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Targeting the centromedian thalamic nucleus for deep brain stimulation.

Sun, 01/26/2020 - 16:00
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Targeting the centromedian thalamic nucleus for deep brain stimulation.

J Neurol Neurosurg Psychiatry. 2020 Jan 24;:

Authors: Warren AEL, Dalic LJ, Thevathasan W, Roten A, Bulluss KJ, Archer J

Abstract
OBJECTIVES: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI).
METHODS: 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest.
RESULTS: The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex.
CONCLUSIONS: In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.

PMID: 31980515 [PubMed - as supplied by publisher]

Patterns of olfactory functional networks in Parkinson's disease dementia and Alzheimer's dementia.

Sun, 01/26/2020 - 16:00
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Patterns of olfactory functional networks in Parkinson's disease dementia and Alzheimer's dementia.

Neurobiol Aging. 2019 Dec 30;:

Authors: Lee YH, Bak Y, Park CH, Chung SJ, Yoo HS, Baik K, Jung JH, Sohn YH, Shin NY, Lee PH

Abstract
Hyposmia is common in Alzheimer's dementia (AD) and Parkinson's disease dementia (PDD). We evaluated the pattern of olfactory functional connectivity (FC) in AD and PDD to uncover neural correlates that are related to olfactory dysfunction. This study enrolled 57 patients with AD and PDD and 25 control subjects. Using a seed-based approach, we compared the resting-state network from the seed-region-of-interest in the olfactory bulb, olfactory tract, piriform cortex, and orbitofrontal cortex (OFC) between groups. The PDD group showed lower FC with striatal-thalamic-frontal regions from the olfactory bulb than the AD group. The PDD group showed lower FC from left OFC with striatal-frontal regions and lower FC from right OFC with left fronto-temporal areas than the AD group. In a correlation analysis, the FC from left OFC with right insula that differed between the PDD and control groups was positively correlated with olfactory function. The present study demonstrated that this distinct olfactory functional network pattern may represent different neural mechanisms for olfactory dysfunction in AD and PDD.

PMID: 31980278 [PubMed - as supplied by publisher]

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Sat, 01/25/2020 - 15:20
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Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Neuroimage Clin. 2020 Jan 14;25:102182

Authors: Broadhouse KM, Singh MF, Suo C, Gates N, Wen W, Brodaty H, Jain N, Wilson GC, Meiklejohn J, Singh N, Baune BT, Baker M, Foroughi N, Wang Y, Kochan N, Ashton K, Brown M, Li Z, Mavros Y, Sachdev PS, J Valenzuela M

Abstract
Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

PMID: 31978826 [PubMed - as supplied by publisher]

Resting-state effective connectivity in the motive circuit of methamphetamine users: a case controlled fMRI study.

Sat, 01/25/2020 - 15:20
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Resting-state effective connectivity in the motive circuit of methamphetamine users: a case controlled fMRI study.

Behav Brain Res. 2020 Jan 21;:112498

Authors: Siyah Mansoory M, Farnia V

Abstract
Methamphetamine (MA) and other psychostimulants target the motive circuit of the brain, which is involved in reward, behavioral sensitization, and relapse to drug-seeking/taking behavior. In spite of this fact, the data regarding the effective connectivity (EC) in this circuit among MA users is scarce. The present study aimed to assess resting-state EC in the motive circuit of MA users during abstinence using the fMRI technique. Seventeen MA users after abstinence and 18 normal controls were examined using a 3 T Siemens fMRI scanner. After extracting time series of the motive circuit, EC differences in the motive circuit were analyzed using dynamic causal modeling (DCM). The findings revealed that abstinent MA users had an enhanced EC from the prefrontal cortex (PFC) to the ventral palladium (VP) (PFC→VP) and on the mediodorsal thalamus (MD) self-loop (MD→MD), but they showed a decreased connectivity on the VP self-loop (VP→VP) compared to healthy controls. The findings suggest that abstinent MA users may suffer from a limited pathology in connectivity within the motive circuit involved in reward, behavioral sensitization, and relapse. The enhanced PFC→VP seems to be a compensatory mechanism to control or regulate the subcortical regions involved in reward and behavioral sensitization. Furthermore, the enhanced connectivity on the MD self-loop and the decreased connectivity on the VP self-loop in abstinent MA users may, at least partially, affect the output of the limbic system, which can be seen in the behavioral sensitization and relapse processes. Nonetheless, further investigation in this area is strongly recommended to elucidate the exact mechanisms involved.

