Biosublime.com/LSD, Birth & TraumaThe Biological Role of the
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REM Sleep Healing Role
R1 REM Sleep Heals Noxious Memories
The main clue to the idea of the healing role of REM sleep is the mystifying character of M’s flashbacks in taking on a life of their own and completing the disappearance or erasure of the noxious memory. This process repeated itself spontaneously soon after awakening in the morning and at certain times of the day without any apparent input from the outside. These were exact encores of the original LSD recall and its somatic effects diminished little by little until their last traces were gone, never to return. The palate pressure was the last sensation to disappear after a few weeks, which was consistent with the area of highest pressure from the obstetrician's fingers. Apparently, a natural spontaneous process exists that expresses some genetically determined function to clear out the baggage of noxious memory, roughly analogous to the healing of a physical wound. Such a process might be expected to follow a regular and continuing schedule to maintain the brain's uncluttered function during the day. The main suspect would be REM sleep, a condition that occurs in several mammals and is associated with vivid dreams in humans.
In considering the role of REM sleep as a healing process for trauma, it's helpful to recall the central issue that arises from M's LSD recall and the discussion of Twilight sleep. It is that trauma has a specific definition that distinguishes it from the kinds of memory related to cognitive learning. In this definition, the phrase, "trauma memory" is redundant. Trauma is the memory, a memory of associated noxious elements stored in a manner that keeps it hidden away from conscious detection for decades. Terms like "memory trace", "engram" and "imprint" are synonomous with this definition of trauma, and most likely share its brainstem mechanisms for consolidation and release. When this hidden memory does reach cortical interpretation it is involuntary and manifests as an encore of the original insult, as in M's case, or as an interloper altering normal behavior and sleep patterns, i.e., PTSD. It may be a variation of "intrinsic" memory, which is also involuntary as in the recall of a childhood memory from a certain odor and, like trauma, is hidden for the very long term. Like "intrinsic" memory, its recall is evoked by an outside perception, as in the case of the war veteran's chaotic physiology triggered by the sound of an exhaust backfire years after the injury. Unlike some kinds of "intrinsic" memory, trauma recall is noxious and corrupting to the normal balance of brain activity. As long as it is maintained in some storage nucleus within the cerebellum or the hippocampus, it will influence the mind's ability in decision making and in altered behavior.
As already discussed in Part 1, Twilight Sleep, the RaRN model is bidirectional, where recall of noxious memory can further traumatize as long as the memory substrate, now opened by the 5-HT1a agonist, remains receptive to internal and external events. The question is whether trauma gives rise to dreams. This raises the consideration that the RaRN model might not operate to reconsolidate the memory; it would only be involved in releasing noxious memory for stepwise erasure and lose its bidirectional property. This expectation is based on the fact that M's flashbacks returned as a stepwise depletion of the memory, once the first stimulation of recall by LSD took place. The subject was not overwhelmed by the intensity of the trauma's recall. As a form of healing flashback taken to into cerebral interpretation, these dreams would be expected to occur in the same manner as the flashbacks M experienced after the first LSD recall, in a more gentle stepwise manner until the trauma completely disappeared. Accordingly, the REM dreams would repeat themselves, as bad dreams often do, until the underlying issue disappeared. As a point of nomenclature, dreams that would manifest as trauma recall would be trauma dreams, not traumatic dreams, since the latter would seem to be unlikely if REM sleep is a healing process.
Thus, as form of flashbacks, REM dreams would belong to a different category than dreams not associated with noxious memory storage. Clearly, some dreams are re-enactments of this hidden memory, since some produce symbols that are accurately recognized as part of the dreamer’s unique history within the play of otherwise distorted dream imagery (Jung, 1943). In M’s experience the disappearance and non-retrieval of these flashbacks with further LSD trials strongly implies the complete erasure of the memory. It would follow from these two observations that REM sleep might be a natural (hallucinogenic) state of the sleep cycle that heals by inducing reticular activation (raphe suppression) to erase the burden of traumatic memory. Since REM occurs in almost all known mammals, it would represent the natural biological process that evolved for conserving energy, the coin of natural selection, by eliminating the energy needed for the constant firing of raphe neurons that keeps the memory hidden. Energy would be conserved, as well, by obviating trauma’s strenuous unconscious effects on behavior and on PTSD. Depriving a subject of REM sleep results in more erratic, irritating, hypersexual behavior and decreased cognitive ability, as if a process sorely needing completion has been interrupted. Notably, this same kind of “hangover” resulted from the deliberate experimental interruption of fetal movements in the adult on LSD (see Part 2.
As a nightly schedule for opening, releasing and erasing trauma (as defined here), REM sleep has certain attributes that are provocative with respect to its brainstem mechanisms and its similarity to some earmarks of the hallucinogenic state: 1) The REM state might be hallucinogenic, as it conforms to a well-known earmark of hallucinogenic state, i.e., reticular activation and alertness, well documented by the similarity of REM EEG tracings to the awake state. This alertness reflects thalamocortical activation seen in a REM-fMRI study (Wherie et al, 2007) and involves brainstem reticular activation with contributions from the orexin system of the hypothalamus, which is subject to 5-HT1a-ligand binding (Muraki et al, 2004). 2) The inability to move, as in REM atonia, is seen on occasion in human subjects on higher doses of both indole and phenethylamine hallucinogens. Muscle atonia is reported to be mediated by the "medullar" raphe nucleus (Hoffman et al, 2007; Brown et al, 2008; Chiu and Mishra, 1980). 3) Similarities are seen in brainstem neurotransmitter sites controlling both REM and the RaRN model (below). REM saccadic eye movements aren't seen in hallucinogenic trips, but originate also from the brainstem. While dream imagery certainly requires cerebral function, it is likely that some dreams originate from trauma and, by association, from the RaRN mechanism involving a 5-HT1a agonist to open the memory substrate in the cerebellum and/or the hippocampus for cortical dream imagery.
