Most recent paper
Pre-operative Limbic System Functional Connectivity Distinguishes Responders From Non-responders to Surgical Treatment for Trigeminal Neuralgia
Front Neurol. 2021 Oct 4;12:716500. doi: 10.3389/fneur.2021.716500. eCollection 2021.
Background: Trigeminal neuralgia (TN) is a severe facial pain condition often requiring surgical treatment. Unfortunately, even technically successful surgery fails to achieve durable pain relief in many patients. The purpose of this study was to use resting-state functional magnetic resonance imaging (fMRI) to: (1) compare functional connectivity between limbic and accessory sensory networks in TN patients vs. healthy controls; and (2) determine if pre-operative variability in these networks can distinguish responders and non-responders to surgery for TN. Methods: We prospectively recruited 22 medically refractory classic or idiopathic TN patients undergoing surgical treatment over a 3-year period, and 19 age- and sex-matched healthy control subjects. fMRI was acquired within the month prior to surgery for all TN patients and at any time during the study period for controls. Functional connectivity analysis was restricted to six pain-relevant brain regions selected a priori: anterior cingulate cortex (ACC), posterior cingulate cortex, hippocampus, amygdala, thalamus, and insula. Two comparisons were performed: (1) TN vs. controls; and (2) responders vs. non-responders to surgical treatment for TN. Functional connectivity was assessed with a two-sample t-test, using a statistical significance threshold of p < 0.050 with false discovery rate (FDR) correction for multiple comparisons. Results: Pre-operative functional connectivity was increased in TN patients compared to controls between the right insular cortex and both the left thalamus [t (39) = 3.67, p = 0.0007] and right thalamus [t (39) = 3.22, p = 0.0026]. TN patients who were non-responders to surgery displayed increased functional connectivity between limbic structures, including between the left and right hippocampus [t (18) = 2.85, p = 0.0106], and decreased functional connectivity between the ACC and both the left amygdala [t (18) = 2.94, p = 0.0087] and right hippocampus [t (18) = 3.20, p = 0.0049]. Across all TN patients, duration of illness was negatively correlated with connectivity between the ACC and left amygdala (r 2 = 0.34, p = 0.00437) as well as the ACC and right hippocampus (r 2 = 0.21, p = 0.0318). Conclusions: TN patients show significant functional connectivity abnormalities in sensory-salience regions. However, variations in the strength of functional connectivity in limbic networks may explain why some TN patients fail to respond adequately to surgery.
Regulatory Effects of Acupuncture on Emotional Disorders in Patients With Menstrual Migraine Without Aura: A Resting-State fMRI Study
Front Neurosci. 2021 Oct 4;15:726505. doi: 10.3389/fnins.2021.726505. eCollection 2021.
Background: Menstrual migraine without aura (MMoA) refers to a specific type of migraine that is associated with the female ovarian cycle. It is particularly serious and has brought huge life pressure and mental burden to female patients. Acupuncture has been commonly used to prevent migraines and relieve concomitant emotional disorders; however, the physiological mechanism underlying this intervention remains unclear. This study aimed to use resting-state functional magnetic resonance imaging (rsfMRI) to investigate whether acupuncture can modulate brain function and if the potential influence on brain activity correlates with improving emotional symptoms in MMoA patients. Methods: Overall, 44 patients were randomly divided into a true acupuncture (TA) group and the sham acupuncture (SA) group. Patients underwent rsfMRI before and after 3-month treatment, the amplitude of low-frequency fuctuations (ALFF) and regional homogeneity (ReHo) in rsfMRI were calculated. Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), frequency of migraine attacks, visual analog scale, and intensity of the migraine were used for evaluate the clinical effect. The clinical changes of variables were also used to further assess the correlation with brain activity in MMoA patients. Results: After acupuncture treatment, the emotional symptoms of both groups of patients improved, and the clinical symptoms of migraine were alleviated. The major finding of our study was that patients with MMoA showed lower ALFF value in the left anterior cingulate and the value was positively correlated with the decreases in the SAS and SDS scores. In the SA group, common brain regions responded both in ALFF and regional homogeneity values mainly in the insula, and no significant correlations were observed between brain regions and clinical variables. Conclusions: These results indicated that both two acupuncture treatments were helpful in treating migraine and could improve emotion symptoms. TA had a relatively better effect in reducing the frequency of migraine attack than SA. The two therapies have different modulation effects as TA regulates emotional disorders by modulating the frontal-limbic regions, and SA may modulate pain perception through the placebo effect on insula and by indirectly regulating emotional disorders. These findings provided evidence that acupuncture is a complementary and alternative therapy to relieve clinical symptoms in female patients with migraines and could help enhance clinical diagnosis and treatment. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR-IOR-15006648. Registered 23 June 2015].
