Ipsilateral Nucleus Research Articles

Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

Chronic H3R activation reduces L-Dopa-induced dyskinesia, normalizes cortical GABA and glutamate levels, and increases striatal dopamine D1R mRNA expression in 6-hydroxydopamine-lesioned malerats.

Dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), are the major complication in the pharmacological treatment of Parkinson's disease. LIDs induce overactivity of the glutamatergic cortico-striatal projections, and drugs that reduce glutamatergic overactivity exert antidyskinetic actions. Chronic administration of immepip, agonist at histamine H3 receptors (H3R), reduces LIDs and diminishes GABA and glutamate content in striatal dialysates (Avila-Luna et al., Psychopharmacology 236: 1937-1948, 2019). In rats unilaterally lesioned with 6-hydroxydopamine in the substantia nigra pars compacta (SNc), we examined whether the chronic administration of immepip and their withdrawal modify LIDs, the effect of L-Dopa on glutamate and GABA content, and mRNA levels of dopamine D1 receptors (D1Rs) and H3Rs in the cerebral cortex and striatum. The administration of L-Dopa for 21 days induced LIDs. This effect was accompanied by increased GABA and glutamate levels in the cerebral cortex ipsi and contralateral to the lesioned SNc, and immepip administration prevented (GABA) or reduced (glutamate) these actions. In the striatum, GABA content increased in the ipsilateral nucleus, an effect prevented by immepip. L-Dopa administration had no significant effects on striatal glutamate levels. In lesioned and L-Dopa-treated animals, D1R mRNA decreased in the ipsilateral striatum, an effect prevented by immepip administration. Our results indicate that chronic H3R activation reduces LIDs and the overactivity of glutamatergic cortico-striatal projections, providing further evidence for an interaction between D1Rs and H3Rs in the cortex and striatum under normal and pathological conditions.

Whole-Brain Monosynaptic Afferents to Rostromedial Tegmental Nucleus Gamma-Aminobutyric Acid-Releasing Neurons in Mice.

Increasing evidence has revealed that the rostromedial tegmental area (RMTg) mediates many behaviors, including sleep and addiction. However, presynaptic patterns governing the activity of γ-aminobutyric acid-releasing (GABAergic) neurons, the main neuronal type in the RMTg, have not been defined. Here, we used cell-type-specific retrograde trans-synaptic rabies viruses to map and quantify the monosynaptic afferents to RMTg GABAergic neurons in mouse whole brains. We identified 71 ascending projection brain regions. Sixty-eight percent of the input neurons arise from the ipsilateral and 32% from the contralateral areas of the brain. The first three strongest projection regions were the ipsilateral lateral hypothalamus, zone incerta, and contralateral pontine reticular nucleus. Immunohistochemistry imaging showed that the input neurons in the dorsal raphe, laterodorsal tegmentum, and dorsal part of zone incerta were colocalized with serotoninergic, cholinergic, and neuronal nitric oxide synthetase-expressing neurons, respectively. However, in the lateral hypothalamus, a few input neurons innervating RMTg GABAergic neurons colocalized orexinergic neurons but lacked colocalization of melanin-concentrating hormone neurons. Our findings provide anatomical evidence to understand how RMTg GABAergic neurons integrate diverse information to exert varied functions.

