Structural Plasticity Research Articles

Structural basis for the minimal bifunctional alginate epimerase AlgE3 from Azotobacter chroococcum.

Among the epimerases specific to alginate, some of them in Azotobacter genera convert β-d-mannuronic acid to α-l-guluronic acid but also have lyase activity to degrade alginate. The remarkable characteristics of these epimerases make it a promising enzyme for tailoring alginates to meet specific demands. Here, we determined the structure of the bifunctional mannuronan C-5 epimerase AlgE3 from Azotobacter chroococcum (AcAlgE3) in complex with several mannuronic acid oligomers as well as in apo form, which allowed us to elucidate the binding manner of each mannuronic acid oligomer, and the structural plasticity, which is dependent on calcium ions. Moreover, a comprehensive analysis of the lyase activity profiles of AcAlgE3 combined with structural characteristics explained the preference for different chain length oligomers.

REASONS AND REGULARITIES OF THE INFLUENCE OF MAGNETIC FIELDS ON THE MECHANICAL PROPERTIES AND STRUCTURE OF DEFORMABLE METALS

Background. The strength of metals greatly limits the possibility of obtaining products by plastic deformation. The electromagnetic nature of the processes of structure formation and plastic deformation provided the basis for the application of additional influence of the magnetic field. A fairly large volume of research material has been accumulated on the topic of additional influence of the magnetic field on ferro-, dia- and paramagnetic metals. The researches of recent years have an applied nature of studying the magnetoplasticity of technical alloys. Their generalization will make it possible to move from laboratory research to the development of equipment and technologies for combined pressure processing of metal products in a weak magnetic field. Objective. Generalization and analysis of the results of laboratory and theoretical studies of the additional application of the magnetic field in the processes of mechanical testing of metals and alloys.Methods. Literary review of materials of articles, monographs, dissertations. Results. Reasonable use of a magnetic field for plastic deformation of metals. The explanation of the mechanism of the influence of the magnetic field on the structural elements of metals based on the effect of magnetoplasticity has been made. The description of changes in the mechanical properties of metals and alloys under the additional influence of a magnetic field is given. Conclusions. The phenomenon of magnetoplasticity has been studied for a wide range of materials such as pure metals and their alloys, including industrial steels and alloys. Various types of positive effects of a magnetic field on the mechanical properties of metals have been established: a decrease in the yield strength and deformation resistance, an increase in strain, relaxation of internal stresses, and a decrease in dislocation density. There is also a reverse, negative effect of the influence of a magnetic field: increased rate of hardening, embrittlement, increased creep of metals. What will be the effect of a magnetic field on a specific metal cannot be guaranteed with high accuracy.

The Role of Tenascin-C on the Structural Plasticity of Perineuronal Nets and Synaptic Expression in the Hippocampus of Male Mice.

Neuronal plasticity is a crucial mechanism for an adapting nervous system to change. It is shown to be regulated by perineuronal nets (PNNs), the condensed forms of the extracellular matrix (ECM) around neuronal bodies. By assessing the changes in the number, intensity, and structure of PNNs, the ultrastructure of the PNN mesh, and the expression of inhibitory and excitatory synaptic inputs on these neurons, we aimed to clarify the role of an ECM glycoprotein, tenascin-C (TnC), in the dorsal hippocampus. To enhance neuronal plasticity, TnC-deficient (TnC-/-) and wild-type (TnC+/+) young adult male mice were reared in an enriched environment (EE) for 8 weeks. Deletion of TnC in TnC-/- mice showed an ultrastructural reduction of the PNN mesh and an increased inhibitory input in the dentate gyrus (DG), and an increase in the number of PNNs with a rise in the inhibitory input in the CA2 region. EE induced an increased inhibitory input in the CA2, CA3, and DG regions; in DG, the change was also followed by an increased intensity of PNNs. No changes in PNNs or synaptic expression were found in the CA1 region. We conclude that the DG and CA2 regions emerged as focal points of alterations in PNNs and synaptogenesis with EE as mediated by TnC.

Longitudinal microstructural changes in 18 amygdala nuclei resonate with cortical circuits and phenomics.

