Open monitoring meditation alters the EEG gamma coherence in experts meditators: The expert practice exhibit greater right intra-hemispheric functional coupling.

AIM: This study investigated the differences in frontoparietal EEG gamma coherence between expert meditators (EM) and naïve meditators (NM). MATERIAL AND METHODS: This is a cross-sectional study with a sample of twenty-one healthy adults divided under two groups (experts meditators vs. naive-meditators), with analyzing the intra-hemispheric coherence of frontoparietal gamma oscillations by electroencephalography during the study steps: EEG resting-state 1, during the open presence meditation practice, and EEG resting-state 2. RESULTS: The findings demonstrated greater frontoparietal EEG coherence in gamma for experts meditators in the Fp1-P3, F4-P4, F8-P4 electrode pairs during rest 1 and rest 2 (p ≤ 0.0083). In addition, we evidenced differences in the frontoparietal EEG coherence for expert meditators in F4-P4, F8-P4 during the meditation (p ≤ 0.0083). CONCLUSION: Our results can support evidence that the connectivity of the right frontoparietal network acts as a biomarker of the enhanced Open monitoring meditation training.

Bromazepam increases the error of the time interval judgments and modulates the EEG alpha asymmetry during time estimation.

AIM: This study investigated the bromazepam effects in male subjects during the time estimation performance and EEG alpha asymmetry in electrodes associated with the frontal and motor cortex. MATERIAL AND METHODS: This is a double-blind, crossover study with a sample of 32 healthy adults under control (placebo) vs. experimental (bromazepam) during visual time-estimation task in combination with electroencephalographic analysis. RESULTS: The results demonstrated that the bromazepam increased the relative error in the 4 s, 7 s, and 9 s intervals (p = 0.001). In addition, oral bromazepam modulated the EEG alpha asymmetry in cortical areas during the time judgment (p ≤ 0.025). CONCLUSION: The bromazepam decreases the precision of time estimation judgments and modulates the EEG alpha asymmetry, with greater left hemispheric dominance during time perception. Our findings suggest that bromazepam influences internal clock synchronization via the modulation of GABAergic receptors, strongly relating to attention, conscious perception, and behavioral performance.

Non-immersive 3D virtual stimulus alter the time production task performance and increase the EEG theta power in dorsolateral prefrontal cortex.

AIM: The study investigated the cortical activity changes and time production task performance induced by changes in motion speed of a non-immersive 3D virtual stimulus. MATERIAL AND METHODS: Twenty-one individuals were participated in the crossover study with the visual-time reproduction task under three-speed conditions: original, slow and fast virtual stimulus. In addition, the electroencephalographic analysis of the theta band power in the dorsolateral prefrontal cortex was done simultaneously with time production task execution. RESULTS: The results demonstrated that in the slow speed condition, there is an increase in the error in the time production task after virtual reality (p < 0.05). There is also increased EEG theta power in the right dorsolateral prefrontal cortex in all speed conditions (p < 0.05). CONCLUSIONS: We propose that the modulations of speed of virtual stimulus may underlie the accumulation of temporal pulses, which could be responsible for changes in the performance of the production task of the time intervals and a substantial increase in right dorsolateral prefrontal cortex activity related to attention and memory, acting in cognitive domains of supraseconds.

Unskilled shooters improve both accuracy and grouping shot having as reference skilled shooters cortical area: An EEG and tDCS study.

Transcranial direct current stimulation (tDCS) has been used as a non-invasive method for enhanced motor and cognitive abilities. However, no previous study has investigated if the tDCS application in unskilled shooters on cortical sites, selected based on the cortical activity of skilled shooters, improves the accuracy and shot grouping. Sixty participants were selected, which included 10 skilled shooters and 50 unskilled shooters. After we identified the right dorsolateral prefrontal cortex (DLPFC) as the area with the highest activity in skilled shooters, we applied anodal tDCS over the right DLPFC in the unskilled shooters under two conditions: sham-tDCS (placebo) and real-tDCS (anodal tDCS). We also analyzed electroencephalography. Our results indicated that anodal tDCS application enhanced the shot accuracy (p = 0.001). Furthermore, the beta power in the EEG recording was higher in the left DLPFC, left and right parietal cortex (p = 0,001) after applying anodal tDCS, while the low-gamma power was higher in the right DLPFC in sham-tDCS (p = 0.001) and right parietal cortex after anodal-tDCS (p = 0.001). Our findings indicate that anodal tDCS can improve accuracy and shot grouping when applied over the unskilled shooters' right DLPFC. Furthermore, beta and low-gamma bands are influenced by anodal tDCS over the right DLPFC, which may be predictive of skill improvement.