PMID: 31978492 [PubMed - as supplied by publisher]

Weighted average of shared trajectory: a new estimator for dynamic functional connectivity efficiently estimates both rapid and slow changes over time.

Sat, 01/25/2020 - 15:20
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Weighted average of shared trajectory: a new estimator for dynamic functional connectivity efficiently estimates both rapid and slow changes over time.

J Neurosci Methods. 2020 Jan 21;:108600

Authors: Faghiri A, Iraji A, Damaraju E, Belger A, Ford J, Mathalon D, Mcewen S, Mueller B, Pearlson G, Preda A, Turner J, Vaidya JG, Van Erp T, Calhoun VD

Abstract
BACKGROUND: Dynamic functional network connectivity (dFNC) of the brain has attracted considerable attention recently. Many approaches have been suggested to study dFNC with sliding window Pearson correlation (SWPC) being the most well-known. SWPC needs a relatively large sample size to reach a robust estimation but using large window sizes prevents us to detect rapid changes in dFNC.
NEW METHOD: Here we first calculate the gradients of each time series pair and use the magnitude of these gradients to calculate weighted average of shared trajectory (WAST) as a new estimator for dFNC.
RESULTS: Using WAST to compare healthy control and schizophrenia patients using a large dataset, we show disconnectivity between different regions associated with schizophrenia. In addition, WAST results reveals patients with schizophrenia stay longer in a connectivity state with negative connectivity between motor and sensory regions than do healthy controls.
COMPARISON WITH EXISTING METHODS: We compare WAST with SWPC and multiplication of temporal derivatives (MTD) using different simulation scenarios. We show that WAST enables us to detect very rapid changes in dFNC (undetected by SWPC) while MTD performance is generally lower.
CONCLUSIONS: As large window sizes are unable to detect short states, using shorter window size is desirable if the estimator is robust enough. We provide evidence that WAST requires fewer samples (compared to SWPC) to reach a robust estimation. As a result, we were able to identify rapidly varying dFNC patterns undetected by SWPC while still being able to robustly estimate slower dFNC patterns.

PMID: 31978489 [PubMed - as supplied by publisher]

Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress.

Sat, 01/25/2020 - 15:20
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Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress.

NMR Biomed. 2020 Jan 24;:e4248

Authors: Sampath S, Parimal AS, Huang W, Manigbas E, Gsell W, Chang MML, Qiu A, Jacobsen K, Evelhoch JL, Chin CL

Abstract
Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τi ) has been shown to be partially inversely related to Na, K-ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τi using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman primate (NHP) heart and evaluate its region-specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naïve cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual-bolus DCE and tagging MRI experiments. The shutter-speed model was employed to quantify regional τi from the DCE-MR images. Additionally, τi values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τi (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (-15.4% ± 2.7% vs -10.1% ± 2.9% at rest, P < 0.05). Specifically, slice-level analysis further revealed that a greater significant decrease in mean τi was observed in the apical region (ΔτI = 182.4 ms) compared with the basal (Δτi = 113.2 ms) and midventricular regions (Δτi = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τi in the anterior (Δτi = 243.9 ms) and antero-lateral (Δτi = 177.2 ms) regions. In the inferior and infero-septal regions, although a decrease in τi was observed, it was not significant. Whole heart regional quantification of τi is feasible using DCE-MRI. τi is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.

PMID: 31977123 [PubMed - as supplied by publisher]

Human hippocampal CA3 damage disrupts both recent and remote episodic memories.

Sat, 01/25/2020 - 15:20
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Human hippocampal CA3 damage disrupts both recent and remote episodic memories.

Elife. 2020 Jan 24;9:

Authors: Miller TD, Chong TT, Aimola Davies AM, Johnson MR, Irani SR, Husain M, Ng TW, Jacob S, Maddison P, Kennard C, Gowland PA, Rosenthal CR

Abstract
Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance.

PMID: 31976861 [PubMed - in process]

Regional Increases in Brain Signal Variability Are Associated with Pain Intensity Reductions Following Repeated Eccentric Exercise Bouts.

Sat, 01/25/2020 - 15:20
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Regional Increases in Brain Signal Variability Are Associated with Pain Intensity Reductions Following Repeated Eccentric Exercise Bouts.

