An investigation of Hebbian phase sequences as assembly graphs

Hebb proposed that synapses between neurons that fire synchronously are strengthened, forming cell assemblies and phase sequences. The former, on a shorter scale, are ensembles of synchronized cells that function transiently as a closed processing system; the latter, on a larger scale, correspond to the sequential activation of cell assemblies able to represent percepts and behaviors. Nowadays, the recording of large neuronal populations allows for the detection of multiple cell assemblies. Within Hebb's theory, the next logical step is the analysis of phase sequences. Here we detected phase sequences as consecutive assembly activation patterns, and then analyzed their graph attributes in relation to behavior. We investigated action potentials recorded from the adult rat hippocampus and neocortex before, during and after novel object exploration (experimental periods). Within assembly graphs, each assembly corresponded to a node, and each edge corresponded to the temporal sequence of consecutive node activations. The sum of all assembly activations was proportional to firing rates, but the activity of individual assemblies was not. Assembly repertoire was stable across experimental periods, suggesting that novel experience does not create new assemblies in the adult rat. Assembly graph attributes, on the other hand, varied significantly across behavioral states and experimental periods, and were separable enough to correctly classify experimental periods (Naïve Bayes classifier; maximum AUROCs ranging from 0.55 to 0.99) and behavioral states (waking, slow wave sleep, and rapid eye movement sleep; maximum AUROCs ranging from 0.64 to 0.98). Our findings agree with Hebb's view that assemblies correspond to primitive building blocks of representation, nearly unchanged in the adult, while phase sequences are labile across behavioral states and change after novel experience. The results are compatible with a role for phase sequences in behavior and cognition.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients' relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.

ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Thesis (Ph.D, Psychology) -- Queen's University, 2016-10-04 17:37:07.888

Block of the Mitral-pulmonary Isthmus During Ablation of a Single Left-sided Accessory Pathway Causing Different Patterns of Retrograde Atrial Activation

The case of a 16-year-old patient with atrioventricular tachycardia caused by a single left anterolateral accessory pathway is reported. When the patient underwent radiofrequency ablation, a lesion on the mitral annulus lateral wall produced changes in the retrograde atrial activation pattern determined by that pathway; changes ranged from a delay in depolarization of the annulus posterior portions to full left atrium counterclockwise activation. Such phenomena were probably caused by a block in the isthmus between the annulus and the lower left pulmonary vein ostium. This case illustrates the importance of the mitral-pulmonary isthmus in the process of left atrium activation, an alert to changes induced by its unintentional block during accessory pathway ablation.

Cardiovascular patterns associated with appetitive and defensive activation during affective picture viewing

Descriptors: cardiovascular patterns, emotion, affective pictures In this study we assessed blood pressure (BP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) in response to 13 picture series in 18 men and 19 women in order to investigate their hemodynamic responses associated with activation of the appetitive and defensive motivational systems underlying emotional experience. Skin conductance level (SCL) was also recorded. BP and SV increased with increasing self-rated arousal both for appetitive and defensive activation, whereas HR decelerated more in response to negative than positive and neutral pictures. TPR showed a general increase from baseline to picture processing but was unrelated to self-rated valence and arousal. These findings suggest that affective modulation of the cardiovascular response to affective pictures is primarily myocardial. The observed response pattern is consistent with a configuration of cardiac sympathetic-parasympathetic coactivation. The relationships between self-reported arousal, BP and SV were mainly exhibited by men suggesting that increases in the sympathetic inotropic effect to the heart with increasing self-rated arousal might be larger in men than in women. In contrast, SCL covaried positively with self-rated arousal both in men and women. This suggests that sex differences in the affective modulation of the responses to pictures may be restricted to specific cardiovascular parameters and support the contention that the sympathetic nervous system does not discharge as a whole.

