Most recent paper

Neural Correlates of Non-clinical Internet Use in the Motivation Network and Its Modulation by Subclinical Autistic Traits.

Front Hum Neurosci. 2018;12:493

Authors: Fujiwara H, Yoshimura S, Kobayashi K, Ueno T, Oishi N, Murai T

Abstract
Background: Increasing evidence regarding the neural correlates of excessive or pathological internet use (IU) has accumulated in recent years, and comorbidity with depression and autism has been reported in multiple studies. However, psychological and neural correlates of non-clinical IU in healthy individuals remain unclear. Objectives: The aim of the current study was to investigate the relationships between non-clinical IU and functional connectivity (FC), focusing on the brain's motivation network. We sought to clarify the influence of depression and autistic traits on these relationships in healthy individuals. Methods: Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy volunteers. IU, depression, and autistic traits were assessed using the Generalized Problematic Internet Use Scale 2 (GPIUS2), Beck Depression Inventory-II (BDI-II), and the autism spectrum quotient (AQ) scale, respectively. Correlational analyses were performed using CONN-software within the motivation-related network, which consisted of 22 brain regions defined by a previous response-conflict task-based fMRI study with a reward cue. We also performed mediation analyses via the bootstrap method. Results: Total GPIUS2 scores were positively correlated with FC between the (a) left middle frontal gyrus (MFG) and bilateral medial prefrontal cortex; (b) left MFG and right supplementary motor area (SMA); (c) left MFG and right anterior insula, and (d) right MFG and right insula. The "Mood Regulation" subscale of the GPIUS2 was positively correlated with FC between left MFG and right SMA. The "Deficient Self-Regulation" subscale was positively correlated with FC between right MFG and right anterior insula (statistical thresholds, FDR < 0.05). Among these significant correlations, those between GPIUS2 (total and "Mood Regulation" subscale) scores and FC became stronger after controlling for AQ scores (total and "Attention Switching" subscale), indicating significant mediation by AQ (95% CI < 0.05). In contrast, BDI-II had no mediating effect. Conclusion: Positive correlations between IU and FC in the motivation network may indicate health-promoting effects of non-clinical IU. However, this favorable association is attenuated in individuals with subclinical autistic traits, suggesting the importance of a personalized educational approach for these individuals in terms of adequate IU.

PMID: 30618678 [PubMed]

Altered Brain Structure and Functional Connectivity of Primary Visual Cortex in Optic Neuritis.

Front Hum Neurosci. 2018;12:473

Authors: Huang J, Duan Y, Liu S, Liang P, Ren Z, Gao Y, Liu Y, Zhang X, Lu J, Li K

Abstract
Previous studies have revealed brain adaptations to injury that occurs in optic neuritis (ON); however, the mechanisms underlying the functional connectivity (FC) and gray matter volume (GMV) changes in ON have not been clarified. Here, 51 single attack ON patients and 45 recurrent attacks ON patients were examined using structural MRI and resting-state functional MRI (RS-fMRI), and compared to 49 age- and gender-matched healthy controls (HC). FC analysis with a seed in primary visual cortex (V1 area) was used to assess the differences among three groups. Whole brain GMV was assessed using voxel-based morphometry (VBM). Correlation analyses were performed between FC results, structural MRI and clinical variables. We found positive correlations between the Paced Auditory Serial Addition Test (PASAT) score and FC in V1 area with bilateral middle frontal gyrus. Disease duration is significantly negatively related to FC in V1 area with the left inferior parietal lobule. Compared to the HC, single attack ON patients were found to have decreased FC values in the frontal, temporal lobes, right inferior occipital gyrus, right insula, right inferior parietal lobule, and significant increased FC values in the left thalamus. Recurrent attacks ON patients had the same pattern with single attack ON. No significant differences were found in brain GMV among three groups. This study provides the imaging evidence that impairment and compensation of V1 area connectivity coexist in ON patients, and provides important insights into the underlying neural mechanisms of ON.

PMID: 30618673 [PubMed]

Multi-Granularity Whole-Brain Segmentation Based Functional Network Analysis Using Resting-State fMRI.

