Dissociable roles of the dorsolateral and ventromedial prefrontal cortex in human categorization.

Models of human categorization predict the prefrontal cortex (PFC) serves a central role in category learning. The dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) have been implicated in categorization; however, it is unclear whether both are critical for categorization and whether they support unique functions. We administered three categorization tasks to patients with PFC lesions (mean age = 69.6 years; 5 men, 5 women) to examine how prefrontal subregions contribute to categorization. These included a rule-based (RB) task that was solved via a unidimensional rule, an information integration (II) task that was solved by combining information from two stimulus dimensions, and a deterministic/probabilistic (DP) task with stimulus features that had varying amounts of category-predictive information. Compared to healthy comparison participants, both patient groups had impaired performance. Impairments in the dlPFC patients were largest during the RB task, whereas impairments in the vmPFC patients were largest during the DP task. A hierarchical model was fit to the participants' data to assess learning deficits in the patient groups. PFC damage was correlated with a regularization term that limited updates to attention after each trial. Our results suggest that the PFC, as a whole, is important for learning to orient attention to relevant stimulus information. The dlPFC may be especially important for rule-based learning, whereas the vmPFC may be important for focusing attention on deterministic (highly diagnostic) features and ignoring less predictive features. These results support overarching functions of the dlPFC in executive functioning and the vmPFC in value-based decision making.Significance Statement Category learning creates flexible memory representations that easily generalize to novel situations. Although it is generally established that the prefrontal cortex is central to categorization, it is unclear how different prefrontal subregions contribute to learning. Separate literatures have implicated both the dorsolateral prefrontal cortex (dlPFC) and the ventromedial prefrontal cortex (vmPFC) in categorization, but there has been little effort to bridge these literatures. The current study is the first to examine categorization in patients with lesions centered in the dlPFC and vmPFC. We found that, as a whole, the PFC orients attention to relevant stimulus information. The dlPFC is important for rule-based learning, whereas the vmPFC is important for focusing attention on highly diagnostic features and ignoring less predictive features.

Dynamic Changes in Local Activity and Network Interactions among the Anterior Cingulate, Amygdala, and Cerebellum during Associative Learning.

Communication between the cerebellum and forebrain structures is necessary for motor learning and has been implicated in a variety of cognitive functions. The exact nature of cerebellar-forebrain interactions supporting behavior and cognition is not known. We examined how local and network activity support learning by simultaneously recording neural activity in the cerebellum, amygdala, and anterior cingulate cortex while male and female rats were trained in trace eyeblink conditioning. Initially, the cerebellum and forebrain signal the contingency between external stimuli through increases in theta power and synchrony. Neuronal activity driving expression of the learned response was observed in the cerebellum and became evident in the anterior cingulate and amygdala as learning progressed. Aligning neural activity to the training stimuli or learned response provided a way to differentiate between learning-related activity driven by different mechanisms. Stimulus and response-related increases in theta power and coherence were observed across all three areas throughout learning. However, increases in slow gamma power and coherence were only observed when oscillations were aligned to the cerebellum-driven learned response. Percentage of learned responses, learning-related local activity, and slow gamma communication from cerebellum to forebrain all progressively increased during training. The relatively fast frequency of slow gamma provides an ideal mechanism for the cerebellum to communicate learned temporal information to the forebrain. This cerebellar response-aligned slow gamma then provides enrichment of behavior-specific temporal information to local neuronal activity in the forebrain. These dynamic network interactions likely support a wide range of behaviors and cognitive tasks that require coordination between the forebrain and cerebellum.SIGNIFICANCE STATEMENT This study presents new evidence for how dynamic learning-related changes in single neurons and neural oscillations in a cerebellar-forebrain network support associative motor learning. The current results provide an integrated mechanism for how bidirectional communication between the cerebellum and forebrain represents important external events and internal neural drive. This bidirectional communication between the cerebellum and forebrain likely supports a wide range of behaviors and cognitive tasks that require temporal precision.

Central amygdala contributes to stimulus facilitation and pre-stimulus vigilance during cerebellar learning.