Brain network effects by continuous theta burst stimulation in Mal de Debarquement Syndrome: simultaneous EEG and fMRI study
J Neural Eng. 2021 Oct 20. doi: 10.1088/1741-2552/ac314b. Online ahead of print.
OBJECTIVE: Heterogeneous clinical responses to treatment with non-invasive brain stimulation are commonly observed, making it necessary to determine personally optimized stimulation parameters. We investigated neuroimaging markers of effective brain targets of treatment with continuous theta burst stimulation (cTBS) in Mal de Débarquement Syndrome (MdDS), a balance disorder of persistent oscillating vertigo previously shown to exhibit abnormal intrinsic functional connectivity.
APPROACH: Twenty-four right-handed, cTBS-naive individuals with MdDS received single administrations of cTBS over one of three stimulation targets in randomized order. The optimal target was determined based on the assessment of acute changes after the administration of cTBS over each target. Repetitive cTBS sessions were delivered on three consecutive days with the optimal target chosen by the participant. EEG was recorded at single-administration test sessions of cTBS. Simultaneous EEG and fMRI data were acquired at baseline and after completion of 10-12 sessions. Network connectivity changes after single and repetitive stimulations of cTBS were analyzed.
MAIN RESULTS: Using electrophysiological source imaging and a data-driven method, we identified network-level connectivity changes in EEG that correlated with symptom responses after completion of multiple sessions of cTBS. We further determined that connectivity changes demonstrated by EEG during test sessions of single administrations of cTBS were signatures that could predict optimal targets.
SIGNIFICANCE: Our findings demonstrate the effect of cTBS on resting state brain networks and suggest an imaging-based, closed-loop stimulation paradigm that can identify optimal targets during short-term test sessions of stimulation. ClinicalTrials.gov Identifier: NCT02470377.
Neuroimaging Systematic Review in Persistent Postural-Perceptual Dizziness: The Elaborate Alterations in the Delicate Network to Remain Balanced
Otol Neurotol. 2021 Oct 20. doi: 10.1097/MAO.0000000000003389. Online ahead of print.
OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder that may have normal physical examination, clinical laboratory testing and vestibular evaluation. However, advances in neuroimaging have provided new insights in brain functional connectivity and structure in patients with PPPD. This systematic review was aimed at identifying significant structural or alterations in functional connectivity in patients with PPPD.
DATABASES REVIEWED: Science Direct, Pubmed, Embase via Ovid databases, and Cochrane library.
METHODS: This review following the guidelines of PRISMA, systematically and independently examined papers published up to March 2021 which fulfilled the predetermined criteria. PROSPERO Registration (CRD42020222334).
RESULTS: A total of 15 studies were included (MRI = 4, SPECT = 1, resting state fMRI = 4, task-based fMRI = 5, task-based fMRI + MRI = 1). Significant changes in the gray matter volume, cortical folding, blood flow, and connectivity were seen at different brain regions involved in vestibular, visual, emotion, and motor processing.
CONCLUSION: There is a multisensory dimension to the impairment resulting in chronic compensatory changes in PPPD that is evident by the significant alterations in multiple networks involved in maintaining balance. These changes observed offer some explanation for the symptoms that a PPPD patient may experience.Systematic Review Registration: This study is registered with PROSPERO (CRD42020222334).
mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity
Nat Commun. 2021 Oct 19;12(1):6084. doi: 10.1038/s41467-021-26131-z.
Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI). These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism.
The amplitude of low-frequency fluctuation predicts levodopa treatment response in patients with Parkinson's disease
Parkinsonism Relat Disord. 2021 Oct 6;92:26-32. doi: 10.1016/j.parkreldis.2021.10.003. Online ahead of print.
INTRODUCTION: Levodopa has become the main therapy for motor symptoms of Parkinson's disease (PD). This study aimed to test whether the amplitude of low-frequency fluctuation (ALFF) computed by fMRI could predict individual patient's response to levodopa treatment.