Front Neurosci. 2018;12:942

Authors: Gong Y, Wu H, Li J, Wang N, Liu H, Tang X

Abstract
In this work, we systematically analyzed the effects of various nodal definitions, as determined by a multi-granularity whole-brain segmentation scheme, upon the topological architecture of the human brain functional network using the resting-state functional magnetic resonance imaging data of 19 healthy, young subjects. A number of functional networks were created with their nodes defined according to two types of anatomical definitions (Type I and Type II) each of which consists of five granularity levels of whole brain segmentations with each level linked through ontology-based, hierarchical, structural relationships. Topological properties were computed for each network and then compared across levels within the same segmentation type as well as between Type I and Type II. Certain network architecture patterns were observed in our study: (1) As the granularity changes, the absolute values of each node's nodal degree and nodal betweenness change accordingly but the relative values within a single network do not change considerably; (2) The average nodal degree is generally affected by the sparsity level of the network whereas the other topological properties are more specifically affected by the nodal definitions; (3) Within the same ontology relationship type, as the granularity decreases, the network becomes more efficient at information propagation; (4) The small-worldness that we observe is an intrinsic property of the brain's resting-state functional network, independent of the ontology type and the granularity level. Furthermore, we validated the aforementioned conclusions and measured the reproducibility of this multi-granularity network analysis pipeline using another dataset of 49 healthy young subjects that had been scanned twice.

PMID: 30618571 [PubMed]

Dynamic functional network connectivity in Huntington's disease and its associations with motor and cognitive measures.

Hum Brain Mapp. 2019 Jan 07;:

Authors: Espinoza FA, Liu J, Ciarochi J, Turner JA, Vergara VM, Caprihan A, Misiura M, Johnson HJ, Long JD, Bockholt JH, Paulsen JS, Calhoun VD

Abstract
Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] and N = 78 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs-fMRI data to obtain whole-brain resting state networks. FNC was defined as the correlation between RSN time-courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k-means clustering algorithm. HDgmc individuals spent significantly more time in State-1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State-4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State-1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.

PMID: 30618191 [PubMed - as supplied by publisher]

Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain.

Brain Imaging Behav. 2019 Jan 08;:

Authors: Sevel L, Boissoneault J, Alappattu M, Bishop M, Robinson M

Abstract
Analgesic treatments that aim to eliminate pain display marginal success in relieving chronic pain and may increase pain vulnerability. Repeated exposure to pain may result in increased pain modulation via engagement of anti-nociceptive brain regions. It was hypothesized that repeated exposure to delayed onset muscle soreness (DOMS) would result in increased pain modulatory capacity (PMC) via functional neural adaptation. 23 healthy participants completed Baseline and Follow Up resting-state fMRI and quantitative sensory testing (QST) visits 40 days apart. Participants were randomized to two groups: A Repeated DOMS Group (RD Group) that received four, weekly DOMS inductions and a Control Group that received one baseline induction. Daily pain ratings were collected for seven days post-induction, as were quantitative sensory testing (QST) metrics at baseline and Follow Up. Regional functional connectivity (FC) was estimated among areas involved in pain modulation. Seed and network FC was estimated among areas involved in pain modulation and sensory processing. Changes in FC were compared between groups. The RD Group displayed significant reductions in post-DOMS pain ratings and significant changes in thermal QST measures. RD Group participants displayed greater adaptation in nucleus accumbens-medial prefrontal cortex (NAc-mPFC) FC and in sensorimotor network (SMN) connectivity with the dorsomedial, ventromedial, and rostromedial prefrontal cortices. Changes in SMN-PFC connectivity correlated with reductions in post-DOMS affective distress. Results suggest that repeated exposure to clinically-relevant pain results in adaptations among brain regions involved in pain modulation. Repeated exposure to clinically-relevant pain may serve as a mechanism to increase PMC via inhibition of emotional valuation of painful stimuli.

PMID: 30617786 [PubMed - as supplied by publisher]

Chemotherapy-induced functional changes of the default mode network in patients with lung cancer.