Our previous studies found that the central amygdala (CeA) modulates cerebellum-dependent eyeblink conditioning (EBC) using muscimol inactivation. We also found that CeA inactivation decreases cerebellar neuronal activity during the conditional stimulus (CS) from the start of training. Based on these findings, we hypothesized that the CeA facilitates CS input to the cerebellum. The current study tested the CS facilitation hypothesis using optogenetic inhibition with archaerhodopsin (Arch) and excitation with channelrhodopsin (ChR2) of the CeA during EBC in male rats. Optogenetic manipulations were administered during the 400 ms tone CS or during a 400 ms pre-CS period. As predicted by the CS facilitation hypothesis CeA inhibition during the CS impaired EBC and CeA excitation during the CS facilitated EBC. Unexpectedly, CeA inhibition just prior to the CS also impaired EBC, while CeA excitation during the pre-CS pathway did not facilitate EBC. The results suggest that the CeA contributes to CS facilitation and vigilance during the pre-CS period. These putative functions of the CeA may be mediated through separate output pathways from the CeA to the cerebellum.

Disrupting dorsal hippocampus impairs category learning in rats.

Categorization requires a balance of mechanisms that can generalize across common features and discriminate against specific details. A growing literature suggests that the hippocampus may accomplish these mechanisms by using fundamental mechanisms like pattern separation, pattern completion, and memory integration. Here, we assessed the role of the rodent dorsal hippocampus (HPC) in category learning by combining inhibitory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and simulations using a neural network model. Using touchscreens, we trained rats to categorize distributions of visual stimuli containing black and white gratings that varied along two continuous dimensions. Inactivating the dorsal HPC impaired category learning and generalization, suggesting that the rodent HPC plays an important role during categorization. Hippocampal inactivation had no effect on a control discrimination task that used identical trial procedures as the categorization tasks, suggesting that the impairments were specific to categorization. Model simulations were conducted with variants of a neural network to assess the impact of selective deficits on category learning. The hippocampal inactivation groups were best explained by a model that injected random noise into the computation that compared the similarity between category stimuli and existing memory representations. This model is akin to a deficit in mechanisms of pattern completion, which retrieves similar memory representations using partial information.

Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.

Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2-/-) and heterozygous mice (Prickle2-/+) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility. Growing evidence implicates the cerebellum in ASD. As Prickle2 is expressed in the cerebellum, this animal model presents a unique opportunity to investigate the cerebellar contribution to autism-like phenotypes. Here, we explore cerebellar structural and physiological abnormalities in animals with Prickle2 knockdown using immunohistochemistry, whole-cell patch clamp electrophysiology, and several cerebellar-associated motor and timing tasks, including interval timing and eyeblink conditioning. Histologically, Prickle2-/- mice have significantly more empty spaces or gaps between Purkinje cells in the posterior lobules and a decreased propensity for Purkinje cells to fire action potentials. These structural cerebellar abnormalities did not impair cerebellar-associated behaviors as eyeblink conditioning and interval timing remained intact. Therefore, although Prickle-/- mice show classic phenotypes of ASD, they do not recapitulate the involvement of the adult cerebellum and may not represent the pathophysiological heterogeneity of the disorder.

Curtobacterium salicis sp. nov., isolated from willow tree stems in Washington state.

Curtobacterium sp. strain WW7 is a Gram-positive, non-motile, orange rod-shaped bacterium isolated from branches of wild willow (Salix sitchensis) trees. The WW7T strain has optimum growth in the temperature range between 25 and 30 °C, a pH range of 6-7.7, and tolerates up to 5.5% (w/v) of NaCl. The genome sequencing of strain WW7T revealed a genome size of approximately 3.8 Mbp and a G + C content of 71.3 mol%. The phylogenomic analyses support the WW7T affiliation to a novel Curtobacterium lineage, with Curtobacterium herbarum being the closest type-strain. Chemotaxonomic analysis indicates that the carbon sources assimilation profile of strain WW7T was similar to the type strains, i.e. Curtobacterium luteum, Curtobacterium albidum, and Curtobacterium flaccumfaciens, while no assimilation of the organic acids succinate, alpha-ketobutyrate, mono methyl-succinate, and lactate was observed. Finally, fatty acid methyl ester analysis identifies anteiso-C15:0 and anteiso-C17:0 as major cellular fatty acids which is a common feature for members of the Curtobacterium genus. Based on the results of phylogenomic and chemotaxonomic analyses, strain WW7T represents a novel Curtobacterium lineage, for which the name Curtobacterium salicis sp. nov. is proposed. The type strain is WW7T (DSM 34805T-NRRL B-68078T).