The amygdala nuclei modulate distributed neural circuits that most likely evolved to respond to environmental threats and opportunities. So far, the specific role of unique amygdala nuclei in the context processing of salient environmental cues lacks adequate characterization across neural systems and over time. Here, we present amygdala nuclei morphometry and behavioral findings from longitudinal population data (>1400 subjects, age range 40-69 years, sampled 2-3 years apart): the UK Biobank offers exceptionally rich phenotyping along with brain morphology scans. This allows us to quantify how 18 microanatomical amygdala subregions undergo plastic changes in tandem with coupled neural systems and delineating their associated phenome-wide profiles. In the context of population change, the basal, lateral, accessory basal, and paralaminar nuclei change in lockstep with the prefrontal cortex, a region that subserves planning and decision-making. The central, medial and cortical nuclei are structurally coupled with the insular and anterior-cingulate nodes of the salience network, in addition to the MT/V5, basal ganglia, and putamen, areas proposed to represent internal bodily states and mediate attention to environmental cues. The central nucleus and anterior amygdaloid area are longitudinally tied with the inferior parietal lobule, known for a role in bodily awareness and social attention. These population-level amygdala-brain plasticity regimes in turn are linked with unique collections of phenotypes, ranging from social status and employment to sleep habits and risk taking. The obtained structural plasticity findings motivate hypotheses about the specific functions of distinct amygdala nuclei in humans.

Clathrin assemblies at a glance.

Clathrin assembles into honeycomb-like lattices at the plasma membrane but also on internal membranes, such as at the Golgi and tubular endosomes. Clathrin assemblies primarily regulate the intracellular trafficking of different cargoes, but clathrin also has non-endocytic functions in cell adhesion through interactions with specific integrins, contributes to intraluminal vesicle formation by forming flat bilayered coats on endosomes and even assembles on kinetochore k-fibers during mitosis. In this Cell Science at a Glance article and the accompanying poster, we review our current knowledge on the different types of canonical and non-canonical membrane-associated clathrin assemblies in mammalian cells, as observed by thin-section or platinum replica electron microscopy in various cell types, and discuss how the structural plasticity of clathrin contributes to its functional diversity.

Spiking neural P systems with structural plasticity and mute rules

Spiking neural P systems (SNP systems) are a kind of distributed parallel device inspired by spike coding and communication of biological neurons. A new variant–spiking neural P systems with structural plasticity and mute rules (SNSMP systems) is proposed by this article, which introduce mute rules into SNP systems with structural plasticity. SNSMP systems implement the function of creating and deleting synapses between neurons by using structural plasticity rules, as well as using mute rules to increase or to decrease spikes themselves. The computing power of the SNSMP systems as a number generation and an accepting device are shown to be Turing complete, and also as a computing function device.

The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase.

Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments. ClpL shows increased thermal stability and enhanced disaggregation power compared to Hsp70/ClpB, enabling it to withstand severe heat stress and to solubilize tight aggregates. ClpL binds to protein aggregates via aromatic residues present in its N-terminal domain (NTD) that adopts a partially folded and dynamic conformation. Target specificity is achieved by simultaneous interactions of multiple NTDs with the aggregate surface. ClpL shows remarkable structural plasticity by forming diverse higher assembly states through interacting ClpL rings. NTDs become largely sequestered upon ClpL ring interactions. Stabilizing ring assemblies by engineered disulfide bonds strongly reduces disaggregation activity, suggesting that they represent storage states.

The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase

Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments. ClpL shows increased thermal stability and enhanced disaggregation power compared to Hsp70/ClpB, enabling it to withstand severe heat stress and to solubilize tight aggregates. ClpL binds to protein aggregates via aromatic residues present in its N-terminal domain (NTD) that adopts a partially folded and dynamic conformation. Target specificity is achieved by simultaneous interactions of multiple NTDs with the aggregate surface. ClpL shows remarkable structural plasticity by forming diverse higher assembly states through interacting ClpL rings. NTDs become largely sequestered upon ClpL ring interactions. Stabilizing ring assemblies by engineered disulfide bonds strongly reduces disaggregation activity, suggesting that they represent storage states.

Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling

The ability of neurons to rapidly remodel their synaptic structure and strength in response to neuronal activity is highly conserved across species and crucial for complex brain functions. However, mechanisms required to elicit and coordinate the acute, activity-dependent structural changes across synapses are not well understood, as neurodevelopment and structural plasticity are tightly linked. Here, using an RNAi screen in Drosophila against genes affecting nervous system functions in humans, we uncouple cellular processes important for synaptic plasticity and synapse development. We find mutations associated with neurodegenerative and mental health disorders are 2-times more likely to affect activity-induced synaptic remodeling than synapse development. We report that while both synapse development and activity-induced synaptic remodeling at the fly NMJ require macroautophagy (hereafter referred to as autophagy), bifurcation in the autophagy pathway differentially impacts development and synaptic plasticity. We demonstrate that neuronal activity enhances autophagy activation but diminishes degradative autophagy, thereby driving the pathway towards autophagy-based secretion. Presynaptic knockdown of Snap29, Sec22, or Rab8, proteins implicated in the secretory autophagy pathway, is sufficient to abolish activity-induced synaptic remodeling. This study uncovers secretory autophagy as a transsynaptic signaling mechanism modulating synaptic plasticity.

Distinct forms of structural plasticity of adult-born interneuron spines in the mouse olfactory bulb induced by different odor learning paradigms

The morpho-functional properties of neural networks constantly adapt in response to environmental stimuli. The olfactory bulb is particularly prone to constant reshaping of neural networks because of ongoing neurogenesis. It remains unclear whether the complexity of distinct odor-induced learning paradigms and sensory stimulation induces different forms of structural plasticity. In the present study, we automatically reconstructed spines in 3D from confocal images and performed unsupervised clustering based on morphometric features. We show that while sensory deprivation decreased the spine density of adult-born neurons without affecting the morphometric properties of these spines, simple and complex odor learning paradigms triggered distinct forms of structural plasticity. A simple odor learning task affected the morphometric properties of the spines, whereas a complex odor learning task induced changes in spine density. Our work reveals distinct forms of structural plasticity in the olfactory bulb tailored to the complexity of odor-learning paradigms and sensory inputs.

Using miniature experiments to reveal strength gradients in battery casings

Complex metallic structures are often manufactured through multi-step forming or casting processes that induce severe mechanical property variations within the final part. Instead of using the virgin material properties to predict the final part performance, the local material properties after manufacturing need to be known. A novel comprehensive testing methodology is presented allowing the resolution of spatial gradients in the plasticity and fracture properties in metallic structures. It involves using a recently-developed miniature linear-motion system that probes the material within 2 mm wide gage sections (uniaxial, notched and central hole tension, in-plane shear). Additionally, a novel mini-bulge testing system is presented along with a mini-punch system to provide further insight into the local material response for biaxial loading conditions. A full testing campaign comprising 60 miniature samples is performed on all sides of a prismatic aluminum casing for Li-ion battery cells. The results demonstrate significant property variations with more than 30 % higher yield stresses for the side walls as compared to the bottom section. The miniature specimens allow identifying a location-dependent anisotropy, which would otherwise be missed by standard-sized samples. Furthermore, it is shown that the anisotropic Yld2000 plasticity model and the stress-state dependent Hosford-Coulomb fracture initiation model can be fully identified using results from experiments on miniature specimens only.

Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.

Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic structural and functional plasticity in the spinal nociceptive network. Tiam1 is a Rac1 GTPase guanine nucleotide exchange factor that promotes excitatory synaptogenesis by modulating actin cytoskeletal dynamics. We found that prolonged morphine treatment activated Tiam1 in the spinal dorsal horn and Tiam1 ablation from spinal neurons eliminated morphine antinociceptive tolerance and OIH. At the same time, the pharmacological blockade of Tiam1-Rac1 signalling prevented the development and reserved the established tolerance and OIH. Prolonged morphine treatment increased dendritic spine density and synaptic NMDA receptor activity in spinal dorsal horn neurons, both of which required Tiam1. Furthermore, co-administration of the Tiam1 signalling inhibitor NSC23766 was sufficient to abrogate morphine tolerance in chronic pain management. These findings identify Tiam1-mediated maladaptive plasticity in the spinal nociceptive network as an underlying cause for the development and maintenance of morphine tolerance and OIH and provide a promising therapeutic target to reduce tolerance and prolong morphine use in chronic pain management.