Eur J Pain. 2020 Jan 24;:

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

Abstract
BACKGROUND: Traditional pain interventions limit fluctuations in pain sensation, which may paradoxically impair endogenous pain modulatory systems (EPMS). However, controlled exposures to clinically relevant pain (e.g. delayed onset muscle soreness, DOMS) may build capacity in the EPMS. Emerging evidence suggests regional signal variability (RSV) may be an important indicator of efficiency and modulatory capacity within brain regions. The present study sought to determine the role of RSV in both susceptibility to and trainability of pain response following repeated DOMS inductions.
METHODS: Baseline and follow-up resting-state fMRI was performed on 12 healthy volunteers ~40 days apart. Between scanning visits, participants received four weekly DOMS inductions in alternating elbow flexors and supplied seven days of post-induction pain ratings. Voxel-wise standard deviation of signal intensity was calculated to measure RSV. Associations among DOMS-related pain and RSV were assessed with regression. Relationships among baseline and change measurements were probed (i.e. susceptibility to DOMS; trainability following multiple inductions).
RESULTS: Significant association between baseline RSV in left MFG and right cerebellum and reductions in DOMS-related pain unpleasantness were detected. Furthermore, increases in RSV were associated with reduced DOMS pain intensity (left lingual gyrus, right MTG, left MTG, left precuneus) and unpleasantness (left MTG, right SFG).
DISCUSSION: Findings suggest that RSV may be an indicator of EPMS resilience and responsivity to training, as well as an indicator that is responsive to training. Involved regions underlie cognitive, affective, and representation processes. Results further clarify the potential role of RSV as an indicator of pain modulation and resilience.
SIGNIFICANCE: Regional signal variability may be an important indicator of endogenous pain modulatory system responsivity to training following repeated bouts of clinically relevant pain and may in fact be responsive to training itself.

PMID: 31976587 [PubMed - as supplied by publisher]

Functional disconnection of the dentate nucleus in essential tremor.

Sat, 01/25/2020 - 15:20
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Functional disconnection of the dentate nucleus in essential tremor.

J Neurol. 2020 Jan 23;:

Authors: Tikoo S, Pietracupa S, Tommasin S, Bologna M, Petsas N, Bharti K, Berardelli A, Pantano P

Abstract
Despite previous functional MRI studies on alterations within the cerebello-thalamo-cortical circuit in patients with essential tremor (ET), the specific role of disconnection of the dentate nucleus (DN), the main output cerebellar pathway, still needs clarification. In this study, we evaluated DN functional connectivity (FC) changes and their relationship with motor and non-motor symptoms in ET. We studied 25 ET patients and 26 healthy controls. Tremor severity was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and tremor amplitude and frequency were evaluated using kinematic techniques. Cognitive profile was assessed by montreal cognitive assessment (MoCA) and frontal assessment battery (FAB). All participants underwent a 3 T MRI protocol including resting-state blood oxygenation level dependent and diffusion tensor sequences. We used a seed-based approach to investigate DN FC and to explore the diffusion properties of cerebellar peduncles. There was significantly decreased DN FC with cortical, subcortical, and cerebellar areas in ET patients compared with healthy controls. Correlation analysis showed that: (1) the DN FC with the supplementary motor area, pre and postcentral gyri, and prefrontal cortex negatively correlated with FTM-TRS score and disease duration; (2) DN FC changes in the thalamus and caudate negatively correlated with peak tremor frequency, changes in the cerebellum positively correlated with tremor amplitude, and changes in the bilateral thalamus negatively correlated with tremor amplitude, and (3) DN FC with the associative prefrontal and parietal cortices, basal ganglia, and thalamus positively correlated with the MoCA score. Diffusion abnormalities were found in the three cerebellar peduncles, which did not correlate with clinical scores.

PMID: 31974808 [PubMed - as supplied by publisher]

Consciousness-specific dynamic interactions of brain integration and functional diversity.

Sat, 01/25/2020 - 15:20
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Consciousness-specific dynamic interactions of brain integration and functional diversity.

Nat Commun. 2019 10 10;10(1):4616

Authors: Luppi AI, Craig MM, Pappas I, Finoia P, Williams GB, Allanson J, Pickard JD, Owen AM, Naci L, Menon DK, Stamatakis EA

Abstract
Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain's default mode network exhibit reductions in both functional diversity and integration with the rest of the brain during unconsciousness. These results show that human consciousness relies on spatio-temporal interactions between brain integration and functional diversity, whose breakdown may represent a generalisable biomarker of loss of consciousness, with potential relevance for clinical practice.

