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Brain Sci., Volume 11, Issue 4 (April 2021) – 115 articles

Cover Story (view full-size image): The increased use of multivariate analysis approaches using positron emission tomography (PET) imaging has allowed the investigation of brain molecular processes underlying neural circuit functional interactions. The accumulation of misfolded proteins can cause a cascade of related pathological events, starting at the microscopic level and ultimately affecting the macroscopic scale level, leading to neuronal network failure. PET metabolic and neurotransmission connectome can reveal these brain region interactions in normality and disease. This review is an overview of concepts and methods of PET molecular and metabolic connectivity based on covariance assessment in neurodegenerative conditions, including Alzheimer’s disease and the Lewy Body disease spectrum. View this paper
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Article
The Impact of COVID-19 on Depressive Symptoms through the Lens of Sexual Orientation
Brain Sci. 2021, 11(4), 523; https://doi.org/10.3390/brainsci11040523 - 20 Apr 2021
Cited by 4 | Viewed by 2050
Abstract
This research seeks to explore the impact of COVID-19 on depressive symptoms, analyzing discrepancies of sexual orientation in a Portuguese-speaking sample. 1590 individuals participated, of which 63% were women, and 88% self-identified as straight. Participants responded to the depression sub-scale of the Beck [...] Read more.
This research seeks to explore the impact of COVID-19 on depressive symptoms, analyzing discrepancies of sexual orientation in a Portuguese-speaking sample. 1590 individuals participated, of which 63% were women, and 88% self-identified as straight. Participants responded to the depression sub-scale of the Beck Symptoms Iventory-18, the fear of COVID-19 scale and the COVID-19 negative impact scale. Depressive symptoms observed were higher than expected, and several significant differences were obtained: women and self-identified bisexual participants had higher levels of depressive symptoms compared to male and straight and gay or lesbian participants. Depressive symptoms negatively correlated with age and positively correlated with COVID-19 aggravated responses, fear of COVID-19, and negative impact of COVID-19. Hierarchical linear regression analysis showed that age, gender and sexual orientation explained 6% of the variance of depressive symptoms, and when fear and the negative impact of COVID-19 was added, the model explained 23% of results. This study provides an important contribution to the understanding of factors arising from the pandemic that may have an impact on the mental health of sexual minorities. Full article
Review
Behavior Testing in Rodents: Highlighting Potential Confounds Affecting Variability and Reproducibility
Brain Sci. 2021, 11(4), 522; https://doi.org/10.3390/brainsci11040522 - 20 Apr 2021
Cited by 15 | Viewed by 2035
Abstract
Rodent models of brain disorders including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases are essential for increasing our understanding of underlying pathology and for preclinical testing of potential treatments. Some of the most important outcome measures in such studies are behavioral. Unfortunately, reports from different [...] Read more.
Rodent models of brain disorders including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases are essential for increasing our understanding of underlying pathology and for preclinical testing of potential treatments. Some of the most important outcome measures in such studies are behavioral. Unfortunately, reports from different labs are often conflicting, and preclinical studies in rodent models are not often corroborated in human trials. There are many well-established tests for assessing various behavioral readouts, but subtle aspects can influence measurements. Features such as housing conditions, conditions of testing, and the sex and strain of the animals can all have effects on tests of behavior. In the conduct of behavior testing, it is important to keep these features in mind to ensure the reliability and reproducibility of results. In this review, we highlight factors that we and others have encountered that can influence behavioral measures. Our goal is to increase awareness of factors that can affect behavior in rodents and to emphasize the need for detailed reporting of methods. Full article
(This article belongs to the Special Issue Neuro-Developmental Disorders: Bench-to-Bedside)
Article
Differentiating Real-World Autobiographical Experiences without Recourse to Behaviour
Brain Sci. 2021, 11(4), 521; https://doi.org/10.3390/brainsci11040521 - 20 Apr 2021
Viewed by 1592
Abstract
Investigating human consciousness based on brain activity alone is a key challenge in cognitive neuroscience. One of its central facets, the ability to form autobiographical memories, has been investigated through several fMRI studies that have revealed a pattern of activity across a network [...] Read more.
Investigating human consciousness based on brain activity alone is a key challenge in cognitive neuroscience. One of its central facets, the ability to form autobiographical memories, has been investigated through several fMRI studies that have revealed a pattern of activity across a network of frontal, parietal, and medial temporal lobe regions when participants view personal photographs, as opposed to when they view photographs from someone else’s life. Here, our goal was to attempt to decode when participants were re-experiencing an entire event, captured on video from a first-person perspective, relative to a very similar event experienced by someone else. Participants were asked to sit passively in a wheelchair while a researcher pushed them around a local mall. A small wearable camera was mounted on each participant, in order to capture autobiographical videos of the visit from a first-person perspective. One week later, participants were scanned while they passively viewed different categories of videos; some were autobiographical, while others were not. A machine-learning model was able to successfully classify the video categories above chance, both within and across participants, suggesting that there is a shared mechanism differentiating autobiographical experiences from non-autobiographical ones. Moreover, the classifier brain maps revealed that the fronto-parietal network, mid-temporal regions and extrastriate cortex were critical for differentiating between autobiographical and non-autobiographical memories. We argue that this novel paradigm captures the true nature of autobiographical memories, and is well suited to patients (e.g., with brain injuries) who may be unable to respond reliably to traditional experimental stimuli. Full article
(This article belongs to the Special Issue Brain Bases of Conscious Awareness and Self-Representation)
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Communication
Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth
Brain Sci. 2021, 11(4), 520; https://doi.org/10.3390/brainsci11040520 - 19 Apr 2021
Cited by 7 | Viewed by 1447
Abstract
Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth [...] Read more.
Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth history. The present retrospective study investigated four patient-specific aneurysms, once at initial diagnosis and then at follow-up, to analyze hemodynamic and morphological changes. Aneurysm geometries were segmented via the medical image processing software Mimics. The geometries were meshed and a computational fluid dynamics (CFD) analysis was performed using ANSYS. Results showed that major geometry bulk growth occurred in areas of low wall shear stress (WSS). Wall shape remodeling near neck impingement regions occurred in areas with large gradients of WSS and oscillatory shear index. This study found that growth occurred in areas where low WSS was accompanied by high velocity gradients between the aneurysm wall and large swirling flow structures. A new finding was that all cases showed an increase in kinetic energy from the first time point to the second, and this change in kinetic energy seems correlated to the change in aneurysm volume. Full article
(This article belongs to the Special Issue Neurosurgery for Cerebral Aneurysms)
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Article
Microsurgical Anatomy of the Anterior Circulation of the Brain Adjusted to the Neurosurgeon’s Daily Practice
Brain Sci. 2021, 11(4), 519; https://doi.org/10.3390/brainsci11040519 - 19 Apr 2021
Cited by 3 | Viewed by 2172
Abstract
The study of cerebrovascular anatomy can be difficult and may take time due to its intrinsic complexity. However, it can also be difficult for the following reasons: the excessive description of neuroanatomy making articles hard to read, the unclear clinical application of what [...] Read more.
The study of cerebrovascular anatomy can be difficult and may take time due to its intrinsic complexity. However, it can also be difficult for the following reasons: the excessive description of neuroanatomy making articles hard to read, the unclear clinical application of what is written, the use of simplified or intricate schematic drawings that are not always appropriate for effective teaching, the poor quality of neuroanatomy dissections and the use of unusual views of figures that are not strictly related to the most frequent neuroimages to be interpreted in daily practice. Because of this, we designed an article that incorporates original and accurate anatomical dissections in an attempt to improve its comprehensibility. Five formalin-fixed adult cadaveric heads, whose vessels were injected with a colored silicone mixture (red for arteries and blue for veins), were dissected and examined under a microscope with magnifications from 3× to 40×. Special emphasis has been placed on correlating topographic anatomy with routine neuroimaging studies from computed tomographic angiography (CTA) and digital subtraction angiography (DSA). The essential surgical anatomy in a neurosurgeon’s daily practice is also described. The cadaveric dissections included in this study contribute to the understanding of the cerebrovascular anatomy necessary for the neurosurgeon’s daily practice. Full article
(This article belongs to the Special Issue Neurosurgery and Neuroanatomy)
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Systematic Review
Vibrotactile-Based Rehabilitation on Balance and Gait in Patients with Neurological Diseases: A Systematic Review and Metanalysis
Brain Sci. 2021, 11(4), 518; https://doi.org/10.3390/brainsci11040518 - 19 Apr 2021
Cited by 2 | Viewed by 2176
Abstract
Postural instability and fear of falling represent two major causes of decreased mobility and quality of life in cerebrovascular and neurologic diseases. In recent years, rehabilitation strategies were carried out considering a combined sensorimotor intervention and an active involvement of the patients during [...] Read more.
Postural instability and fear of falling represent two major causes of decreased mobility and quality of life in cerebrovascular and neurologic diseases. In recent years, rehabilitation strategies were carried out considering a combined sensorimotor intervention and an active involvement of the patients during the rehabilitation sessions. Accordingly, new technological devices and paradigms have been developed to increase the effectiveness of rehabilitation by integrating multisensory information and augmented feedback promoting the involvement of the cognitive paradigm in neurorehabilitation. In this context, the vibrotactile feedback (VF) could represent a peripheral therapeutic input, in order to provide spatial proprioceptive information to guide the patient during task-oriented exercises. The present systematic review and metanalysis aimed to explore the effectiveness of the VF on balance and gait rehabilitation in patients with neurological and cerebrovascular diseases. A total of 18 studies met the inclusion criteria and were included. Due to the lack of high-quality studies and heterogeneity of treatments protocols, clinical practice recommendations on the efficacy of VF cannot be made. Results show that VF-based intervention could be a safe complementary sensory-motor approach for balance and gait rehabilitation in patients with neurological and cerebrovascular diseases. More high-quality randomized controlled trials are needed. Full article
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Editorial
Quantitative EEG in Cognitive Neuroscience
Brain Sci. 2021, 11(4), 517; https://doi.org/10.3390/brainsci11040517 - 19 Apr 2021
Cited by 2 | Viewed by 2329
Abstract
Quantitative electroencephalography (EEG) distinguishes itself from clinical EEG by the application of mathematical approaches and computer scientific methods [...] Full article
(This article belongs to the Special Issue Quantitative EEG and Cognitive Neuroscience)
Article
EEG—Single-Channel Envelope Synchronisation and Classification for Seizure Detection and Prediction
Brain Sci. 2021, 11(4), 516; https://doi.org/10.3390/brainsci11040516 - 19 Apr 2021
Cited by 4 | Viewed by 1472
Abstract
This paper tackles the complex issue of detecting and classifying epileptic seizures whilst maintaining the total calculations at a minimum. Where many systems depend on the coupling between multiple sources, leading to hundreds of combinations of electrodes, our method calculates the instantaneous phase [...] Read more.
