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סרוטונין, דופמין - DMT- חרדה- פלאשבקים - גלי GAMMA - פוסט בבניה - לא לקרוא כרגע רק אוספת מידע

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https://www.liveabout.com/haunted-by-black-cloaked-entity-2596482

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https://treehouserecoverypdx.com/addiction-blog/shame-is-a-guilty-pleasure-you-should-stop-indulging-in/#:~:text=When%20dopamine%20gets%20to%20the,they%20neurologically%20feel%20so%20good.

SHAME IS A GUILTY PLEASURE YOU SHOULD STOP INDULGING IN

October 10, 2017Leave a Comment

Guilt is at once described as toxic and a pleasure. We try to rid ourselves of unnecessary guilt because it is a useless and damaging emotion. Guilt is not without it’s importance. Helping us differentiate right from wrong, guilt has an instructional presence in our lives. Yet, when guilt surpasses its necessity, it can create a pathology of behaviors, thoughts, and actions which are a detriment rather than an advantage. Yet, we also refer to things in life as a “guilty pleasure”. These are things which are so “bad”, they’re “good”. Whether it is that forbidden spoonful of raw cookie dough, a Netflix binge spent in secrecy, or a hidden hobby, the things that we sometimes love the most are the things for which we feel the most shame. That driving sense of guilt fuels the pleasure of the activity, which might act more like an addiction than we are willing to admit.

According to Alex Korb, author of The Upward Spiral, as reported on by Stuff.co of New Zealand, “Pride, shame and guilt all activate similar neural circuits…” However, guilt and shame have a greater presence in the nucleus accumbens, which is the reward center of the brain. Addiction takes part in the brain through the nucleus accumbens. When drugs and alcohol are abused, they create a surplus of a neurotransmitter called dopamine. Neurotransmitters are like chemical messaging systems in the brain that communicate ‘pleasure’ throughout different parts of the brain, like the nucleus accumbens. When dopamine gets to the reward center, the reward center takes note of the fact that drugs and alcohol created these pleasurable, rewarding sensations. Guilt and shame have so much presence in our lives because they, in part, activate our reward center and though they feel so “bad”, they neurologically feel so good.

Through our therapy we learn that even the things that makes us feel the worst have some kind of a payoff. Our compulsive behaviors with drugs and alcohol are painful, full of shame and full of guilt. Addiction is just one of a long list of behaviors which provide this effect. The things we do, the thoughts we think, the ways we behave, which hurt us, hurt others, and hurt our quality of life have some kind of benefit or payoff. Whatever the payoff is, it may not seem beneficial on the surface, but it serves a purpose of reward underneath. The more we can discover, acknowledge, and work through these cycles of guilt and shame the more free we can become, letting guilt be guilt, as well as shame be shame, and pleasure be pleasure, on their own.

There is no shame in asking for help if you are struggling with a drug and alcohol addiction. There is no shame in seeking the best of long term residential treatment to take the time you need to heal as sustainably as possible in order to ensure lifelong recovery. Tree House Recovery, a men’s residential treatment program in Portland, Oregon, teaches men how to find freedom from addiction by creating sustainable change. Call us today for information: (503) 850-2474

קטמין

https://vila-balance.co.il/%D7%94%D7%AA%D7%9E%D7%9B%D7%A8%D7%95%D7%99%D7%95%D7%AA/%D7%A1%D7%9E%D7%99%D7%9D-%D7%A7%D7%A9%D7%99%D7%9D/%D7%A7%D7%98%D7%9E%D7%99%D7%9F/

Colla, M., Scheerer, H., Weidt, S., Seifritz, E., & Kronenberg, G. (2021). Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review. Frontiers in behavioral neuroscience, 15, 759466. https://doi.org/10.3389/fnbeh.2021.759466

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Here, we provide a brief overview of current theories of antidepressant drug action including monoaminergic signaling, disinhibition of glutamatergic neurotransmission, neurotrophic and neuroplastic effects, and how these might relate to ketamine. Given that research into ketamine has not yet yielded new therapies beyond ketamine itself, current knowledge gaps and limitations of available studies are also discussed.

An obvious conceptual problem with the monoamine hypothesis lies in the fact that changes in neurotransmitter concentrations (along with the onset of typical side effects) occur within a few hours while conventional antidepressants typically require several days to weeks to take effect. Neurobiological research into the mechanisms underpinning the antidepressant response has therefore pivoted to longer-term adaptive changes downstream of the acute effects on biogenic amines.

Ketamine’s principal pharmacological action is as an N-methyl-D-aspartate (NMDA) receptor antagonist. However, in a manner somewhat reminiscent of clozapine, ketamine is a “dirty” drug. Multiple off-target effects including on monoamine systems need to be considered. In vitro, ketamine displays affinity to dopamine D2 and serotonin 5-HT2 receptors in the same range as its affinity for the NMDA receptor (Kapur and Seeman, 2002). It has also been reported that ketamine inhibits monoamine transporters in cultured cells (Nishimura et al., 1998) and blocks the uptake of [3H]-dopamine into rat striatal synaptosomes (Keita et al., 1996).

The N-methyl-D-aspartate (NMDA) receptor is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain. It plays an integral role in synaptic plasticity, which is a neuronal mechanism believed to be the basis of memory formation

אז אולי הוא מאיץ תהליכים פלסטיים ובעצם תערובת שלו עם אנטי דפרסנטים תוביל ליעילות גבוהה יותר?

Repeated ketamine injections increase the firing rate of norepinephrine neurons in the locus coeruleus and of dopaminergic neurons in the ventral tegmental area in rats (Iro et al., 2021). Microdialysis studies have demonstrated increased serotonin release by ketamine in the rodent prefrontal cortex (Ago et al., 2019; López-Gil et al., 2019).

כלומר מפעיל נוירונים של נוירואדרנלין ב לוקוס סירליוס, ו דופמין ב VTA - את מסלול הדופמין הקורטיקלי. ומשחרר סרוטונין בקורטקס...

While the available literature indicates that ketamine leads to increased dopamine levels in frontal cortex, striatum, and nucleus accumbens in rodents, the picture is less clear for the primate and human brain, given methodological issues and the scant available literature (Kokkinou et al., 2018). From a clinical perspective, the fact that haloperidol is able to ameliorate ketamine-induced psychosis argues for a role of dopaminergic pathways in ketamine’s psychotropic effects (Giannini et al., 2000).

Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin that belongs to NGF-beta family. BDNF can bind to its high affinity receptor TrkB and activates signal transduction cascades (IRS1/2, PI3K, Akt). BDNF can also bind to the p75NTR, but the affinity for the p75NTR receptor is lower than for TrkB. BDNF is a neurotransmitter modulator, and is vital in maturation, survival and differentiation of neuronal populations during development. BDNF also participates in neuronal plasticity, which is essential for learning and memory. BDNF is widely expressed in the CNS. BDNF Protein, Human is a recombinant human BDNF (H129-R247) without tag, which is produced in E.coli.

סרוטונין ודופמין - רקע ורפרנסים

השאלה שעיניינה אותי היתה היה היחס בין סרוטונין ודופמין. בעיקרון נראה היה שהם אמורים לווסת אלה את אלה - להשלים אלה את אלה, אבל הנסיון הפסיכיאטרי מראה על יחסי גומלין מורכבים. לדוגמה - אדם שמקבל נוגדי דיכאון שמתכוונינים לסרוטונין וקופץ למאניה (דופמין), או העובדה שפסיכדלים שנמצאים באינטרקציה עם סרטונין והטרנספרטרים/הרצפטורים וכו של סרוטונין פורצים את שערי התודעה דומים בחלק מהפעולות שלהם (הזיות וערוב חושים) לפעולת הקנביס שגורם לשיחרור של הרבה דפמין מה VTA. ועוד. לכן האיסוף הראשון היה לברר מה עושה הסרוטונין. תשובה או מודל אפשרי שמצאתי אחרי חיפושים רבים היתה - היחוד של הסרוטונין הוא שהוא פועל הן כנוירוטרנסמיטור (קישור בין נוירונים) והן בתוך התאים של נוירונים שונים - כולל כאלה שמיצרים דופמין. אם כמות הסרוטונין או חיקוייו (חומרים שונים) גדולה מיכולת הקליטה של התאים - הם יכולים להספג לתוך תאים דופמינרגיים (יצריני דופמין) , להגביר את ייצור האנרגיה בתוכם (מיטוכונדריה) ולהגביר את קצב הייצר והשיחרור של הדופמין מהם. את חלק מממסלול החיפושים שלי שמרתי כאן. סרוטונין ודופמין הייאנג והיין של הנפש. הרפרנסים נמצאים בסוף הפוסט הזה.

אני משתמשת בפוסט הזה כדי להשאיר בו רפרנסים לעצמי אודות מאמרים ונקודות עוגן לנושאים רבים שונים.

למי שמתעניין בסרוטונין וכו מוצע לדפדף לסוף הפוסט הזה.

המחשה לשימוש ב שינוי דינמי של רמת הקושי במשחקי וידאו והשפעתם על האנגאגמנט של השחקנים.

https://digitalcommons.morris.umn.edu/cgi/viewcontent.cgi?article=1105&context=horizons#:~:text=Dynamic%20Difficulty%20Adjustment%20(DDA)%20is,concept%20referred%20to%20as%20Flow.

4. DDA AND MULTIPLAYER PLAY In a single player game, the challenge to a player is the AI. The level of difficulty can be controlled. In multiplayer games, games where players face off against one another, the challenge to a player is the other player(s). The question for game developers is then how to implement DDA and provide a balanced challenge for each player, but at the same time not inhibit the gameplay experience of other players. In a study by Baldwin et al., around 150 participants were surveyed about their perspective on usage of multiplayer DDA (MDDA) in video games. Player performance has moments of high level and low level gameplay, especially when competing against other people. To account for the range of gameplay, players gave feedback from a high performance perspective (HPP) and low performance perspective (LPP). The players are questioned about instances of MDDA. An instance is defined as “a gameplay feature in competitive multiplayer video games designed to reduce the difference in challenge experienced by all players through adjusting the potential performance of certain players”. [1] Essentially, instances are opportunities to balance a game so all players face the same level of challenge. An example of this is in the racing game Mario Kart. Players that are losing the race can receive a blue shell which slows down the racer in first place when used. This allows the other racers the chance to catch up to the leader.