New Insights into Hsp90 Structural Plasticity Revealed by cryoEM

Heat Shock Protein 90 (Hsp90) acts as a crucial molecular chaperone, playing an essential role in activating numerous signaling proteins. The intricate mechanism of Hsp90 involving ATPase-coupled conformational changes and interactions with cochaperone proteins has been elucidated through biochemical and structural analyses, revealing its activation mechanism and its diverse set of “client” proteins. Despite recent advancements, certain aspects of Hsp90’s ATPase-coupled mechanism remain contentious, and the specific nature of the alterations induced by Hsp90 in client proteins remains largely undiscovered. In this review, we explore the current understanding of Hsp90’s structure and function, drawing insights from single-particle cryoEM studies. Structural studies on Hsp90 using cryoEM have provided valuable insights into the structural dynamics and interactions of this molecular chaperone. CryoEM structures have been instrumental in understanding the ATPase-coupled conformational changes that Hsp90 undergoes during its chaperone cycle. We also highlight recent progress in elucidating the structure of the ATP-bound state of the complete dimeric chaperone. Furthermore, we delve into the roles played by the multitude of cochaperones that collaborate with Hsp90, providing a glimpse into their biochemical mechanisms through the newly obtained cryoEM structures of Hsp90 cochaperone complexes.

Perovskite‐Nanowire‐Array‐Based Continuous‐State Programmable Artificial Synapse for Neuromorphic Computing

Perovskite‐based memristors with tunable nonvolatile states are developed to mimic the synaptic interconnects of biological nervous systems and map neuromorphic computing networks to integrated circuits. To emulate the plasticity of synaptic structures, memristors with robust multilevel resistive states are fabricated in this work using high‐density polycrystalline MAPbCl3 nanowires (NWs) array that vertically integrated using solution method. In particular, the fabricated memristors exhibit both short‐ and long‐term plasticity and traits akin to biological synapses. A fabricated memristor device is precisely programmed to 18 resistive states and each state exhibits stable data retention of more than 100 000 s. Furthermore, a matrix processing unit using a 4‐by‐4 memristor array is fabricated as the hardware core of an encoder–decoder artificial neural network to demonstrate high accuracy and reliable in‐image font conversion. The resistive states of the 16 memristors are precisely programmed to the corresponding resistance values for specific synaptic weights of the artificial‐neural‐network‐trained offline. In addition, experimental characterization and first‐principles simulations attribute the continuous programmability and high reliability features of the memristors to the confinement mechanisms of the horizontal grain‐boundary structure in polycrystalline perovskite NWs.

Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit.

Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.

Suppression of Cofilin function in the somatosensory cortex alters social contact behavior in the BTBR mouse inbred line.

Sensory differences are a core feature of autism spectrum disorders (ASD) and are predictive of other ASD core symptoms such as social difficulties. However, the neurobiological substrate underlying the functional relationship between sensory and social functioning is poorly understood. Here, we examined whether misregulation of structural plasticity in the somatosensory cortex modulates aberrant social functioning in BTBR mice, a mouse model for autism spectrum disorder-like phenotypes. By locally expressing a dominant-negative form of Cofilin (CofilinS3D; a key regulator of synaptic structure) in the somatosensory cortex, we tested whether somatosensory suppression of Cofilin activity alters social functioning in BTBR mice. Somatosensory Cofilin suppression altered social contact and nest-hide behavior of BTBR mice in a social colony, assessed for seven consecutive days. Subsequent behavioral testing revealed that altered social functioning is related to altered tactile sensory perception; CofilinS3D-treated BTBR mice showed a time-dependent difference in the sensory bedding preference task. These findings show that Cofilin suppression in the somatosensory cortex alters social functioning in BTBR mice and that this is associated with tactile sensory processing, a critical indicator of somatosensory functioning.

The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond.

Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.

Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity

Long noncoding RNAs (lncRNAs) play crucial roles in maintaining cell homeostasis and function. However, it remains largely unknown whether and how neuronal activity impacts the transcriptional regulation of lncRNAs, or if this leads to synapse-related changes and contributes to the formation of long-term memories. Here, we report the identification of a lncRNA, SLAMR, which becomes enriched in CA1-hippocampal neurons upon contextual fear conditioning but not in CA3 neurons. SLAMR is transported along dendrites via the molecular motor KIF5C and is recruited to the synapse upon stimulation. Loss of function of SLAMR reduces dendritic complexity and impairs activity-dependent changes in spine structural plasticity and translation. Gain of function of SLAMR, in contrast, enhances dendritic complexity, spine density, and translation. Analyses of the SLAMR interactome reveal its association with CaMKIIα protein through a 220-nucleotide element also involved in SLAMR transport. A CaMKII reporter reveals a basal reduction in CaMKII activity with SLAMR loss-of-function. Furthermore, the selective loss of SLAMR function in CA1 disrupts the consolidation of fear memory in male mice, without affecting their acquisition, recall, or extinction, or spatial memory. Together, these results provide new molecular and functional insight into activity-dependent changes at the synapse and consolidation of contextual fear.