This paper tackles the complex issue of detecting and classifying epileptic seizures whilst maintaining the total calculations at a minimum. Where many systems depend on the coupling between multiple sources, leading to hundreds of combinations of electrodes, our method calculates the instantaneous phase between non-identical upper and lower envelopes of a single-electroencephalography channel reducing the workload to the total number of electrode points. From over 600 h of simulations, our method shows a sensitivity and specificity of 100% for high false-positive rates and 83% and 75%, respectively, for moderate to low false positive rates, which compares well to both single- and multi-channel-based methods. Furthermore, pre-ictal variations in synchronisation were detected in over 90% of patients implying a possible prediction system. Full article
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Article
Patisiran in hATTR Amyloidosis: Six-Month Latency Period before Efficacy
Brain Sci. 2021, 11(4), 515; https://doi.org/10.3390/brainsci11040515 - 19 Apr 2021
Cited by 5 | Viewed by 1485
Abstract
Hereditary amyloidosis associated with mutations in the transthyretin gene (hATTR) is a progressive devastating disease, with a fatal outcome occurring within 10years after onset. In recent years, TTR gene silencing therapy appeared as a promising therapeutic strategy, showing evidence that disease progression can [...] Read more.
Hereditary amyloidosis associated with mutations in the transthyretin gene (hATTR) is a progressive devastating disease, with a fatal outcome occurring within 10years after onset. In recent years, TTR gene silencing therapy appeared as a promising therapeutic strategy, showing evidence that disease progression can be slowed and perhaps reversed. We report here 18 subjects affected by hATTR amyloidosis treated with patisiran, a small interfering RNA acting as TTR silencer, and evaluated with a PND score, the NIS and NIS-LL scale, and a Norfolk QOL-DN questionnaire at baseline and then every 6 months. A global clinical stabilizationwas observed for the majority of the patients, with mild-moderate improvements in some cases, even in advanced disease stage (PND score > 2). Analysis of NIS, NIS-LL and Norfolk QOL-DN results, and PND score variation suggest the possible presence of a 6-month latency period prior to benefit of treatment. Full article
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Brief Report
Corticospinal Excitability during a Perspective Taking Task as Measured by TMS-Induced Motor Evoked Potentials
Brain Sci. 2021, 11(4), 513; https://doi.org/10.3390/brainsci11040513 - 18 Apr 2021
Viewed by 1559
Abstract
Only by understanding the ability to take a third-person perspective can we begin to elucidate the neural processes responsible for one’s inimitable conscious experience. The current study examined differences in hemispheric laterality during a first-person perspective (1PP) and third-person perspective (3PP) taking task, [...] Read more.
Only by understanding the ability to take a third-person perspective can we begin to elucidate the neural processes responsible for one’s inimitable conscious experience. The current study examined differences in hemispheric laterality during a first-person perspective (1PP) and third-person perspective (3PP) taking task, using transcranial magnetic stimulation (TMS). Participants were asked to take either the 1PP or 3PP when identifying the number of spheres in a virtual scene. During this task, single-pulse TMS was delivered to the motor cortex of both the left and right hemispheres of 10 healthy volunteers. Measures of TMS-induced motor-evoked potentials (MEPs) of the contralateral abductor pollicis brevis (APB) were employed as an indicator of lateralized cortical activation. The data suggest that the right hemisphere is more important in discriminating between 1PP and 3PP. These data add a novel method for determining perspective taking and add to the literature supporting the role of the right hemisphere in meta representation. Full article
(This article belongs to the Special Issue Brain Bases of Conscious Awareness and Self-Representation)
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Article
Nutritional Intervention Facilitates Food Intake after Epilepsy Surgery
Brain Sci. 2021, 11(4), 514; https://doi.org/10.3390/brainsci11040514 - 17 Apr 2021
Viewed by 873
Abstract
Background: We investigated whether nutritional intervention affected food intake after epilepsy surgery and if intravenous infusions were required in patients with epilepsy. We hypothesized that postoperative food intake would be increased by nutritional intervention. The purpose of this study was to compare postoperative [...] Read more.