Cardiovascular patterns associated with appetitive and defensive activation during affective picture viewing

In this study we assessed blood pressure (BP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) in response to 13 picture series in 37 participants in order to investigate their hemodynamic response associated with activation of the appetitive and defensive motivational systems underlying emotional experience. BP and SV, but not TPR, increased with increasing self-rated arousal, whereas HR decelerated more in response to negative than positive and neutral pictures. These findings suggest that modulation of the cardiovascular response to pictures is primarily myocardial. The observed response pattern is consistent with a configuration of cardiac sympathetic-parasympathetic coactivation. The relationships between self-rated arousal, BP, and SV were mainly exhibited by men, suggesting that increases in the sympathetic inotropic effect to the heart with self-rated arousal may be larger in men than in women.

Patterns of fos activation in rat raphe nuclei during feeding behavior

To analyze the differential recruitment of the raphe nuclei during different phases of feeding behavior, rats were subjected to a food restriction schedule (food for 2 h/day, during 15 days). The animals were submitted to different feeding conditions, constituting the experimental groups: search for food (MFS), food ingestion (MFI), satiety (MFSa) and food restriction control (MFC). A baseline condition (BC) group was included as further control. The MFI and MFC groups, which presented greater autonomic and somatic activation, had more FOS-immunoreactive (FOS-IR) neurons. The MFI group presented more labeled cells in the linear (LRN) and dorsal (DRN) nuclei; the MFC group showed more labeling in the median (MRN), pontine (PRN), magnus (NRM) and obscurus (NRO) nuclei; and the MFSa group had more labeled cells in the pallidus (NRP). The BC exhibited the lowest number of reactive cells. The PRN presented the highest percentage of activation in the raphe while the DRN the lowest. Additional experiments revealed few double-labeled (FOS-IR+ 5-HT-IR) cells within the raphe nuclei in the MFI group, suggesting little serotonergic activation in the raphe during food ingestion. These findings suggest a differential recruitment of raphe nuclei during various phases of feeding behavior. Such findings may reflect changes in behavioral state (e.g., food-induced arousal versus sleep) that lead to greater motor activation, and consequently increased FOS expression. While these data are consistent with the idea that the raphe system acts as gain setter for autonomic and somatic activities, the functional complexity of the raphe is not completely understood. (c) 2008 Elsevier B.V. All rights reserved.

Maternal immune activation increases the corticosterone response to acute stress without affecting the hypothalamic monoamine content and sleep patterns in male mice offspring

Background/Aims: Early life experiences are homeostatic determinants for adult organisms. We evaluated the impact of prenatal immune activation during late gestation on the neuroimmune-endocrine function of adult offspring and its interaction with acute stress. Methods: Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. Adult male offspring were assigned to the control or restraint stress condition. We analyzed plasmatic corticosterone and catecholamine levels, the monoamine content in the hypothalamus, striatum and frontal cortex, and the sleep-wake cycle before and after acute restraint stress. Results and Conclusion: Offspring from LPS-treated dams had increased baseline norepinephrine levels and potentiated corticosterone secretion after the acute stressor, and no effect was observed on hypothalamic monoamine content or sleep behavior. The offspring of immune-activated dams exhibited impairments in stress-induced serotonergic and dopaminergic alterations in the striatum and frontal cortex. The data demonstrate a distinction between the plasmatic levels of corticosterone in response to acute stress and the hypothalamic monoamine content and sleep patterns. We provide new evidence regarding the influence of immune activation during late gestation on the neuroendocrine homeostasis of offspring.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.

Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (μm) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU). RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.

Kinematic, kinetic and EMG patterns during downward squatting

The aim of this study was to investigate the kinematic, kinetic, and electromyographic pattern before, during and after downward squatting when the trunk movement is restricted in the sagittal plane. Eight healthy subjects performed downward squatting at two different positions, semisquatting (40 degrees knee flexion) and half squatting (70 degrees knee flexion). Electromyographic responses of the vastus medialis oblique, vastus medialis longus, rectus femoris, vastus lateralis, biceps femoris, semitendineous, gastrocnemius lateralis, and tibialis anterior were recorded. The kinematics of the major joints were reconstructed using an optoelectronic system. The center of pressure (COP) was obtained using data collected from one force plate, and the ankle and knee joint torques were calculated using inverse dynamics. In the upright position there were small changes in the COP and in the knee and ankle joint torques. The tibialis anterior provoked the disruption of this upright position initiating the squat. During the acceleration phase of the squat the COP moved posteriorly, the knee joint torque remained in flexion and there was no measurable muscle activation. As the body went into the deceleration phase, the knee joint torque increased towards extension with major muscle activities being observed in the four heads of the quadriceps. Understanding these kinematic, kinetic and EMG strategies before, during and after the squat is expected to be beneficial to practitioners for utilizing squatting as a task for improving motor function. (C) 2006 Elsevier Ltd. All rights reserved.