The Role of Orthoses in Chronic Axial Spinal Conditions.

PURPOSE OF REVIEW: Bracing represents a prevalent conservative, non-surgical approach used in the management of chronic spinal conditions such as spondylosis, degenerative disc disease, and spondylolisthesis. A wide variety of orthoses are available to aid in addressing cervical, thoracic, lumbar, thoracic, and SI joint pain. In this review, we aim to comprehensively examine brace types with their current applications and implications of usage. RECENT FINDINGS: There are multiple cervical bracing options, such as soft and rigid collars, to assist in managing acute trauma and chronic degenerative conditions. The review highlights the nuanced decision-making process between hard and soft collars based on the severity of bone or ligamentous injury and neurological findings. Orthoses for low back pain are commonly used. The review highlights the challenges of chronic neck and lower back pain, emphasizing the importance of clinicians exploring all treatment strategies including braces which can improve function and reduce pain.

Variations in Management and Clinical Outcomes for Children With Diabetic Ketoacidosis in an Academic Pediatric Versus Community Emergency Department Setting.

OBJECTIVES: Our objectives were to characterize variations from standardized, evidence-based guidelines in the management of pediatric patients with diabetic ketoacidosis (DKA) based on initial presentation to a tertiary pediatric emergency department (PED) versus a community emergency department (OSH) and compare clinical outcomes. METHODS: We conducted a retrospective study on children 18 years and younger with DKA who presented to an OSH or PED over a 3-year period. Treatments monitored for variation included intravenous fluid management, insulin delivery, and sodium bicarbonate administrations. Clinical outcomes included time to anion gap correction and on insulin infusion, hypokalemia, hypoglycemia, rapid serum glucose decline, cerebral edema, mechanical ventilation, mortality, and time from initial presentation to hospital discharge. RESULTS: Children with DKA who presented to an OSH (n = 250) were more acidotic (pH 7.11 vs. 7.13, P = 0.001) and had larger anion gaps (28.8 vs. 25.5, P < 0.001) compared with children presenting to the PED (n = 237). The OSH patients were more likely to receive larger fluid boluses (>20 cc/kg or >1000 ml, 43% vs. 4%, P < 0.001), sodium bicarbonate (5% vs. 0%, P < 0.001), and intravenous bolus insulin (28% vs. 0%, P < 0.001). The OSH group were less likely to be started on maintenance intravenous fluids (70% vs. 99%, P < 0.001) or receive potassium in maintenance intravenous fluids (14% vs. 42%, P < 0.001). The OSH group had longer anion gap correction times (754 vs. 541 mins, P < 0.001), insulin infusion times (1018 vs. 854 min, P = 0.003), and times to hospital discharge (3358 vs. 3045 mins, P < 0.001). Incidence of hypokalemia, hypoglycemia, rapid glucose decline, cerebral edema, and deaths were similar between the 2 groups. CONCLUSIONS: Our study demonstrated significant variations in the initial management of pediatric DKA patients by OSH facilities that deviated from an evidence-based treatment pathway utilized by a PED. Statewide quality improvement initiatives could help improve the overall clinical care provided to pediatric DKA patients.

Dorsomedial striatum, but not dorsolateral striatum, is necessary for rat category learning.