Time estimation exposure modifies cognitive aspects and cortical activity of attention deficit hyperactivity disorder adults.

AIM: This study investigated whether time-estimation task exposure influences the severity of Attention Deficit Hyperactivity Disorder (ADHD), as well as theta band activity in the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex. MATERIAL AND METHODS: Twenty-two patients with ADHD participated in a crossover experiment with a visual time-estimation task under control conditions (without exposure to time estimation tasks) and experimental (thirty days exposure to time-estimation tasks) in association with electroencephalographic analysis of theta band. RESULTS: ADHD patients with thirty days of time-estimation task exposure presented a worse performance of the time-estimation task, as revealed by the measurements of the absolute error and relative error (p ≤ 0.05). However, our findings show the improvement of self-reported symptoms of attention, impulsivity, and emotional control in patients after the time-estimation task exposure (p = 0.0001). Moreover, the theta band oscillations in the right dorsolateral prefrontal cortex and in the ventrolateral prefrontal increased with thirty days of time-estimation task exposure (p ≤ 0.05). CONCLUSION: We propose that the decrease in EEG theta power may indicate an efficient accumulation of temporal pulses, which could be responsible for the improvement in the patient cognitive aspects as demonstrated by the current study. Time-estimation task improves ADHD cognitive symptoms, with a substantial increase in cortical areas activity related to attention and memory, suggesting its use as a tool for cognitive timing function management and non-invasive therapeutic aid in ADHD.

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance.

AIM OF THE STUDY: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction. MATERIALS AND METHODS: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz). RESULTS: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05). CONCLUSIONS: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

The dopaminergic system dynamic in the time perception: a review of the evidence.

Dopaminergic system plays a key role in perception, which is an important executive function of the brain. Modulation in dopaminergic system forms an important biochemical underpinning of neural mechanisms of time perception in a very wide range, from milliseconds to seconds to longer daily rhythms. Distinct types of temporal experience are poorly understood, and the relationship between processing of different intervals by the brain has received little attention. A comprehensive understanding of interval timing functions should be sought within a wider context of temporal processing, involving genetic aspects, pharmacological models, cognitive aspects, motor control and the neurological diseases with impaired dopaminergic system. Particularly, an unexplored question is whether the role of dopamine in interval timing can be integrated with the role of dopamine in non-interval timing temporal components. In this review, we explore a wider perspective of dopaminergic system, involving genetic polymorphisms, pharmacological models, executive functions and neurological diseases on the time perception. We conclude that the dopaminergic system has great participation in impact on time perception and neurobiological basis of the executive functions and neurological diseases.

Time Perception Mechanisms at Central Nervous System.

The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson's disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks.

Processing of sub- and supra-second intervals in the primate brain results from the calibration of neuronal oscillators via sensory, motor, and feedback processes.

The processing of time intervals in the sub- to supra-second range by the brain is critical for the interaction of primates with their surroundings in activities, such as foraging and hunting. For an accurate processing of time intervals by the brain, representation of physical time within neuronal circuits is necessary. I propose that time dimension of the physical surrounding is represented in the brain by different types of neuronal oscillators, generating spikes or spike bursts at regular intervals. The proposed oscillators include the pacemaker neurons, tonic inputs, and synchronized excitation and inhibition of inter-connected neurons. Oscillators, which are built inside various circuits of brain, help to form modular clocks, processing time intervals or other temporal characteristics specific to functions of a circuit. Relative or absolute duration is represented within neuronal oscillators by "neural temporal unit," defined as the interval between regularly occurring spikes or spike bursts. Oscillator output is processed to produce changes in activities of neurons, named frequency modulator neuron, wired within a separate module, represented by the rate of change in frequency, and frequency of activities, proposed to encode time intervals. Inbuilt oscillators are calibrated by (a) feedback processes, (b) input of time intervals resulting from rhythmic external sensory stimulation, and (c) synchronous effects of feedback processes and evoked sensory activity. A single active clock is proposed per circuit, which is calibrated by one or more mechanisms. Multiple calibration mechanisms, inbuilt oscillators, and the presence of modular connections prevent a complete loss of interval timing functions of the brain.

