New resting-state fMRI related studies at PubMed

Cereb Cortex. 2023 May 25:bhad185. doi: 10.1093/cercor/bhad185. Online ahead of print.

ABSTRACT

Schizophrenia is a self-disorder characterized by disrupted brain dynamics and architectures of multiple molecules. This study aims to explore spatiotemporal dynamics and its association with psychiatric symptoms. Resting-state functional magnetic resonance imaging data were collected from 98 patients with schizophrenia. Brain dynamics included the temporal and spatial variations in functional connectivity density and association with symptom scores were evaluated. Moreover, the spatial association between dynamics and receptors/transporters according to prior molecular imaging in healthy subjects was examined. Patients demonstrated decreased temporal variation and increased spatial variation in perceptual and attentional systems. However, increased temporal variation and decreased spatial variation were revealed in higher order networks and subcortical networks in patients. Specifically, spatial variation in perceptual and attentional systems was associated with symptom severity. Moreover, case-control differences were associated with dopamine, serotonin and mu-opioid receptor densities, serotonin reuptake transporter density, dopamine transporter density, and dopamine synthesis capacity. Therefore, this study implicates the abnormal dynamic interactions between the perceptual system and cortical core networks; in addition, the subcortical regions play a role in the dynamic interaction among the cortical regions in schizophrenia. These convergent findings support the importance of brain dynamics and emphasize the contribution of primary information processing to the pathological mechanism underlying schizophrenia.

PMID:37231204 | DOI:10.1093/cercor/bhad185

Brain Stimul. 2023 May 23:S1935-861X(23)01773-4. doi: 10.1016/j.brs.2023.05.006. Online ahead of print.

ABSTRACT

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow.

PMID:37230462 | DOI:10.1016/j.brs.2023.05.006

J Clin Neurosci. 2023 May 23;113:86-92. doi: 10.1016/j.jocn.2023.05.011. Online ahead of print.

ABSTRACT

Previous studies have reported that patients with white matter lesions (WMLs) have abnormal spontaneous brain activity in the resting state. However, the spontaneous neuronal activity of specific frequency bands in WMLs patients is unknown. Here, we included 16 WMLs patients and 13 gender and age-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI) scan and studied the specificity of the amplitude of low-frequency fluctuations (ALFF) in WMLs patients in the slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and typical (0.01-0.08 Hz) frequency bands. In addition, ALFF values of different frequency bands were extracted as classification features and support vector machines (SVM) were used to classify WMLs patients. In all three frequency bands, significant increases in ALFF values in WMLs patients were observed in the cerebellum. In the slow-5 band, the ALFF values of the left anterior cingulate and paracingulate gyri (ACG), and the right precentral gyrus, rolandic operculum and inferior temporal gyrus in WMLs patients were lower than those in HCs. In the slow-4 band, ALFF values were lower in WMLs patients than in HCs at the left ACG, the right median cingulate and paracingulate gyri, parahippocampal gyrus, caudate nucleus, and the bilateral lenticular nucleus, putamen. In the SVM classification model, the classification accuracy of slow-5, slow-4 and typical frequency bands is 75.86%, 86.21% and 72.41%, respectively. The results indicate that the ALFF abnormalities in WMLs patients have frequency specificity, and the ALFF abnormalities in the slow-4 frequency band may serve as imaging markers for WMLs.

PMID:37229795 | DOI:10.1016/j.jocn.2023.05.011

J Infect Dis. 2023 May 25:jiad180. doi: 10.1093/infdis/jiad180. Online ahead of print.

ABSTRACT

BACKGROUND: This study examined the effects of HIV on resting state functional connectivity (RSFC) in a large cohort of people living with HIV (PWH) and healthy controls without HIV (PWoH). Within PWH analyses focused on the effects of viral suppression and cognitive impairment on RSFC.

METHODS: A total of 316 PWH on stable combination antiretroviral therapy and 209 demographically matched PWoH were scanned at a single institution. Effects of the virus were examined by grouping PWH by detectable (viral load > 20 copies/ml; VLD) and undetectable (VLU) viral loads and as being cognitively impaired (CI) (Global Deficit Score ≥ 0.5) or cognitively normal (CN). Regression analysis, Object Oriented Data Analysis, and spring embedded graph models were applied to RSFC measures from 298 established brain ROIs comprising 13 brain networks to examine group differences.

RESULTS: No significant RSFC differences were observed between PWH and PWoH. Within PWH, there were no significant differences in RSFC between VLD and VLU subgroups and CI and CN subgroups.