Categorization is an adaptive cognitive function that allows us to generalize knowledge to novel situations. Converging evidence from neuropsychological, neuroimaging, and neurophysiological studies suggest that categorization is mediated by the basal ganglia; however, there is debate regarding the necessity of each subregion of the basal ganglia and their respective functions. The current experiment examined the roles of the dorsomedial striatum (DMS; homologous to the head of the caudate nucleus) and dorsolateral striatum (DLS; homologous to the body and tail of the caudate nucleus) in category learning by combining selective lesions with computational modeling. Using a touchscreen apparatus, rats were trained to categorize distributions of visual stimuli that varied along two continuous dimensions (i.e., spatial frequency and orientation). The tasks either required attention to one stimulus dimension (spatial frequency or orientation; 1D tasks) or both stimulus dimensions (spatial frequency and orientation; 2D tasks). Rats with NMDA lesions of the DMS were impaired on both the 1D tasks and 2D tasks, whereas rats with DLS lesions showed no impairments. The lesions did not affect performance on a discrimination task that had the same trial structure as the categorization tasks, suggesting that the category impairments effected processes relevant to categorization. Model simulations were conducted using a neural network to assess the effect of the DMS lesions on category learning. Together, the results suggest that the DMS is critical to map category representations to appropriate behavioral responses, whereas the DLS is not necessary for categorization.

Microbial endophytes and compost improve plant growth in two contrasting types of hard rock mining waste.

The re-vegetation of mining wastes with native plants is a comparatively low-cost solution for mine reclamation. However, re-vegetation fails when extreme pH values, low organic matter, or high concentrations of phytotoxic elements inhibit plant establishment and growth. Our aim was to determine whether the combined addition of municipal waste compost and diazotrophic endophytes (i.e., microorganisms that fix atmospheric N2 and live within plants) could improve plant growth, organic matter accumulation, and phytostabilization of trace element contaminants in two types of hard rock mine waste. We grew a widespread native perennial grass, Bouteloua curtipendula, for one month in alkaline waste rock (porphyry copper mine) and tailings (Ag-Pb-Au mine, amended with dolomite) sourced from southeastern Arizona, United States. B. curtipendula tolerated elevated concentrations of multiple phytotoxic trace elements in the tailings (Mn, Pb, Zn), stabilizing them in roots without foliar translocation. Adding compost and endophyte seed coats improved plant growth, microbial biomass, and organic matter accumulation despite stark differences in the geochemical and physical characteristics of the mining wastes. The widespread grass B. curtipendula is a potential candidate for re-vegetating mine wastes when seeded with soil additives to increase pH and with microbial and organic amendments to increase plant growth.

This study quantifies improvements to plant growth, soil fertility, and trace element stabilization with a municipal waste compost topdressing and diazotrophic endophyte seed coating in two common hard rock mining wastes of the western United States. It establishes that a widespread perennial grass, Bouteloua curtipendula, can grow despite high concentrations of phytotoxic trace elements and minimal soil nutrients, and stabilizes trace elements on or in its roots, making it a suitable option for re-vegetation or phytostabilization of hard rock mining wastes.

Acetylenotrophic and Diazotrophic Bradyrhizobium sp. Strain I71 from TCE-Contaminated Soils.