Background: We investigated whether nutritional intervention affected food intake after epilepsy surgery and if intravenous infusions were required in patients with epilepsy. We hypothesized that postoperative food intake would be increased by nutritional intervention. The purpose of this study was to compare postoperative food intake in the periods before and after nutritional intervention. Methods: Between September 2015 and October 2020, 124 epilepsy surgeries were performed. Of these, 65 patients who underwent subdural electrode placement followed by open cranial epilepsy surgery were studied. Postoperative total food intake, rate of maintenance of food intake, and total intravenous infusion were compared in the periods before and after nutritional intervention. Results: A total of 26 females and 39 males (age range 3–60, mean 27.1, standard deviation (SD) 14.3, median 26 years) were enrolled. Of these, 18 females and 23 males (3–60, mean 28.2, SD 15.1, median 26 years) were in the pre-nutritional intervention period group, and eight females and 16 males (5–51, mean 25.2, SD 12.9, median 26.5 years) were in the post-nutritional intervention period group. The post-nutritional intervention period group showed significantly higher food intake (p = 0.015) and lower total infusion (p = 0.006) than the pre-nutritional intervention period group. Conclusion: The nutritional intervention increased food intake and also reduced the total amount of intravenous infusion. To identify the cut-off day to cease the intervention and to evaluate whether the intervention can reduce the complication rate, a multicenter study with a large number of patients is warranted. Full article
(This article belongs to the Special Issue Surgical Management of Medically Intractable Epilepsy)
Article
How Much of Me Do I See in Other Minds? Modulating Egocentricity in Emotion Judgments by tDCS
Brain Sci. 2021, 11(4), 512; https://doi.org/10.3390/brainsci11040512 - 16 Apr 2021
Viewed by 1324
Abstract
When inferring the mental states of others, individuals’ judgments are influenced by their own state of mind, an effect often referred to as egocentricity. Self–other differentiation is key for an accurate interpretation of other’s mental states, especially when these differ from one’s own [...] Read more.
When inferring the mental states of others, individuals’ judgments are influenced by their own state of mind, an effect often referred to as egocentricity. Self–other differentiation is key for an accurate interpretation of other’s mental states, especially when these differ from one’s own states. It has been suggested that the right supramarginal gyrus (rSMG) is causally involved in overcoming egocentricity in the affective domain. In a double-blind randomized study, 47 healthy adults received anodal (1 mA, 20 min) or sham transcranial direct current stimulation (tDCS) to the rSMG prior to performing a newly developed paradigm, the self–other facial emotion judgment (SOFE) task. In this task, participants made judgments of facial emotional expressions while having been previously confronted with congruent or incongruent emotion-inducing situations. To differentiate between emotional and cognitive egocentricity, participants additionally completed an established visual perspective-taking task. Our results confirmed the occurrence of emotional egocentric biases during the SOFE task. No conclusive evidence of a general role of the rSMG in emotional egocentricity was found. However, active as compared to sham tDCS induced descriptively lower egocentric biases when judging incongruent fearful faces, and stronger biases when judging incongruent happy faces, suggesting emotion-specific tDCS effects on egocentric biases. Further, we found significant tDCS effects on cognitive egocentricity. Results of the present study expanded our understanding of emotional egocentricity and point towards emotion-specific patterns of the underlying functionality. Full article
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Review
Cerebral Autoregulation in Ischemic Stroke: From Pathophysiology to Clinical Concepts
Brain Sci. 2021, 11(4), 511; https://doi.org/10.3390/brainsci11040511 - 16 Apr 2021
Cited by 4 | Viewed by 2314
Abstract
Ischemic stroke (IS) is one of the most impacting diseases in the world. In the last decades, new therapies have been introduced to improve outcomes after IS, most of them aiming for recanalization of the occluded vessel. However, despite this advance, there are [...] Read more.
Ischemic stroke (IS) is one of the most impacting diseases in the world. In the last decades, new therapies have been introduced to improve outcomes after IS, most of them aiming for recanalization of the occluded vessel. However, despite this advance, there are still a large number of patients that remain disabled. One interesting possible therapeutic approach would be interventions guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). Supportive hemodynamic therapies aiming to optimize perfusion in the ischemic area could protect the brain and may even extend the therapeutic window for reperfusion therapies. However, the knowledge of how to implement these therapies in the complex pathophysiology of brain ischemia is challenging and still not fully understood. This comprehensive review will focus on the state of the art in this promising area with emphasis on the following aspects: (1) pathophysiology of CA in the ischemic process; (2) methodology used to evaluate CA in IS; (3) CA studies in IS patients; (4) potential non-reperfusion therapies for IS patients based on the CA concept; and (5) the impact of common IS-associated comorbidities and phenotype on CA status. The review also points to the gaps existing in the current research to be further explored in future trials. Full article
(This article belongs to the Special Issue Cerebral Autoregulation and Cardiovascular Health)
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Article
Structural Changes on MRI Demonstrate Specific Cerebellar Involvement in SLE Patients—A VBM Study
Brain Sci. 2021, 11(4), 510; https://doi.org/10.3390/brainsci11040510 - 16 Apr 2021
Viewed by 1296
Abstract
The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with [...] Read more.
