Pain-Related Brain Connectivity Changes in Migraine: A Narrative Review and Proof of Concept about Possible Novel Treatments Interference

A neuronal dysfunction based on the imbalance between excitatory and inhibitory cortical-subcortical neurotransmission seems at the basis of migraine. Intercritical neuronal abnormal excitability can culminate in the bioelectrical phenomenon of Cortical Spreading Depression (CSD) with secondary involvement of the vascular system and release of inflammatory mediators, modulating in turn neuronal activity. Neuronal dysfunction encompasses the altered connectivity between the brain areas implicated in the genesis, maintenance and chronic evolution of migraine. Advanced neuroimaging techniques allow to identify changes in functional connectivity (FC) between brain areas involved in pain processes. Through a narrative review, we re-searched case-control studies on FC in migraine, between 2015 and 2020, by inserting the words migraine, fMRI, EEG, MEG, connectivity, pain in Pubmed. Studies on FC have shown that cortical processes, in the neurolimbic pain network, are likely to be prevalent for triggering attacks, in response to predisposing factors, and that these lead to a demodulation of the subcortical areas, at the basis of migraine maintenance. The link between brain dysfunction and peripheral interactions through the inhibition of CGRP, the main mediator of sterile migraine inflammation needs to be further investigated. Preliminary evidence could suggest that peripheral nerves inference at somatic and trigeminal levels, appears to change brain FC.

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Pain Sensitivity in Schizophrenia Spectrum Disorders: A Narrative Review of Recent Work

Psychiatry International ◽

10.3390/psychiatryint2010004 ◽

2021 ◽

Vol 2 (1) ◽

pp. 48-58

Author(s):

Alexandre González-Rodríguez ◽

Javier Labad ◽

Mary V. Seeman

Keyword(s):

Pain Sensitivity ◽

Pain Perception ◽

Experimental Studies ◽

Preliminary Evidence ◽

Narrative Review ◽

Sensory Threshold ◽

Schizophrenia Spectrum Disorders ◽

Physical Pain ◽

Constant Pain ◽

Search For Information

Many patients with schizophrenia seem relatively immune to physical pain while others complain of constant pain. This may result from disturbances or alterations of the sensory threshold for pain in populations with psychosis, a possibility for which there is some preliminary evidence. The inconsistency in pain perception may, in part, be explained by the treatments patients receive, but treatment-naïve patients also exhibit differences in response to pain. This suggests that decreased pain sensitivity may represent a specific psychosis endophenotype. Thus far, few experimental studies have investigated sensory thresholds, pain modalities, or other factors contributing to the perception or expression of physical pain in psychosis. A digital search for information on this topic was conducted in PubMed and Google Scholar. The result is a non-systematic, narrative review focusing on recent clinical and experimental findings of pain sensitivity in patients with psychosis. Importantly, physical and mental pain are closely connected constructs that may be difficult to differentiate. Our hope is that the review provides some clarity to the field in the specific context of schizophrenia.

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Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review

Brain and Neuroscience Advances ◽

10.1177/23982128211055426 ◽

2021 ◽

Vol 5 ◽

pp. 239821282110554

Author(s):

Vasileia Kotoula ◽

Toby Webster ◽

James Stone ◽

Mitul A Mehta

Keyword(s):

Resting State ◽

Emotional Regulation ◽

Brain Connectivity ◽

Brain Activity ◽

Reward Processing ◽

Brain Areas ◽

Delayed Effects ◽

Treatment Naïve ◽

Resting State Connectivity ◽

The Brain

Acute ketamine administration has been widely used in neuroimaging research to mimic psychosis-like symptoms. Within the last two decades, ketamine has also emerged as a potent, fast-acting antidepressant. The delayed effects of the drug, observed 2–48 h after a single infusion, are associated with marked improvements in depressive symptoms. At the systems’ level, several studies have investigated the acute ketamine effects on brain activity and connectivity; however, several questions remain unanswered around the brain changes that accompany the drug’s antidepressant effects and how these changes relate to the brain areas that appear with altered function and connectivity in depression. This review aims to address some of these questions by focusing on resting-state brain connectivity. We summarise the studies that have examined connectivity changes in treatment-naïve, depressed individuals and those studies that have looked at the acute and delayed effects of ketamine in healthy and depressed volunteers. We conclude that brain areas that are important for emotional regulation and reward processing appear with altered connectivity in depression whereas the default mode network presents with increased connectivity in depressed individuals compared to healthy controls. This finding, however, is not as prominent as the literature often assumes. Acute ketamine administration causes an increase in brain connectivity in healthy volunteers. The delayed effects of ketamine on brain connectivity vary in direction and appear to be consistent with the drug normalising the changes observed in depression. The limited number of studies however, as well as the different approaches for resting-state connectivity analysis make it very difficult to draw firm conclusions and highlight the importance of data sharing and larger future studies.