Acetylene (C2H2) is a molecule rarely found in nature, with very few known natural sources, but acetylenotrophic microorganisms can use acetylene as their primary carbon and energy source. As of 2018 there were 15 known strains of aerobic and anaerobic acetylenotrophs; however, we hypothesize there may yet be unrecognized diversity of acetylenotrophs in nature. This study expands the known diversity of acetylenotrophs by isolating the aerobic acetylenotroph, Bradyrhizobium sp. strain I71, from trichloroethylene (TCE)-contaminated soils. Strain I71 is a member of the class Alphaproteobacteria and exhibits acetylenotrophic and diazotrophic activities, the only two enzymatic reactions known to transform acetylene. This unique capability in the isolated strain may increase the genus' economic impact beyond agriculture as acetylenotrophy is closely linked to bioremediation of chlorinated contaminants. Computational analyses indicate that the Bradyrhizobium sp. strain I71 genome contains 522 unique genes compared to close relatives. Moreover, applying a novel hidden Markov model of known acetylene hydratase (AH) enzymes identified a putative AH enzyme. Protein annotation with I-TASSER software predicted the AH from the microbe Syntrophotalea acetylenica as the closest structural and functional analog. Furthermore, the putative AH was flanked by horizontal gene transfer (HGT) elements, like that of AH in anaerobic acetylenotrophs, suggesting an unknown source of acetylene or acetylenic substrate in the environment that is selecting for the presence of AH. IMPORTANCE The isolation of Bradyrhizobium strain I71 expands the distribution of acetylene-consuming microbes to include a group of economically important microorganisms. Members of Bradyrhizobium are well studied for their abilities to improve plant health and increase crop yields by providing bioavailable nitrogen. Additionally, acetylene-consuming microbes have been shown to work in tandem with other microbes to degrade soil contaminants. Based on genome, cultivation, and protein prediction analysis, the ability to consume acetylene is likely not widespread within the genus Bradyrhizobium. These findings suggest that the suite of phenotypic capabilities of strain I71 may be unique and make it a good candidate for further study in several research avenues.

The dorsal hippocampus' role in context-based timing in rodents.

To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations. However, these models often overlook the fact that situational factors frequently modulate temporal expectations. For example, in realistic environments, the intervals associated with different cues will often covary due to a common underlying cause. According to the 'common cause hypothesis,' observers anticipate this covariance such that, when one cue's interval changes, temporal expectations for other cues shift in the same direction. Furthermore, as conditions will often differ across environments, the same cue can mean different things in different contexts. Therefore, updates to temporal expectations should be context-specific. Behavioral work supports these predictions, yet their underlying neural mechanisms are unclear. Here, we asked whether the dorsal hippocampus mediates context-based timing, given its broad role in context-conditioning. Specifically, we trained rats with either hippocampal or sham lesions that two cues predicted reward after either a short or long duration elapsed (e.g., tone-8 s/light-16 s). Then, we moved rats to a new context and extended the long cue's interval (e.g., light-32 s). This caused rats to respond later to the short cue, despite never being trained to do so. Importantly, when returned to the initial training context, sham rats shifted back toward both cues' original intervals. In contrast, lesion rats continued to respond at the long cue's newer interval. Surprisingly, they still showed contextual modulation for the short cue, responding earlier like shams. These data suggest the hippocampus only mediates context-based timing if a cue is explicitly paired and/or rewarded across distinct contexts. Furthermore, as lesions did not impact timing measures at baseline or acquisition for the long cue's new interval, our data suggests that the hippocampus only modulates timing when context is relevant.

Theta oscillations in rat infralimbic cortex are associated with the inhibition of cocaine seeking during extinction.

Infralimbic cortical (IL) manipulations indicate that this region mediates extinction learning and suppresses cocaine seeking following cocaine self-administration. However, little work has recorded IL activity during the inhibition of cocaine seeking due to the difficulty of determining precisely when cocaine-seeking behaviour is inhibited within a cocaine-seeking session. The present study used in vivo electrophysiology to examine IL activity across extinction as well as during cocaine self-administration and reinstatement. Sprague-Dawley rats underwent 6-h access cocaine self-administration in which the response lever was available during discrete signalled trials, a procedure which allowed for the comparison between epochs of cocaine seeking versus the inhibition thereof. Subsequently, rats underwent extinction and cocaine-primed reinstatement using the same procedure. Results indicate that theta rhythms (4-10 Hz) dominated IL local-field potential (LFP) activity during all experimental stages. During extinction, theta power fluctuated significantly surrounding the lever press and was lower when rats engaged in cocaine seeking versus when they withheld from doing so. These patterns of oscillatory activity differed from self-administration and reinstatement stages. Single-unit analyses indicate heterogeneity of IL unit responses, supporting the idea that multiple neuronal subpopulations exist within the IL and promote the expression of different and even opposing cocaine-seeking behaviours. Together, these results are consistent with the idea that aggregate synaptic and single-unit activity in the IL represent the engagement of the IL in action monitoring to promote adaptive behaviour in accordance with task contingencies and reveal critical insights into the relationship between IL activity and the inhibition of cocaine seeking.