Midazolam reduces the selective activation of the rhinal cortex by contextual fear stimuli

Independent brain circuits appear to underlie different forms of conditioned fear, depending on the type of conditioning used, such as a context or explicit cue paired with footshocks. Several clinical reports have associated damage to the medial temporal lobe (MTL) with retrograde amnesia. Although a number of studies have elucidated the neural circuits underlying conditioned fear, the involvement of MTL components in the aversive conditioning paradigm is still unclear. To address this issue, we assessed freezing responses and Fos protein expression in subregions of the rhinal cortex and ventral hippocampus of rats following exposure to a context, light or tone previously paired with footshock (Experiment 1). A comparable degree of freezing was observed in the three types of conditioned fear, but with distinct patterns of Fos distribution. The groups exposed to cued fear conditioning did not show changes in Fos expression, whereas the group subjected to contextual fear conditioning showed selective activation of the ectorhinal (Ect), perirhinal (Per), and entorhinal (Ent) cortices, with no changes in the ventral hippocampus. We then examined the effects of the benzodiazepine midazolam injected bilaterally into these three rhinal subregions in the expression of contextual fear conditioning (Experiment 2). Midazolam administration into the Ect, Per, and Ent reduced freezing responses. These findings suggest that contextual and explicit stimuli endowed with aversive properties through conditioning recruit distinct brain areas, and the rhinal cortex appears to be critical for storing context-, but not explicit cue-footshock, associations. (C) 2010 Elsevier B.V. All rights reserved.

Fronto-parietal activation in attention-deficit hyperactivity disorder, combined type: functional magnetic resonance imaging study

A functional magnetic resonance imaging mental rotation paradigm was used to investigate the patterns of activation of fronto-parietal brain areas in male adolescents with attention-deficit hyperactivity disorder, combined type (ADHD-CT) compared with age-, gender-, handedness- and performance IQ-matched healthy controls. The ADHD-CT group had (a) decreased activation of the 'action-attentional' system (including Brodmann's areas (BA) 46, 39,40) and the superior parietal (BA7) and middle frontal (BA10) areas and (b) increased activation of the posterior midline attentional system. These different neuroactivation patterns indicate widespread frontal, striatal and parietal dysfunction in adolescents with ADHD-CT. Declaration of interest None.

Glutamatergic Antagonism in the NTS Decreases Post-Inspiratory Drive and Changes Phrenic and Sympathetic Coupling During Chemoreflex Activation

Costa-Silva JH, Zoccal DB, Machado BH. Glutamatergic antagonism in the NTS decreases post-inspiratory drive and changes phrenic and sympathetic coupling during chemoreflex activation. J Neurophysiol 103: 2095-2106, 2010. First published February 17, 2010; doi: 10.1152/jn.00802.2009. For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.

Ageing and surface EMG activity patterns of masticatory muscles

P>The purpose of this study was to evaluate the influence of age on the electromyographic activity of masticatory muscles. All volunteers were Brazilian, fully dentate (except for Group I - mixed dentition), Caucasian, aged 7-80, and divided into five groups: I (7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years) and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided with respect to gender (20 M/20 F). Surface electromyographic records of masticatory muscles were obtained at rest and during maximal voluntary contraction, right and left laterality, maximal jaw protrusion and maximal clenching in the intercuspal position. Statistically significant differences (P < 0 center dot 05) were found in all clinical conditions among the different age groups. Considerably different patterns of muscle activation were found across ages, with greater electromyographic activity in children and youth, and decreasing from adults to aged people.