Estradiol treatment prevents injury induced enhancement in spinal cord dynorphin expression.

Administration of the ovarian steroid estradiol in male and female animals has been shown to have neuromodulatory and neuroprotective effects in a variety of experimental models. In the present study, spinal tissues from dermatomes just above (T5-T7, at level) a severe chronic spinal cord injury (SCI) at T8 were analyzed for expression levels of prodynorphin (PRDN) and phospho-(serine 369) κ-opioid receptor (KOR-P) in 17 ß estradiol (EB)- and placebo-treated adult male rats. Dynorphin was targeted since (1) it has previously been shown to be elevated post-SCI, (2) intrathecal injection of dynorphin produces several of the same adverse effects seen with a SCI, and (3) its increased expression is known to occur in a variety of different experimental models of central neuropathic pain. A significant elevation of extracellular levels of both PRDN and KOR-P in the placebo-treated SCI group relative to uninjured surgical sham controls was found in spinal tissues above the injury level, indicating increased dynorphin levels. Importantly, the EB-treated SCI group did not show elevations of PRDN levels at 6 weeks post-injury. Immunohistochemical analysis of at level tissues revealed that EB treatment significantly prevented a post-SCI increase in expression of PRDN puncta co-labeling synapsin I, a nerve terminal marker. The dynorphin-containing terminals co-labeled vesicular glutamate receptor-2 (a marker of glutamatergic terminals), a finding consistent with a non-opioid basis for the adverse effects of dynorphin. These results support a beneficial role for EB treatment post-SCI through a reduction in excessive spinal cord levels of dynorphin. Studies manipulating the timing of the EB treatment post-injury along with specific functional assessments will address whether the beneficial effects are due to EB's potential neuromodulatory or neuroprotective action.

Bilateral bulbospinal projections to pudendal motoneuron circuitry after chronic spinal cord hemisection injury as revealed by transsynaptic tracing with pseudorabies virus.

Complications of spinal cord injury in males include losing brainstem control of pudendal nerve-innervated perineal muscles involved in erection and ejaculation. We previously described, in adult male rats, a bulbospinal pathway originating in a discrete area within the medullary gigantocellularis (GiA/Gi), and lateral paragigantocellularis (LPGi) nuclei, which when electrically microstimulated unilaterally, produces a bilateral inhibition of pudendal motoneuron reflex circuitry after crossing to the contralateral spinal cord below T8. Microstimulation following a long-term lateral hemisection, however, revealed reflex inhibition from both sides of the medulla, suggesting the development or unmasking of an injury-induced bulbospinal pathway crossing the midline cranial to the spinal lesion. In the present study, we investigated this pathway anatomically using the transsynaptic neuronal tracer pseudorabies virus (PRV) injected unilaterally into the bulbospongiosus muscle in uninjured controls, and ipsilateral to a chronic (1-2 months) unilateral lesion of the lateral funiculus. At 4.75 days post-injection, PRV-labeled cells were found bilaterally in the GiA/Gi/LPGi with equal side-to-side labeling in uninjured controls, and with significantly greater labeling contralateral to the lesion/injection in lesioned animals. The finding of PRV-labeled neurons on both sides of the medulla after removing the mid-thoracic spinal pathway on one side provides anatomical evidence for the bilaterality in both the brainstem origin and the lumbosacral pudendal circuit termination of the spared lateral funicular bulbospinal pathway. This also suggests that this bilaterality may contribute to the quick functional recovery of bladder and sexual functions observed in animals and humans with lateral hemisection injury.