PMID: 31601811 [PubMed - indexed for MEDLINE]

Measurement of Active Motor Threshold Using a Dynamometer During Navigated Transcranial Magnetic Stimulation in a Patient with Postoperative Brain Tumor: Technical Note.

Sat, 01/25/2020 - 15:20
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Measurement of Active Motor Threshold Using a Dynamometer During Navigated Transcranial Magnetic Stimulation in a Patient with Postoperative Brain Tumor: Technical Note.

World Neurosurg. 2020 Jan;133:42-48

Authors: Ferreira-Pinto PHC, Nigri F, Caparelli-Daquer EM, Dutra do Souto AA, de Miranda Chaves Christiani M

Abstract
BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is being used for different purposes in patients with brain tumors. However, the procedure requires a positive electrophysiological response. For patients with negative response in rest conditions, active motor threshold (AMT) may be used. However, sometimes it is difficult to obtain AMT measures owing to inability of the patient to sustain steady muscle contraction. Herein, we describe a simple method by using a hand dynamometer to obtain AMT measures during nTMS session.
CASE DESCRIPTION: A woman aged 68 years underwent total removal of a right frontal lobe oligodendroglioma World Health Organization grade II 15 years ago. Cranial magnetic resonance imaging during follow-up revealed local recurrence. In the postoperative period, she developed left upper limb paresis. A postoperative nTMS session was performed for motor electrophysiological evaluation. However, using the standard technique for AMT measurement, the patient was unable to perform sustained muscle contraction as required. A hand dynamometer was used. It allowed sustained muscle contraction for AMT measurement. A counter force for the index finger flexion, the hand support to stabilize hand joints, and a numerical screen serving for both the examiner and the patient as a feedback parameter may explain the success obtained with this simple device.
CONCLUSIONS: Although more studies are necessary to validate the method, the hand dynamometer should be considered for patients unable to sustain muscle contraction during AMT measurement.

PMID: 31550542 [PubMed - indexed for MEDLINE]

Chronic pain in adults with sickle cell disease is associated with alterations in functional connectivity of the brain.

Sat, 01/25/2020 - 15:20
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Chronic pain in adults with sickle cell disease is associated with alterations in functional connectivity of the brain.

PLoS One. 2019;14(5):e0216994

Authors: Karafin MS, Chen G, Wandersee NJ, Brandow AM, Hurley RW, Simpson P, Ward D, Li SJ, Field JJ

Abstract
Chronic pain affects 50% of adults with sickle cell disease (SCD). Although central sensitization is thought to contribute to the pathogenesis of this chronic pain, no studies have examined differences in functional connectivity of the brain between patients with SCD with and without chronic pain. We performed an observational cohort study using resting-state functional MRI (rsfMRI) of the brain on adults with SCD with and without chronic pain. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have differences in functional connectivity between the periaqueductal grey (PAG) and other regions of the brain. Twenty-two adults with SCD, 15 with chronic pain and 7 without chronic pain, as well as 10 African-American controls, underwent rsfMRI of the brain. When SCD patients with chronic pain were compared to those without chronic pain, significant differences in connectivity were noted between the PAG and 9 regions of the brain, including several in the default mode network, a network involved in introspection that has been implicated in other chronic pain syndromes. Changes in functional connectivity between patients with SCD with and without chronic pain suggest a mechanism for chronic pain that involves neuro-plastic changes to the brain.

PMID: 31107926 [PubMed - indexed for MEDLINE]

Multimodal assessment of recovery from coma in a rat model of diffuse brainstem tegmentum injury.

Sat, 01/25/2020 - 15:20
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Multimodal assessment of recovery from coma in a rat model of diffuse brainstem tegmentum injury.

Neuroimage. 2019 04 01;189:615-630

Authors: Pais-Roldán P, Edlow BL, Jiang Y, Stelzer J, Zou M, Yu X

Abstract
Despite the association between brainstem lesions and coma, a mechanistic understanding of coma pathogenesis and recovery is lacking. We developed a coma model in the rat mimicking human brainstem coma, which allowed multimodal analysis of a brainstem tegmentum lesion's effects on behavior, cortical electrophysiology, and global brain functional connectivity. After coma induction, we observed a transient period (∼1h) of unresponsiveness accompanied by cortical burst-suppression. Comatose rats then gradually regained behavioral responsiveness concurrent with emergence of delta/theta-predominant cortical rhythms in primary somatosensory cortex. During the acute stage of coma recovery (∼1-8h), longitudinal resting-state functional MRI revealed an increase in functional connectivity between subcortical arousal nuclei in the thalamus, basal forebrain, and basal ganglia and cortical regions implicated in awareness. This rat coma model provides an experimental platform to systematically study network-based mechanisms of coma pathogenesis and recovery, as well as to test targeted therapies aimed at promoting recovery of consciousness after coma.