CONCLUSION: There were no significant effects of HIV on RSFC in our relatively large cohort of PWH and PWoH. Future studies could increase the sample size and combine with other imaging modalities.

PMID:37228129 | DOI:10.1093/infdis/jiad180

BMJ Open. 2023 May 24;13(5):e069413. doi: 10.1136/bmjopen-2022-069413.

ABSTRACT

INTRODUCTION: Regular aerobic exercise is associated with improved cognitive function, implicating it as a strategy to reduce dementia risk. This is reinforced by the association between greater cardiorespiratory fitness and larger brain volume, superior cognitive performance and lower dementia risk. However, the optimal aerobic exercise dose, namely the intensity and mode of delivery, to improve brain health and lower dementia risk has received less attention. We aim to determine the effect of different doses of aerobic exercise training on markers of brain health in sedentary middle-aged adults, hypothesising that high-intensity interval training (HIIT) will be more beneficial than moderate-intensity continuous training (MICT).

METHODS AND ANALYSIS: In this two-group parallel, open-label blinded endpoint randomised trial, 70 sedentary middle-aged (45-65 years) adults will be randomly allocated to one of two 12-week aerobic exercise training interventions matched for total exercise training volume: (1) MICT (n=35) or HIIT (n=35). Participants will perform ~50 min exercise training sessions, 3 days per week, for 12 weeks. The primary outcome will be measured as between-group difference in cardiorespiratory fitness (peak oxygen uptake) change from baseline to the end of training. Secondary outcomes include between-group differences in cognitive function and ultra-high field MRI (7T) measured markers of brain health (brain blood flow, cerebrovascular function, brain volume, white matter microstructural integrity and resting state functional brain activity) changes from baseline to the end of training.

ETHICS AND DISSEMINATION: The Victoria University Human Research Ethics Committee (VUHREC) has approved this study (HRE20178), and all protocol modifications will be communicated to the relevant parties (eg, VUHREC, trial registry). Findings from this study will be disseminated via peer-review publications, conference presentations, clinical communications and both mainstream and social media.

TRIAL REGISTRATION NUMBER: ANZCTR12621000144819.

PMID:37225276 | DOI:10.1136/bmjopen-2022-069413

Psychiatry Res Neuroimaging. 2023 May 12;333:111656. doi: 10.1016/j.pscychresns.2023.111656. Online ahead of print.

ABSTRACT

The aim of this study was to investigate whether the alterations of topological properties can facilitate the diagnosis of generalized anxiety disorder (GAD). Twenty first-episode drug-naive Chinese individuals with GAD and twenty age-sex-education-matched healthy controls (HCs) were included in the primary training set, and the results of which were validated using nineteen drug-free patients with GAD and nineteen unmatched HCs. Two 3 T scanners were used to acquire T1, diffusion tensor, and resting-state functional images. Topological properties were altered in the functional cerebral networks among patients with GAD, but not in the structural networks. Using the nodal topological properties in the anti-correlated functional networks, machine learning models distinguished drug-naive GADs from their matched HCs independent of the type of kernels and the amount of features. Although the models built with drug-naive GADs failed to distinguish drug-free GADs from HCs, the features selected for those models could be used to build new models for distinguishing drug-free GADs from HCs. Our findings suggested that it is feasible to utilize the topological characteristics of brain network to facilitate the diagnosis of GAD. However, further research with decent sample sizes, multimodal features, and improved modeling methods are needed to build more robust models.

PMID:37224661 | DOI:10.1016/j.pscychresns.2023.111656

Neuroimage Clin. 2023 May 19;38:103440. doi: 10.1016/j.nicl.2023.103440. Online ahead of print.

ABSTRACT

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by continued amplification of pain intensity. Given the pivotal roles of the insula in the perception and interpretation of pain, we examined insular functional connectivity and its associations with clinical characteristics in patients with CRPS.

METHODS: Twenty-one patients with CRPS and 49 healthy controls underwent resting-state functional magnetic resonance imaging. The seed-to-seed functional connectivity analysis was performed for the bilateral insulae and cognitive control regions including the dorsal anterior cingulate cortex (dACC) and bilateral dorsolateral prefrontal cortex (DLPFC) between the two groups. Correlations between altered functional connectivity and clinical characteristics were assessed in CRPS patients.