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Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders Benedetta Conio1,2 ● Matteo Martino3 ● Paola Magioncalda1,2,4,5 ● Andrea Escelsior1,2 ● Matilde Inglese2,6,7 ● Mario Amore1,2 ● Georg Northoff8,9,10 Received: 15 September 2018 / Revised: 18 January 2019 / Accepted: 5 March 2019 © Springer Nature Limited 2019

Alterations in brain intrinsic activity—as organized in resting-state networks (RSNs) such as sensorimotor network (SMN), salience network (SN), and default-mode network (DMN)—and in neurotransmitters signaling—such as dopamine (DA) and serotonin (5-HT)—have been independently detected in psychiatric disorders like bipolar disorder and schizophrenia.

Thus, the aim of this work was to investigate the relationship between such neurotransmitters and RSNs in healthy, by reviewing the relevant work on this topic and performing complementary analyses, in order to better understand their physiological link, as well as their alterations in psychiatric disorders

According to the reviewed data, neurotransmitters nuclei diffusively project to subcortical and cortical regions of RSNs. In particular, the dopaminergic substantia nigra (SNc)-related nigrostriatal pathway is structurally and functionally connected with core regions of the SMN, whereas the ventral tegmental area (VTA)-related mesocorticolimbic pathway with core regions of the SN.

The serotonergic raphe nuclei (RNi) connections involve regions of the SMN and DMN. Coherently, changes in neurotransmitters activity impact the functional configuration and level of activity of RSNs, as measured by functional connectivity (FC) and amplitude of low-frequency fluctuations/temporal variability of BOLD signal.

Specifically, DA signaling is associated with increase in FC and activity in the SMN (hypothetically via the SNc-related nigrostriatal pathway) and SN (hypothetically via the VTA-related mesocorticolimbic pathway), as well as concurrent decrease in FC and activity in the DMN.

By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity.

Complementally, our empirical data showed a positive correlation between SNc-related FC and SMN activity, whereas a negative correlation between RNi-related FC and SMN activity (along with tilting of networks balance toward the DMN).

According to these data, we hypothesize that the activity of neurotransmitter-related neurons synchronize the low-frequency oscillations within different RSNs regions, thus affecting the baseline level of RSNs activity and their balancing.

In our model, DA signaling favors the predominance of SMN-SN activity, whereas 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns.

In turn, alterations in neurotransmitters signaling (or its disconnection) may favor a correspondent functional reorganization of RSNs, manifesting in distinct psychopathological states. The here suggested model carries important implications for psychiatric disorders, providing novel and well testable hypotheses especially on bipolar disorder and schizophrenia

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The SMN—which comprises the middle cingulate cortex (MCC), dorsal striatum, ventral nuclei of thalamus and postcentral gyrus, pre-central gyrus, premotor and supplemental motor areas (SMAs)—is involved in sensory processing and motor functions [8, 36].

The DMN—which mainly concerns cortical midline regions, such as the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), along with parietotemporal multimodal association cortices—is involved in ideation, internal thought, and mind wandering [6, 37–39].

The SN—which includes the supragenual ACC (SACC), amygdala, nucleus accumbens (NAc), dorsomedial thalamus, insula, and ventrolateral prefrontal cortex (VLPFC)— is involved in salience attribution, interoceptive awareness, and reward system [7, 12, 40, 41].

37. Christoff K, Gordon AM, Smallwood J, Smith R, Schooler JW. Experience sampling during fMRI reveals default network and executive system contributions to mind wandering. Proc Natl Acad Sci USA. 2009;106:8719–24.

38. Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science. 2007;315:393–5.

39. Davidson RJ. Affective style, psychopathology, and resilience: brain mechanisms and plasticity. Am Psychol. 2000;55:1196–214.

40. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.

41. Geng H, Li X, Chen J, Gu R. Decreased intra- and inter-salience network functional connectivity is related to trait anxiety in adolescents. Front Behav Neurosci. 2015;9:350.

Optogenetic stimulation of the dopaminergic neurons of SNc was shown to facilitate motor activity (e.g., [45]). Thus, the resulting effect of DA activity is a facilitation of goal-directed movements [43, 46]

VTA

The resulting effects of DA activity favor motivation and reward-related behaviors, as well as cognitive functions such as attention and working memory [43, 48, 49].

The SNc projects mainly to the dorsal striatum, including dorsolateral portions of the caudate and putamen, in addition to the globus pallidus, subthalamic nucleus, and ventral thalamic nuclei [43, 44]. Dopaminergic projections modulate neuronal activity in these dorsal parts of striatopallidal regions by acting on excitatory D1 receptors, mainly located in the excitatory direct pathway, and inhibitory D2 receptors, mainly located in the inhibitory indirect pathway [43]. Moreover, DA neurons project diffusely to the cortex mainly via D1 signaling, where motor areas (in particular premotor and SMA) display greater innervation than sensory areas [43]. Optogenetic stimulation of the dopaminergic neurons of SNc was shown to facilitate motor activity (e.g., [45]). Thus, the resulting effect of DA activity is a facilitation of goal-directed movements [43, 46]. The VTA projects to the medial PFC—including the medial orbitofrontal cortex (OFC) and ACC—ventral striatum—including the NAc and the ventral parts of caudate and putamen—and dorsomedial thalamus [43, 47]. In particular, ACC mainly expresses D1 receptors, the ventral parts of striatopallidal regions mainly expresses D2-like receptors, whereas dorsomedial thalamus mainly expresses D1 and D3 receptors [43]. The resulting effects of DA activity favor motivation and reward-related behaviors, as well as cognitive functions such as attention and working memory [43, 48, 49].

מתוך: ראו מתחת לציטוט

Conio B, Martino M, Magioncalda P, Escelsior A, Inglese M, Amore M, Northoff G. Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders. Mol Psychiatry. 2020 Jan;25(1):82-93. doi: 10.1038/s41380-019-0406-4. Epub 2019 Apr 5. PMID: 30953003.

The serotonergic raphe nuclei (RNi) project to the striatum and thalamus (including the posterior complex and lateral geniculate nuclei, the ventral anterior and ventrolateral nuclei, and the dorsomedial nucleus), as well as the cingulate cortex, PFC (including medial OFC), temporal, and sensory cortices [50–54]. In particular, the basal ganglia regions express 5-HT2A receptors, mainly in the dorsal striatum, as well as 5-HT1B, 5-HT4, and 5-HT6 receptors, mainly in the ventral striatum [50]; the thalamic regions express 5-HT1A and 5-HT2 receptors (mainly in the ventral nuclei), 5-HT2C receptors (mainly in the geniculate complexes), and 5-HT7 receptors (mainly in the dorsomedial nucleus) [50, 51]; prefrontal and cingulate cortex mainly express 5-HT1A and 5-HT1B receptors, as well as 5-HT2A and 5-HT2C receptors [50], whereas motor and sensory cortices (i.e., somatosensory, auditory and visual areas), which are densely innervated by serotonergic projections, mainly express 5-HT1 receptors [51, 55–57]. Optogenetic stimulation of the serotonergic neurons of RNi resulted in inhibition of sensory responsivity (gating sensory-driven responses), delayed responses, patience or waiting behavior, and slower motor activity [58–63]. Thus, the resulting effect of 5-HT activity is a modulation of sensory processing along with inhibition of motor functions and impulsive behaviors [51, 64]. See Supplemental Fig

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הפרעות חרדה ניירוביולוגיה , אמיגדלה, ניורוטרנסמיטורים וכו

Martin EI, Ressler KJ, Binder E, Nemeroff CB. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr Clin North Am. 2009 Sep;32(3):549-75. doi: 10.1016/j.psc.2009.05.004. PMID: 19716990; PMCID: PMC3684250.

The emotional-processing brain structures historically are referred to as the “limbic system” (Fig. 1). The limbic cortex is part of the phylogenetically ancient cortex. It includes the insular cortex and cingulate cortex. The limbic cortex integrates the sensory, affective, and cognitive components of pain and processes information regarding the internal bodily state.4,5 The hippocampus is another limbic system structure; it has tonic inhibitory control over the hypothalamic stress-response system and plays a role in negative feedback for the hypothalamic–pituitary–adrenal (HPA) axis. Hippocampal volume and neurogenesis (growth of new cells) in this structure have been implicated in stress sensitivity and resiliency in relationship to mood and anxiety disorders.

The amygdala is responsible for the expression of fear and aggression as well as species-specific defensive behavior, and it plays a role in the formation and retrieval of emotional and fear-related memories. (Fig. 2 depicts the amygdala’s involvement in fear circuitry). The central nucleus of the amygdala (CeA) is heavily interconnected with cortical regions including the limbic cortex. It also receives input from the hippocampus, thalamus, and hypothalamus.

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Serotonin Deficiency Increases Context-Dependent Fear Learning Through Modulation of Hippocampal Activity

ORIGINAL RESEARCH article

Front. Neurosci., 24 April 2019 Sec. Neuropharmacology Volume 13 - 2019 | https://doi.org/10.3389/fnins.2019.00245 This article is part of the Research Topic Serotonin, Receptors and Transporters: Exploring New and Known Signaling Pathways to Improve the Efficacy of Antidepressant Treatment View all 10 Articles

Studies in animals demonstrate a direct anatomical connection between the main sources of serotonin in the brain, the brainstem dorsal and median raphe nuclei as well as forebrain limbic structures, such as the medial prefrontal cortex, hippocampus, and amygdala, that control anxiety and fear responses (Maier et al., 2006; Hale and Lowry, 2011; Fernandez et al., 2016; Muzerelle et al., 2016). Of particular interest to contextual fear conditioning is the dorsal hippocampus (dHip; Bauer, 2015), which receives serotonergic projections primarily from the median raphe nucleus (Azmitia and Whitaker-Azmitia, 1995; McQuade and Sharp, 1997; Lowry, 2002).

Consistent with this hypothesis, acute adm

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פלאשבקים, הסימפטומים וכו

טריגר להופעה חוזרת - שימוש בגראס ואפטמינים. וחלק גם מאלכוהול.

חזרה על החוויה לאו דווקא על כולה - חלק חוזרים למראות ולחוויות הויזואליותוכו שחוו במהלך השימוש ב LSD, וחלק לתחושות ולתופעות השונות (כולל חדות עם העולה, דה-פרסונאליזציה, חרדה, פאניקה, וכו).