PMID: 30708105 [PubMed - indexed for MEDLINE]

Quantification of structural brain connectivity via a conductance model.

Sat, 01/25/2020 - 15:20
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Quantification of structural brain connectivity via a conductance model.

Neuroimage. 2019 04 01;189:485-496

Authors: Frau-Pascual A, Fogarty M, Fischl B, Yendiki A, Aganj I, Alzheimer's Disease Neuroimaging Initiative

Abstract
Connectomics has proved promising in quantifying and understanding the effects of development, aging and an array of diseases on the brain. In this work, we propose a new structural connectivity measure from diffusion MRI that allows us to incorporate direct brain connections, as well as indirect ones that would not be otherwise accounted for by standard techniques and that may be key for the better understanding of function from structure. From our experiments on the Human Connectome Project dataset, we find that our measure of structural connectivity better correlates with functional connectivity than streamline tractography does, meaning that it provides new structural information related to function. Through additional experiments on the ADNI-2 dataset, we demonstrate the ability of this new measure to better discriminate different stages of Alzheimer's disease. Our findings suggest that this measure is useful in the study of the normal brain structure, and for quantifying the effects of disease on the brain structure.

PMID: 30677502 [PubMed - indexed for MEDLINE]

Creative music therapy to promote brain function and brain structure in preterm infants: A randomized controlled pilot study.

Fri, 01/24/2020 - 14:20
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Creative music therapy to promote brain function and brain structure in preterm infants: A randomized controlled pilot study.

Neuroimage Clin. 2020 Jan 13;25:102171

Authors: Haslbeck FB, Jakab A, Held U, Bassler D, Bucher HU, Hagmann C

Abstract
Cognitive and neurobehavioral problems are among the most severe adverse outcomes in very preterm infants. Such neurodevelopmental impairments may be mitigated through nonpharmacological interventions such as creative music therapy (CMT), an interactive, resource- and needs-oriented approach that provides individual social contact and musical stimulation. The aim was to test the feasibility of a study investigating the role of CMT and to measure the short- and medium-term effects of CMT on structural and functional brain connectivity with MRI. In this randomized, controlled clinical pilot feasibility trial, 82 infants were randomized to either CMT or standard care. A specially trained music therapist provided CMT via infant-directed humming and singing in lullaby style. To test the short-term effects of CMT on brain structure and function, diffusion tensor imaging data and resting-state functional imaging data were acquired. Clinical feasibility was achieved despite moderate parental refusal mainly in the control group after randomization. 40 infants remained as final cohort for the MRI analysis. Structural brain connectivity appears to be moderately affected by CMT, structural connectomic analysis revealed increased integration in the posterior cingulate cortex only. Lagged resting-state MRI analysis showed lower thalamocortical processing delay, stronger functional networks, and higher functional integration in predominantly left prefrontal, supplementary motor, and inferior temporal brain regions in infants treated with CMT. This trial provides unique evidence that CMT has beneficial effects on functional brain activity and connectivity in networks underlying higher-order cognitive, socio-emotional, and motor functions in preterm infants. Our results indicate the potential of CMT to improve long-term neurodevelopmental outcomes in children born very preterm.

PMID: 31972397 [PubMed - as supplied by publisher]

The functional implications and modifiability of resting-state brain network complexity in older adults.

Fri, 01/24/2020 - 14:20
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The functional implications and modifiability of resting-state brain network complexity in older adults.