METHODS: We included 40 patients. Treatment efficacy was defined based on motor symptoms improvement from the state of medication off to medication on, as assessed by the Unified Parkinson's Disease Rating Scale score III. Two machine learning models were constructed to test the prediction ability of ALFF. First, the ensemble method was implemented to predict individual treatment responses. Second, the categorical boosting (CatBoost) classification was used to predict individual levodopa responses in patients classified as moderate and superior responders, according to the 50% threshold of improvement. The age, disease duration and treatment dose were controlled as covariates.
RESULTS: No significant difference in clinical data were observed between moderate and superior responders. Using the ensemble method, the regression model showed a significant correlation between the predicted and the observed motor symptoms improvement (r = 0.61, p < 0.01, mean absolute error = 0.11 ± 0.02), measured as a continuous variable. The use of the Catboost algorithm revealed that ALFF was able to differentiate between moderate and superior responders (area under the curve = 0.90). The mainly contributed regions for both models included the bilateral primary motor cortex, the occipital cortex, the cerebellum, and the basal ganglia.
CONCLUSION: Both continuous and binary ALFF values have the potential to serve as promising predictive markers of dopaminergic therapy response in patients with PD.
Impact of App-Delivered Mindfulness Meditation on Functional Connectivity, Mental Health, and Sleep Disturbances Among Physician Assistant Students: Randomized, Wait-list Controlled Pilot Study
JMIR Form Res. 2021 Oct 19;5(10):e24208. doi: 10.2196/24208.
BACKGROUND: Health care provider and trainee burnout results in substantial national and institutional costs and profound social effects. Identifying effective solutions and interventions to cultivate resilience among health care trainees is critical. Although less is known about the mental health needs of physician assistants (PAs) or PA students, accumulating research indicates that they experience similarly alarming rates of burnout, depression, and emotional exhaustion. Mobile app-delivered mindfulness meditation may be an effective part of salubrious programming to bolster long-term resilience and health among PA students.
OBJECTIVE: This study aims to examine the impact of app-delivered mindfulness meditation on self-reported mental health symptoms among PA students. A secondary aim is to investigate changes in brain connectivity to identify neurobiological changes related to changes in mental health symptoms.
METHODS: We recruited PA students enrolled in their third semester of PA school and used a longitudinal, randomized, wait-list-controlled design. Participants randomized to the mindfulness group were provided 1-year subscriptions to the 10% Happier app, a consumer-based meditation app, and asked to practice every day for 8 weeks. Before randomization and again after completion of the 8-week program, all participants completed resting-state functional magnetic resonance imaging as well as self-report assessments of burnout, depression, anxiety, and sleep impairment. App use was acquired as a measure of mindfulness practice time.
RESULTS: PA students randomized to the mindfulness group reported improvements in sleep impairment compared with those randomized to the wait-list control group (ηp2=0.42; P=.01). Sleep impairment decreased significantly in the mindfulness group (19% reduction; P=.006) but not in the control group (1% reduction; P=.71). There were no other significant changes in mental health for those randomized to app-delivered mindfulness. Across all students, changes in sleep impairment were associated with increased resting-state functional connectivity between the medial prefrontal cortex (a component of the default mode network) and the superior temporal gyrus, as well as between areas important for working memory. Changes in connectivity predicted categorical conversion from impaired to nonimpaired sleep in the mindfulness group.
CONCLUSIONS: This pilot study is the first to examine app-based mindfulness for PA students' mental health and investigate the impact of mindfulness on PA students' brain function. These findings suggest that app-delivered mindfulness may be an effective tool to improve sleep dysfunction and that it may be an important part of the programming necessary to reduce the epidemic of suffering among health profession trainees.
Changes in cognitive and behavioral control after lamotrigine and intensive dialectical behavioral therapy for severe, multi-impulsive bulimia nervosa: an fMRI case study
Eat Weight Disord. 2021 Oct 18. doi: 10.1007/s40519-021-01308-z. Online ahead of print.
PURPOSE: Adults with bulimia nervosa (BN) and co-occurring emotional dysregulation and multiple impulsive behaviors are less responsive to existing interventions. Initial data suggest that the combination of Dialectical Behavior Therapy (DBT) and a mood stabilizer, lamotrigine, significantly reduces symptoms of affective and behavioral dysregulation in these patients. Identifying candidate neurobiological mechanisms of change for this novel treatment combination may help guide future randomized controlled trials and inform new and targeted treatment development. Here, we examined neurocognitive and symptom changes in a female patient with BN and severe affective and behavioral dysregulation who received DBT and lamotrigine.
