67 first-episode, drug naïve MDD patients and 69 healthy subjects were enrolled in the study. The MATRICS Consensus Cognitive Battery (MCCB) and the Functioning Assessment Short Test (FAST) were used to assess functional impairment in patients. Brain activity was assessed using ReHo and ALFF measurements. The relationship between the clinical features and altered brain function was evaluated using correlation analysis. There were significant differences in the ReHo and ALFF values between MDD patients and healthy subjects. The reduction in ReHo in the left calcarine/lingual gyrus/cuneus was negatively correlated with occupational functioning and the total FAST scores. The reduction in ALFF in the right calcarine/lingual gyrus was positively correlated with the verbal learning aspects of the MCCB. These findings suggest that the altered brain function in the default mode network (DMN) may be related to functional impairments in patients with first-episode, drug naïve major depressive disorder. [ABSTRACT FROM AUTHOR]

Focal brain lesions may induce dysfunctions in distant brain regions leading to behavioral impairments. Based on this concept of 'diaschisis', spatial neglect following stroke has been related to structural damage of the right-lateralized ventral attention network (VAN) and disrupted inter-hemispheric functional connectivity (FC) in the bilateral dorsal attention network (DAN). We questioned whether neglect-related behavioral deficits may be determined by local dysfunction of a specific region within these brain networks. We investigated acute right-hemisphere stroke patients with left hemispatial neglect using resting-state functional MRI, neuropsychological tests of spatial attention and clinical assessment of neglect-related functional disability. In addition to conventional FC analyses between different cortical regions of interest (ROIs) in the DAN/VAN, we extracted the fractional amplitude of low frequency fluctuations (fALFF) from each ROI as a marker of regional spontaneous neuronal activity. Although DAN regions (as opposed to the VAN regions) were largely spared from structural brain damage, they exhibited a significant reduction of inter-hemispheric FC. However, significant fMRI-behavior correlations were revealed specifically for the fALFF of one DAN-ROI in the right superior parietal lobule (SPL): the smaller the fALFF in the right posterior intraparietal sulcus, the more severe the patient's pathological attention bias and neglect-related functional impairment. In line with 'diaschisis', our findings confirm a crucial role of the non-lesioned but dysfunctional right SPL for the emergence of spatial neglect and its behavioral consequences. They further support targeting the SPL dysfunction by non-invasive brain stimulation in neglect rehabilitation. • Spatial neglect after stroke is not solely explained by the structural brain damage. • Functional connectivity between bilateral attention network regions is disrupted. • fALFF analysis of resting-state fMRI can assess neuronal activity within a brain region. • Reduced activity in right SPL correlated strongly with patients' behavioral impairments. • Targeting right SPL dysfunction may support neglect rehabilitation in the future. [ABSTRACT FROM AUTHOR]