Neurosci Lett. 2020 Jan 20;:134775

Authors: Zhou J, Lo OY, Halko MA, Harrison R, Lipsitz LA, Manor B

Abstract
The dynamics of the resting-state activity in brain functional networks are complex, containing meaningful patterns over multiple temporal scales. Such physiologic complexity is often diminished in older adults. Here we aim to examine if the resting-state complexity within functional brain networks is sensitive to functional status in older adults and if repeated exposure to transcranial direct current stimulation (tDCS) would modulate such complexity. Twelve older adults with slow gait and mild-to-moderate executive dysfunction and 12 age- and sex-matched controls completed a baseline resting-state fMRI (rs-fMRI). Ten participants in the functionally-limited group then completed ten 20-minute sessions of real (n = 6) or sham (n = 4) tDCS targeting the left prefrontal cortex over a two-week period as well as a follow-up rs-fMRI. The resting-state complexity associated with seven functional networks was quantified by averaging the multiscale entropy (MSE) of the blood oxygen level-dependent (BOLD) time-series for all voxels within each network. Compared to controls, functionally-limited group exhibited lower complexity in the motor, ventral attention, limbic, executive and default mode networks (F > 6.3, p < 0.02). Within this group, those who received tDCS exhibited greater complexity within the ventral, executive and limbic networks (p < 0.04) post intervention as compared to baseline, while no significant changes in sham group was observed. This study provides preliminary evidence that older adults with functional limitations had diminished complexity of resting-state brain network activity and repeated exposure to tDCS may increase that resting-state complexity, warranting future studies to establish such complexity as a marker of brain health in older adults.

PMID: 31972253 [PubMed - as supplied by publisher]

Behavioral deficits in left hemispatial neglect are related to a reduction of spontaneous neuronal activity in the right superior parietal lobule.

Fri, 01/24/2020 - 14:20
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Behavioral deficits in left hemispatial neglect are related to a reduction of spontaneous neuronal activity in the right superior parietal lobule.

Neuropsychologia. 2020 Jan 20;:107356

Authors: Machner B, von der Gablentz J, Göttlich M, Heide W, Helmchen C, Sprenger A, Münte TF

Abstract
Focal brain lesions may induce dysfunctions in distant brain regions leading to behavioral impairments. Based on this concept of 'diaschisis', spatial neglect following stroke has been related to structural damage of the right-lateralized ventral attention network (VAN) and disrupted inter-hemispheric functional connectivity (FC) in the bilateral dorsal attention network (DAN). We questioned whether neglect-related behavioral deficits may be determined by local dysfunction of a specific region within these brain networks. We investigated acute right-hemisphere stroke patients with left hemispatial neglect using resting-state functional MRI, neuropsychological tests of spatial attention and clinical assessment of neglect-related functional disability. In addition to conventional FC analyses between different cortical regions of interest (ROIs) in the DAN/VAN, we extracted the fractional amplitude of low frequency fluctuations (fALFF) from each ROI as a marker of regional spontaneous neuronal activity. Although DAN regions (as opposed to the VAN regions) were largely spared from structural brain damage, they exhibited a significant reduction of inter-hemispheric FC. However, significant fMRI-behavior correlations were revealed specifically for the fALFF of one DAN-ROI in the right superior parietal lobule (SPL): the smaller the fALFF in the right posterior intraparietal sulcus, the more severe the patient's pathological attention bias and neglect-related functional impairment. In line with 'diaschisis', our findings confirm a crucial role of the non-lesioned but dysfunctional right SPL for the emergence of spatial neglect and its behavioral consequences. They further support targeting the SPL dysfunction by non-invasive brain stimulation in neglect rehabilitation.

PMID: 31972231 [PubMed - as supplied by publisher]

Antidepressants normalize brain flexibility associated with multi-dimensional symptoms in major depressive patients.

Fri, 01/24/2020 - 14:20
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Antidepressants normalize brain flexibility associated with multi-dimensional symptoms in major depressive patients.

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jan 20;:109866

Authors: Tian S, Zhang S, Mo Z, Chattun MR, Wang Q, Wang L, Zhu R, Shao J, Wang X, Yao Z, Si T, Lu Q