Lateralizing Characteristics of Morphometric Changes to Hippocampus and Amygdala in Unilateral Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Background andObjective: In the present study, a detailed investigation of substructural volume change in the hippocampus (HC) and amygdala (AMG) was performed and the association with clinical features in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) determined. Methods: The present study included 22 patients with left-sided TLE-HS (LTLE-HS) and 26 patients with right-sided TLE-HS (RTLE-HS). In addition, 28 healthy controls underwent high-resolution T2-weighted image (T2WI) and T1-weighted image (T1WI) MRI scanning. Subfield analysis of HC and AMG was performed using FreeSurfer version 6.0. Results: Patients with TLE-HS showed a decrease in the volume of substructures in both HC and AMG, and this change was observed on the contralateral side and the ipsilateral side with HS. The volume reduction pattern of substructures showed laterality-dependent characteristics. Patients with LTLE-HS had smaller volumes of the ipsilateral subiculum (SUB), contralateral SUB, and ipsilateral cortical nucleus of AMG than patients with RTLE-HS. Patients with RTLE-HS had reduced ipsilateral cornu ammonis (CA) 2/3 and contralateral cortico-amygdaloid transition area (CAT) volumes. The relationship between clinical variables and subregions was different based on the lateralization of the seizure focus. Focal to bilateral tonic-clonic seizures (FTBTCS) was associated with contralateral and ipsilateral side subregions only in LTLE-HS. The abdominal FAS was associated with the volume reduction of AMG subregions only in LTLE-HS, but the volume reduction was less than in patients without FAS. Conclusions: The results indicate that unilateral TLE-HS is a bilateral disease that shows different laterality-dependent characteristics based on the subfield analysis of HC and AMG. Subfield volumes of HC and AMG were associated with clinical variables, and the more damaged substructures depended on laterality in TLE-HS. These findings support the evidence that LTLE-HS and RTLE-HS are disparate epilepsy entities rather than simply identical syndromes harboring a mesial temporal lesion. In addition, the presence of FAS supports good localization value, and abdominal FAS has a high localization value, especially in patients with LTLE-HS.

Alterations in pain processing circuitries in episodic migraine

BackgroundThe precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.MethodsFunctional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.ResultsDespite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.ConclusionsThese data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.

Basal forebrain magnocellular cholinergic systems are damaged in mice following neonatal hypoxia-ischemia.

Neonatal hypoxic-ischemic encephalopathy (HIE) causes lifelong neurologic disability. Despite the use of therapeutic hypothermia, memory deficits and executive functions remain severely affected. Cholinergic neurotransmission from the basal forebrain to neocortex and hippocampus is central to higher cortical functions. We examined the basal forebrain by light microscopy and reported loss of choline acetyltransferase-positive (ChAT)+ neurons, at postnatal day (P) 40, in the ipsilateral medial septal nucleus (MSN) after neonatal hypoxia-ischemia (HI) in mice. There was no loss of ChAT+ neurons in the ipsilateral nucleus basalis of Meynert (nbM) and striatum. Ipsilateral striatal and nbM ChAT+ neurons were abnormal with altered immunoreactivity for ChAT, shrunken and crenated somas, and dysmorphic appearing dendrites. Using confocal images with 3D reconstruction, nbM ChAT+ dendrites in HI mice were shorter than sham (p=.0001). Loss of ChAT+ neurons in the MSN directly correlated with loss of ipsilateral hippocampal area. In the nbM and striatum, percentage of abnormal ChAT+ neurons correlated with loss of ipsilateral cerebral cortical and striatal area, respectively. Acetylcholinesterase (AChE) activity increased in adjacent ipsilateral cerebral cortex and hippocampus and the increase was linearly related to loss of cortical and hippocampal area. Numbers and size of cathepsin D+ lysosomes increased in large neurons in the ipsilateral nbM. After neonatal HI, abnormalities were found throughout the major cholinergic systems in relationship to amount of forebrain area loss. There was also an upregulation of cathepsin D+ particles within the nbM. Cholinergic neuropathology may underlie the permanent dysfunction in learning, memory, and executive function after neonatal brain injury.

Ethanol-Dependent Synthesis of Salsolinol in the Posterior Ventral Tegmental Area as Key Mechanism of Ethanol's Action on Mesolimbic Dopamine.