The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1-weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18–51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23–52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs (p = 0.05, r = 0.21), which is in line with its presumed role as a sensorimotor processing area. Full article
(This article belongs to the Special Issue Advances in Neuropsychiatric Systemic Lupus Erythematosus)
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Article
Adjust Neuronal Reactions to Pulses of High-Frequency Stimulation with Designed Inter-Pulse-Intervals in Rat Hippocampus In Vivo
Brain Sci. 2021, 11(4), 509; https://doi.org/10.3390/brainsci11040509 - 16 Apr 2021
Viewed by 952
Abstract
Sequences of electrical pulses have been applied in the brain to treat certain disorders. In recent years, altering inter-pulse-interval (IPI) regularly or irregularly in real time has emerged as a promising way to modulate the stimulation effects. However, algorithms to design IPI sequences [...] Read more.
Sequences of electrical pulses have been applied in the brain to treat certain disorders. In recent years, altering inter-pulse-interval (IPI) regularly or irregularly in real time has emerged as a promising way to modulate the stimulation effects. However, algorithms to design IPI sequences are lacking. This study proposed a novel strategy to design pulse sequences with varying IPI based on immediate neuronal reactions. Firstly, to establish the correlationship between the neuronal reactions with varying IPIs, high-frequency stimulations with varying IPI in the range of 5–10 ms were applied at the alveus of the hippocampal CA1 region of anesthetized rats in vivo. Antidromically-evoked population spikes (APS) following each IPI were recorded and used as a biomarker to evaluate neuronal reactions to each pulse. A linear mapping model was established to estimate the varied APS amplitudes by the two preceding IPIs. Secondly, the mapping model was used to derive an algorithm for designing an IPI sequence that would be applied for generating a desired neuronal reaction pre-defined by a particular APS distribution. Finally, examples of stimulations with different IPI sequences designed by the algorithm were verified by rat experiments. The results showed that the designed IPI sequences were able to reproduce the desired APS responses of different distributions in the hippocampal stimulations. The novel algorithm of IPI design provides a potential way to obtain various stimulation effects for brain stimulation therapies. Full article
(This article belongs to the Section Computational Neuroscience and Neuroinformatics)
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Article
Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses
Brain Sci. 2021, 11(4), 508; https://doi.org/10.3390/brainsci11040508 - 16 Apr 2021
Cited by 1 | Viewed by 1488
Abstract
Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held [...] Read more.
Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals. Full article
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Article
Impaired Audiovisual Representation of Phonemes in Children with Developmental Language Disorder
Brain Sci. 2021, 11(4), 507; https://doi.org/10.3390/brainsci11040507 - 16 Apr 2021
Cited by 1 | Viewed by 1241
Abstract
We examined whether children with developmental language disorder (DLD) differed from their peers with typical development (TD) in the degree to which they encode information about a talker’s mouth shape into long-term phonemic representations. Children watched a talker’s face and listened to rare [...] Read more.
We examined whether children with developmental language disorder (DLD) differed from their peers with typical development (TD) in the degree to which they encode information about a talker’s mouth shape into long-term phonemic representations. Children watched a talker’s face and listened to rare changes from [i] to [u] or the reverse. In the neutral condition, the talker’s face had a closed mouth throughout. In the audiovisual violation condition, the mouth shape always matched the frequent vowel, even when the rare vowel was played. We hypothesized that in the neutral condition no long-term audiovisual memory traces for speech sounds would be activated. Therefore, the neural response elicited by deviants would reflect only a violation of the observed audiovisual sequence. In contrast, we expected that in the audiovisual violation condition, a long-term memory trace for the speech sound/lip configuration typical for the frequent vowel would be activated. In this condition then, the neural response elicited by rare sound changes would reflect a violation of not only observed audiovisual patterns but also of a long-term memory representation for how a given vowel looks when articulated. Children pressed a response button whenever they saw a talker’s face assume a silly expression. We found that in children with TD, rare auditory changes produced a significant mismatch negativity (MMN) event-related potential (ERP) component over the posterior scalp in the audiovisual violation condition but not in the neutral condition. In children with DLD, no MMN was present in either condition. Rare vowel changes elicited a significant P3 in both groups and conditions, indicating that all children noticed auditory changes. Our results suggest that children with TD, but not children with DLD, incorporate visual information into long-term phonemic representations and detect violations in audiovisual phonemic congruency even when they perform a task that is unrelated to phonemic processing. Full article
(This article belongs to the Special Issue The Impact of Non-Speech Cues on Speech Perception across Development)
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Article
Enhanced White Matter Fiber Tracts in Advanced Jazz Improvisers
Brain Sci. 2021, 11(4), 506; https://doi.org/10.3390/brainsci11040506 - 16 Apr 2021
Cited by 3 | Viewed by 1592
Abstract
Human cognition and behavior arise from neuronal interactions over brain structural networks. These neuronal interactions cause changes in structural networks over time. How a creative activity such as musical improvisation performance changes the brain structure is largely unknown. In this diffusion magnetic resonance [...] Read more.