RESULTS: CRPS patients exhibited lower functional connectivity within the bilateral anterior insulae, between the insular and cognitive control regions (the bilateral anterior/posterior insulae-dACC; the right posterior insula-left DLPFC), as compared with healthy controls at false discovery rate-corrected p < 0.05. In CRPS patients, pain severity was associated negatively with the left-right anterior insular functional connectivity (r = -0.49, p = 0.03), yet positively with the left anterior insula-dACC functional connectivity (r = 0.51, p = 0.02).

CONCLUSIONS: CRPS patients showed lower functional connectivity both within the bilateral anterior insulae and between the insular and cognitive control regions. The current findings may suggest pivotal roles of the insula in dysfunctional pain processing of CRPS patients.

PMID:37224606 | PMC:PMC10220260 | DOI:10.1016/j.nicl.2023.103440

Eur Child Adolesc Psychiatry. 2023 May 24. doi: 10.1007/s00787-023-02238-0. Online ahead of print.

ABSTRACT

The coupling between resting-state cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signals reflects the mechanism of neurovascular coupling (NVC), which have not been illustrated in attention-deficit/hyperactivity disorder (ADHD). Fifty ADHD and 42 age- and gender-matched typically developing controls (TDs) were enrolled. The NVC imaging metrics were investigated by exploring the Pearson correlation coefficients between CBF and BOLD-derived quantitative maps (ALFF, fALFF, DCP maps). Three types of NVC metrics (CBF-ALFF, CBF-fALFF, CBF-DCP coupling) were compared between ADHD and TDs group, and the inner association between altered NVC metrics and clinical variables in ADHD group was further analyzed. Compared to TDs, ADHD showed significantly reduced whole-brain CBF-ALFF coupling (P < 0.001). Among regional level (all PFDR < 0.05), ADHD showed significantly lower CBF-ALFF coupling in bilateral thalamus, default-mode network (DMN) involving left anterior cingulate (ACG.L) and right parahippocampal gyrus (PHG.R), execution control network (ECN) involving right middle orbital frontal gyrus (ORBmid.R) and right inferior frontal triangular gyrus (IFGtriang.R), and increased CBF-ALFF coupling in attention network (AN)-related left superior temporal gyrus (STG.L) and somatosensory network (SSN))-related left rolandic operculum (ROL.L). Furthermore, increased CBF-fALFF coupling was found in the visual network (VN)-related left cuneus and negatively correlated with the concentration index of ADHD (R = - 0.299, PFDR = 0.035). Abnormal regional NVC metrics were at widespread neural networks in ADHD, mainly involved in DMN, ECN, SSN, AN, VN and bilateral thalamus. Notably, this study reinforced the insights into the neural basis and pathophysiological mechanism underlying ADHD.

PMID:37222790 | DOI:10.1007/s00787-023-02238-0

J Alzheimers Dis Rep. 2023 May 12;7(1):399-413. doi: 10.3233/ADR-220062. eCollection 2023.

ABSTRACT

BACKGROUND: Despite growing evidence regarding the association between exercise training (ET) and functional brain network connectivity, little is known about the effects of ET on large-scale within- and between-network functional connectivity (FC) of core brain networks.

OBJECTIVE: We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). The association between ET-induced changes in FC and cognitive performance was examined.

METHODS: 33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in this study. Before and after a 12-week walking ET intervention, participants underwent a graded exercise test, Controlled Oral Word Association Test (COWAT), Rey Auditory Verbal Learning Test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within (W) and between (B) network connectivity of the DMN, FPN, and SAL. We used linear regression to examine associations between ET-related changes in network connectivity and cognitive function.

RESULTS: There were significant improvements in cardiorespiratory fitness, COWAT, RAVLT, and LM after ET across participants. Significant increases in DMNW and SALW, and DMN-FPNB, DMN-SALB, and FPN-SALB were observed after ET. Greater SALW and FPN-SALB were associated with enhanced LM immediate recall performance after ET in both groups.

CONCLUSION: Increased within- and between-network connectivity following ET may subserve improvements in memory performance in older individuals with intact cognition and with MCI due to Alzheimer's disease.

PMID:37220620 | PMC:PMC10200248 | DOI:10.3233/ADR-220062

Hum Brain Mapp. 2023 May 23. doi: 10.1002/hbm.26313. Online ahead of print.