Brain Imaging Behav. 2019 Jan 07;:

Authors: Zhang Y, Chen YC, Hu L, You J, Gu W, Li Q, Chen H, Mao C, Yin X

Abstract
Previous studies have demonstrated that cognitive impairment is associated with neurophysiological changes in lung cancer following chemotherapy. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in patients with lung cancer revealed by resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI scans were acquired from 21 post-chemotherapy and 27 non-chemotherapy lung cancer patients and 30 healthy controls. All groups were age, gender and education-matched. The posterior cingulate cortex (PCC) was chosen as the seed region to detect the FC patterns and then determine whether these changes were related with specific cognitive performance. Compared with non-chemotherapy lung cancer patients, chemotherapy patients revealed decreased FC between the PCC and the right anterior cingulate cortex (ACC), left inferior parietal lobule (IPL), and left medial prefrontal cortex (mPFC), as well as increased FC with the left postcentral gyrus (PoCG). Relative to healthy controls, post-chemotherapy patients exhibited reduced FC between the PCC and the left ACC and left temporal lobe, as well as increased FC with the right PoCG. Moreover, the decreased FC of the PCC to bilateral ACC in post-chemotherapy patients was positively associated with reduced MoCA scores (left: r = 0.529, p = 0.029; right: r = 0.577, p = 0.015). The current study mainly demonstrated reduced resting-state FC pattern within the DMN regions that was linked with impaired cognitive function in lung cancer patients after chemotherapy. These findings illustrated the potential role of the DMN in lung cancer patients that will provide novel insight into the underlying neuropathological mechanisms in chemotherapy-induced cognitive impairment.

PMID: 30617783 [PubMed - as supplied by publisher]

Disruption of functional connectivity among subcortical arousal system and cortical networks in temporal lobe epilepsy.

Brain Imaging Behav. 2019 Jan 07;:

Authors: Li R, Hu C, Wang L, Liu D, Liu D, Liao W, Xiao B, Chen H, Feng L

Abstract
Growing evidence has demonstrated widespread brain network alterations in temporal lobe epilepsy (TLE). However, the relatively accurate portrait of the subcortical-cortical relationship for impaired consciousness in TLE remains unclear. We proposed that consciousness-impairing seizures may invade subcortical arousal system and corresponding cortical regions, resulting in functional abnormalities and information flow disturbances between subcortical and cortical networks. We performed resting-state fMRI in 26 patients with TLE and 30 matched healthy controls. All included patients were diagnosed with impaired awareness during focal temporal lobe seizures. Functional connectivity density was adopted to determine whether local or distant network alterations occurred in TLE, and Granger causality analysis (GCA) was utilized to assess the direction and magnitude of causal influence among these altered brain networks further. Patients showed increased local functional connectivity in several arousal structures, such as the midbrain, thalamus, and cortical regions including bilateral prefrontal cortex (PFC), left superior temporal pole, left posterior insula, and cerebellum (P < 0.05, FDR corrected). GCA analysis revealed that the casual effects among these regions in patients were significantly sparser than those in controls (P < 0.05, uncorrected), including decreased excitatory and inhibitory effects among the midbrain, thalamus and PFC, and decreased inhibitory effect from the cerebellum to PFC. These findings suggested that consciousness-impairing seizures in TLE are associated with functional alterations and disruption of information process between the subcortical arousal system and cortical network. Understanding the functional networks and innervation pathway involved in TLE can provide insights into the mechanism underlying seizure-related loss of consciousness.

PMID: 30617780 [PubMed - as supplied by publisher]

Intrinsic thalamocortical connectivity varies in the age of onset subtypes in major depressive disorder.

Neuropsychiatr Dis Treat. 2019;15:75-82

Authors: Brown EC, Clark DL, Hassel S, MacQueen G, Ramasubbu R

Abstract
Background: Differences in the thalamocortical system have been shown in patients with major depressive disorder (MDD). Given prior evidence of phenotypic heterogeneity by the age of onset in MDD, we examined whether differences in thalamocortical connectivity could identify biological subtypes of MDD defined by the age of illness onset.
Methods: A total of 94 subjects including 20 early-onset (EO) MDD (onset, 18 years), 34 adult-onset (AO) MDD, and 40 healthy controls (HCs) underwent resting-state functional MRI. Blood-oxygen-level-dependent time courses were extracted from six cortical regions of interest (ROIs) consisting of frontal, temporal, parietal, and occipital lobes and precentral and postcentral gyri. Each ROI's time course was then correlated with each voxel in thalamus, while covarying out signal from every other ROI.
Results: The analysis of variance results showed significant main effects of group in frontal and temporal connectivity with thalamus. Group contrasts showed a right fronto-thalamic hypo-connectivity only in AO-MDD, but not in EO-MDD, when compared to HCs. However, direct comparison between EO-MDD and AO-MDD showed no differences. Furthermore, there was a right temporal-thalamic hyperconnectivity in both EO-MDD and AO-MDD patients relative to HCs. These results were not accounted for by sex, age, or illness burden.
Conclusion: The age of illness onset may be a source of heterogeneity in fronto-thalamic intrinsic connectivity in MDD.