Interventional Treatment Modalities for Chronic Abdominal and Pelvic Visceral Pain.

PURPOSE OF REVIEW: Chronic abdominal and pelvic visceral pain is an oftentimes difficult to treat pain condition that requires a multidisciplinary approach. This article specifically reviews the interventional treatment options for pain resulting from visceral abdominal and pelvic pain. RECENT FINDINGS: Sympathetic nerve blocks are the main interventional option for the treatment of chronic abdominal and pelvic visceral pain. Initially, nerve blocks are performed, and subsequently, neurolytic injections (alcohol or phenol) are longer term options. This review describes different techniques for sympathetic blockade. Neuromodulation is a potential option via dorsal column stimulation or dorsal root ganglion stimulation. Finally, intrathecal drug delivery is sometimes appropriate for refractory cases. This paper will review interventional options for the treatment of chronic abdominal and pelvic visceral pain.

Prelimbic cortex maintains attention to category-relevant information and flexibly updates category representations.

Category learning groups stimuli according to similarity or function. This involves finding and attending to stimulus features that reliably inform category membership. Although many of the neural mechanisms underlying categorization remain elusive, models of human category learning posit that prefrontal cortex plays a substantial role. Here, we investigated the role of the prelimbic cortex (PL) in rat visual category learning by administering excitotoxic lesions before category training and then evaluating the effects of the lesions with computational modeling. Using a touchscreen apparatus, rats (female and male) learned to categorize distributions of category stimuli that varied along two continuous dimensions. For some rats, categorizing the stimuli encouraged selective attention towards a single stimulus dimension (i.e., 1D tasks). For other rats, categorizing the stimuli required divided attention towards both stimulus dimensions (i.e., 2D tasks). Testing sessions then examined generalization to novel exemplars. PL lesions impaired learning and generalization for the 1D tasks, but not the 2D tasks. Then, a neural network was fit to the behavioral data to examine how the lesions affected categorization. The results suggest that the PL facilitates category learning by maintaining attention to category-relevant information and updating category representations.

Comprehensive Review of Topical Analgesics for Chronic Pain.

PURPOSE OF REVIEW: Topical analgesics are a non-opioid option for the treatment of chronic pain conditions including neuropathic pain, musculoskeletal pain, and osteoarthritis. There are many topical medications available; however their efficacy is variable. This article reviews the various topical analgesics, their mechanisms of action, and their efficacy. RECENT FINDINGS: Studies have found topical NSAIDs are useful in treating acute musculoskeletal pain syndromes (strains and sprains) and show some efficacy in treating hand and knee osteoarthritis (Derry et al. Cochrane Database Syst Rev 5:CD008609, 2017). Topical capsaicin 8% has been shown to be efficacious in the treatment of postherpetic neuralgia, painful diabetic peripheral neuropathy, and HIV-neuropathy (Derry et al. Cochrane Database Syst Rev 1:CD007393, 2017). Topical lidocaine has been widely studied and found to reduce pain in patients with postherpetic neuralgia (Knezevic et al. Pain Manag 7:537-58, 2017). Although many other topical analgesics are available, there is limited data to support the efficacy of other agents. Topical analgesics are a relatively benign treatment for chronic pain conditions including neuropathic pain, musculoskeletal, and myofascial pain. There is evidence to support the use of topical NSAIDs, high concentration topical capsaicin, and topical lidocaine for various painful conditions.

Interventional Modalities to Treat Complex Regional Pain Syndrome.

PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS. RECENT FINDINGS: Sympathetic nerve blocks (stellate ganglion and lumbar sympathetic) are the first-line interventional treatment options for patients with CRPS of the upper and lower extremities, respectively. Fluoroscopic techniques for lumbar sympathetic blocks have not significantly changed throughout the years. However, both novel fluoroscopic and ultrasound approaches to stellate ganglion blockade have arisen. In addition, novel neuromodulation therapies to treat CRPS have been developed to include new waveforms with dorsal column stimulation and entirely new nerve targets such as dorsal root ganglion stimulation. This paper will review the latest interventional treatment options available for the treatment of CRPS.