Abnormal consumption of ethanol, the ingredient responsible for alcoholic drinks’ addictive liability, causes millions of deaths yearly. Ethanol’s addictive potential is triggered through activation, by a still unknown mechanism, of the mesolimbic dopamine (DA) system, part of a key motivation circuit, DA neurons in the posterior ventral tegmental area (pVTA) projecting to the ipsilateral nucleus accumbens shell (AcbSh). The present in vivo brain microdialysis study, in dually-implanted rats with one probe in the pVTA and another in the ipsilateral or contralateral AcbSh, demonstrates this mechanism. As a consequence of the oral administration of a pharmacologically relevant dose of ethanol, we simultaneously detect a) in the pVTA, a substance, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), untraceable under control conditions, product of condensation between DA and ethanol’s first by-product, acetaldehyde; and b) in the AcbSh, a significant increase of DA release. Moreover, such newly generated salsolinol in the pVTA is responsible for increasing AcbSh DA release via μ opioid receptor (μOR) stimulation. In fact, inhibition of salsolinol’s generation in the pVTA or blockade of pVTA μORs prevents ethanol-increased ipsilateral, but not contralateral, AcbSh DA release. This evidence discloses the long-sought key mechanism of ethanol’s addictive potential and suggests the grounds for developing preventive and therapeutic strategies against abnormal consumption.

Neuropathic pain increases spontaneous and noxious-evoked activity of locus coeruleus neurons

The noradrenergic locus coeruleus nucleus is an important station in both the ascending and descending pain regulatory pathways. These neurons discharge in tonic and phasic modes in response to sensory stimuli. However, few studies have set out to characterize the electrophysiological response of the locus coeruleus to noxious stimuli in conditions of neuropathic pain. Thus, the effects of mechanical nociceptive stimulation of the sciatic nerve area on spontaneous (tonic) and sensory-evoked (phasic) locus coeruleus discharge were studied by extracellular recording in anesthetized rats seven, fourteen and twenty-eight days after chronic constriction injury. Minor significant electrophysiological changes were found seven and fourteen days after nerve injury. However, alterations to the spontaneous activity in both the ipsilateral and contralateral locus coeruleus were found twenty-eight days after nerve constriction, as witnessed by an increase of burst firing incidence and irregular firing patterns. Furthermore, noxious-evoked responses were exacerbated in the contralateral and ipsilateral nucleus at twenty-eight days after injury, as were the responses evoked when stimulating the uninjured paw. In addition, mechanical stimulation of the hindpaw produced a significant sensitization of neuronal tonic activity after 28 days of neuropathy. In summary, long-term nerve injury led to higher spontaneous activity and exacerbated noxious-evoked responses in the locus coeruleus to stimulation of nerve-injured and even uninjured hindpaws, coinciding temporally with the development of depressive and anxiogenic-like behavior.

Nicotine-induced Brain Stimulation Reward is Modulated by Melanocortin-4 Receptors in Ovariectomized Rats

Apart from reproduction, estrogen influences a multitude of processes. Increase in estrogen levels in women is known to promote reward probably mediated via the melanocortin and dopamine systems. Reduced estrogen in post-menopausal women attenuates reward, evoking the need for stimulation with greater rewarding salience. This is reflected in the well-recognized phenomena of difficulty in quitting and increased craving for nicotine in women following the onset of menopause. The present study aims at understanding the role of melanocortin receptors (MC-R) in nicotine-induced reward behavior following ovariectomy in rats. The MC4-R mRNA level was increased in ipsilateral nucleus accumbens (Acb) of the intact rats implanted with electrode in medial forebrain bundle and trained in intracranial self-stimulation (ICSS) paradigm. Additional groups of ICSS trained rats were ovariectomized (OVX) and subjected to reward evaluation. Trained OVX rats revealed a significant increase in threshold frequency and rightward shift in rate frequency curve, suggesting reward deficit behavior. However, pre-administration with nicotine, alpha-melanocyte stimulating hormone (α-MSH) or NDP-MSH (MC4-R agonist) to OVX animals restored the rewarding activity in ICSS protocol; HS014 (MC4-R antagonist) suppressed the lever press activity. Prior treatment with sub-effective doses of α-MSH or NDP-MSH potentiated the reward effect of nicotine, but was attenuated by HS014. Alpha-MSH-immunoreactivity was decreased in the Acb shell, arcuate and paraventricular nucleus of hypothalamus, and ventral bed nucleus of stria terminalis in the OVX rats, while nicotine treatment restored the same. We suggest a role for the endogenous MC system, perhaps acting via MC4-R, in the nicotine-induced reward in OVX rats.