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Rosecrans JA, Lovell RA, and Freedman DX (1967) Effects of lysergic acid diethylamide on the metabolism of brain 5-hydroxytryptamine. Biochem Pharmacol 16: 2011–2021.

1521-0081/68/2/264–355$25.00 http://dx.doi.org/10.1124/pr.115.011478 PHARMACOLOGICAL REVIEWS Pharmacol Rev 68:264–355, April 2016 Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: ERIC L. BARKER Psychedelics David E. Nichols Eschelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina

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Barron et al. (1970) reported ‘‘recurrences of ‘trip phenomena’,’’ lasting up to 3 months, in 11 (55%) of 20 community hallucinogen users recruited by advertisement. The most common symptoms noted were brief episodes of depersonalization, disorientation, and the spontaneous appearance of color hazes or curtains. Some subjects also described recurrent visual hallucinations of ‘‘devils’ faces’’, peculiar, transient, tactile phenomena (itching skin), and episodes of anxiety, depression or paranoid thought, all of which were claimed as first experienced during hallucinogen intoxication. At the time of interview, 100% of subjects were active marijuana users, and 80% active amphetamine users; alcohol use is not reported

בארון וחב'. (1970) דיווחו על ''הישנות של 'תופעות טיול'' שנמשכו עד 3 חודשים, ב-11 (55%) מתוך 20 משתמשי הזיה בקהילה שגויסו באמצעות פרסומת

התסמינים השכיחים ביותר שצוינו היו אפיזודות קצרות של דה-פרסונליזציה, חוסר התמצאות והופעה ספונטנית של אובך צבעוני או וילונות. חלק מהנבדקים תיארו גם הזיות חזותיות חוזרות ונשנות של "פרצופים של שדים", תופעות מוזרות, חולפות, מישוש (עור גירוד), ואפיזודות של חרדה, דיכאון או מחשבה פרנואידית, אשר כולן נטען כי חוו לראשונה במהלך שיכרון הזיה. בזמן הראיון, 100% מהנבדקים היו משתמשי מריחואנה פעילים, ו-80% משתמשי אמפטמין פעילים; שימוש באלכוהול לא מדווח

ed.’’ Moskowitz (1971) reported using haloperidol successfully to treat flashbacks in eight military prisoners. Overall, he found that one third of LSD users in this prison experienced ‘‘spontaneous recurrences (flashbacks) of LSD reactions’’. The case descriptions suggest that several subjects also possessed chronic psychotic symptoms, which raises the possibility that some of the cases may have been due to an underlying primary psychotic disorder

מושקוביץ (1971) דיווח על שימוש בהלופרידול בהצלחה לטיפול בפלאשבקים בשמונה אסירים צבאיים. בסך הכל, הוא גילה ששליש ממשתמשי ה-LSD בכלא זה חוו ''חזרות ספונטניות (פלאשבקים) של תגובות אל-אס-די''. תיאורי המקרים מצביעים על כך שלמספר נבדקים היו גם תסמינים פסיכוטיים כרוניים, מה שמעלה את האפשרות שחלק מהמקרים נבעו מהפרעה פסיכוטית ראשונית.

. Matefy and Krall (1974) recruited through campus newspaper advertisements 44 college students with a history of hallucinogen use; 22 (50%) reported subsequent episodes of flashbacks. Many of these cases appear to meet criteria for HPPD; however, one subject attributed flashbacks to prior hashish use, and another to prior ‘nondrug’ events. Also, episodes of depression (19%), paranoia (26%), and anxiety/tension (17%) were claimed as typical flashback effects. Heaton and Victor recruited 32 hall

 (1974) גייסו באמצעות פרסומות בעיתונים בקמפוס 44 סטודנטים עם היסטוריה של שימוש בסמי הזיות; 22 (50%) דיווחו על אפיזודות עוקבות של פלאשבקים. נראה שרבים מהמקרים הללו עומדים בקריטריונים של HPPD; עם זאת, נבדק  אחד ייחס פלאשבקים לשימוש קודם בחשיש, ואחר לאירועים קודמים של 'לא סמים'. כמו כן, אפיזודות של דיכאון (19%), פרנויה (26%) וחרדה/מתח (17%) טוענים כאפקטי פלאשבק אופייניים.

. Matefy et al. (1978, 1978) and Matefy (1980) recruited 87 subjects, primarily college students, by advertisement; 63 were ‘‘psychedelic drug users’’, of whom 34 (54%) acknowledged ‘flashbacks’ in response to an initial interview question regarding ‘‘...recurrences of sensations, feelings, and thoughts which were previously experienced during the drug trip. These experiences recur at some time after the last ingestion of the psychedelic drug and after a period of relative normalcy’’. Only 20 (59%) of the 34 subjects described ‘‘perceptual illusions’’ as a feature of their flashbacks; the other common features reported were depersonalization (18 subjects), anxiety, tension, or panic (15), disorientation or confusion (15), and ‘‘union with the world’’ (14). Thus, a majority of the subjects do not appear to meet the specific perceptual criteria required for HPPD. Also, 22 (65%) subjects had flashbacks triggered by marijuana or alcohol*/raising the question of how often flashbacks were experienced as part of the intoxication with another drug.

 87 נבדקים, בעיקר סטודנטים, לפי פרסומת; 63 היו ''משתמשי סמים פסיכדליים'', מתוכם 34 (54%) הודו ב'פלאשבקים' בתגובה לשאלת ראיון ראשונית בנוגע ל''...חזרות של תחושות, רגשות ומחשבות שנחוו בעבר במהלך הטיול בסמים . חוויות אלו חוזרות על עצמן בשלב מסוים לאחר הבליעה האחרונה של הסם הפסיכדלי ולאחר תקופה של נורמליות יחסית''. רק 20 (59%) מתוך 34 הנבדקים תיארו ''אשליות תפיסתיות'' כמאפיין של הפלאשבקים שלהם; המאפיינים הנפוצים האחרים שדווחו היו דה-פרסונליזציה (18 נבדקים), חרדה, מתח או פאניקה (15), חוסר התמצאות או בלבול (15), ו"איחוד עם העולם" (14). לפיכך, נראה שרוב הנבדקים אינם עומדים בקריטריונים התפיסתיים הספציפיים הנדרשים עבור HPPD. כמו כן, ל-22 (65%) נבדקים היו פלאשבקים שהופעלו על ידי מריחואנה או אלכוהול*/העלו את השאלה באיזו תדירות חוו פלאשבקים כחלק מהשכרות בסם אחר.

. The two greatest triggers for flashbacks were entering a dark environment (16%) and intention (14%), but many subjects reported flashbacks when intoxicated with another drug, such as marijuana, amphetamines, or alcohol. In a subsequent communication, Abraham (1984) noted that one of the LSD users complaining of flashbacks in the study was later diagnosed with temporal lobe epilepsy and responded to treatment with carbamazepine. In another communication (Abraham, 1986), he offered further details about eight other study participants experiencing flashbacks: four had ‘‘concomitant anxiety or panic disorders’, ‘three had major affective disorders’, and seven ‘had temporoparietal abnormalities...according to conventional tests and according to brain electrical activity mapping (BEAM) studies’’. Abraham and Wolf (1988) also administered visual function tests of dark adaptation (DA) and critical flicker frequency (CFF) to 24 LSD users and

שני הטריגרים הגדולים ביותר לפלאשבקים היו כניסה לסביבה חשוכה (16%) והתכוונות (14%), אך נבדקים רבים דיווחו על פלאשבקים כשהם שיכרו מסם אחר, כגון מריחואנה, אמפטמינים או אלכוהול. 

בתקשורת לאחר מכן, אברהם (1984) ציין שאחד ממשתמשי ה-LSD שהתלונן על פלאשבקים במחקר אובחן מאוחר יותר עם אפילפסיה באונה הטמפורלית והגיב לטיפול ב-carbamazepine. במאמר אחר(אברהם, 1986), הוא הציע פרטים נוספים על שמונה משתתפי מחקר אחרים שחוו פלאשבקים: לארבעה היו ''הפרעות חרדה או פאניקה נלוות', 'לשלושה היו הפרעות רגשיות גדולות', ולשבעה 'היו הפרעות טמפרופריאטליות... לבדיקות קונבנציונליות ולפי מחקרי מיפוי פעילות חשמלית במוח (BEAM)''. אברהם וולף (1988) ערכו גם מבחני תפקוד ראייה של הסתגלות כהה (DA) ותדירות הבהוב קריטית (CFF) ל-24 משתמשי LSD ו

excluded. Hemsley and Ward (1985) administered questions about LSD intoxication and flashbacks to 29 poly-drug abusers admitted to an inpatient drug dependence unit. Fifteen subjects reported experiencing ‘‘flashbacks or other drug effects after the drug should have worn off’’. The symptoms, frequency, and duration of flashbacks are not reported. The frequency, but not the persistence, of flashbacks was associated with extent of LSD use and number of ‘‘bad trips’’

התדירות, אך לא ההתמדה (אורך החוויה), של פלאשבקים הייתה קשורה להיקף השימוש ב-LSD ולמספר ה''נסיעות רעות''.

מהסיכום של המאמר:

Several general impressions emerge from our review. First, the term ‘flashback’ has been defined in so many ways that it has become virtually useless. Some studies describe specific recurrent perceptual phenomena, similar to those enumerated in DSM-IV criterion A for HPPD, but most studies also include other psychiatric symptoms, such as panic attacks, psychosis, mood changes, depersonalization, dissociation, or experiences of ‘unity’ and transcendence, under the heading of ‘flashbacks’.

מספר רשמים כלליים עולים מהסקירה שלנו. ראשית, המונח 'פלאשבק' הוגדר בכל כך הרבה דרכים שהוא הפך למעשה חסר תועלת. חלק מהמחקרים מתארים תופעות תפיסתיות חוזרות ונשנות ספציפיות, דומות לאלו המנויות בקריטריון DSM-IV A עבור HPPD, אך רוב המחקרים כוללים גם תסמינים פסיכיאטריים אחרים, כגון התקפי פאניקה, פסיכוזה, שינויים במצב הרוח, דה-פרסונליזציה, דיסוציאציה או חוויות של 'אחדות'. והתעלות, תחת הכותרת של 'פלאשבקים'

In general, it appears that individuals administered LSD in therapeutic or research settings are far less likely to develop HPPD than individuals using LSD illicitly. This lower incidence has been attributed to the fact that ‘‘individuals (both normal volunteers and patients) are carefully screened and prepared, supervised, and followed up, and given judicious doses of pharmaceutical quality drug’’ (Strassman, 1984).