METHODS: Go/no-go task performance data and resting-state functional MRI scans were acquired before the initiation of lamotrigine (after 6 weeks in an intensive DBT program), and again after reaching and maintaining a stable dose of lamotrigine. The patient completed a battery of symptom measures biweekly for 18 weeks over the course of treatment.
RESULTS: After lamotrigine initiation, the patient made fewer errors on a response inhibition task and showed increased and new connectivity within frontoparietal and frontolimbic networks involved in behavioral and affective control. Accompanying this symptom improvement, the patient reported marked reductions in bulimic symptoms, behavioral dysregulation, and reactivity to negative affect, along with increases in DBT skills use.
CONCLUSION: Improved response inhibition and cognitive control network connectivity should be further investigated as neurocognitive mechanisms of change with combined DBT and lamotrigine for eating disorders. Longitudinal, controlled trials integrating neuroimaging and symptom measures are needed to fully evaluate the effects of this treatment.
LEVEL OF EVIDENCE: IV: Evidence obtained from multiple time series with or without the intervention, such as case studies.
Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction
Neural Plast. 2021 Oct 8;2021:7031178. doi: 10.1155/2021/7031178. eCollection 2021.
Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.
Altered Functional Connectivity of the Nucleus Accumbens Network Between Deficit and Non-deficit Schizophrenia
Front Psychiatry. 2021 Sep 30;12:704631. doi: 10.3389/fpsyt.2021.704631. eCollection 2021.
Deficit schizophrenia (DS), which is marked by stable negative symptoms, is regarded as a homogeneous subgroup of schizophrenia. While DS patients have structurally altered nucleus accumbens (NAcc) compared to non-deficit schizophrenia (NDS) patients and healthy individuals, the investigation of NAcc functional connectivity (FC) with negative symptoms and neurocognition could provide insights into the pathophysiology of schizophrenia. 58 DS, 93 NDS, and 113 healthy controls (HCs) underwent resting-state functional magnetic resonance (rsfMRI). The right and left NAcc were respectively used as seed points to construct the functional NAcc network in whole-brain FC analysis. ANCOVA compared the differences in NAcc network FC and partial correlation analysis explored the relationships between altered FC of NAcc, negative symptoms and neurocognition. Compared to HCs, both DS and NDS patients showed decreased FC between the left NAcc (LNAcc) and bilateral middle cingulate gyrus, and between the right NAcc (RNAcc) and right middle frontal gyrus (RMFG), as well as increased FC between bilateral NAcc and bilateral lingual gyrus. Moreover, the FC between the LNAcc and bilateral calcarine gyrus (CAL) was lower in the DS group compared to NDS patients. Correlation analysis indicated that FC value of LNAcc-CAL was negatively correlated to negative symptoms. Furthermore, aberrant FC values within the NAcc network were correlated with severity of clinical symptoms and neurocognitive impairments in DS and NDS patients. This study demonstrated abnormal patterns of FC in the NAcc network between DS and NDS. The presence of altered LNAcc-CAL FC might be involved in the pathogenesis of negative symptoms in schizophrenia.
Altered Brain Functional Connectivity at Resting-State in Patients With Non-arteritic Anterior Ischemic Optic Neuropathy
Front Neurosci. 2021 Oct 1;15:712256. doi: 10.3389/fnins.2021.712256. eCollection 2021.
Purpose: To investigate the possible changes in functional connectivity (FC) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) using resting-state functional MRI (fMRI). Methods: Thirty-one NAION patients and 31 healthy controls were recruited and underwent resting-state fMRI scans. Regions of interest (ROIs) were defined as bilateral Brodmann's area 17 (BA17). FC analysis was performed between the ROIs and the rest of the brain regions, and the between group comparisons of FC were performed. We conducted correlation analysis between the FC changes and the clinical variables in NAION patients. Results: Compared with healthy controls, patients with NAION showed significantly decreased FC between the left BA17 and the right inferior frontal gyrus, left caudate nucleus. As for the right BA17, patients exhibited significantly increased FC with the left olfactory gyrus and decreased FC with the right superior frontal gyrus (SFG), right insula. Moreover, FC values between the right insula and the right BA17 were positively correlated with the right side of mean sensitivity in the central visual field (r = 0.52, P < 0.01) and negatively correlated with the right side of mean defect in the central visual field (r = -0.55, P < 0.01). Conclusion: Our study indicated that patients with NAION showed significantly abnormal functional reorganization between the primary visual cortex and several other brain regions not directly related to visual function, which supports that NAION may not only be an ophthalmic disease but also a neuro-ophthalmological disease.