Sex and hormonal variations in the development of at-level allodynia in a rat chronic spinal cord injury model.

The development of central neuropathic pain varies among patients with spinal cord injury (SCI). The factors contributing to the development and perpetuation of segmental pain (at-level allodynia) has been the focus of ongoing experiments in our laboratory. One such factor is hormonal status. We have shown previously, using a male rat model of SCI, that a severe contusion injury is necessary for the development of allodynia in trunk regions at and just above the level of a T8 injury. In this study, we examined at-level sensitivity for SCI ovariectomized (ovx) and cycling female rats as well as for SCI males implanted with either a placebo pellet or one that slowly releases 17beta-estradiol. The proportion of ovx SCI female rats and placebo-treated SCI males displaying pain-like behaviors to touch/pressure of at-level dermatomes up to 6 weeks post-injury (67% and 75%, respectively) was similar to our previous studies on SCI males (69%). In contrast, significantly fewer cycling SCI female rats and 17beta-estradiol treated SCI male rats showed sensitivity to touch at-level (26% and 30%, respectively). These results implicate 17beta-estradiol as a potential target that can readily be modulated to prevent segmental pain following SCI.

Spinal cord injuries containing asymmetrical damage in the ventrolateral funiculus is associated with a higher incidence of at-level allodynia.

UNLABELLED: Approximately 70% of male rats receiving severe T8 spinal contusions develop allodynia in T5-7 dermatomes (at-level) beginning 2 weeks after injury. In contrast, rats having either complete transections or dorsal hemisections do not develop allodynia at-level after chronic spinal cord injury (SCI). In the present study, incomplete laceration and contusion injuries were made to test for neuroanatomical correlates between areas of white matter damage/sparing at the lesion epicenter and the presence/absence of allodynia. After incomplete laceration lesions and 6 weeks of behavioral testing, histological reconstruction and analysis of the lesion epicenters revealed a significant difference (P < .001) in the amount of ventrolateral funiculus (VLF) asymmetry between rats showing pain-like responses evoked by touch (74.5% +/- 8.4% side-to-side difference in VLF damage) versus those not responding to touch (11.3% +/- 4.4% side-to-side difference in VLF damage). A 5-week mean allodynia score for each rat that incorporates a full range of forces that are all innocuous in intact controls revealed that the degree of hypersensitivity at level is related to the extent of VLF asymmetry after SCI. No other damaged spinal white matter or gray matter area was correlated with sensitivity to touch. Similar findings were obtained for rats receiving T8 contusions, a more clinically relevant injury. These data suggest that different extents of damage/sparing between the 2 sides of VLF probably are a requisite for the development of allodynia after SCI. PERSPECTIVE: A side-to-side lesion asymmetry after chronic SCI in a rodent model was found to be highly correlated with the presence and degree of allodynia. Greater insight of key factors contributing to the development and maintenance of chronic neuropathic pain is important for improving quality of life.

Relationship of spinal dynorphin neurons to delta-opioid receptors and estrogen receptor alpha: anatomical basis for ovarian sex steroid opioid antinociception.

Pharmacological and behavioral studies suggest that spinal delta- and kappa-opioid antinociceptive systems are functionally associated with ovarian sex steroids. These interactions can be demonstrated specifically during pregnancy or hormone-simulated pregnancy (HSP). The analgesia associated with both conditions can be abolished by blockade of either spinal kappa-opioid receptors or delta-opioid receptors (DOR). Furthermore, both dynorphin (DYN) release (J Pharmacol Exp Ther 298:1213-1220, 2001) and the processing of the DYN precursor (J Neurochem 65:1374-1380, 1995) are significantly increased in the spinal cord during HSP. We undertook the current study to determine whether DYN, DOR, and estrogen receptor alpha (ERalpha) share anatomical relationships that permit their direct interaction. Coexpression of DOR or ERalpha by DYN neurons was assessed using fluorescence immunohistochemistry and a synaptosomal release assay. Findings show that ERalpha and DYN are coexpressed. Moreover, in the spinal cord of HSP animals, there were significant increases in the number of DYN-immunoreactive (DYN-ir) cells, ERalpha-ir cells, cells double-labeled for DYN-ir and ERalpha-ir and the proportion of DYN-ir cells coexpressing ERalpha. Some varicose fibers in the spinal cord dorsal horn and intermediate gray matter that expressed DYN-ir also expressed DOR-ir. Activation of DORs located on DYN terminals was sufficient to inhibit K(+)-evoked DYN release. These data define, at least in part, the anatomical substrates that may be relevant to the antinociception of gestation and its hormonal simulation. Furthermore, they provide a framework for understanding sex-based nociception and antinociception and suggest novel strategies for treating pain.