Human cognition and behavior arise from neuronal interactions over brain structural networks. These neuronal interactions cause changes in structural networks over time. How a creative activity such as musical improvisation performance changes the brain structure is largely unknown. In this diffusion magnetic resonance imaging study, we examined the brain’s white matter fiber properties in previously identified functional networks and compared the findings between advanced jazz improvisers and non-musicians. We found that, for advanced improvisers compared with non-musicians, the normalized quantitative anisotropy (NQA) is elevated in the lateral prefrontal areas and supplementary motor area, and the underlying white matter fiber tracts connecting these areas. This enhancement of the diffusion anisotropy along the fiber pathway connecting the lateral prefrontal and supplementary motor is consistent with the functional networks during musical improvisation tasks performed by expert jazz improvisers. These findings together suggest that experts’ creative skill is associated with the task-relevant, long-timescale brain structural network changes, in support of related cognitive underpinnings. Full article
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Article
A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers
Brain Sci. 2021, 11(4), 505; https://doi.org/10.3390/brainsci11040505 - 16 Apr 2021
Viewed by 1243
Abstract
Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate [...] Read more.
Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response. Axonal damage may lead to spike-train delays, evoked potentials, an increase in the refractoriness of the system, and intermittent blockage of spikes. We demonstrate how such effects applied to mechanoreceptor and nociceptor fibers in the pain processing circuit can give rise to dramatically distinct responses at the network/population level. The computational modeling of damaged neuronal assemblies may help unravel the myriad of responses observed in painful neuropathies and improve diagnostics and treatment protocols. Full article
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Article
Efficacy of Mechanical Thrombectomy using Penumbra ACETM Aspiration Catheter Compared to Stent Retriever SolitaireTM FR in Patients with Acute Ischemic Stroke
Brain Sci. 2021, 11(4), 504; https://doi.org/10.3390/brainsci11040504 - 16 Apr 2021
Cited by 2 | Viewed by 1505
Abstract
Background: Mechanical thrombectomy is the standard therapy in patients with acute ischemic stroke (AIS). The primary aim of our study was to compare the procedural efficacy of the direct aspiration technique, using Penumbra ACETM aspiration catheter, and the stent retriever technique, with [...] Read more.
Background: Mechanical thrombectomy is the standard therapy in patients with acute ischemic stroke (AIS). The primary aim of our study was to compare the procedural efficacy of the direct aspiration technique, using Penumbra ACETM aspiration catheter, and the stent retriever technique, with a SolitaireTM FR stent. Secondarily, we investigated treatment-dependent and treatment-independent factors that predict a good clinical outcome. Methods: We analyzed our series of mechanical thrombectomies using a SolitaireTM FR stent and a Penumbra ACETM catheter. The clinical and radiographic data of 76 patients were retrospectively reviewed. Using binary logistic regression, we looked for the predictors of a good clinical outcome. Results: In the Penumbra ACETM group we achieved significantly higher rates of complete vessel recanalization with lower device passage counts, shorter recanalization times, shorter procedure times and shorter fluoroscopy times (p < 0.001) compared to the SolitaireTM FR group. We observed no significant difference in good clinical outcomes (52.4% vs. 56.4%, p = 0.756). Predictors of a good clinical outcome were lower initial NIHSS scores, pial arterial collateralization on admission head CT angiography scan, shorter recanalization times and device passage counts. Conclusions: The aspiration technique using Penumbra ACETM catheter is comparable to the stent retriever technique with SolitaireTM FR regarding clinical outcomes. Full article
Article
Assessing the Three Attentional Networks and Vigilance in the Adolescence Stages
Brain Sci. 2021, 11(4), 503; https://doi.org/10.3390/brainsci11040503 - 16 Apr 2021
Cited by 6 | Viewed by 1259
Abstract
Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to assess the attentional networks and vigilance in adolescents aged between 10 and 19 years using the attentional network test for interaction and vigilance (ANTI-V). One [...] Read more.
Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to assess the attentional networks and vigilance in adolescents aged between 10 and 19 years using the attentional network test for interaction and vigilance (ANTI-V). One hundred and eighty-two adolescents divided into three groups (early adolescents, middle adolescents, late adolescents) participated in the study. The results indicate that after age 15, adolescents adopt a more conservative response strategy and increase the monitoring of self-errors. All the attentional networks seem to continue to develop during the age range considered in this study (10–19 y). Performance improved from early adolescence to middle adolescence and began to stabilize in late adolescence. Moreover, a low level of vigilance seems to harm alerting and orienting abilities. Full article
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Article
A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis
Brain Sci. 2021, 11(4), 502; https://doi.org/10.3390/brainsci11040502 - 16 Apr 2021
Cited by 5 | Viewed by 1351
Abstract
Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham [...] Read more.
Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function. Full article
(This article belongs to the Special Issue Cognitive Involvement in Multiple Sclerosis)
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Article
The Efficiency of Spa Rehabilitation in Chronic Ischemic Stroke Patients—Preliminary Reports
Brain Sci. 2021, 11(4), 501; https://doi.org/10.3390/brainsci11040501 - 15 Apr 2021
Cited by 2 | Viewed by 1327
Abstract
Background: Rehabilitation-oriented therapy after a stroke must continue in various forms as a life-long effort. Aim: The study investigated the impact of spa rehabilitation on the quality of life and functional efficiency in patients after an ischemic stroke at a chronic stage of [...] Read more.
Background: Rehabilitation-oriented therapy after a stroke must continue in various forms as a life-long effort. Aim: The study investigated the impact of spa rehabilitation on the quality of life and functional efficiency in patients after an ischemic stroke at a chronic stage of recovery. Methods: The assessment was carried out in a spa resort in southeastern Poland. It involved 32 patients with strokes who participated in a three-week rehabilitation program. Three examinations were performed: upon admission, on the day of discharge and at a two-month follow-up. The quality of life and functional efficiency were assessed with the WHOQOL-BREF and Barthel Index. Results: The quality of life was significantly higher in Exam II compared with Exam I (p < 0.001), and improvement was retained at the follow-up. The Barthel scores were higher in Exam II compared with Exam I (79.84 vs. 68.59), while the differences between the scores in Exams II and III were small (p = 0.039). Conclusions: Three-week spa rehabilitation seems to favorably affect the functional efficiency and quality of life after a stroke. The effects appear to be long-term. The gender, age and time from stroke onset do not seem to impact short-term effects. However, long-term effects are related to the time from stroke onset. Full article
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Communication
Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson’s Disease
Brain Sci. 2021, 11(4), 500; https://doi.org/10.3390/brainsci11040500 - 15 Apr 2021
Viewed by 2013
Abstract
Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: [...] Read more.
Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results. Full article
(This article belongs to the Special Issue Balance Rehabilitation in Neurological Disorders)
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Article
Functional Activation of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis
Brain Sci. 2021, 11(4), 499; https://doi.org/10.3390/brainsci11040499 - 15 Apr 2021
Cited by 4 | Viewed by 1844
Abstract
Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these [...] Read more.
Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry. Full article
(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)
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Article
Node Centrality Measures Identify Relevant Structural MRI Features of Subjects with Autism
Brain Sci. 2021, 11(4), 498; https://doi.org/10.3390/brainsci11040498 - 14 Apr 2021
Cited by 4 | Viewed by 1290
Abstract
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social interaction and communication and restricted patterns of behavior, interests, and activities. Although the etiopathogenesis of idiopathic ASD has not been fully elucidated, compelling evidence suggests an interaction [...] Read more.
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social interaction and communication and restricted patterns of behavior, interests, and activities. Although the etiopathogenesis of idiopathic ASD has not been fully elucidated, compelling evidence suggests an interaction between genetic liability and environmental factors in producing early alterations of structural and functional brain development that are detectable by magnetic resonance imaging (MRI) at the group level. This work shows the results of a network-based approach to characterize not only variations in the values of the extracted features but also in their mutual relationships that might reflect underlying brain structural differences between autistic subjects and healthy controls. We applied a network-based analysis on sMRI data from the Autism Brain Imaging Data Exchange I (ABIDE-I) database, containing 419 features extracted with FreeSurfer software. Two networks were generated: one from subjects with autistic disorder (AUT) (DSM-IV-TR), and one from typically developing controls (TD), adopting a subsampling strategy to overcome class imbalance (235 AUT, 418 TD). We compared the distribution of several node centrality measures and observed significant inter-class differences in averaged centralities. Moreover, a single-node analysis allowed us to identify the most relevant features that distinguished the groups. Full article
(This article belongs to the Special Issue Recent Advances in Human Brain Connectivity)
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Case Report
Neural Correlates of a Trance Process and Alternative States of Consciousness in a Traditional Healer
Brain Sci. 2021, 11(4), 497; https://doi.org/10.3390/brainsci11040497 - 14 Apr 2021
Cited by 2 | Viewed by 1830
Abstract
Trance processes are a form of altered states of consciousness (ASC) widely reported across cultures. Entering these states is often linked to auditory stimuli such as singing, chanting, or rhythmic drumming. While scientific research into this phenomenon is relatively nascent, there is emerging [...] Read more.