PMID: 30613149 [PubMed]

[Changes in regional homogeneity of brain activity in patients with diabetic peripheral].

Nan Fang Yi Ke Da Xue Xue Bao. 2018 Dec 30;38(12):1433-1439

Authors: Qiu L, Tan X, Zou M, Lao B, Xu Y, Xue Y, Gao F, Cao Y

Abstract
OBJECTIVE: To investigate the abnormalities in regional homogeneity of brain activity in patients with diabetic peripheral neuropathy (DPN) using resting-state functional magnetic resonance imaging (rs-fMRI) and explore the association between brain activity changes and DPN.
METHODS: A regional homogeneity (ReHo) approach was used to compare the local synchronization of rs-fMRI signals among 20 patients with painful DPN, 16 patients with painless DPN, and 16 type 2 diabetic patients without DPN (non-DPN group).
RESULTS: Compared with the those without DPN, the patients with painful DPN showed high ReHo in the left inferior temporal gyrus and the right central posterior gyrus, and low ReHo in the posterior cingulate gyrus, right inferior parietal gyrus, and the left superior parietal gyrus (P &lt; 0.05);the patients with painless DPN group showed high ReHo in the left inferior temporal gyrus, the right middle temporal gyrus, and the right superior frontal gyrus, and low ReHo in the left thalamus (P &lt; 0.05).No significant differences in ReHo were found between the patients with painful DPN and painless DPN (P&gt;0.05).
CONCLUSIONS: The patients with DPN have altered ReHo in multiple brain regions and impairment of a default mode network, for which the left temporal gyrus may serve as a functional compensatory brain area. ReHo disturbance in the central right posterior gyrus may play a central role in the pain symptoms associated with painful DPN.

PMID: 30613010 [PubMed - in process]

Common Dysfunction of Large-Scale Neurocognitive Networks Across Psychiatric Disorders.

Biol Psychiatry. 2018 Nov 23;:

Authors: Sha Z, Wager TD, Mechelli A, He Y

Abstract
BACKGROUND: Cognitive dysfunction is one of the most prominent characteristics of psychiatric disorders. Currently, the neural correlates of cognitive dysfunction across psychiatric disorders are poorly understood. The aim of this study was to investigate functional connectivity and structural perturbations across psychiatric diagnoses in three neurocognitive networks of interest: the default mode network (DMN), the frontoparietal network (FPN), and the salience network (SN).
METHODS: We performed meta-analyses of resting-state functional magnetic resonance imaging whole-brain seed-based functional connectivity in 8298 patients (involving eight disorders) and 8165 healthy control subjects and a voxel-based morphometry analysis of structural magnetic resonance imaging data in 14,027 patients (involving eight disorders) and 14,504 healthy control subjects. To aid the interpretation of the results, we examined neurocognitive function in 776 healthy participants from the Human Connectome Project.
RESULTS: We found that the three neurocognitive networks of interest were characterized by shared alterations of functional connectivity architecture across psychiatric disorders. More specifically, hypoconnectivity was expressed between the DMN and ventral SN and between the SN and FPN, whereas hyperconnectivity was evident between the DMN and FPN and between the DMN and dorsal SN. This pattern of network alterations was associated with gray matter reductions in patients and was localized in regions that subserve general cognitive performance.
CONCLUSIONS: This study is the first to provide meta-analytic evidence of common alterations of functional connectivity within and between neurocognitive networks. The findings suggest a shared mechanism of network interactions that may associate with the generalized cognitive deficits observed in psychiatric disorders.

PMID: 30612699 [PubMed - as supplied by publisher]

Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms.

Brain Imaging Behav. 2019 Jan 05;:

Authors: Gao J, Tang X, Wang C, Yu M, Sha W, Wang X, Zhang H, Zhang X, Zhang X

Abstract
Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.

PMID: 30612342 [PubMed - as supplied by publisher]

Changed hub and functional connectivity patterns of the posterior fusiform gyrus in chess experts.