Excitotoxic neurodegeneration is associated with a focal decrease in metabotropic glutamate receptor type 5 availability: an in vivo PET imaging study

Metabotropic glutamate receptors (mGluRs) have been proposed as promising therapeutic targets to correct the dysregulated glutamate signaling, associated with neurodegenerative pathologies. Of all mGluR subtypes, especially mGluR5 acts as a modulator of glutamate-induced excitotoxicity. To study the behavior of mGluR5 following localized excitotoxicity, we utilised a pharmacological model that portrays exacerbated neuronal glutamate release, mediated by the endogenous excitotoxin quinolinic acid (QA). Using longitudinal positron emission tomography (PET) with [18F]FPEB, we investigated cerebral changes in mGluR5 following striatal QA-lesioning. Behavioral tests were executed to monitor motor and cognitive performance. Decreased mGluR5 binding potential (BPND) was found in the affected striatum and globus pallidus of QA-lesioned rats at week 3, and further decreased at week 7, as compared to sham-injected controls. mGluR5 availability in the ipsilateral nucleus accumbens was significantly decreased at 7 weeks post-injection. QA rats performed significantly worse on motor coordination and balance compared to control rats. Correlation analysis indicated a positive correlation between striatal mGluR5 BPND and rotarod performance whereas print width of the unaffected forepaws showed a positive relation with mGluR5 BPND in the contralateral motor cortex. Together, our results suggest decreased mGluR5 availability to be related to excitotoxin-induced neurodegeneration and symptomatology although late stage effects do indicate possible cortical mGluR5-mediated effects on motor behavior.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms. Methods Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis. Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P 0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P 0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms. Key words: Parkinson disease; Dopamine plasma membrane transport proteins; Signs and symptoms; Positron-emission computed; Deoxyglucose

Application of 18F-DOPA PET imaging in the diagnosis and assessment of early-stage Parkinson′s disease

Objective To investigate the clinical values of L-6-18F-fluoro-3, 4-dihydroxyphenylalanine (18F-DOPA) PET in the diagnosis and severity assessment of early-stage Parkinson′s disease (PD). Methods Thirty-eight patients (24 males, 14 females; age: 34-74 years) with early-stage PD (Hoehn-Yahr (H-Y) staging: 1-2) and 5 age-matched healthy volunteers (all males; age: 45-65 years) from July 2016 to March 2017 were included and underwent 18F-DOPA PET scan in this retrospective study. The striatal-to-occipital ratio (SOR) was calculated and compared between PD patients and healthy volunteers. The unified PD rating scale (UPDRS) Ⅲ score and H-Y staging were used to evaluate the clinical symptoms. Two-sample t test and Pearson correlation analysis were used. Results In the control group, 18F-DOPA SORs in bilateral putamen and caudate nucleus were 2.50±0.24 and 2.61±0.23, respectively. In PD group, the SORs of ipsilateral and contralateral putamen nucleus were 2.02±0.27 and 1.80±0.26 respectively, lower than those in the control group (t values: -4.006, -5.440, both P<0.01). The SORs of ipsilateral and contralateral caudate nucleus were 2.16±0.32 and 2.08±0.28 respectively, lower than those in the control group (t values: -2.990, -4.047, both P<0.01). The SORs of contralateral putamen and caudate nucleus were significantly lower than those of the ipsilateral striatum respectively (t values: -6.431, -3.837, both P<0.01). Furthermore, the SORs in the striatum (putamen and caudate nucleus) were negatively correlated with UPDRS Ⅲ score, H-Y staging, and duration of disease (r values: from -0.526 to -0.369, all P<0.05). Conclusions 18F-DOPA PET can reflect the changes in the striatum neurons, and it may be an important method in the diagnosis and assessment of early-stage PD patients. Key words: Parkinson disease; Positron-emission tomography; Tomography, X-ray computed; Levodopa; Fluorine radioisotopes

Gamma and infra-slow oscillations shape neuronal firing in the rat subcortical visual system.