Trance processes are a form of altered states of consciousness (ASC) widely reported across cultures. Entering these states is often linked to auditory stimuli such as singing, chanting, or rhythmic drumming. While scientific research into this phenomenon is relatively nascent, there is emerging interest in investigating the neural correlates of altered states of consciousness such as trance. This report aims to add to this field of ASC through exploring how the perception of an experienced Sangoma (traditional South African healer) entering a trance process correlates to blood-oxygen-level-dependent (BOLD) signal modulation with auditory stimuli. Functional Magnetic Resonance Imaging (fMRI) data were analyzed using a General Linear Model comparing music versus no music condition multiplied by the percept of experiencing trance (High or Low). Positive BOLD activation was shown in the auditory cortex in both hemispheres during a trance process. Other brain regions tightly correlated to trance perception were the right parietal, right frontal, and area prostriata (p < 0.05, Bonferroni corrected). The orbitofrontal cortex (part of the Default Mode Network) was negatively activated and most correlated with music when trance was high, showing the largest differential between high and low trance perception. This is the first study to directly correlate BOLD signal variations in an expert subject’s percept of trance onset and intensity, providing insight into the neural signature and dynamics of this unique form of ASC. Future studies should examine in greater detail the perception of trance processes in expert subjects, adding other neuroimaging modalities to further investigate how these brain regions are modulated by trance expertise. Full article
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Article
Recalled Parental Bonding Interacts with Oxytocin Receptor Gene Polymorphism in Modulating Anxiety and Avoidance in Adult Relationships
Brain Sci. 2021, 11(4), 496; https://doi.org/10.3390/brainsci11040496 - 14 Apr 2021
Cited by 4 | Viewed by 2354
Abstract
Early interactions with significant individuals affect social experience throughout the course of a lifetime, as a repeated and prolonged perception of different levels of care, independence, or control influences the modulation of emotional regulatory processes. As many factors play a role in shaping [...] Read more.
Early interactions with significant individuals affect social experience throughout the course of a lifetime, as a repeated and prolonged perception of different levels of care, independence, or control influences the modulation of emotional regulatory processes. As many factors play a role in shaping the expectations and features of social interaction, in this study, we considered the influence of parental bonding and genetic allelic variation of oxytocin receptor gene polymorphism (rs53576) over levels of experienced anxiety and avoidance in 313 young adults belonging to two different cultural contexts, namely Italy and Singapore. Results highlighted a major effect of maternal characteristics, care, and overprotection, with differences between the two cultural groups. Additionally, the interaction between rs53576 and maternal overprotection suggested different environmental susceptibility in the Italian sample and the Singaporean one. Implications for clinical work and future steps are described in the Conclusion. Full article
(This article belongs to the Special Issue Hypothalamus, Neuropeptides and Socioemotional Behavior)
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Article
Childhood Maltreatment and Its Interaction with Hypothalamic–Pituitary–Adrenal Axis Activity and the Remission Status of Major Depression: Effects on Functionality and Quality of Life
Brain Sci. 2021, 11(4), 495; https://doi.org/10.3390/brainsci11040495 - 13 Apr 2021
Viewed by 1183
Abstract
Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in [...] Read more.
Relationships among childhood maltreatment (CM), hypothalamic-pituitary-adrenal (HPA) axis disturbances, major depressive disorder (MDD), poor functionality, and lower quality of life (QoL) in adulthood have been described. We aimed to study the roles of the remission status of depression and HPA axis function in the relationships between CM and functionality and QoL. Ninety-seven patients with MDD and 97 healthy controls were included. The cortisol awakening response, cortisol suppression ratio in the dexamethasone suppression test, and diurnal cortisol slope were assessed. Participants completed measures of psychopathology, CM, functionality, and QoL. Multiple linear regression analyses were performed to study the relationships between CM and functionality and QoL. Only non-remitted MDD patients showed lower functionality and QoL than controls, indicating that depressive symptoms may partly predict functionality and QoL. Cortisol measures did not differ between remitted and non-remitted patients. Although neither HPA axis measures nor depression remission status were consistently associated with functionality or QoL, these factors moderated the effects of CM on functionality and QoL. In conclusion, subtle neurobiological dysfunctions in stress-related systems could help to explain diminished functionality and QoL in individuals with CM and MDD and contribute to the persistence of these impairments even after the remission of depressive symptoms. Full article
(This article belongs to the Special Issue Psychoneuroendocrinology of Psychosis and Major Mood Disorders)
Article
The Effects of Functionally Guided, Connectivity-Based rTMS on Amygdala Activation
Brain Sci. 2021, 11(4), 494; https://doi.org/10.3390/brainsci11040494 - 13 Apr 2021
Cited by 3 | Viewed by 1663
Abstract
While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected [...] Read more.
While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected subcortical structures. Recent advances in task-related functional connectivity provide a means to better link superficial and deeper cortical sources with the possibility of increasing fronto-limbic modulation to induce stronger therapeutic effects. The objective of this pilot study was to test whether task-related, connectivity-based rTMS could modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). fMRI was collected to identify a node in the mPFC showing the strongest connectivity with the amygdala, as defined by psychophysiological interaction analysis. To promote Hebbian-like plasticity, and potentially stronger modulation, 5 Hz rTMS was applied while participants viewed frightening video-clips that engaged the fronto-limbic network. Significant increases in both the mPFC and amygdala were found for active rTMS compared to sham, offering promising preliminary evidence that functional connectivity-based targeting may provide a useful approach to treat network dysregulation. Further research is needed to better understand connectivity influences on rTMS effects to leverage this information to improve therapeutic applications. Full article
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