Brain Imaging Behav. 2019 Jan 05;:

Authors: Song L, Peng Q, Liu S, Wang J

Abstract
The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, the effects of long-term practice on functional network hubs in chess experts are largely undefined. Here, we investigated whether alterations of hubs can be detected in chess experts using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods. We first mapped the whole-brain voxel-wise functional connectivity and calculated the functional connectivity strength (FCS) map in each of the 28 chess players and 27 gender- and age-matched healthy novice players. Whole-brain resting-state functional connectivity analyses for the changed hub areas were conducted to further elucidate the corresponding changes of functional connectivity patterns in chess players. The hub analysis revealed increased FCS in the right posterior fusiform gyrus of the chess players, which was supported by analyses of this area's regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and fractional amplitude of low frequency fluctuations (fALFF). The following functional connectivity analyses revealed increased functional connectivities between the right posterior fusiform gyrus and the visuospatial attention and motor networks in chess players. These findings demonstrate that cognitive expertise has a positive influence on the functions of the brain regions associated with the chess expertise and that increased functional connections might in turn facilitate within and between networks communication for expert behavior to get superior performance.

PMID: 30612341 [PubMed - as supplied by publisher]

Awake and behaving mouse fMRI during Go/No-Go task.

Neuroimage. 2019 Jan 03;:

Authors: Han Z, Chen W, Chen X, Zhang K, Tong C, Zhang X, Li CT, Liang Z

Abstract
Functional magnetic imaging (fMRI) has been widely used to examine the functional neural networks in both the evoked and resting states. However, most fMRI studies in rodents are performed under anesthesia, which greatly limits the scope of their application, and behavioral relevance. Efforts have been made to image rodents in the awake condition, either in the resting state or in response to sensory or optogenetic stimulation. However, fMRI in awake behaving rodents has not yet been achieved. In the current study, a novel fMRI paradigm for awake and behaving mice was developed, allowing functional imaging of the mouse brain in an olfaction-based go/no-go task. High resolution functional imaging with limited motion and image distortion were achieved at 9.4T with a cryogenic coil in awake and behaving mice. Distributed whole-brain spatiotemporal patterns were revealed, with drastically different activity profiles for go versus no-go trials. Therefore, we have demonstrated the feasibility of functional imaging of an olfactory behavior in awake mice. This fMRI paradigm in awake behaving mice could lead to novel insights into neural mechanisms underlying behaviors at a whole-brain level.

PMID: 30611875 [PubMed - as supplied by publisher]

Early childhood network alterations in severe autism.

Asian J Psychiatr. 2018 Dec 21;39:114-119

Authors: Kaku SM, Jayashankar A, Girimaji SC, Bansal S, Gohel S, Bharath RD, Srinath S

Abstract
OBJECTIVE: To examine the differences in whole brain topology and connectivity in 17 children of the ages 3-8 years across severity of ASD, we performed resting state fMRI using a 3T MRI scanner and graph theoretical analysis of networks.
METHOD: Patients were partitioned into two cohorts based on the severity of ASD, determined using the Childhood Autism Rating Scale (CARS) scores (Mild, 30-36; Severe, 37+). Standard preprocessing pipeline was used, followed by independent component analysis (ICA) to identify regions of interest (ROIs) to construct subject-specific Z-correlation matrices representing the whole brain network. Following which, graph theory measures were calculated in the range of sparsity 6%-35% and statistically analyzed, and corrected for significance (FDR corrected, p < 0.05). Regional clustering coefficient that revealed significant between-group (mild vs. severe) differences were correlated against clinical scores (CARS).
RESULTS: Children with severe ASD revealed significantly increased clustering coefficient and small-worldness compared to those with mild or moderate ASD. Region of interest analysis revealed altered clustering in the Heschl's gyrus that significantly correlated with CARS scores.
CONCLUSION: The findings from the current study provide early stage evidence of aberrant brain connectivity appearing in severe ASD, prior to the effect of environmental bias and pruning mechanisms. The clustering of the Heschl's gyrus correlated to the severity of ASD symptoms and agrees with current literature on ASD-associated cortical changes, reflecting early changes to language processing regions.

PMID: 30610990 [PubMed - as supplied by publisher]

Diagnostic and prognostic biomarkers for HAND.