Neuronal oscillations observed in sensory systems are physiological carriers of information about stimulus features. Rhythm in the infra-slow range, originating from the retina, was previously found in the firing of subcortical visual system nuclei involved in both image and non-image forming functions. The present study shows that the firing of neurons in the lateral geniculate nucleus is also governed by gamma oscillation (∼35Hz) time-locked to high phase of infra-slow rhythm that codes the intensity of transient light stimulation. We show that both physiological rhythms are synchronized within and between ipsilateral nuclei of the subcortical visual system and are dependent on retinal activity. The present study shows that neurophysiological oscillations characterized by various frequencies not only coexist in the subcortical visual system, but also are subjected to complex interference and synchronization processes. The physiological function of rhythmic firing in the neuronal networks of sensory systems has been linked with information coding. Also, neuronal oscillations in different frequency bands often change as a signature of brain state or sensory processing. Infra-slow oscillation (ISO) in the neuronal firing dependent on the retinal network has been described previously in the structures of the subcortical visual system. In the present study, we show for the first time that firing of ISO neurons in the lateral geniculate nucleus is also characterized by a harmonic discharge pattern (i.e. action potentials are separated by the intervals governed by fundamental frequency in the gamma range: ∼35Hz). A similar phenomenon was recently described in the suprachiasmatic nuclei of the hypothalamus: the master biological clock. We found that both gamma and ISO rhythms were synchronized within and between ipsilateral nuclei of the subcortical visual system and were dependent on the retinal activity of the contralateral eye. These oscillatory patterns were differentially influenced by transient and prolonged light stimulation with respect to both frequency change direction and sustainability. The results of the present study show that the firing pattern of neurons in the subcortical visual system is shaped by oscillations from infra-slow and gamma frequency bands that are plausibly generated by the retinal network. Additionally, the results demonstrate that both rhythms are not a distinctive feature of image or non-image forming visual systems but, instead, they comprise two channels carrying distinctive properties of photic information.

Abstract WP252: Mechanism of Secondary Thalamic Injury Induced by Focal Cortical Stroke

Remote secondary injury in the thalamus has been observed following rodent and human stroke and is associated with poorer recovery. However the mechanisms and resultant molecular changes whereby cortical infarction leads to remote injury in distant regions of brain are not well defined. The present studies utilize a mouse model of permanent distal MCAO (pdMCAO) with delayed secondary thalamic injury. We have measured time dependent molecular and cellular events, focusing on glial activation and neuronal death in the thalamus. These studies provide an important foundation for future studies aimed at reducing secondary brain injury. Methods: Cortical infarction by pdMCAO was induced by microcauterization of the distal MCA in male C57BL/6J mice (11-13 wks). Cresyl violet (CV), fluoro-jade C (FJC) and immunochemical staining were performed at 24 hours, 3 days, 1 week, and 2 weeks after stroke (n=5, each time point) and in shams (n=3). Results: First, we confirmed with TTC staining that the primary infarction induced by pdMCAO was restricted to the cortex of the MCA territory at 72 hours, and that no infarct was seen in the thalamus. Microglia and astrocyte activation (IBA-1 and GFAP, respectively) was first detectable in the ipsilateral ventral posteromedial nucleus (VPN) of the thalamus at 3 days after stroke, and progressively increased at 1 and 2 weeks. However, thalamic neuronal injury (by FJC staining) was not evident until 1 week after stroke. At 2 weeks following stroke, the number of FJC positive neurons further increased and significant morphological changes were evident by CV staining, including shrunken cytoplasm and condensed pyknotic nuclei. Conclusions: We present a mouse stroke model for studying the mechanisms of secondary thalamic injury. In this model, primary cortical injury results in delayed cellular events in the ipsilateral thalamus, including an initial activation of microglia and astrocytes with subsequent neuronal injury and death. These studies provide necessary foundation for designing future interventional strategies aimed at reducing secondary injury following stroke.