ABSTRACT

The perception and imagery of landmarks activate similar content-dependent brain areas, including occipital and temporo-medial brain regions. However, how these areas interact during visual perception and imagery of scenes, especially when recollecting their spatial location, remains unknown. Here, we combined functional magnetic resonance imaging (fMRI), resting-state functional connectivity (rs-fc), and effective connectivity to assess spontaneous fluctuations and task-induced modulation of signals among regions entailing scene-processing, the primary visual area and the hippocampus (HC), responsible for the retrieval of stored information. First, we functionally defined the scene-selective regions, that is, the occipital place area (OPA), the retrosplenial complex (RSC) and the parahippocampal place area (PPA), by using the face/scene localizer, observing that two portions of the PPA-anterior and posterior PPA-were consistently activated in all subjects. Second, the rs-fc analysis (n = 77) revealed a connectivity pathway similar to the one described in macaques, showing separate connectivity routes linking the anterior PPA with RSC and HC, and the posterior PPA with OPA. Third, we used dynamic causal modelling to evaluate whether the dynamic couplings among these regions differ between perception and imagery of familiar landmarks during a fMRI task (n = 16). We found a positive effect of HC on RSC during the retrieval of imagined places and an effect of occipital regions on both RSC and pPPA during the perception of scenes. Overall, we propose that under similar functional architecture at rest, different neural interactions take place between regions in the occipito-temporal higher-level visual cortex and the HC, subserving scene perception and imagery.

PMID:37219891 | DOI:10.1002/hbm.26313

Cereb Cortex. 2023 May 22:bhad176. doi: 10.1093/cercor/bhad176. Online ahead of print.

ABSTRACT

Depression during pregnancy is common and the prevalence further increased during the COVID pandemic. Recent findings have shown potential impact of antenatal depression on children's neurodevelopment and behavior, but the underlying mechanisms are unclear. Nor is it clear whether mild depressive symptoms among pregnant women would impact the developing brain. In this study, 40 healthy pregnant women had their depressive symptoms evaluated by the Beck Depression Inventory-II at ~12, ~24, and ~36 weeks of pregnancy, and their healthy full-term newborns underwent a brain MRI without sedation including resting-state fMRI for evaluation of functional connectivity development. The relationships between functional connectivities and maternal Beck Depression Inventory-II scores were evaluated by Spearman's rank partial correlation tests using appropriate multiple comparison correction with newborn's gender and gestational age at birth controlled. Significant negative correlations were identified between neonatal brain functional connectivity and mother's Beck Depression Inventory-II scores in the third trimester, but not in the first or second trimester. Higher depressive symptoms during the third trimester of pregnancy were associated with lower neonatal brain functional connectivity in the frontal lobe and between frontal/temporal lobe and occipital lobe, indicating a potential impact of maternal depressive symptoms on offspring brain development, even in the absence of clinical depression.

PMID:37218652 | DOI:10.1093/cercor/bhad176

Network. 2023 May 22:1-16. doi: 10.1080/0954898X.2023.2215860. Online ahead of print.

ABSTRACT

BACKGROUND: The use of shorter TR and finer atlases in rs-fMRI can provide greater detail on brain function and anatomy. However, there is limited understanding of the effect of this combination on brain network properties.

METHODS: A study was conducted with 20 healthy young volunteers who underwent rs-fMRI scans with both shorter (0.5s) and long (2s) TR. Two atlases with different degrees of granularity (90 vs 200 regions) were used to extract rs-fMRI signals. Several network metrics, including small-worldness, Cp, Lp, Eloc, and Eg, were calculated. Two-factor ANOVA and two-sample t-tests were conducted for both the single spectrum and five sub-frequency bands.

RESULTS: The network constructed using the combination of shorter TR and finer atlas showed significant enhancements in Cp, Eloc, and Eg, as well as reductions in Lp and γ in both the single spectrum and subspectrum (p < 0.05, Bonferroni correction). Network properties in the 0.082-0.1 Hz frequency range were weaker than those in the 0.01-0.082 Hz range.

CONCLUSION: Our findings suggest that the use of shorter TR and finer atlas can positively affect the topological characteristics of brain networks. These insights can inform the development of brain network construction methods.

PMID:37218163 | DOI:10.1080/0954898X.2023.2215860

Brain Res. 2023 May 20:148418. doi: 10.1016/j.brainres.2023.148418. Online ahead of print.