The data remain unclear as to what might cause these phenomena. Three principal explanations emerge from the literature. First, the perceptual phenomena described by some individuals with ‘flashbacks’ might simply represent a heightened awareness of normal visual phenomena (Horowitz, 1969; Wesson and Smith, 1976). For example, one psychiatrist reported that he was able to personally induce symptoms similar to those of his own patient with HPPD by suspending his ‘‘habitual state of consciousness’’ (Genova, 2000). These symptoms included ‘‘visual ‘trails’ of moving objects, various line-shape illusions such as level bookshelves slanting, ‘aeropsia’ (a sense of bright whiteness in the air between [individuals] and observed objects), and ‘dancing bright spots’ originating between the letters and words on a printed page’’.

Second, some ‘flashbacks’ might represent merely instances of normal memory accompanied by emotional distress so upsetting to a subset of individuals that their clinicians are informed about them. Several investigators have published theoretical articles surmising that ‘flashbacks’ reflect lasting memories from the unusually distinct and powerfully emotional experiences induced under hallucinogen intoxication (Shick and Smith, 1970; Wesson and Smith, 1976; Fischer, 1977; McGee, 1984).

Fischer, R., 1971. The ‘flashback’: arousal-state bound recall of experience. J. Psychedelic Drugs 3, 31/39.

Fischer, R., 1977. On flashback and hypnotic recall. Int. J. Clin. Exp. Hypn. XXV, 217/235.

Hypnotic recall and flashback: the remembrance of things present R Fischer

PMID: 1030660

Abstract There are two kinds of flashbacks: the self-programed or intra-individual variety and pre-programed or inter-individual flashbacks re-presenting mythical and narrative event structures which contribute to the survival of the species.

Both types of experiences are arousal-state bound and stage (set and setting) or culture bound. Flashbackers may be characterized by (1) their variability (large SD) on perceptual-behavioural tasks pointing to their extensive cognitive or interpretive repertoire, (2) they are minimizers (or reducers) of sensory input (particularly at the peak of a hallucinogenic drug experience)

ישנם שני סוגים של פלאשבקים: כאלה הקשורים לתכנים אישיים התוך-פרטייים, וכאלה "תוכנתים מראש" או בין-אישיים המציגים מחדש מבני אירועים מיתיים ונרטיביים התורמים להישרדות המין. שני סוגי החוויות קשורים למצבים עוררות ותלויים בסביבה התרבותית ובסטינג של החוויה.  
פלאשבקים עשויים להיות מאופיינים על ידי (1) השונות שלהם (SD גדול) במשימות תפיסתיות-התנהגותיות המצביעות על הרפרטואר הקוגניטיבי או הפרשני הנרחב שלהם, (2) הם ממזערים (או מפחיתים) של קלט חושי (במיוחד בשיא של התנסות בסם הזיה )

(3) as group they display high resting heart rates, (4) are hypnotizable and hence (5) prefer righ cerebral hemispheric cognition, (6) displaying EEG-alpha dominance in the resting, waking state.

Flashback and hypnotic recall differ only in the ways and means by which they are induced. Hypnotic induction, however, is not to be confused with the induced state that may be any ordinary or non-ordinary state of consciousness on the perception-hallucination-meditation continuum which the subject has a least once experienced before. If mind is an open system comprising the individual's mind and the minds of his total environment, i.e. his past and present sets and settings, then for many of us thoughts and actions are hypnotically induced, and memories are flashbacks of those experiences.

עם זאת, אין לבלבל אינדוקציה היפנוטית עם המצב המושרה שעשוי להיות כל מצב תודעה רגיל או לא רגיל על רצף התפיסה-הזיה-מדיטציה שהנבדק חווה לפחות פעם אחת בעבר. אם התודעה היא מערכת פתוחה הכוללת את מוחו של הפרט ואת מוחות הסביבה הכוללת שלו, כלומר מערכות והגדרות העבר וההווה שלו, אז עבור רבים מאיתנו מחשבות ופעולות נגרמות בצורה היפנוטית, וזיכרונות הם פלאשבקים של חוויות אלו.

Memory

Zhongzhi Shi, in Intelligence Science, 2021

8.3.1.2 Spreading activation model

The spreading activation model was proposed by Collins et al. [13]. It is also a network model. Different from the hierarchical network model, this model organizes concepts by semantic connection or semantic similarity instead of hierarchical structure of concept. Fig. 8.6 reveals a fragment of the spreading activation model. Those squares are nodes of network representing concepts. The length of lines means a compact degree of relation—for example, a shorter length indicates that the relationship is close and that there are more common features between two concepts—or if more lines between two nodes with common features mean their relationship is compact, the connected concepts denote their relationship.

Lewis-Peacock, J. A., & Postle, B. R. (2008). Temporary activation of long-term memory supports working memory. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(35), 8765–8771. https://doi.org/10.1523/JNEUROSCI.1953-08.2008

This study describes a functional magnetic resonance imaging study of humans engaged in long-term memory (LTM) and working memory tasks. A pattern classifier learned to identify patterns of brain activity associated with viewing and making judgments about three categories of pictures (famous people, famous locations, and common objects). The evaluation of these stimuli relied on perception and long-term semantic and/or episodic memories. We investigated whether this classifier could successfully decode brain activity from a subsequent delayed paired-associate recognition working memory task that required the short-term retention of the same stimuli. We reasoned that the LTM-trained classifier would be able to decode delay-period activity only if that activity reflected, to some extent, the temporary activation of LTM. Our results demonstrated successful decoding: delay-period activity from a distributed network of brain regions matched learned patterns of activity for task-relevant stimuli to a greater extent than for task-irrelevant stimuli. In varying degrees throughout the delay, activity reflected the target (a retrospective code) and its associate (a prospective code) with considerable variability among subjects. Although prefrontal cortex (PFC) demonstrated category-specific patterns of activity during the LTM task, these patterns were not reinstated in PFC during the working memory task. We conclude that the short-term retention of information can be supported by the temporary reactivation of LTM representations.

Slotnick S. D. (2022). Does working memory activate the hippocampus during the late delay period?. Cognitive neuroscience, 13(3-4), 182–207. https://doi.org/10.1080/17588928.2022.2075842

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Gonçalves, Ó., Soares, J., Carvalho, S. et al. Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder. Sci Rep7, 44468 (2017). https://doi.org/10.1038/srep44468

Sridharan D, Levitin DJ, Menon V. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12569-74. doi: 10.1073/pnas.0800005105. Epub 2008 Aug 22. PMID: 18723676; PMCID: PMC2527952.

In a recent meta-analysis, Dosenbach and colleagues hypothesized that several brain regions that overlap with the CEN and SN are important for multiple cognitive control functions, including initiation, maintenance, and adjustment of attention (7). However, no studies to date have directly assessed the temporal dynamics and causal interactions of specific nodes within the CEN, SN, and DMN. Converging evidence from a number of brain imaging studies across several task domains suggests that the FIC and ACC nodes of the SN, in particular, respond to the degree of subjective salience, whether cognitive, homeostatic, or emotional (4, 8–11). The CEN, on the other hand, is critical for the active maintenance and manipulation of information in working memory, and for judgment and decision making in the context of goal directed behavior (12–18). We therefore hypothesized a key role for the SN in the hierarchical initiation of cognitive control signals, specifically with respect to activation and deactivation in the CEN and DMN, and the dynamics of switching between these two networks.

By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity.

In our model, DA signaling favors the predominance of SMN-SN activity, whereas 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns.

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38. Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science. 2007;315:393–5.

39. Davidson RJ. Affective style, psychopathology, and resilience: brain mechanisms and plasticity. Am Psychol. 2000;55:1196–214.

40. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.

41. Geng H, Li X, Chen J, Gu R. Decreased intra- and inter-salience network functional connectivity is related to trait anxiety in adolescents. Front Behav Neurosci. 2015;9:350.

VTA

The resulting effects of DA activity favor motivation and reward-related behaviors, as well as cognitive functions such as attention and working memory [43, 48, 49].

מתוך: ראו מתחת לציטוט

DMN

Conio, B., Martino, M., Magioncalda, P., Escelsior, A., Inglese, M., Amore, M., & Northoff, G. (2020). Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders. Molecular psychiatry, 25(1), 82–93. https://doi.org/10.1038/s41380-019-0406-4

המוח פעיל גם ללא משימה חיצונית. איך יודעים? מחקרים ב fmri משווים את הפעילות המטאבולית של המוח BOLD בזמן שעל הנבדק מוטלת משימה (סנסורית, מוטורית, קוגניטיבית) יחסית למצב מנוחה או מצב קונטרול אחר. מחקרים רבים מראים

Both PET and fMRI measure local increase of blood flow and oxygen availability in tissue. fMRI detects changes in the blood oxygen level dependent (BOLD) signal as local neural activity manifests as a relative decrease in concentration of deoxy-hemoglobin in the blood.

The paradigm most often used in studying the brain with fMRI is that of imposing a cognitive, sensory, or motor task and subsequently observing the change in BOLD signal during the task performance relative to rest or control periods. For the purpose of this review, we will refer to these studies as task-based fMRI (T-fMRI).

Numerous tasks have been studied and reported in the literature, providing us a wide understanding of the many different systems that function across the brain. One important observation from these studies is that brain metabolism is only minimally altered by the performance of mentally demanding tasks 6.

The implication of this observation is that the intrinsic activity of the brain at rest uses a substantial amount of energy, and thus must be of great importance for the normal function of the brain. There are several techniques used to study intrinsic or resting state brain activity. However, in this manuscript we will focus on fMRI, and we will refer to this activity as resting state fMRI (RS-fMRI).

במה המוח משקיע את האנרגיה שלו בזמן מנוחה?

סיכרון בין ההמיספרות (לדוגמה בין המערכת המוטורית ב 2 ההמיספרות).
סיכרון כזה נמצא גם בשינה. וגם לאורך הסולם האבולוציוני. ולכן מוצע שיש ל חשיבות - אחרת לא היו מבזבזים עליו משאבים...

Resting State Networks (RSNs)

Biswal et al. 9 are credited with the first observation that resting state activity is synchronous (correlated) between the left and right motor cortex, as well as most other brain regions involved in movement, and this synchronous activity was subsequently found to be present across multiple brain systems in addition to the motor system 10,11.