Polysialylated Neural Cell Adhesion Molecule Supports Regeneration of Neurons in the Nucleus Ambiguus After Unilateral Recurrent Laryngeal Nerve Avulsion in Adult Rats

A correlation appears to exist between the expression of the polysialic acid neural cell adhesion molecule (PSA-NCAM) and repair in central nervous system (CNS) diseases. However, the expression of PSA-NCAM in the CNS after peripheral nerve injury remains unclear. This study aimed to evaluate the expression of PSA-NCAM in the ipsilateral nucleus ambiguus (NA) after unilateral recurrent laryngeal nerve (RLN) avulsion. The left RLN of adult Sprague Dawley rats were avulsed. The expression of PSA-NCAM, PSA-NCAM/NeuN, and PSA-NCAM/Tuj1 in the brain stem was investigated using immunohistochemistry. The results were subjected to one-way analysis of variance followed by the Tukey post hoc test for statistical analyses. PSA-NCAM-positive and PSA-NCAM/NeuN and PSA-NCAM/Tuj1 double-labeled positive cells were observed 7 days post injury in the ipsilateral NA. PSA-NCAM/NeuN and PSA-NCAM/Tuj1 double-labeled cells were observed at 21 and 7 days post injury, respectively. PSA-NCAM/NeuN double-labeled cells were also found in the contralateral NA. After unilateral avulsion of the RLN, the expression of PSA-NCAM in the ipsilateral NA was correlated with the proliferation and the differentiation of neural cells. PSA-NCAM expression may be used as a predictor of the initiation of repair in neural cells.

Cued Reinstatement of Cocaine but Not Sucrose Seeking Is Dependent on Dopamine Signaling in Prelimbic Cortex and Is Associated with Recruitment of Prelimbic Neurons That Project to Contralateral Nucleus Accumbens Core.

BackgroundDrug cues recruit prelimbic cortex neurons that project to ipsilateral nucleus accumbens core. However, it is not known if the same is true for prelimbic cortex projections that decussate to innervate contralateral nucleus accumbens core. Further, a role for prelimbic cortex dopamine signaling in cued reinstatement of cocaine seeking has not been shown.MethodsWe assessed Fos expression in prelimbic cortex neurons that project to contralateral nucleus accumbens core following cued reinstatement of cocaine or sucrose seeking. We also tested the effect of intra-prelimbic cortex infusions of the D1/D2 antagonist fluphenazine on cued cocaine and sucrose seeking.ResultsPrelimbic cortex-contralateral nucleus accumbens core projections were activated by cocaine cues but not sucrose cues, and this activation correlated with reinstatement behavior. Blockade of prelimbic cortex dopamine signaling prevented cued reinstatement of cocaine- but not sucrose-seeking behavior.ConclusionsCued cocaine seeking is associated with activation of the prelimbic cortex-contralateral nucleus accumbens core pathway. Prelimbic cortex dopamine signaling is necessary for cues to reinstate drug-seeking behavior.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794).