ABSTRACT

The insula contributes to the detection of salient events during goal-directed behavior and participates in the coordination of motor, multisensory, and cognitive systems. Recent task-fMRI studies with trained singers suggest that singing experience can enhance the access to these resources. However, the long-term effects of vocal training on insula-based networks are still unknown. In this study, we employed resting-state fMRI to assess experience-dependent differences in insula co-activation patterns between conservatory-trained singers and non-singers. Results indicate enhanced bilateral anterior insula connectivity in singers relative to non-singers with constituents of the speech sensorimotor network. Specifically, with the cerebellum (lobule V-VI) and the superior parietal lobes. The reversed comparison showed no effects. The amount of accumulated singing training predicted enhanced bilateral insula co-activation with primary sensorimotor areas representing the diaphragm and the larynx/phonation area-crucial regions for cortico-motor control of complex vocalizations-as well as the bilateral thalamus and the left putamen. Together, these findings highlight the neuroplastic effect of expert singing training on insula-based networks, as evidenced by the association between enhanced insula co-activation profiles in singers and the brain's speech motor system components.

PMID:37217111 | DOI:10.1016/j.brainres.2023.148418

Front Psychiatry. 2023 May 5;14:1147540. doi: 10.3389/fpsyt.2023.1147540. eCollection 2023.

ABSTRACT

PURPOSE: Studies of the neural underpinnings of bipolar type I disorder have focused on the emotional control network. However, there is also growing evidence for cerebellar involvement, including abnormal structure, function, and metabolism. Here, we sought to assess functional connectivity of the cerebellar vermis with the cerebrum in bipolar disorder and to assess whether connectivity might depend on mood.

METHODS: This cross-sectional study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed a 3 T magnetic resonance imaging (MRI) study, which included anatomical as well as resting state Blood Oxygenation Level Dependent (BOLD) imaging. Functional connectivity of the cerebellar vermis to all other brain regions was assessed. Based on quality control metrics of the fMRI data, 109 participants with bipolar disorder and 79 controls were included in the statistical analysis comparing connectivity of the vermis. In addition, the data was explored for the potential impacts of mood, symptom burden, and medication in those with bipolar disorder.

RESULTS: Functional connectivity between the cerebellar vermis and the cerebrum was found to be aberrant in bipolar disorder. The connectivity of the vermis was found to be greater in bipolar disorder to regions involved in motor control and emotion (trending), while reduced connectivity was observed to a region associated with language production. In the participants with bipolar disorder, past depression symptom burden affected connectivity; however, no effects of medication were observed. Functional connectivity between the cerebellar vermis and all other regions revealed an inverse association with current mood ratings.

CONCLUSION: Together the findings may suggest that the cerebellum plays a compensatory role in bipolar disorder. The proximity of the cerebellar vermis to the skull may make this region a potential target for treatment with transcranial magnetic stimulation.

PMID:37215681 | PMC:PMC10196126 | DOI:10.3389/fpsyt.2023.1147540

bioRxiv. 2023 May 12:2023.05.11.540409. doi: 10.1101/2023.05.11.540409. Preprint.

ABSTRACT

Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain's control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT's effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.

PMID:37214949 | PMC:PMC10197635 | DOI:10.1101/2023.05.11.540409

Front Neurosci. 2023 May 4;17:1076824. doi: 10.3389/fnins.2023.1076824. eCollection 2023.

ABSTRACT

BACKGROUND: A variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or "scrubbing" volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection.

RESULTS: The data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed pre-processing scripts.

CONCLUSION: Visual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis.

PMID:37214404 | PMC:PMC10192849 | DOI:10.3389/fnins.2023.1076824

Front Neurosci. 2023 May 5;17:1147547. doi: 10.3389/fnins.2023.1147547. eCollection 2023.

ABSTRACT

INTRODUCTION: Deep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip. Here, we expand the technique by introducing a tetrahedral stimulation probe that enables adjustment of the primary electric field direction freely at any angle in a 3D space around the stimulating probe. OSS in 3D will enable better targeting of the electric field according to the local brain anatomy. We tested its utility in a rat model of DBS for treatment-resistant depression. The stimulation directed to the subgenual anterior cingulate cortex (sgACC) has yielded dramatic improvement in individual patients suffering from therapy resistant depression, but no consistent benefit in larger series. This failure has been ascribed to the challenging anatomy of sgACC with several crossing neural tracts and individual differences in the local anatomy.

METHODS: We stimulated infralimbic cortex (IL), the rat analog of sgACC, and recorded local electrical responses in amygdala (AMG) that is monosynaptically connected to IL and plays a central role in emotional states. We further traced AMG-IL connections using a viral vector and tractography using diffusion magnetic resonance imaging (MRI). Finally, we mimicked the clinical situation by delivering sustained 130 Hz stimulation at IL at the most effective field orientation and followed changes in resting-state functional connectivity with IL using functional MRI. To help interpretation of responses in functional connectivity, we stimulated only the left IL, which we did not expect to evoke measurable changes in the rat behavior.