Sex-/ovarian steroid-dependent release of endomorphin 2 from spinal cord.

Mu-opioid receptor (MOR) agonists have been shown to be more potent analgesics in male than female rodents. Regulation of spinal MOR-coupled antinociception by 17beta-estradiol (estrogen, E2) and progesterone (P) is also sexually dimorphic; pregnancy levels of E2/P activate MOR-coupled analgesic pathways in male but not female rats. We hypothesized that the sexual dimorphic characteristics of MOR-coupled antinociception reflects sexual dimorphism in the regulation of the release from spinal cord of the endogenous MOR agonist, endomorphin 2 (EM2). Parameters of spinal EM2 release manifesting sexual dimorphism include its 1) magnitude: in vitro basal and K+-evoked release of EM2 from spinal tissue of male rats is approximately 50% greater than that observed from spinal cord of females; 2) modulation by ovarian sex steroids: E2/P treatment significantly enhanced K+-evoked EM2 release from spinal tissue of males, but not females; and 3) enhancement by opioid receptor blockade: naloxone enhanced stimulated EM2 release from spinal tissue of both males and females, but it augmented basal release from spinal tissue of only males. Enhancement of EM2 release by naloxone reflects negative coupling of MOR to EM2 release and hence its modulation by negative feedback since only activation of MOR, not kappa-or delta-opioid receptors, was able to inhibit evoked EM2 release. These data reveal that the EM2-MOR spinal analgesic system is more robust and "higher gain" in male versus female rodents. These findings could provide a mechanistic rubric for understanding the male female dichotomy in prevalence and intensity of chronic pain syndromes.

Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia.

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long-term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness.

Influence of ovarian sex steroids on spinal methionine-enkephalin release: comparison with dynorphin reveals asymmetrical regulation.

The concomitant activation of spinal kappa- and delta-opioid systems is a prerequisite for the antinociception of gestation and its hormonal simulation [via 17 beta-estradiol and progesterone administration; hormone-simulated pregnancy (HSP)]. However, it is not known whether the release of kappa- and delta-opioids is also concomitantly regulated. This study investigates whether the release of methionine-enkephalin and modulation thereof is altered during HSP, as has been reported for dynorphin. K+-stimulated release of spinal methionine-enkephalin from lumbar spinal tissue obtained from control animals is negatively modulated by nociceptin (orphanin FQ; N/OFQ) in a dose-dependent manner, but not by opioids. Conversely, selective blockade of spinal N/OFQ, but not opioid receptors, augments the K+-induced increase in methionine-enkephalin release, indicating that endogenous N/OFQ also functions as a negative modulator of methionine-enkephalin release. The magnitude of K+-evoked methionine-enkephalin release from spinal tissue obtained from ovarian steroid-treated animals remains unchanged, consistent with the insensitivity of its modulation by N/OFQ to the ovarian sex steroid milieu. These characteristics of methionine-enkephalin release stand in sharp contrast to those previously reported for the evoked release of spinal dynorphin. Dynorphin release is subject to negative modulation by opioid (predominantly delta) as well as N/OFQ, both of which are offset during HSP, resulting in an approximately 2-fold increase in the magnitude of its release. These observations reveal that regulation of spinal dynorphin/kappa- and methionine-enkephalin/delta-spinal opioid antinociceptive systems is independent, divergent, and not symmetrical and support the formulation that spinal methionine-enkephalin/delta-opioid tone acts in a permissive/facilitative capacity to accentuate spinal dynorphin/kappa-activity.