Post-discectomy pseudocyst after transformimal percutaneous endoscopic discectomy: two cases reports and related literature review

Objective To investigate the clinical features and treatment of post-discectomy pseudocyst after transformimal percutaneous endoscopic discectomy. Methods Two patients from two different hospitals were retrospectively studied. One was male whose age was 26 years old, and the other was female whose age was 34 years old. Both cases presented with radiating unilateral leg pain and were diagnosed with ipsilateral herniated nucleus pulposus at L4,5 based on MRI. They both experienced recurrent symptoms after successful transformimal percutaneous endoscopic discectomy. The mean time to relapsing radiculopathy was 1.5 months (1-2 months) with 8 on the visual analogue scale scores. On the postoperative MRI, cystic lesion of T2WI high (similar to cerebrospinal fluid) and T1W low at discectomy site was found in both patients. Results One case was conducted with partial hemilaminectomy and discectomy. A dark red cystic mass containing old bloody fluid was found intra-operatively, and the histology of the cyst wall showed nucleus-like tissue, and inflammatory granulation tissue containing neovascularization and inflammatory cell infiltration in some area. The other case was conducted transformimal percutaneous endoscopic discectomy again, and dark red granulation tissue was found intra-operatively, and the histology of capsule wall showed fibrous connective tissue. Both cases achieved successful pain relief after the second surgeries. And MRI demonstrated the pseudocysts disappeared 3 months follow-up postoperatively. Conclusion Symptomatic post-discectomy pseudocyst is a rare complication after transformimal percutaneous endoscopic discectomy. It usually occurs in the early period postoperatively. MRI can confirm the diagnosis. Patients with failed conservative treatment can treat with surgery, and the prognosis is good. Key words: Diskectomy; Endoscopy; Postoperative complications

Effect of Stellate Ganglion Block on the Cerebral Cortex: A Functional Magnetic Resonance Imaging Study

The objective of this study is to investigate the neural activities in the human brain after stellate ganglion block (SGB) treatment using functional magnetic resonance imaging (fMRI). Thirteen healthy female volunteers from the local community participated in the study. An echo planar imaging sequence for fMRI has used to examine the effect on the cerebral cortex before and after SGB stimulation at 1.5T MRI. We used 6 mL of 1 % mepivacaine hydrochloride as a local anesthetic. Two control groups with and without a saline injection were also included. FMRI data were processed using statistical parametric mapping. The blood-oxygen-level-dependent fMRI signal intensities increased in contralateral anterior cingulate cortex, hypothalamus, ventral putamen, and parahippocampal gyrus after SGB stimulation, while the signal intensities had decreased in contralateral thalamus and dorsal putamen, and ipsilateral caudate nucleus. In the saline control group, the signal intensities in ipsilateral posterior putamen and superior temporal gyrus and both insular cortices have increased significantly. The present study could show the changes by SGB in the several important brain areas associated with sympathetic nervous system. The non-invasive and repeatable imaging technique of fMRI could provide some useful information for better understanding of the neural mechanisms involved in SGB treatments.

Catecholamine inputs to expiratory laryngeal motoneurons in rats.

Many respiration-related interneurons and motoneurons receive a catecholaminergic input, but the extent and distribution of this input to recurrent laryngeal motoneurons that innervate intrinsic muscles of the larynx are not clear. In the present study, we examined the catecholaminergic input to expiratory laryngeal motoneurons in the caudal nucleus ambiguus by combining intracellular labeling of single identified motoneurons, with immunohistochemistry to reveal tyrosine hydroxylase immunoreactive (catecholaminergic) terminal varicosities. Close appositions were found between the two structures, with 18 ± 5 close appositions per motoneuron (n = 7). Close appositions were more frequently observed on distal rather than proximal dendrites. Axosomatic appositions were not seen. In order to determine the source of this input, microinjections of cholera toxin B subunit (1%, 20 nl) were made into the caudal nucleus ambiguus. Retrogradely labeled neurons, located in the ipsilateral nucleus tractus solitarius and the area postrema, were tyrosine hydroxylase-positive. Our results not only demonstrate details of the extent and distribution of potential catecholamine inputs to the expiratory laryngeal motoneuron, but further indicate that the inputs, at least in part, originate from the dorsomedial medulla, providing a potential anatomical basis for previously reported catecholaminergic effects on the laryngeal adductor reflex.