Areas of the brain that demonstrate synchronous activity have been called functional systems, intrinsic connectivity networks, and, as we refer to them here, resting state networks (RSNs). The topography of RSNs closely corresponds to responses elicited by a wide variety of sensory, motor, and cognitive tasks 12,13

Intrinsic activity persists in a modified form during sleep 14 and under certain types of sedation 15,16. Several RSNs have been identified in all mammalian species investigated to date 17,18. This phylogenetic conservation implies that coherent intrinsic activity must be physiologically important despite its high metabolic cost 19.

Functional connectivity in the resting brain: A network analysis of the default mode hypothesis

Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253–258. https://doi.org/10.1073/pnas.0135058100

Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

The cingulate cortex and limbic systems for emotion, action, and memory

Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal cortical areas. It is argued that these inputs allow the cingulate cortex to perform action–outcome learning, with outputs from the midcingulate motor area to premotor areas. In addition, because the anterior cingulate cortex connects rewards to actions, it is involved in emotion; and because the posterior cingulate cortex has outputs to the hippocampal system, it is involved in memory. These apparently multiple different functions of the cingulate cortex are related to the place of this proisocortical limbic region in brain connectivity.

A key area included by Broca in his limbic lobe (Broca 1878) is the cingulate cortex, which hooks around the corpus callosum. The term limbic used by Broca referred to structures that are at the border or edge (the literal meaning of limbic) of the hemispheres (when seen in medial view), and led to the development of the concept of a limbic system (Pessoa and Hof 2015). Other limbic structures include the hippocampus, and the amygdala (which has major connections with the orbitofrontal cortex). These structures appear to have very different connections and functions. The amygdala and orbitofrontal cortex are key structures involved in emotion and reward value with connections from ventral stream processing areas that decode ‘what’ the stimulus is (Rolls 2014b, 2016a, 2019a, b). The hippocampus is a key structure in episodic memory with inputs from the dorsal stream cortical areas about space, action, and ‘where’ events occur, as well as from the ‘what’ ventral processing stream (Kesner and Rolls 2015; Rolls 2018b). Because of the different connectivity and functions of these limbic structures (amygdala, orbitofrontal cortex, and hippocampus) in emotion and in memory, it has been suggested that the concept of a single ‘limbic system’ is not realistic, and that we should consider separately the connectivity and functions of different limbic structures in emotion and memory (Rolls 2015).

However, that leaves the cingulate cortex in an interesting position straddling the emotional and memory domains. The anterior cingulate cortex receives inputs from the orbitofrontal cortex and amygdala which receive from ventral stream areas. The posterior cingulate cortex receives from dorsal stream areas including the parietal cortex and has connections to the hippocampal memory system. Moreover, there is evidence relating the cingulate cortex to what is apparently something else, action–outcome learning, in which actions are learned to obtain goals based on the outcomes, the rewards and punishers, received for different actions (Rushworth et al. 2012; Kolling et al. 2016; Rolls 2019a).

Many previous contributions have been valuable in leading towards an understanding of the cingulate cortex (Devinsky et al. 1995; Vogt 2009, 2016; Rushworth et al. 2011). This paper focusses on research on the cingulate and orbitofrontal cortex in primates including humans, rather than on research in rodents (Izquierdo 2017; Wikenheiser and Schoenbaum 2016), because of the great development of these regions in primates (Passingham and Wise 2012; Rolls 2014a, 2018a, 2019a). For example, rodents have no posterior cingulate cortex (Vogt 2009) and most of the orbito-frontal cortex (apart from the agranular areas posteriorly) may not be present in rodents (Passingham and Wise 2012; Rolls 2019a).

Evidence implicating the subgenual and more generally the subcallosal cingulate cortex in depression includes evidence that neurons in this region in humans can respond to unpleasant stimuli; that the subgenual cingulate cortex may be overactive in depression; and that deep brain stimulation may help to treat depression in some individuals (Hamani et al. 2011; Laxton et al. 2013; Rolls 2018a).

In terms of functional connectivity, voxels in the anterior cingulate cortex have higher functional connectivity in unmedicated depressed patients with a number of brain areas (Rolls et al. 2018, 2019b). Higher functional connectivity in depression is found of the subcallosal anterior cingulate with the lateral orbitofrontal cortex; of the pregenual/supracallosal anterior cingulate with the medial orbitofrontal cortex; and of parts of the anterior cingulate with the inferior frontal gyrus. The high functional connectivity in depression between the lateral orbitofrontal cortex and the subcallosal anterior cingulate may relate to more non-reward information transmission to the anterior cingulate, contributing to depression. The high functional connectivity between the medial orbitofrontal cortex and supracallosal anterior cingulate in depression may also contribute to depressive symptoms, in that medial orbitofrontal cortex signals are being routed through a non-reward part of the ACC (Rolls et al. 2018).

In a resting state functional connectivity neuroimaging study of depression, voxels in the posterior cingulate cortex had higher connectivity with the lateral orbitofrontal cortex (Cheng et al. 2018a), involved in non-reward and thereby implicated in depression (Rolls 2016b, 2018a; Rolls et al. 2019b). This connectivity was lower in medicated individuals. It was found in healthy controls that the posterior cingulate cortex has high functional connectivity with the parahippocampal regions which are involved in memory. These discoveries (Cheng et al. 2018a) support the theory that the non-reward system in the lateral orbitofrontal cortex has increased effects on memory systems in depression, which contribute to the rumination about sad memories and events (Rolls 2016b, 2018a).

Dreaming and the Default Mode Network https://doi.org/10.1080/00107530.2013.10746548

his article makes a brief contribution to the ongoing dialogue on dreams between neuroscience and psychoanalysis by linking several converging lines of evidence. Recent evidence indicates that the default mode network (DMN), a highly interconnected set of “hubs” in the brain, is active during sleep. In addition, activity in the DMN is strongly associated with mental imagery that is not directly tied to current perception (“stimulus-independent thought”), which is also a central feature of dreams. Finally, the elimination of dreams is correlated with lesions in areas that have a high degree of overlap with two regions of the DMN, the ventromedial prefrontal cortex (vmPFC) and the temporo-occipital junction. Given that the vmPFC is a key node in brain circuitry regulating motivation, these converging lines of evidence support the basic psychoanalytic idea that dreams arise from wishful impulses and other emotional motivations.

Core Network Principles

Warren W. Tryon, in Cognitive Neuroscience and Psychotherapy, 2014Default Mode Network fMRI Studies Hans Berger discovered that the brain was constantly active in 1929, even during sleep, when he recorded the first electroencephalogram (EEG; Haas, 2003). Somehow this fact was minimized by fMRI investigators who considered that the brain was completely at rest during the control condition when participants lie quietly in an fMRI machine with eyes closed or eyes open fixed on a cross. Images taken under these conditions were considered to be just noise. The active experimental condition typically entailed the presentation of a stimulus; participation in a cognitive task. Only then was the brain expected to become active. There are two main approaches to analyzing the resulting data. The classic approach is to subtract the control image from the experimental image to see what brain networks were activated, turned on, by the stimulus or task. This approach assumes that all higher brain networks are quiet unless externally stimulated. No unconscious processing is thought to occur. Activity in lower brain structures responsible for autonomic functions such as respiration, heart rate, body temperature, blood pressure, and other autonomic functions is considered to be noise that is measured during the control condition. In short, this approach assumes a Pavlovian reflex perspective where the brain is passive until externally stimulated. This remains the dominant cognitive science research perspective. The Default Mode Network (DMN) was discovered by Raichle et al. (2001). It was discovered by reversing the data subtraction procedure. The experimental image was subtracted from the control image to see what brain networks were deactivated, turned off when the brain attends to an external stimulus. This approach is based on the inverse perspective that the brain is always very busy doing its own thing while in the so-called ‘resting’ state, and interrupts itself when it needs to attend to an external stimulus or engage in a particular task.25 These interactive neural networks constitute the Default Mode Network (DMN). Upwards of 90% of the energy consumed by the brain is used to support the DMN (Raichle & Snyder, 2007). The DMN continues to be active during sleep. DMN activity persists even during light anesthesia (Raichle, 2009). The supporting evidence for the DMN has now been sufficiently well replicated that it is a neuroscience fact. The main point of interest for this section is that people are totally unaware of the massive amount of unconscious processing that is continuously done by the DMN. To mistake the activities of the DMN for rest demonstrates how far outside of consciousness it operates. No degree of introspection provides any access to the DMN. These findings alone provide sufficient reason to replace the contemporary conscious-centric approach to psychology with an unconscious-centric approach. The research supporting the DMN also pertains to the question of whether all behavior is rule-governed, as alleged by the critics of dual-processing theories discussed above. Do these critics seriously believe that the DMN operates on the basis of rules? Would these be unconscious rules? It seems to me that the DMN conclusively demonstrates the existence of unconscious processing that is not rule-based and therefore single-process theories based on rule-following are false.

סרוטונין

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לסרוטונין יש תפקיד חשוב בהומהוסטזיס של האנרגיה של התאים. ז"א מדבר עם המיטוכונדריה של התאים.

Yu, Seungyoon B.; Pekkurnaz, Gulcin (2018). Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis. Journal of Molecular Biology, (), S002228361830891X–. doi:10.1016/j.jmb.2018.07.027

To maintain homeostasis, every cell must constantly monitor its energy level and appropriately adjust energy, in the form of ATP, production rates based on metabolic demand. Continuous fulfillment of this energy demand depends on the ability of cells to sense, metabolize, and convert nutrients into chemical energy.

מחפשת תשובה לשאלות

מה התפקיד של סרוטונין ומה האינטרקציות שלו עם דופמין, נירואדרנלין, והורמוני מין

מה הקשר ל פטריות הזייה ולפרוק העצמי.

וגם

involvment of serotonin in regulation of dophamine

לא ברור לי למה לפעמים כשמקבלים תרופות פסיכיאטריות שמעלות את רמת הסרוטונין בסינפסות באמצעות התרופות קופצים למאניה. אולי הן מעלות גם נוירואדרנלין?

התשובה כנראה נעוצה בכך שכשיש יותר מדי סרוטונין, הטרנספורטרים של הדופמין, שיש להם אפיניטי נמוך, נבלעים בתוך הוזיקולות של הדופמין.... כך שכשהVTA לדוגמה משחרר דופמין הוא משחרר דופמין וסרוטונין ביחד...