Front Neurosci. 2021 Oct 1;15:688247. doi: 10.3389/fnins.2021.688247. eCollection 2021.
Background: Sleep deprivation can markedly influence vigilant attention that is essential to complex cognitive processes. The hypothalamus plays a critical role in arousal and attention regulation. However, the functional involvement of the hypothalamus in attentional impairments after total sleep deprivation (TSD) remains unclear. The purpose of this study is to investigate the alterations in hypothalamic functional connectivity and its association with the attentional performance following TSD. Methods: Thirty healthy adult males were recruited in the study. Participants underwent two resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI for the left and right hypothalamus. Vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered hypothalamic functional connectivity and PVT performance after TSD. Results: After TSD, enhanced functional connectivity was observed between the left hypothalamus and bilateral thalamus, bilateral anterior cingulate cortex, right amygdala, and right insula, while reduced functional connectivity was observed between the left hypothalamus and bilateral middle frontal gyrus (AlphaSim corrected, P < 0.01). However, significant correlation between altered hypothalamic functional connectivity and PVT performance was not observed after Bonferroni correction (P > 0.05). Conclusion: Our results suggest that TSD can lead to disrupted hypothalamic circuits, which may provide new insight into neural mechanisms of attention impairments following sleep deprivation.
Differences in Functional Brain Networks Between Subjective Cognitive Decline with and without Worry Groups: A Graph Theory Study from SILCODE
J Alzheimers Dis. 2021 Oct 10. doi: 10.3233/JAD-215156. Online ahead of print.
BACKGROUND: Evidence suggests that subjective cognitive decline (SCD) individuals with worry have a higher risk of cognitive decline. However, how SCD-related worry influences the functional brain network is still unknown.
OBJECTIVE: In this study, we aimed to explore the differences in functional brain networks between SCD subjects with and without worry.
METHODS: A total of 228 participants were enrolled from the Sino Longitudinal Study on Cognitive Decline (SILCODE), including 39 normal control (NC) subjects, 117 SCD subjects with worry, and 72 SCD subjects without worry. All subjects completed neuropsychological assessments, APOE genotyping, and resting-state functional magnetic resonance imaging (rs-fMRI). Graph theory was applied for functional brain network analysis based on both the whole brain and default mode network (DMN). Parameters including the clustering coefficient, shortest path length, local efficiency, and global efficiency were calculated. Two-sample T-tests and chi-square tests were used to analyze differences between two groups. In addition, a false discovery rate-corrected post hoc test was applied.
RESULTS: Our analysis showed that compared to the SCD without worry group, SCD with worry group had significantly increased functional connectivity and shortest path length (p = 0.002) and a decreased clustering coefficient (p = 0.013), global efficiency (p = 0.001), and local efficiency (p < 0.001). The above results appeared in both the whole brain and DMN.
CONCLUSION: There were significant differences in functional brain networks between SCD individuals with and without worry. We speculated that worry might result in alterations of the functional brain network for SCD individuals and then result in a higher risk of cognitive decline.
Problem-solving training modifies cognitive functioning and related functional connectivity in healthy adults
Neuropsychol Rehabil. 2021 Oct 17:1-36. doi: 10.1080/09602011.2021.1987277. Online ahead of print.
Cognitive functioning evolves throughout life. Regular practice of stimulating activities maintains or even strengthens cognitive skills. This study investigated the effects of a cognitive training programme based on complex closed-ended problem solving on innovative thinking. To this end, using partial least squares variance-based structural equation modeling, we first evaluated in 83 healthy adults how inhibition, cognitive flexibility, and reasoning were related to the distinct dimensions of innovative thinking. Second, we assessed how these interactions were modified after cognitive training based on problem solving in a subgroup of 16 subjects compared to leisure activity based on crossword solving in another subgroup of 15 subjects. Third, in a pilot fMRI study, we evaluated changes in brain connectivity at rest as a result of training in the problem solving group. Data on cognitive measures showed that innovative thinking was influenced by reasoning in control subjects, whereas it was influenced by cognitive flexibility following problem-solving training. These findings highlight that a cognitive intervention based on complex closed-ended problem solving promotes innovative thinking by changing the way subjects recruit and use relevant cognitive processes. Modifications in the resting-state connectivity of attention, default mode and visual networks were observed in the problem solving group.