Abstract
BACKGROUND: The fundamental pathophysiology of major depressive disorder (MDD) could be characterized by functional brain networks which tightly and dynamically connect into groups as communities, making the flexible brain possible to external multifarious demands. We aim to scrutinize what brain dynamics go awry in MDD and antidepressants effects on multi-dimensional symptoms.
METHODS: Thirty-five patients and thirty-five controls underwent resting-state functional magnetic resonance imaging (MRI). Patients were scanned before and after 8 or 12 weeks of pharmacotherapy. Group independent component analysis decomposed resting-state images to instinct networks and networks' integrated flexibility was calculated. Network flexibility between patients at baseline and after therapy were compared.
RESULTS: All patients completed the clinical trial and MRI scans. Following antidepressants treatment, we found significant normalization of reduced network flexibility in default mode network (DMN) and cognitive control network (CCN) of MDD patients. Selectively significant correlations between network flexibility and multi-dimensional symptoms such as anxiety/somatization and hysteresis factor were also found.
CONCLUSIONS: "Hypoflexible" CCN may involve in anxiety syndrome. Low flexibility in DMN may be indicative of hysteresis. These suggest an important pathophysiology of depressive manifestation of MDD. The antidepressant-induced normalization of the "hypoflexibility" suggests a selective pathway through which antidepressants may alleviate symptoms in depression.

PMID: 31972187 [PubMed - as supplied by publisher]

Modulation of Distinct Intrinsic Resting State Brain Networks by Acute Exercise Bouts of Differing Intensity.

Fri, 01/24/2020 - 14:20
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Modulation of Distinct Intrinsic Resting State Brain Networks by Acute Exercise Bouts of Differing Intensity.

Brain Plast. 2019 Dec 26;5(1):39-55

Authors: Schmitt A, Upadhyay N, Martin JA, Rojas S, Strüder HK, Boecker H

Abstract
Acute exercise bouts alter resting state functional connectivity (rs-FC) within cognitive, sensorimotor, and affective networks, but it remains unknown how these effects are influenced by exercise intensity. Twenty-five male athletes underwent individual fitness assessments using an incremental treadmill test. On separate days, they performed 'low' (35% below lactate threshold) and 'high' (20% above lactate threshold) intensity exercise bouts of 30 min. Rs-fMRI and Positive and Negative Affect Scale (PANAS) were acquired before and after each exercise bout. Networks of interest were extracted from twenty-two participants (3 dropouts). Pre-to-post changes and between conditions effects were evaluated using FSL's randomise by applying repeated measures ANOVA. Results were reported at p < 0.05, corrected for multiple comparisons using threshold free cluster enhancement. PANAS revealed a significant increase in positive mood after both exercise conditions. Significant effects were observed between conditions in the right affective and reward network (ARN), the right fronto parietal network (FPN) and the sensorimotor network (SMN). Pre-to-post comparisons after 'low' exercise intensity revealed a significant increase in rs-FC in the left and right FPN, while after 'high'-intensity exercise rs-FC decreased in the SMN and the dorsal attention network (DAN) and increased in the left ARN. Supporting recent findings, this study is the first to report distinct rs-FC alterations driven by exercise intensity: (i) Increased rs-FC in FPN may indicate beneficial functional plasticity for cognitive/attentional processing, (ii) increased rs-FC in ARN may be linked to endogenous opioid-mediated internal affective states. Finally, (iii) decreased rs-FC in the SMN may signify persistent motor fatigue. The distinct effects on rs-FC fit with theories of transient persistent network alterations after acute exercise bouts that are mediated by different exercise intensities and impact differentially on cognitive/attentional or affective responses.

PMID: 31970059 [PubMed]

Current Challenges in Translational and Clinical fMRI and Future Directions.

Fri, 01/24/2020 - 14:20
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Current Challenges in Translational and Clinical fMRI and Future Directions.

Front Psychiatry. 2019;10:924

Authors: Specht K

Abstract
Translational neuroscience is an important field that brings together clinical praxis with neuroscience methods. In this review article, the focus will be on functional neuroimaging (fMRI) and its applicability in clinical fMRI studies. In the light of the "replication crisis," three aspects will be critically discussed: First, the fMRI signal itself, second, current fMRI praxis, and, third, the next generation of analysis strategies. Current attempts such as resting-state fMRI, meta-analyses, and machine learning will be discussed with their advantages and potential pitfalls and disadvantages. One major concern is that the fMRI signal shows substantial within- and between-subject variability, which affects the reliability of both task-related, but in particularly resting-state fMRI studies. Furthermore, the lack of standardized acquisition and analysis methods hinders the further development of clinical relevant approaches. However, meta-analyses and machine-learning approaches may help to overcome current shortcomings in the methods by identifying new, and yet hidden relationships, and may help to build new models on disorder mechanisms. Furthermore, better control of parameters that may have an influence on the fMRI signal and that can easily be controlled for, like blood pressure, heart rate, diet, time of day, might improve reliability substantially.

PMID: 31969840 [PubMed]

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