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Inflammation and Cognition in Depression: A Narrative Review

Journal of Clinical Medicine ◽

10.3390/jcm10245859 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5859

Author(s):

Katarzyna Wachowska ◽

Piotr Gałecki

Keyword(s):

Inflammatory Markers ◽

Health Condition ◽

Narrative Review ◽

Brain Areas ◽

Mediating Factors ◽

Hormonal Imbalance ◽

The World ◽

Depressive Patients ◽

The Brain

The authors aim to present a narrative review of research on the inflammatory aetiology of depression. Depression is a psychiatric disorder, constituting the most common reason of disability due to a health condition. It has been estimated that at least one in six people suffer from depression at some point of their lives. The aetiology of depression, although researched extensively all around the world, still remains unclear. Authors discuss the possible role of inflammation in depression, the neurodevelopmental theory of depression as well as associations between cognition and depression. Possible associations between memory dysfunction among depressive patients and inflammatory markers are included. The associations between the immune system, depression and cognition are observed. Possible mediating factors between these areas include personality traits, hormonal imbalance and functioning of the brain areas. The question as to what mediating factors are involved is still open to research.

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Ayres Theories of Autism and Sensory Integration Revisited: What Contemporary Neuroscience Has to Say

Brain Sciences ◽

10.3390/brainsci9030068 ◽

2019 ◽

Vol 9 (3) ◽

pp. 68 ◽

Cited By ~ 10

Author(s):

Emily Kilroy ◽

Lisa Aziz-Zadeh ◽

Sharon Cermak

Keyword(s):

Sensory Processing ◽

Sensory Integration ◽

Autism Spectrum ◽

Therapeutic Interventions ◽

Brain Areas ◽

Sensory Stimuli ◽

Spectrum Disorders ◽

Neural Underpinnings ◽

The Brain ◽

Neuroimaging Techniques

Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970’s. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres’ hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy.

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Functional brain connectivity phenotypes for schizophrenia drug discovery

Journal of Psychopharmacology ◽

10.1177/0269881114563635 ◽

2015 ◽

Vol 29 (2) ◽

pp. 169-177 ◽

Cited By ~ 17

Author(s):

Neil Dawson ◽

Brian J Morris ◽

Judith A Pratt

Keyword(s):

Drug Discovery ◽

Brain Connectivity ◽

Neural System ◽

Brain Dysfunction ◽

Brain Network ◽

Attrition Rate ◽

Rodent Models ◽

Functional Brain ◽

Functional Brain Network ◽

Electrophysiological Studies

While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery.

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Adolescent females exposed to child maltreatment exhibit atypical EEG coherence and psychiatric impairment: Linking early adversity, the brain, and psychopathology

Development and Psychopathology ◽

10.1017/s0954579410000155 ◽

2010 ◽

Vol 22 (2) ◽

pp. 419-432 ◽

Cited By ~ 26

Author(s):

Vladimir Miskovic ◽

Louis A. Schmidt ◽

Katholiki Georgiades ◽

Michael Boyle ◽

Harriet L. Macmillan

Keyword(s):

Child Maltreatment ◽

Left Hemisphere ◽

Brain Connectivity ◽

Preliminary Evidence ◽

Adolescent Females ◽

Group Differences ◽

Early Adversity ◽

Eeg Coherence ◽

Brain Circuitry ◽

The Brain

AbstractAlthough the relation between child maltreatment and psychiatric impairment is well documented and preliminary evidence has linked child maltreatment with aberrant cortical connectivity of the left hemisphere, no investigations have attempted to examine these relations in the same study. Here, we examined the links among early adversity, brain connectivity, and functional outcomes. We collected resting regional EEG intra- and interhemispheric α-band (7.5–12.5 Hz) coherence and measures of general psychiatric impairment from a cohort of 38 adolescent females exposed to child maltreatment (Mage = 14.47) and 24 adolescent females not exposed to child maltreatment (Mage = 14.00). Maltreated youths exhibited more left hemisphere EEG coherence than the control youths, suggesting a suboptimal organization of cortical networks. Maltreated participants also showed reduced frontal (anterior) interhemispheric coherence. These differences in brain circuitry remained statistically significant even after controlling for group differences in pubertal status and socioeconomic status. Measures of functional brain connectivity were associated with several subtypes of abuse and neglect. It was important that atypical left hemisphere EEG coherencemediatedthe effects of child maltreatment on levels of psychiatric impairment. The findings are discussed in the context of models linking early adversity to brain function and psychopathology.