RESULTS: The AMG evoked responses depended systematically on the IL stimulation field orientation and yielded the maximum response in near vertical field orientation in accordance with tractography. Sustained 130 Hz stimulation at a field orientation yielding the strongest AMG evoked responses increased functional connectivity between IL and AMG on the stimulation side.

CONCLUSION: These findings suggest that OSS in 3D provides a new approach to optimize the DBS for every individual patient with a single stimulation probe implantation.

PMID:37214391 | PMC:PMC10198377 | DOI:10.3389/fnins.2023.1147547

J Alzheimers Dis. 2023 May 19. doi: 10.3233/JAD-221163. Online ahead of print.

ABSTRACT

BACKGROUND: Olfactory identification dysfunction (OID) might be an early sign of amnestic mild cognitive impairment (aMCI). However, odor hedonics, the ability to perceive odor pleasantness, is neglected. Also, the neural substrate of OID remains unclear.

OBJECTIVE: To explore the characteristics of odor identification and hedonics in aMCI and examine the potential neural correlates of OID by analyzing olfactory functional connectivity (FC) patterns in MCI.

METHODS: Forty-five controls and 83 aMCI patients were examined. The Chinese smell identification test was used to assess olfaction. Global cognition, memory, and social cognition were assessed. Resting-state functional networks associated with olfactory cortex seeds were compared between the cognitively normal (CN) and aMCI groups, as well as between aMCI subgroups by the degree of OID.

RESULTS: Compared to controls, aMCI patients had a significant deficit in olfactory identification, mainly reflected in the identification of pleasant and neutral odors. aMCI patients also rated pleasant and neutral odors much lower than controls. A positive correlation between olfaction and social cognition was found in aMCI. The seed-based FC analysis found that aMCI patients had higher FC between the right orbitofrontal cortex and right frontal lobe/middle frontal gyrus than controls. Subgroup analysis showed that, compared to aMCI without OID, aMCI with severe OID had abnormal FC in the bilateral piriform region.

CONCLUSION: Our results suggest that OID in aMCI primarily refers to the identification of pleasant and neutral odors. The FC alterations in bilateral orbitofrontal cortex and piriform cortices might contribute to the impairment in odor identification.

PMID:37212099 | DOI:10.3233/JAD-221163

J Alzheimers Dis. 2023 May 12. doi: 10.3233/JAD-221133. Online ahead of print.

ABSTRACT

BACKGROUND: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk.

OBJECTIVE: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language.

METHODS: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups.

RESULTS: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance.

CONCLUSION: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects.

PMID:37212098 | DOI:10.3233/JAD-221133

Comput Biol Med. 2023 May 3;161:107005. doi: 10.1016/j.compbiomed.2023.107005. Online ahead of print.

ABSTRACT

Alzheimer's Disease (AZD) is a neurodegenerative disease for which there is now no known effective treatment. Mild cognitive impairment (MCI) is considered a precursor to AZD and affects cognitive abilities. Patients with MCI have the potential to recover cognitive health, can remain mildly cognitively impaired indefinitely or eventually progress to AZD. Identifying imaging-based predictive biomarkers for disease progression in patients presenting with evidence of very mild/questionable MCI (qMCI) can play an important role in triggering early dementia intervention. Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic resonance imaging (rs-fMRI) has been increasingly studied in brain disorder diseases. In this work, employing a recent developed a time-attention long short-term memory (TA-LSTM) network to classify multivariate time series data. A gradient-based interpretation framework, transiently-realized event classifier activation map (TEAM) is introduced to localize the group-defining "activated" time intervals over the full time series and generate the class difference map. To test the trustworthiness of TEAM, we did a simulation study to validate the model interpretative power of TEAM. We then applied this simulation-validated framework to a well-trained TA-LSTM model which predicts the progression or recovery from questionable/mild cognitive impairment (qMCI) subjects after three years from windowless wavelet-based dFNC (WWdFNC). The FNC class difference map points to potentially important predictive dynamic biomarkers. Moreover, the more highly time-solved dFNC (WWdFNC) achieves better performance in both TA-LSTM and a multivariate CNN model than dFNC based on windowed correlations between timeseries, suggesting that better temporally resolved measures can enhance the model's performance.

PMID:37211004 | DOI:10.1016/j.compbiomed.2023.107005