Eastwood, S. L., Burnet, P. W., Gittins, R., Baker, K., & Harrison, P. J. (2001). Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia. Synapse (New York, N.Y.), 42(2), 104–114. https://doi.org/10.1002/syn.1106

Daws L. C. (2009). Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy. Pharmacology & therapeutics, 121(1), 89–99. https://doi.org/10.1016/j.pharmthera.2008.10.004

Bacqué-Cazenave, J., Bharatiya, R., Barrière, G., Delbecque, J. P., Bouguiyoud, N., Di Giovanni, G., Cattaert, D., & De Deurwaerdère, P. (2020). Serotonin in Animal Cognition and Behavior. International journal of molecular sciences, 21(5), 1649. https://doi.org/10.3390/ijms21051649

the

role of 5-HT is much broader and more complex because it is involved in stress responses and mood disorders at dierent levels [2–4]. The diversity of modulating eects induced by 5-HT in cognitive tasks and behavioral responses is linked to i) its simultaneous eects on a multiplicity of neural targets underlying these functions and ii) to the large number of its receptors with their intracellular signaling pathways and their dierent anities, acting at various neuron locations. Because of these specificities, 5-HT systems can ensure fine-tuning of behaviors in various situations, sometimes by inhibiting learned behavioral responses that would be inappropriate or by adjusting the timing of responses to ensure more adapted behavior [5,6]. We have explored the influence of the 5-HT system in some biological functions in both vertebrates and invertebrates. We have covered specific animal responses

to illustrate our topic as reported in Figure 1.

Figure 1. Functions modulated by 5-hydroxytryptamine (5-HT) in dierent species. (A) functions modulated related to motor activities and locomotion, (B) functions modulated related to sleep and circadian rhythms, (C) functions modulated related to sleep and circadian rhythms, (D) functions modulated related to social interactions, social status and aggressiveness, (E) functions modulated related to anxiety, (F) functions modulated related to mood, (G) functions modulated related to learning and memory.

Andrews, P. W., Bharwani, A., Lee, K. R., Fox, M., & Thomson, J. A., Jr (2015). Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience and biobehavioral reviews, 51, 164–188. https://doi.org/10.1016/j.neubiorev.2015.01.018

Soubrié, P. (1986). Reconciling the role of central serotonin neurons in human and animal behavior. Behavioral and Brain Sciences,9(2), 319-335. doi:10.1017/S0140525X00022871

Abstract

Animal research suggests that central serotonergic neurons are involved in behavioral suppression, particularly anxiety-related inhibition. The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts, and increased anxiety. The target article attempts to reconcile such human and animal findings by investigating whether anxiety reduction or increased impulsivity is more Likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty) are reviewed and compared with the effects of antianxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior toward facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are involved not only in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed, though not necessarily because of the alleviation of anxiety, which might contribute to the suppression.

Bari, A.; Robbins, T.W. Inhibition and impulsivity: Behavioral and neural basis of response control. Prog.Neurobiol. 2013, 108, 44–79

Abstract

In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of 'response inhibition' has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain's emergency 'brake' operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions.

Voronezhskaya E. E. (2022). Serotonin as a volume transmission signal in the "simple nervous system" of mollusks: From axonal guidance to behavioral orchestration. Frontiers in synaptic neuroscience, 14, 1024778. https://doi.org/10.3389/fnsyn.2022.1024778

Taber, K. H., & Hurley, R. A. (2014). Volume transmission in the brain: beyond the synapse. The Journal of neuropsychiatry and clinical neurosciences, 26(1), iv–4. https://doi.org/10.1176/appi.neuropsych.13110351

רפרנס-יפה גם לעניין המתז או הטפטפת

Zhou, F. M., Liang, Y., Salas, R., Zhang, L., De Biasi, M., & Dani, J. A. (2005). Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron, 46(1), 65–74. https://doi.org/10.1016/j.neuron.2005.02.010

Thomas, S., Hnasko., Robert, H., Edwards. (2012). Neurotransmitter Corelease: Mechanism and Physiological Role. Annual Review of Physiology, 74(1):225-243. doi: 10.1146/ANNUREV-PHYSIOL-020911-153315

Dayan, P., & Huys, Q. J. M. (2009). Serotonin in Affective Control. Annual Review of Neuroscience, 32(1), 95–126. doi:10.1146/annurev.neuro.051508.135607

10.1146/annurev.neuro.051508.135607

Wu, H.; Denna, T. H.; Storkersen, J. N.; Gerriets, V. A.Beyond a neurotransmitter: The role of serotonin in inflammation and immunity. Pharmacol. Res.2019, 140, 100– 114, DOI: 10.1016/j.phrs.2018.06.015

[Crossref], [PubMed], [CAS], Google Scholar

introduction

Serotonin (5-HT) is a neurotransmitter involved with the regulation of numerous behavioral and biological functions in the body, playing a role in both psychological processes in the central nervous system (CNS) as well as peripheral tissues such as the bone and gut (1-3). While 5-HT is best known as a neurotransmitter in the brain, close to 95% of the 5-HT in the body is actually synthesized, stored and released by cells in the intestinal mucosa known as enterochromaffin (EC) cells (4-6). EC cells are a subtype of intestinal enteroendocrine cells that generate 5-HT from the dietary amino acid L-tryptophan using the rate-limiting enzyme tryptophan hydroxylase (TPH) (7). The 5-HT is then packaged into vesicles and the majority is released at the basal border of the EC and enters the lamina propria, where the nerve terminals are located (8, 9). Many different cell types are found in the gut, including a large number of peripheral immune cells, which play an important role in the gut to maintain host defense systems in the GI tract and are in close proximity to EC cells (see Figure 1). Why 5-HT is primarily found in the intestinal mucosa is largely unknown, although it may play a role in normal gut functions, including intestinal motility, absorption and transit (6). For this reason, specific 5-HT receptors within the gut, including 5-HT3 and 5-HT4, are the targets of drugs used to treat gastrointestinal issues such as irritable bowel syndrome (10). However, studies using TPH1 knockout mice, in which the enzyme responsible for the synthesis of 5-HT in the intestines is deleted, show that TPH1 knockouts do not have altered intestinal motility or transit, thus the role of TPH and 5-HT in the gut remains unclear (11, 12). A relationship between 5-HT, the brain and gut has been known for quite some time and, more recently, expanded to include the microbiota within the gut. Commonly called the “gut-brain axis” or “microbiota-gut-brain axis”, the interaction between the CNS and enteric nervous system is thought to be bidirectional, linking brain function with a variety of peripheral functions (13-15). While the relationship between 5-HT, the brain and gut is fairly well-established, a growing body of literature has begun to examine connections between 5-HT and the immune system and the potential cross-talk between these systems (16)

סרוטונין ופטריות הזיה -

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Pompili, M., Serafini, G., Innamorati, M., Möller-Leimkühler, A. M., Giupponi, G., Girardi, P., … Lester, D. (2010). The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention. European Archives of Psychiatry and Clinical Neuroscience, 260(8), 583–600. doi:10.1007/s00406-010-0108-z

10.1007/s00406-010-0108-z

Suicide is a complex phenomenon resulting from various factors, including psychiatric, biological and environmental factors. It is well established that there is a substantial genetic contribution to suicidal behavior involving serotonin transporter and 5-HT1A receptors [178].

The HPA-axis has complex interactions with brain serotonergic, noradrenergic, and dopaminergic systems.

What is the relationship between serotonin and the HPA-axis? Roy et al. [210] suggested that serotonin plays an excitatory role in the regulation of the release of CRH. CRH is carried from the hypothalamus via the portal system to the anterior pituitary where it stimulates the secretion of ACTH into the blood. CRH neurons of the central amygdala are directly and indirectly connected to brain nuclei such as the locus coeruleus and raphe nuclei [88, 89, 147], the major source of serotonergic projections which are involved in the stress response [177].

In 88 drug-naive healthy individuals, Praschak-Rieder et al. [191] investigated seasonal variations in serotonin transporter levels and found that serotonin transporter levels were significantly higher in the fall and winter compared with those in spring and summer. Higher serotonin transporter density is associated with lower synaptic serotonin levels. They concluded that serotonin transporter levels vary during the year with the seasons, and there may be lower synaptic serotonin levels in the fall and winter. Therefore, polymorphisms in the promoter region of the 5-HT transporter gene also influence antidepressant efficacy and tolerability, and abnormalities in 5-HT1A may play an important role in suicide

Although the stress response of the body is meant to maintain stability or homeostasis, long-term activation of the stress system may have a hazardous or even lethal effect on the body, increasing the risk of obesity, heart disease, depression and a variety of other illnesses.

The HPA axis is the neuroendocrine system that regulates the body’s response to stress.

CRH and vasopressin are released from neurosecretory nerve terminals at the median eminence. They act synergistically to stimulate the secretion of stored ACTH from corticotroph cells. ACTH is released via different second messenger systems [272– 274]. Both CRH and AVP are required for a normal pituitary and adrenal response to some acute stressful stimuli [125, 199]. In particular, AVP receptor up-regulation may be critical for sustaining the corticotrophic responsiveness in the presence of high circulating glucocorticoid levels during chronic stress or depression [1].

ACTH is transported to the adrenal cortex of the adrenal gland, where it rapidly stimulates biosynthesis of corticosteroids such as cortisol from cholesterol. Corticosteroids produce several behavioral changes [40]. Cortisol is a major stress hormone and has effects on many tissues in the body, including the brain [231]. Cortisol diffuses into the brain and binds with different affinities to two types of corticosteroid receptors: Type I or mineralocorticoid receptors (MR) and Type II or glucocorticoid receptors (GR). Both MR and GR are expressed in human brains [263, 266, 276] and monkey brains [184, 194, 216]. The hippocampus, amygdala and medial prefrontal cortex (mPFC) [60, 216] are mainly occupied during periods of stress [111, 115, 158, 232]. MR has a high binding affinity, is extensively occupied most of the time, and regulates the transcription of genes involved in tonic neurotrophic effects [74, 144, 213, 275]. MR and GR are in relative balance in brain regions that play a role in cognitive and neuroendocrine functions [55, 93, 127, 129]. Patel and colleague

111. Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3:453–462

Mahony, C., & O'Ryan, C. (2022). A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology. Frontiers in psychiatry, 13, 985713. https://doi.org/10.3389/fpsyt.2022.985713

הכיוון של סקירת תפקיד הסרוטונין לאורך הסולם האבולוציוני מעניין.