J Neurovirol. 2019 Jan 03;:

Authors: McLaurin KA, Booze RM, Mactutus CF

Abstract
In 2007, the nosology for HIV-1-associated neurocognitive disorders (HAND) was updated to a primarily neurocognitive disorder. However, currently available diagnostic tools lack the sensitivity and specificity needed for an accurate diagnosis for HAND. Scientists and clinicians, therefore, have been on a quest for an innovative biomarker to diagnose (i.e., diagnostic biomarker) and/or predict (i.e., prognostic biomarker) the progression of HAND in the post-combination antiretroviral therapy (cART) era. The present review examined the utility and challenges of four proposed biomarkers, including neurofilament light (NFL) chain concentration, amyloid (i.e., sAPPα, sAPPβ, amyloid β) and tau proteins (i.e., total tau, phosphorylated tau), resting-state functional magnetic resonance imaging (fMRI), and prepulse inhibition (PPI). Although significant genotypic differences have been observed in NFL chain concentration, sAPPα, sAPPβ, amyloid β, total tau, phosphorylated tau, and resting-state fMRI, inconsistencies and/or assessment limitations (e.g., invasive procedures, lack of disease specificity, cost) challenge their utility as a diagnostic and/or prognostic biomarker for milder forms of neurocognitive impairment (NCI) in the post-cART era. However, critical evaluation of the literature supports the utility of PPI as a powerful diagnostic biomarker with high accuracy (i.e., 86.7-97.1%), sensitivity (i.e., 89.3-100%), and specificity (i.e., 79.5-94.1%). Additionally, the inclusion of multiple CSF and/or plasma markers, rather than a single protein, may provide a more sensitive diagnostic biomarker for HAND; however, a pressing need for additional research remains. Most notably, PPI may serve as a prognostic biomarker for milder forms of NCI, evidenced by its ability to predict later NCI in higher-order cognitive domains with regression coefficients (i.e., r) greater than 0.8. Thus, PPI heralds an opportunity for the development of a brief, noninvasive diagnostic and promising prognostic biomarker for milder forms of NCI in the post-cART era.

PMID: 30607890 [PubMed - as supplied by publisher]

Modulation of anterior cingulate cortex reward and penalty signalling in medication-naive young-adult subjects with depressive symptoms following acute dose lurasidone.

Psychol Med. 2019 Jan 04;:1-13

Authors: Wolke SA, Mehta MA, O'Daly O, Zelaya F, Zahreddine N, Keren H, O'Callaghan G, Young A, Leibenluft E, Pine DS, Stringaris A

Abstract
BACKGROUND: Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression.
METHODS: We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0-43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest.
RESULTS: Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF.
CONCLUSIONS: Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.

PMID: 30606271 [PubMed - as supplied by publisher]

Precuneus and psychiatric manifestations: Novel neurobiological formulations through lesion based connectivity mapping of psychopathology.

Asian J Psychiatr. 2018 Dec 27;39:98-100

Authors: Narasimha VL, Basavaraju R, Mangalore S, Mehta UM

Abstract
Lesion-based investigations of psychopathology have preceded contemporary network-neuroscience initiatives. However, brain-lesions detected in routine psychiatric practice are often considered incidental and therefore ignored. Here, we illustrate a strategy to combine individual subject-level lesion information with open-source normative functional-connectomics data to make putative, neuroscience-informed symptom interpretation. Specifically, we report a patient with left precuneus granulomatous lesion and seizures followed by two distinct symptoms - kinetopsia and delusions of nihilism and guilt - which had a differential treatment response. The lesion-based brain-mapping approach could identify correlated (default-mode) and anti-correlated (temporo-parieto-occipital) networks, which enabled a neurobiological formulation of these diverse clinical manifestations.

PMID: 30599452 [PubMed - as supplied by publisher]

Altered regional homogeneity in patients with somatic depression: A resting-state fMRI study.