Investigating mechanisms of fast BOLD responses: the effects of stimulus intensity and of spatial heterogeneity of hemodynamics
Neuroimage. 2021 Oct 14:118658. doi: 10.1016/j.neuroimage.2021.118658. Online ahead of print.
Recent studies have demonstrated that fast fMRI can track neural activity well above the temporal limit predicted by the canonical hemodynamic response model. While these findings are promising, the biophysical mechanisms underlying these fast fMRI phenomena remain underexplored. In this study, we discuss two aspects of the hemodynamic response, complementary to several existing hypotheses, that can accommodate faster fMRI dynamics beyond those predicted by the canonical model. First, we demonstrate, using both visual and somatosensory paradigms, that the timing and shape of hemodynamic response functions (HRFs) vary across graded levels of stimulus intensity-with lower-intensity stimulation eliciting faster and narrower HRFs. Second, we show that as the spatial resolution of fMRI increases, voxel-wise HRFs begin to deviate from the canonical model, with a considerable portion of voxels exhibiting faster temporal dynamics than predicted by the canonical HRF. Collectively, both stimulus/task intensity and image resolution can affect the sensitivity of fMRI to fast brain activity, which may partly explain recent observations of fast fMRI signals. It is further noteworthy that, while the present investigations focus on fast neural responses, our findings suggest that a revised hemodynamic model may benefit the many fMRI studies using paradigms with wide ranges of contrast levels (e.g., resting or naturalistic conditions) or with modern, high-resolution MR acquisitions.
Hum Brain Mapp. 2021 Oct 16. doi: 10.1002/hbm.25679. Online ahead of print.
Emerging studies corroborate the importance of neuroimaging biomarkers and machine learning to improve diagnostic classification of amyotrophic lateral sclerosis (ALS). While most studies focus on structural data, recent studies assessing functional connectivity between brain regions by linear methods highlight the role of brain function. These studies have yet to be combined with brain structure and nonlinear functional features. We investigate the role of linear and nonlinear functional brain features, and the benefit of combining brain structure and function for ALS classification. ALS patients (N = 97) and healthy controls (N = 59) underwent structural and functional resting state magnetic resonance imaging. Based on key hubs of resting state networks, we defined three feature sets comprising brain volume, resting state functional connectivity (rsFC), as well as (nonlinear) resting state dynamics assessed via recurrent neural networks. Unimodal and multimodal random forest classifiers were built to classify ALS. Out-of-sample prediction errors were assessed via five-fold cross-validation. Unimodal classifiers achieved a classification accuracy of 56.35-61.66%. Multimodal classifiers outperformed unimodal classifiers achieving accuracies of 62.85-66.82%. Evaluating the ranking of individual features' importance scores across all classifiers revealed that rsFC features were most dominant in classification. While univariate analyses revealed reduced rsFC in ALS patients, functional features more generally indicated deficits in information integration across resting state brain networks in ALS. The present work undermines that combining brain structure and function provides an additional benefit to diagnostic classification, as indicated by multimodal classifiers, while emphasizing the importance of capturing both linear and nonlinear functional brain properties to identify discriminative biomarkers of ALS.
Brain Cogn. 2021 Oct 13;154:105806. doi: 10.1016/j.bandc.2021.105806. Online ahead of print.
Attention function is thought to be important in chronic pain, with the pathology of chronic pain closely associated with cognitive-emotional components. However, there have been few neuroimaging studies of the relationship between attention function and chronic pain. We used the method of functional connectivity analysis for resting-state fMRI (rs-fMRI) data and the Attention Network Test-Revision (ANT-R) to clarify the attention-related pathology of chronic pain. We performed rs-fMRI and ANT-R on a group of 26 chronic pain (somatoform pain disorder) patients and 28 age-matched healthy controls. A significant group difference in validity effects, a component of ANT-R, emerged (F1,46 = 5.91, p = 0.019), and the chronic pain group exhibited slower reaction times. Decreased brain connectivity of the left insula and left frontal regions was confirmed in chronic pain patients (pFWE < 0.05), and connectivity was negatively correlated with validity effects (r = -0.29, permutation test p = 0.033). Further, decreased functional connectivity strength of the right insula and left temporal gyrus in the chronic pain group were confirmed (pFWE < 0.05). We conclude that poor control of attention function results from deficits of functional connectivity in the left insula and left frontal regions in chronic pain.