Treadmill exercise pretreatment ameliorated structural synaptic plasticity impairments of medial prefrontal cortex in vascular dementia rat and improved recognition memory

This study aimed to investigate structural synaptic plasticity in the medial prefrontal cortex of rats under treadmill exercise pretreatment or naive conditions in a vascular dementia model, followed by recognition memory performance in a novel object recognition task. In this study, 24 Sprague–Dawley rats were obtained and randomly assigned into 4 groups as follows: control group (Con group, n = 6), vascular dementia (VD group, n = 6), exercise and vascular dementia group (Exe + VD group, n = 6), and exercise group (Exe group, n = 6). Initially, 4 weeks of treadmill exercise intervention was administered to the rats in the Exe + VD and Exe groups. Then, to establish the vascular dementia model, the rats both in the VD and Exe + VD groups were subjected to bilateral common carotids arteries surgery. One week later, open-field task and novel recognition memory task were adopted to evaluate anxiety-like behavior and recognition memory in each group. Then, immunofluorescence and Golgi staining were used to evaluate neuronal number and spine density in the rat medial prefrontal cortex. Transmission electron microscopy was used to observe the synaptic ultrastructure. Finally, microdialysis coupled with high-performance liquid chromatography was used to assess the levels of 5-HT and dopamine in the medial prefrontal cortex. The behavior results showed that 4 weeks of treadmill exercise pretreatment significantly alleviated recognition memory impairment and anxiety-like behavior in VD rats (P < 0.01), while the rats in VD group exhibited impaired recognition memory and anxiety-like behavior when compared with the Con group (P < 0.001). Additionally, NeuN immunostaining results revealed a significant decrease of NeuN-marked neuron in the VD group compared to Con group (P < 0.01), but a significantly increase in this molecular marker was found in the Exe + VD group compared to the Con group (P < 0.01). Golgi staining results showed that the medial prefrontal cortex neurons in the VD group displayed fewer dendritic spines than those in the Con group (P < 0.01), and there were more spines on the dendrites of medial prefrontal cortex cells in Exe + VD rats than in VD rats (P < 0.01). Transmission electron microscopy further revealed that there was a significant reduction of synapses intensity in the medial prefrontal cortex of rats in the VD group when compared with the Con group(P < 0.01), but physical exercise was found to significantly increased synapses intensity in the VD model (P < 0.01). Lastly, the levels of dopamine and 5-HT in the medial prefrontal cortex of rats in the VD group was significantly lower compared to the Con group (P < 0.01), and treadmill exercise was shown to significantly increased the levels of dopamine and 5-HT in the VD rats (P < 0.05). Treadmill exercise pretreatment ameliorated structural synaptic plasticity impairments of medial prefrontal cortex in VD rat and improved recognition memory.

Pain Relief-Related Structural Brain Alterations in Trigeminal Neuralgia Induced by Noninvasive Stereotactic Radiosurgery: A Pilot Study

PurposeTrigeminal neuralgia (TN) is a devastating chronic pain disorder, defined by unilateral shock like pain in at least one division of the trigeminal nerve. Although several studies have investigated structural brain plasticity in TN patients, treatment-induced alterations remain largely uninvestigated. Materials/MethodsCombining T1-weighted magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) and multiple-regression analyses, we assessed gray matter maps of TN patients to investigate changes in gray matter volume (GMV) from before to half a year after stereotactic radiosurgery (SRS). ResultsComparing pre- and post-GMV of 25 TN patients (16 females; mean age 67 years) did not yield any significant clusters, suggesting that the impact of SRS intervention itself on gray matter structure may be negligible. In relation to SRS-induced pain-relief, we found a significant GMV increase in the left superior frontal gyrus associated with greater degrees of pain relief (p=0.024), and a trend toward an increase in GMV in the left dorsolateral prefrontal cortex (p=0.097). ConclusionIn this pilot study, we observed significant increases of GMV in the left superior frontal gyrus with SRS-induced improvements in pain, and a trend for the dorsolateral prefrontal cortex. Future studies are indicated to validate these findings and determine whether SRS-induced decrease in distracting pain events and subsequent increases in GMV result in improved functionality, decreased dependence on "top-down" control, and improved cognitive/executive balance with amelioration of pain events.