J Affect Disord. 2018 Dec 26;246:498-505

Authors: Geng J, Yan R, Shi J, Chen Y, Mo Z, Shao J, Wang X, Lu Q, Yao Z

Abstract
BACKGROUND: Somatic symptoms are common among patients with major depressive disorder (MDD), and are known to negatively impact the course and severity of the disease. Although previous studies have attempted to explore the neuropathology of MDD, little is known regarding the neural basis of somatic symptoms in MDD.
METHODS: Resting-state functional magnetic resonance images of 28 MDD patients with somatic symptoms (somatic depression, SD), 30 patients without somatic symptoms (non-somatic depression, NSD) and 30 healthy controls (HC) were obtained. We investigated the neural basis of MDD with somatic symptoms based on the measure of regional homogeneity (ReHo). We also investigated whether the altered regional homogeneity may be correlated to any clinical features of depression. These comparison were also carried out in female and male subjects respectively.
RESULTS: The SD exhibited higher ReHo in the bilateral parahippocampus and left lingual gyrus than HC, as well as lower ReHo in the right frontal gyrus. Relative to NSD, the SD exhibited lower ReHo in the right middle frontal gyrus and left precentral gyrus. Furthermore, in the SD, ReHo in the left precentral gyrus was positively correlated with cognitive factor scores of the HAMD-17. In female subjects, SD exhibited increased ReHo in the right STG and decreased ReHo in the right MFG, relative to women of the NSD group.
CONCLUSIONS: Our preliminary findings indicated that abnormal ReHo in the frontal and temporal regions may play an important role in the neural basis of somatic depression.

PMID: 30599374 [PubMed - as supplied by publisher]

Enhanced central neural gain compensates acoustic trauma-induced cochlear impairment, but unlikely correlates with tinnitus and hyperacusis.

Neuroscience. 2018 Dec 29;:

Authors: Möhrle D, Hofmeier B, Amend M, Wolpert S, Ni K, Bing D, Klose U, Pichler B, Knipper M, Rüttiger L

Abstract
For successful future therapeutic strategies for tinnitus and hyperacusis, a subcategorization of both conditions on the basis of differentiated neural correlates would be of invaluable advantage. In the present study, we used our refined operant conditioning animal model to divide equally noise-exposed rats into groups with either tinnitus or hyperacusis, with neither condition, or with both conditions co-occurring simultaneously. Using click stimulus and noise burst-evoked Auditory Brainstem Responses (ABR) and Distortion Product Otoacoustic Emissions, no hearing threshold difference was observed between any of the groups. However, animals with neither tinnitus nor hyperacusis responded to noise trauma with shortened ABR wave I and IV latencies and elevated central neuronal gain (increased ABR wave IV/I amplitude ratio), which was previously assumed in most of the literature to be a neural correlate for tinnitus. In contrast, animals with tinnitus had reduced neural response gain and delayed ABR wave I and IV latencies, while animals with hyperacusis showed none of these changes. Preliminary studies, aimed at establishing comparable non-invasive objective tools for identifying tinnitus in humans and animals, confirmed reduced central gain and delayed response latency in human and animals. Moreover, the first ever resting state functional Magnetic Resonance Imaging (rs-fMRI) analyses comparing humans and rats with and without tinnitus showed reduced rs-fMRI activities in the auditory cortex in both patients and animals with tinnitus. These findings encourage further efforts to establish non-invasive diagnostic tools that can be used in humans and animals alike and give hope for differentiated classification of tinnitus and hyperacusis.

PMID: 30599268 [PubMed - as supplied by publisher]

Alterations of the default mode network and cognitive impairment in patients with unilateral chronic tinnitus.

Quant Imaging Med Surg. 2018 Nov;8(10):1020-1029

Authors: Chen YC, Zhang H, Kong Y, Lv H, Cai Y, Chen H, Feng Y, Yin X

Abstract
Background: Previous studies have demonstrated that cognitive impairment is linked with neurophysiological alterations in chronic tinnitus. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in tinnitus patients using a resting-state functional magnetic resonance imaging (rs-fMRI).
Methods: Thirty-five chronic unilateral tinnitus patients, and 50 healthy controls were recruited for rsfMRI scanning. Both groups were age, gender and education level well-matched. The posterior cingulate cortex (PCC) was chosen as the region of interest (ROI) for detecting the FC changes, and determining if these abnormalities were related to a specific cognitive performance and tinnitus characteristic.
Results: Relative to the healthy controls, tinnitus patients showed increased FC between the PCC and the right medial prefrontal cortex (mPFC). Moreover, the enhanced FC between the PCC and right mPFC was correlated with the poorer TMT-B scores (r=0.474, P=0.008). These correlations were adjusted by age, gender, education level, GM volume, and mean hearing thresholds. The enhanced FC was not correlated with other tinnitus characteristics or cognitive performances.
Conclusions: The enhanced FC pattern of the PCC that is correlated with cognitive impairment in chronic tinnitus patients, especially the executive dysfunction. Enhanced connectivity pattern within the DMN may play a crucial role in neurophysiological mechanism in tinnitus patients with cognitive dysfunction.

PMID: 30598879 [PubMed]