בעיקרון הטענה הכללית העולה היא שסרוטונין מיועד בעיקר לעשות fine tuning לתגובות ולהתנהגויות,

כך הוא עושה בתלמוס (שערי התודעה) שם הוא גורם לזה שהקלט מהעיניים ילך לפרשנות לראיה, הקלט מהאוזניים ילך לפרשנות השמיעה וכו.

אבל יציאה משיווי משקל של סרוטונין (עודף מוגזם של סרוטונין) מביאה – כמו שקורה ב LSD ופטריות לפריצת שערי התודעה והמחסומים האלה ואז רואים צלילים, שומעים מגע וכו.

יש סיפרי מדע בדיוני המתארים עולמות אלטרנטיביים שמתארים את החוויות האלה. כמו כן זה יכול להסביר למה שימוש באיווסקה לדוגמה יכול להביא לכך שנשברים מחסומים פנימיים שהוקמו על ידי האד בזמן טראומות ונוצרים חיווטים חדשים חופשיים יותר (הטענה של ריסטארט למערכת). מעין מסל"ם (מסלול סלילה מהירה ) הופכי לטראומה. יש להביא בחשבון כשנפרצים שערי התודעה יש עליה גבוהה בסטראס, ובהתאמה – דופמין ונוירואדרנלין.

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Peripheral Serotonin: a New Player in Systemic Energy homeostasis#

Namkung, J., Kim, H., & Park, S. (2015). Peripheral Serotonin: a New Player in Systemic Energy Homeostasis. Molecules and cells, 38(12), 1023–1028. https://doi.org/10.14348/molcells.2015.0258

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696992/#sec-1title

Body energy homeostasis is a primitive and fundamental biological function that is regulated through complex physiological processes. As an ancient neurotransmitter that is conserved throughout the animal phyla, serotonin is a good candidate to play a fundamental role in the regulation of energy homeostasis. At least 14 HTRs, grouped into 7 families according to the signaling mechanisms, are widely expressed in mammalian tissues. This diversity of HTRs can provide diverse effects of serotonin on target cells (Hannon and Hoyer, 2008). Indeed, the functions of serotonin in energy homeostasis range from central control of food intake to direct regulation of adipose tissue activity in the periphery. In this review, we discuss the functional role of serotonin in systemic energy homeostasis.

התיחסות להשמנה ולאנורקסיה

Central serotonin has been considered a target for anti-obesity treatment since an inverse relationship between central serotonin level and food intake was established. Fenfluramine, which increases serotonin release, is the prototypical agent for serotonergic suppression of feeding (Lam and Heisler, 2007). Inhibiting serotonin synthesis in the brain via intraventricular injection of p-chlorophenylalanine (PCPA), an irreversible TPH inhibitor, induces hyperphagia and weight gain in rats (Breisch et al., 1976). Serotonin reuptake inhibitors, such as sibutramine and fluoxetine, and monoamine oxidase inhibitors, such as clorgyline and pargyline, reduce food intake (Feldman, 1988; Heal et al., 1998; Heisler et al., 1997). Thus, central serotonin functions as an anorexigenic neurotransmitter.

מעגל השובע

סרוטונין מפעיל את המסלול הכחול - שמגיע עד מרכז השובע. כשיש לנו סרוטונין והמסלול הכחול מופעל אנחנו מרגישים שבעים.

סרוטונין מפעיל גם את המסלול כתום - הבאז. (הימני). את פעילות הנוירון ה AgRP. כשהמסלול הזה כן מופעל - הוא חוסם את הפעילות של הנוירון הכחול, וחוסם את הפעילות של הנוירון הצהוב (מרכז השובע) ואנחנו מרגישים רעבים.

לדעתי זה רק חלק מהתמונה, כי הקטע המשונה בעיני הוא שכשאני מוצפת דופמין אני לא רעבה בכלל, גם כשנמצאים בסטראס מרמה מסוימת אני לא מסוגלת לאכול (זה ברמה מערכתית) אז זה לא מסתדר לי.

מצד שני, כשנמצאים ביציאה משיווי משקל (נניח מחזור חודשי) א כשהמתח בנוני - אוכלים יותר. אז זה ברמה מערכתית.

ואכן הם כותבים במאמר שניסויים עם עכברים שמככבים להם את הנוירונים הכחולים או הכתומים באיור למעלה לא מביאים לעליה או ירידה במשקל כפי שמצופה מהנ"ל. המסקנה שלהם היא שכנראה קצב הוצאת האנרגיה גדל

Since TPH2 is responsible for the serotonin production in the brain, Tph2 KO mice were expected to be hyperphagic and obese. Although central serotonin levels were selectively decreased, the body weights of Tph2 KO mice were lower than littermate control (Alenina et al., 2009; Gutknecht et al., 2012; Savelieva et al., 2008). In addition, Htr1b KO mice did not develop obesity, despite having hyperphagia (Bouwknecht et al., 2001). These findings suggest that central serotonin may upregulate energy expenditure in the body.

The injection of serotonin into the paraventricular nucleus and ventromedial nucleus of the hypothalamus increases sympathetic tone, resulting in the upregulation of the activity of brown adipose tissue (BAT) (Sakaguchi and Bray, 1989). Fenfluramine also increases sympathetic tone and activates BAT that is reversed by BAT sympathectomy (Arase et al., 1988; Rothwell and Stock, 1987). Taken together, these findings indicate that central serotonin decreases energy intake by reducing appetite and increases energy expenditure by activating BAT through the sympathetic nervous system.

סרוטונין במוח וסרוטונין בבגוף עושים מהלך הפוך. במוח הרבה סרוטונין גורם לשובע? ואנורקסיה. בגוף (מעי, כבד וכו) גורם להשמנת יתר.

In contrast to the anorectic effect of central serotonin, several lines of evidences suggest different functions of serotonin in the periphery. Slc6a4 (SERT) KO mice were expected to be slim due to the increased serotonin activity in the brain; however, they exhibited an obese phenotype (Murphy and Lesch, 2008). Body weight is reduced in Tph1 and Tph2 double KO mice as well as in Tph1 KO mice (Alenina et al., 2009; Gutknecht et al., 2012; Savelieva et al., 2008). In addition, the enhancement of serotonin activity using a selective SERT inhibitor (SSRI) is associated with transient weight loss (Serretti and Mandelli, 2010). These discordant results suggest that peripheral serotonin and central serotonin play opposite roles in the regulation of energy homeostasis.

כדי לייצר תוכנה שתבין : ניסוי

להבין את המשפט אהבה היא כמו אש

לעומת אהבה היא כמו שעון

סריקה של טקסטים ויצירת מפת קישורים של מילים על פי חוקי הב ואנטי הב.

קריאת טקסטים בעזרת מפת בליטות.

בדיקה אם יש מסלול מובחן ובולט בין אהבה לאש. וכו.

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קצת על דסלקציה למידה זיכרון עבודה וקריאה של מרב אחיסר

Why Do Some Children Struggle to Read?

Authors and reviewers

Authors

https://kids.frontiersin.org/articles/10.3389/frym.2020.00061

In order to test the hypothesis that sound memories decay faster in the brain of people with dyslexia, and to understand in which brain areas this faster decay occurs, we conducted another experiment. In this experiment, participants were scanned in a device called a functional magnetic resonance imaging scanner (fMRI scanner

A device using magnetic fields to measure brain activity when the participant is performing different tasks. The measurement is based on the amount of oxygen in the blood flowing in the brain during the task. During the experiment, the participant lies inside a tube-like structure and performs the required task, while the oxygen levels are measured. The measurement is non-invasive and that is why it is very common in the field of neuroscience.

) while performing the same task of listening to sounds and determining which has a higher pitch. The fMRI allowed us to record the activity of the participants’ brain during the experiment.

Generally, when the same sound is presented twice with a short gap in between, the brain’s response to the second presentation is smaller. This phenomenon is called neural adaptation. The smaller response to the second sound tells us that the brain still remembers the first sound in some way, because the first sound still influences the processing of the second sound. In people with dyslexia, we found that this period of subconscious memory of the first sound was shorter. When the gap between sounds was 10 s, the response to the second sound measured in the brains of people without dyslexia was smaller, telling us that the memory of the first sound was still stored in their brains. In contrast, people with dyslexia had a full-intensity response for the second sound if the sounds were 10 s apart, telling us that their brains no longer had available memory of the first sound. This difference in memory duration was observed in multiple areas of the cortex

A part of the brain, its outer layer. The cortex processes auditory (sound) and visual information, deals with problem solving, sending movement messages to the muscles and much more. The cortex is folded, and thus is full of ridges and grooves, which greatly enlarge its surface area. The cortex is divided into a few sub-areas according to the grooves, and these sub-areas are related to different functions.

[4] (Figure 1).

Authors

Eva Kimel

Eva KimelDuring my Ph.D. I have studied how regularities and repetitions in language assist people with and without dyslexia in learning and memory tasks. Ever since I remember myself, I was curious about how we learn, remember, understand, and process the information coming from the world around us. I am still very curious about that, and lately also inspired by the way that my daughter studies the world. I also like some things that are not directly related to science, such as chocolate balls and Zumba. *eva.kelman@gmail.com

Merav Ahissar

↑Jaffe-Dax, S., Kimel, E., and Ahissar, M. (2018). Shorter cortical adaptation in dyslexia is broadly distributed in the superior temporal lobe and includes the primary auditory cortex. eLife 7:1–9. doi: 10.7554/eLife.30018References [1] ↑ Hudson, R. F., Lane, H. B., and Pullen, P. C. 2005. Reading fluency assessment and instruction: what, why, and how? Read. Teach. 58:702–14. doi: 10.1598/RT.58.8.1 [2] ↑ Tallal, P. 1980. Auditory temporal perception, phonics, and reading disabilities in children. Brain Lang. 9:182–98. doi: 10.1016/0093-934X(80)90139-X [3] ↑ Jaffe-Dax, S., Raviv, O., Jacoby, N., Loewenstein, Y., and Ahissar, M. 2015. A computational model of implicit memory captures dyslexics’ perceptual deficits. J. Neurosci. 35:12116–26. doi: 10.1523/JNEUROSCI.1302-15.2015 [4] ↑ Jaffe-Dax, S., Kimel, E., and Ahissar, M. 2018. Shorter cortical adaptation in dyslexia is broadly distributed in the superior temporal lobe and includes the primary auditory cortex. ELife 7:e30018. doi: 10.7554/eLife.30018 [5] ↑ Kimel, E., and Ahissar, M. 2019. Benefits from morphological regularities in dyslexia are task dependent. J. Exp. Psychol. Learn. Mem. Cogn. 46:155–69. doi: 10.1037/xlm0000717 [6] ↑ Kimel, E., Weiss, A. H., Jakoby, H., Daikhin, L., and Ahissar, M. 2019. Spans attributed to short-term memory are explained by sensitivity to long-term statistics in both musicians and individuals with dyslexia. bioXriv. doi: 10.1101/795385

Article information Citation Kimel E and Ahissar M (2020) Why Do Some Children Struggle to Read?. Front. Young Minds. 8:61. doi: 10.3389/frym.2020.00061

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מדריך בדיקות מעבדה – מאת פרופ' בן-עמי סלע / קורטיזול – Cortisol pharmaline.co.ilhttps://www.pharmaline.co.il › article מדידת רמת קורטיזול, מהסטרואידים היותר חשובים בגוף, המופרש מבלוטת יותרת הכליה ... שיעור ההימצאות של אוטיזם עומד על 27.6 פר אלף ילדים בני שמונה בשנת 2020.