Mechanism of Action of Peripheral Nerve Stimulation.

PURPOSE OF REVIEW: The number of applications for peripheral nerve stimulation (PNS) in the pain management field is ever-growing. With the increasing number of clinical applications for peripheral nerve stimulation, the purpose of this article is to review the mechanism of action surrounding PNS, the recent literature from January 2018 to January 2021, and pertinent clinical outcomes. RECENT FINDINGS: The authors searched articles identified from PubMed (January 2018-January 2021), Cochrane Central Register of Controlled Trials databases (January 2018-January 2021), and Scopus (January 2018-January 2021) databases, and manually searched references of identified publications. Broad MeSH terms and Boolean operators were queried in each search, including the following terms and their respective synonyms: peripheral nerve stimulation, mechanism of action, biochemical pathway, and pain pathway. 15 consensus articles were selected for in-depth review and inclusion for qualitative analysis. PNS may activate and modulate higher central nervous system (CNS) centers, including the dorsal lateral prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and parahippocampal areas. Neuromodulatory effects from PNS may also extend into the spinal columns. Also, PNS may lead to changes in endogenous neurotransmitters and affect the plasticity of NMDA pathways.

Cannabinoid agonist administration within the cerebellar cortex impairs motor learning.

Systemic administration of cannabinoid agonists impairs cerebellum-dependent motor learning. The cannabinoid-induced impairment of motor learning has been hypothesized to be due to disruption of Purkinje cell plasticity within the cerebellar cortex. In the current study, we tested this hypothesis in rats with localized microinfusions of cannabinoid agonists and antagonists into the cerebellar cortex during eyeblink conditioning, a type of cerebellum-dependent motor learning. Infusions of the cannabinoid agonists WIN55,212-2 or ACEA directly into the eyeblink conditioning microzone of the cerebellar cortex severely impaired acquisition of eyeblink conditioning, whereas the CB1R antagonist SR141716A did not produce a significant impairment. Infusions of WIN55,212-2 outside of the eyeblink conditioning microzone did not impair motor learning, establishing anatomical specificity for the agonist effects. The motor learning impairment caused by WIN55,212-2 and ACEA was rescued by SR141716A, indicating that the learning deficit was produced through CB1Rs. The current findings demonstrate that the effects of cannabinoid receptor agonists on motor learning are localized to CB1Rs within a discrete microzone of the cerebellar cortex.

The Impact of the Quantity and Quality of Social Support on Patients with Chronic Pain.

PURPOSE OF REVIEW: Social support is an important yet often overlooked aspect of chronic pain management. Understanding the impact of social support on patients with chronic pain and determining if a relationship exists between a patient's perceived social support and their perceived quality of life is a crucial component to completely treating a pain patient. We sought to develop an intervention for patients with chronic pain that addresses the different types of social support, barriers to using social support, and ways to improve the quality of their social support. RECENT FINDINGS: A retrospective review of a prospectively collected database was utilized in an Outpatient Chronic Pain Rehabilitation Program with 23 patients with a chronic pain diagnosis who participated in a 3-week comprehensive pain rehabilitation program. Evaluation, intervention, and discharge were evaluated utilizing The American Chronic Pain Association's Quality of Life Scale and The Canadian Occupational Performance Measure (COPM). The intervention phase comprised a 45-min group session. At discharge, the occupational therapist followed up with the patient regarding the results of their social survey. Overall, the results indicated an underutilization of social support among patients with chronic pain. Out of the four questions asked on the social support survey, patients scored their use of tangible support (Q2) as the lowest. No significant positive correlation (0.27) was found between social support and quality of life which can be attributed to the wide variety of patients seen at the PRC. Social support is an essential part of chronic pain treatment and should be addressed throughout all stages of pain management.