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Mechanisms of action of intravenous immunoglobulin in septic encephalopathy

Reviews in the Neurosciences ◽

10.1515/revneuro-2017-0065 ◽

2018 ◽

Vol 29 (4) ◽

pp. 417-423 ◽

Cited By ~ 2

Author(s):

Figen Esen ◽

Perihan Ergin Ozcan ◽

Erdem Tuzun ◽

M. Dustin Boone

Keyword(s):

Intravenous Immunoglobulin ◽

Apoptotic Cell ◽

Brain Dysfunction ◽

Ivig Treatment ◽

Neuronal Dysfunction ◽

Septic Encephalopathy ◽

Behavioral Deficits ◽

Classical Complement Pathway ◽

Acute Brain Dysfunction ◽

Glial Cell Proliferation

Abstract Acute brain dysfunction associated with sepsis is a serious complication that results in morbidity and mortality. Intravenous immunoglobulin (IVIg) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Our results suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation. IgGAM treatment might suppress classical complement pathway by reducing C5a activity and proapoptotic NF-κB and Bax expressions, thereby, inhibiting major inflammation and apoptosis cascades. Future animal model experiments performed with specific C5aR and NF-κB agonists/antagonists or C5aR-deficient mice might more robustly disclose the significance of these pathways. C5a, C5aR, and NF-κB, which were shown to be the key molecules in brain injury pathogenesis in sepsis, might also be utilized as potential targets for future treatment trials of septic encephalopathy.

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Relationship between Chronic Periodontitis and Erectile Dysfunction: A Narrative Review

Journal of Oral Diseases ◽

10.1155/2016/7824321 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jaffer A. Shariff ◽

Aparna Ingleshwar ◽

Kevin C. Lee ◽

Athanasios I. Zavras

Keyword(s):

Erectile Dysfunction ◽

Cohort Studies ◽

Chronic Periodontitis ◽

Large Scale ◽

Periodontal Therapy ◽

Narrative Review ◽

Cochrane Library ◽

Case Control Studies ◽

Necrosis Factor Alpha ◽

Cross Sectional

Objective. To conduct a descriptive literature review on research studies investigating the association between chronic periodontitis (CP) and erectile dysfunction (ED). Methods. Cohort studies, case-control studies, cross-sectional studies, randomized control trials, and animal studies up to July 2015 that studied the relationship between CP and ED were reviewed and reported. Data sources included PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov. The themes “periodontal disease” and “erectile dysfunction” and the role of periodontal therapy were identified and discussed throughout the narrative review. Results. After reviewing the literature, it was found that an association between CP and vasculogenic ED likely exists. Inflammation resulting from CP promotes endothelial dysfunction by increasing the systemic levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Periodontal therapy attempts to decrease the release of TNF-α and could act to restore endothelial function, particularly in the penile vasculature. Conclusion. Although the literature reported a positive association between CP and ED, the studies were few and possess several methodological limitations. Large-scale cohort studies and confounder analysis are recommended. Dentists and physicians should collaborate to manage patients with either CP or ED because of their potential association not only with each other but also with other serious systemic comorbidities.

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Transcranial magnetic stimulation: studying the brain--behaviour relationship by induction of ‘virtual lesions’

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1999.0476 ◽

1999 ◽

Vol 354 (1387) ◽

pp. 1229-1238 ◽

Cited By ~ 275

Author(s):

Alvaro Pascual-Leone

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Brain Connectivity ◽

Brain Activity ◽

Causal Link ◽

Non Invasive ◽

Invasive Method ◽

Normal Humans ◽

The Brain ◽

Neuroimaging Techniques

Transcranial magnetic stimulation (TMS) provides a non-invasive method of induction of a focal current in the brain and transient modulation of the function of the targeted cortex. Despite limited understanding about focality and mechanisms of action, TMS provides a unique opportunity of studying brain-behaviour relations in normal humans. TMS can enhance the results of other neuroimaging techniques by establishing the causal link between brain activity and task performance, and by exploring functional brain connectivity.

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Source Space Analysis of Event-Related Dynamic Reorganization of Brain Networks

Computational and Mathematical Methods in Medicine ◽

10.1155/2012/452503 ◽

2012 ◽

Vol 2012 ◽

pp. 1-15 ◽

Cited By ~ 21

Author(s):

Andreas A. Ioannides ◽

Stavros I. Dimitriadis ◽

George A. Saridis ◽

Marotesa Voultsidou ◽

Vahe Poghosyan ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Brain Activity ◽

Clinical Applications ◽

Brain Areas ◽

Connectivity Patterns ◽

The Brain ◽

Typical Subject ◽

Different Parts ◽

Neuroimaging Techniques

How the brain works is nowadays synonymous with how different parts of the brain work together and the derivation of mathematical descriptions for the functional connectivity patterns that can be objectively derived from data of different neuroimaging techniques. In most cases static networks are studied, often relying on resting state recordings. Here, we present a quantitative study of dynamic reconfiguration of connectivity for event-related experiments. Our motivation is the development of a methodology that can be used for personalized monitoring of brain activity. In line with this motivation, we use data with visual stimuli from a typical subject that participated in different experiments that were previously analyzed with traditional methods. The earlier studies identified well-defined changes in specific brain areas at specific latencies related to attention, properties of stimuli, and tasks demands. Using a recently introduced methodology, we track the event-related changes in network organization, at source space level, thus providing a more global and complete view of the stages of processing associated with the regional changes in activity. The results suggest the time evolving modularity as an additional brain code that is accessible with noninvasive means and hence available for personalized monitoring and clinical applications.

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