Maria Hernandez-Reif, Nahide Gungordu,

Infant sleep behaviors relate to their later cognitive and language abilities and morning cortisol stress hormone levels, Infant Behavior and Development,

Volume 67, 2022, 101700, ISSN 0163-6383, ttps://doi.org/10.1016/j.infbeh.2022.101700.

Sleep appears to expedite chemical substrates and neural processes, such as synapse formation and pruning, by providing endogenous stimulation to the brain (Mirmiran, Maas, & Ariagno, 2003). For instance, language acquisition seems particularly vulnerable to sleep-wake state organization (Scher, 2005a, Scher, 2005b, Touchette et al., 2007). Two mechanisms have been proposed in the literature to explain the critical role of sleep in young children’s language skill gains and cognitive development. First, poor sleep consolidation might inhibit memory processes (Curcio, Ferrara, & De Gennaro, 2006) required in early language learning. Second, lower-order regulatory systems, such as sleep, may have an organizing effect over higher-order systems involved in cognition (Porges, 1996). Therefore, as children’s sleep-wake cycles mature, so should their skills to regulate attention and operate language during social relationships, resulting in better language skills in children whose sleep consolidation matures earlier (Dionne et al., 2011a, Dionne et al., 2011b, Dionne et al., 2011c). Sleep has been shown to support various aspects of language development, from word learning to rules of grammar (Batterink, Oudiette, Reber, & Paller, 2014; Henderson et al., 2012).

We anticipated that elevated infant cortisol levels would be associated with less optimal home sleep behavior and home sleep environment and to lower cognitive skills in todd

למידה מרווחת

Kristine C. Bloom & Thomas J. Shuell (1981) Effects of Massed and Distributed Practice on the Learning and Retention of Second-Language Vocabulary, The Journal of Educational Research, 74:4, 245-248, DOI: 10.1080/00220671.1981.10885317

Research Article Spacing effects in real-world classroom vocabulary learning Hailey S. Sobel, Nicholas J. Cepeda, Irina V. Kapler First published: 22 September 2010 https://doi.org/10.1002/acp.1747 Citations: 99

Read the full text Sobel, H. S., Cepeda, N. J., & Kapler, I. V. (2010). Spacing effects in real-world classroom vocabulary learning. Applied Cognitive Psychology, 25(5), 763–767. doi:10.1002/acp.1747

Abstract As a primary goal, educators often strive to maximize the amount of information pupils remember. In the lab, psychologists have found efficient memory strategies for retaining school-related materials. One such strategy is the spacing effect, a memory advantage that occurs when learning is distributed across time instead of crammed into a single study session. Spaced learning is not often explicitly utilized in actual classrooms, perhaps due to a paucity of research in applied settings and with school-aged children. The current study examined the spacing effect in real-world fifth-grade classrooms. We taught 39 children unfamiliar English words using both massed and spaced learning. Five weeks later, we tested vocabulary recall. One-week spacing produced superior long-term retention compared to massed learning. This finding demonstrates that the spacing effect can be generalized to vocabulary learning in applied settings and middle-school-aged children. Copyright © 2010 John Wiley & Sons, Ltd.

Participants Forty-six participants (M 10-years-old; 19 female) were recruited from two fifth-grade classrooms in an upper-middle SES Ontario middle school. Data from seven participants were dropped because of failure to complete all sessions due to missing class during one or more sessions, resulting in a final sample size of 39 participants. Materials Eight English words, judged by the experimenters to be new to fifth-grade children, were selected from the GRE word list (i.e. accolade, coerce, edict, gregarious, latent, salient, tacit and vex). According to WordCount.org (Harris, 2003), all words fell outside of the most frequently used 9000 words in spoken and written English. Four words (two adjectives, one noun and one verb) were randomly assigned to each study condition (massed and 1-week); this word assignment was the same for all children. All vocabulary words were presented to children in a workbook consisting of three pages (Appendix A). The first page listed four vocabulary words to be learned; the second page showed the actual definitions of the words; the third page had a space for children to write down the definition of the word and to use the word in a sentence. In addition to the booklets, teachers were given a set of overheads that contained these same words and definitions as well as rules for the exercise.

Design Within each class, all children participated in both massed and spaced conditions. The massed condition consisted of two consecutive learning sessions separated by less than 1 minute, and the 1-week condition consisted of two learning sessions separated by 7 days.

r Procedure Each entire learning episode consisted of five steps that took in total approximately 15 minutes to complete (including distribution/collection of materials, children writing their names, etc.). Formal learning time was 10 minutes, and was the same for both experimental conditions. In Step 1, the booklets were handed out to children, and all four words, their definitions and sample use in a sentence were shown to children using an overhead projector. Children were instructed to read the overhead along with the teacher, who read out the definitions and sample sentences once. The overhead was then removed. In Step 2, the children were given 3 minutes to complete the first page of the booklet (containing vocabulary words only) by writing down the definitions for all four words. In step 3, children were instructed to turn to page two of the booklet (containing the correct definitions of each word). Definitions and use in a sample sentence were repeated by the teacher. Then, children were given 1 min to read over the definitions by themselves. In Step 4, children were given 3 minutes to complete the last page of the booklet, by writing down the definition of each word in the provided space and writing down a novel sentence using each word. Then, the teacher collected the booklets. Because different words were used for each experimental condition, the data from Step 4 of the first learning episode were used to ensure that word difficulty was equal across conditions. During the learning session, the teacher circulated the classroom to ensure that children remained on task and followed instructions. The second learning session took place according to the spacing schedule: either massed, 1 minute after the first learning session; or spaced, 1 week after the first learning session. During the second learning session, children were re-taught the same words, using the same method as during the first learning session. After a retention interval of 5 weeks following the second learning session, children were given a vocabulary test to assess their retention. Children were given a list of four words, and were responsible for writing down the definition of each word. Children were given 10 minutes to complete this task. Each child participated in two final test sessions (four words each), so that retention interval remained constant across massed and spaced conditions

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בושה ציטוט מקפקא

כמעט בכל כתבי קפקא אפשר לחוש באיזה נופך תיאולוגי הנמשך כמו הד משורותיו אך "במחברות האוקטבו" שלו התכונה הזאת גם מקבלת ביטוי קונקרטי, בין היתר כהרהורים סביב פרשת החטא הקדמון. חוויית הבושה עומדת בתשתית סיפור גן העדן בהיותה הביטוי האנושי הראשוני לעמידה החשופה אל מול העולם לאחר האכילה מפרי עץ הדעת. הבושה היא אפוא טביעת הקיום הקמאית של ההכרה, ואולי בשל כך היא גם אותה איכות שנדרשת להוסיף ולחיות אחרינו, כי "אין אדם יכול לחיות בלי אמון תמידי במשהו בלתי־ניתן־להריסה שבו (...) להאמין משמע לשחרר את הבלתי־ניתן־להריסה שבך, או נכון יותר: לשחרר את עצמך, או נכון יותר: להיות בלתי ניתן להריסה, או נכון יותר: להיות".

המשפט שחותם את ההוצאה להורג, ואת הרומן כולו, הוא מהידועים ביותר ביצירת קפקא: "'כמו כלב!' הוא אמר, דומה היה כי על הבושה מוטל להוסיף לחיות אחריו" ("Wie ein Hund!" sagte er, es war, als sollte die Scham ihn überleben")

כיצד יש להבין את המשפט הזה?

מובנו האחד, המיידי, הוא כי ההוצאה להורג, כמיצויו של ההליך המשפטי כולו, היא כה שפלה ומשפילה עד שגם המוות אינו סוף פסוק והבושה תשאר אחריו. שני התרגומים של הרומן לעברית, על אף ההבדלים ביניהם, נוטים לאפשרות זו. כך בתרגומו של ישורון קשת (הוצאת שוקן, 1951): "'ככלב!', אמר, דומה היה כאילו תישאר החרפה קיימת גם לאחר שהוא לא יהיה עוד". וכך בתרגומו של אברהם כרמל (הוצאת שוקן, 1992): "'כמו כלב!' אמר, כאילו ביקש לומר כי הבושה תשרוד אחריו".

ואולם להישארות הבושה יש גם צד שני. המלה sollte מבטאת מעין ציפייה או דרישה מ"הבושה" להוסיף ולחיות אחרי ק'. המספר אינו מפרש את קריאתו של ק' "כמו כלב!" (כפי שאפשר אולי להבין מהתרגום של כרמל) אלא רק מתאר מין תמורה אטמוספרית־אונטולוגית, אפשר כמעט לומר שחלה בעקבות אותה קריאה. שכן הבושה אינה רק שארית מגונה אלא גם ביטויים החריף של חיים שאי־אפשר לחסלם. "אמנם חוקי ההיגיון אינם ניתנים לערעור", אומר ק' כמה משפטים קודם לכן, "אך לעמוד בפני אדם שרוצה לחיות הם אינם מסוגלים".

כוח וההשפעה שלו

Guinote A. (2017). How Power Affects People: Activating, Wanting, and Goal Seeking. Annual review of psychology, 68, 353–381. https://doi.org/10.1146/annurev-psych-010416-044153

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Why Do Some Children Struggle to Read?

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