Neurosci Biobehav Rev. 2021 Oct 13:S0149-7634(21)00455-3. doi: 10.1016/j.neubiorev.2021.10.013. Online ahead of print.
The number of studies investigating exercise and cardiorespiratory fitness (CRF)-related changes in the functional and structural organization of brain networks continues to rise. Functional and structural connectivity are critical biomarkers for brain health and many exercise-related benefits on the brain are better represented by network dynamics. Here, we reviewed neuroimaging literature to better understand of how exercise or CRF may facilitate and maintain the efficiency and integrity of functional and structural aspects of brain networks in both younger and older adults. Converging evidence suggests that increased exercise performance and CRF modulate functional connectivity of the brain in a way that corresponds to behavioral changes such as cognitive and motor performance improvements. Similarly, greater physical activity levels and CRF are associated with better cognitive and motor function, which may be brought about by enhanced structural network integrity. This review will provide a comprehensive understanding of trends in exercise-network studies as well as future directions based on the gaps in knowledge that are currently present in the literature.
Tormenting thoughts: The posterior cingulate sulcus of the default mode network regulates valence of thoughts and activity in the brain's pain network during music listening
Hum Brain Mapp. 2021 Oct 15. doi: 10.1002/hbm.25686. Online ahead of print.
Many individuals spend a significant amount of their time "mind-wandering". Mind-wandering often includes spontaneous, nonintentional thought, and a neural correlate of this kind of thought is the default mode network (DMN). Thoughts during mind-wandering can have positive or negative valence, but only little is known about the neural correlates of positive or negative thoughts. We used resting-state functional magnetic resonance imaging (fMRI) and music to evoke mind-wandering in n = 33 participants, with positive-sounding music eliciting thoughts with more positive valence and negative-sounding music eliciting thoughts with more negative valence. Applying purely data-driven analysis methods, we show that medial orbitofrontal cortex (mOFC, part of the ventromedial prefrontal cortex) and the posterior cingulate sulcus (likely area 23c of the posterior cingulate cortex), two sub-regions of the DMN, modulate the valence of thought-contents during mind-wandering. In addition, across two independent experiments, we observed that the posterior cingulate sulcus, a region involved in pain, shows valence-specific functional connectivity with core regions of the brain's putative pain network. Our results suggest that two DMN regions (mOFC and posterior cingulate sulcus) support the formation of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful.
Functional Brain Imaging During Extra-Ocular Light Stimulation in Anophthalmic and Sighted Participants: No Evidence for Extra-Ocular Photosensitive Receptors
Front Neurosci. 2021 Sep 28;15:744543. doi: 10.3389/fnins.2021.744543. eCollection 2021.
Light plays a critical role in regulating physiology and behavior, including both visual and non-visual responses. In mammals, loss of both eyes abolishes all of these responses, demonstrating that the photoreceptors involved are exclusively ocular. By contrast, many non-mammalian species possess extra-ocular photoreceptors located in the pineal complex and deep brain. Whilst there have been suggestions of extra-ocular photoreception in mammals, including man, evidence for these photoreceptors is limited. One approach to objectively determine the presence of such receptors is to measure brain responses to light using functional magnetic resonance imaging (fMRI). Moreover, by using participants who are clinically anophthalmic (congenital and acquired), it is possible to investigate potential light detection in the absence of the retina. Here we scanned participants with anophthalmia and sighted participants in 4 different conditions; the first 3 conditions had a bright light source applied to the following locations: behind the right ear ("ear"), just below the nasal bridge and between the eyes ("head"), and at the right popliteal fossa ("knee"). In the fourth and final scan, the light source was switched off so that there was no light stimulus. All participants were scanned in a completely dark room. No consistent brain activity was detected during any of the light conditions in either sighted controls or anophthalmic participants. Thus, we do not provide any evidence for the presence of extraocular photoreceptors modulating human brain activity, despite recent evidence for gene transcription that may occur as a result of these photoreceptors.