Furthermore, this conjecture of healing during sleep is not new. Carl Jung documented the gradual spontaneous disappearance of personal issues in sequential dreams long ago (Jung, 1943). Sir Francis Crick (of DNA fame) viewed REM sleep as a state in which memory traces are "forgotten" (Crick and Mitchison, 1983) as a nightly means to re-organize neural memory "nets" by "reverse learning" of unneeded "traces". The Crick-Mitchison theory was built upon and in agreement with earlier work with the same basic view (Newton and Evans, 1965; Gaarder, 1966). Francine Shapiro and Margot Forrest among others have taken the putative trauma-REM connection into practice as a successful therapeutic tool (EMDR) to alleviate trauma and its stressful effects (Shapiro and Forrest, 1997). Shapiro came upon this notion as she relieved uncomfotable mental states by moving her eyes rapidly. Here, the healing connection to REM arrives from a different and independent direction, the REM-flashback connection. As a function of REM sleep, the spontaneous and weakening persistence of flashbacks monitoring the progress of noxious memory erasure would take the altered form of repeated sequential dreaming. Testing of this REM-RaRN idea should be accessible with established neurobiological methods to provide the scientific support to answer criticisms of EMDR therapy and provide a sound basis for increasing its efficacy.
The main clue to the idea of the healing role of REM sleep is the mystifying character of M’s flashbacks in taking on a life of their own and completing the disappearance or erasure of the noxious memory. This process repeated itself spontaneously soon after awakening in the morning and at certain times of the day without any apparent input from the outside. These were exact encores of the original LSD recall and its somatic effects diminished little by little until their last traces were gone, never to return. The palate pressure was the last sensation to disappear after a few weeks, which was consistent with the area of highest pressure from the obstetrician's fingers. Apparently, a natural spontaneous process exists that expresses some genetically determined function to clear out the baggage of noxious memory, roughly analogous to the healing of a physical wound. Such a process might be expected to follow a regular and continuing schedule to maintain the brain's uncluttered function during the day. The main suspect would be REM sleep, a condition that occurs in several mammals and is associated with vivid dreams in humans.
In considering the role of REM sleep as a healing process for trauma, it's helpful to recall the central issue that arises from M's LSD recall and the discussion of Twilight sleep. It is that trauma has a specific definition that distinguishes it from the kinds of memory related to cognitive learning. In this definition, the phrase, "trauma memory" is redundant. Trauma is the memory, a memory of associated noxious elements stored in a manner that keeps it hidden away from conscious detection for decades. Terms like "memory trace", "engram" and "imprint" are synonomous with this definition of trauma, and most likely share its brainstem mechanisms for consolidation and release. When this hidden memory does reach cortical interpretation it is involuntary and manifests as an encore of the original insult, as in M's case, or as an interloper altering normal behavior and sleep patterns, i.e., PTSD. It may be a variation of "intrinsic" memory, which is also involuntary as in the recall of a childhood memory from a certain odor and, like trauma, is hidden for the very long term. Like "intrinsic" memory, its recall is evoked by an outside perception, as in the case of the war veteran's chaotic physiology triggered by the sound of an exhaust backfire years after the injury. Unlike some kinds of "intrinsic" memory, trauma recall is noxious and corrupting to the normal balance of brain activity. As long as it is maintained in some storage nucleus within the cerebellum or the hippocampus, it will influence the mind's ability in decision making and in altered behavior.
As already discussed in Part 1, Twilight Sleep, the RaRN model is bidirectional, where recall of noxious memory can further traumatize as long as the memory substrate, now opened by the 5-HT1a agonist, remains receptive to internal and external events. The question is whether trauma gives rise to dreams. This raises the consideration that the RaRN model might not operate to reconsolidate the memory; it would only be involved in releasing noxious memory for stepwise erasure and lose its bidirectional property. This expectation is based on the fact that M's flashbacks returned as a stepwise depletion of the memory, once the first stimulation of recall by LSD took place. The subject was not overwhelmed by the intensity of the trauma's recall. As a form of healing flashback taken to into cerebral interpretation, these dreams would be expected to occur in the same manner as the flashbacks M experienced after the first LSD recall, in a more gentle stepwise manner until the trauma completely disappeared. Accordingly, the REM dreams would repeat themselves, as bad dreams often do, until the underlying issue disappeared. As a point of nomenclature, dreams that would manifest as trauma recall would be trauma dreams, not traumatic dreams, since the latter would seem to be unlikely if REM sleep is a healing process.
Thus, as form of flashbacks, REM dreams would belong to a different category than dreams not associated with noxious memory storage. Clearly, some dreams are re-enactments of this hidden memory, since some produce symbols that are accurately recognized as part of the dreamer’s unique history within the play of otherwise distorted dream imagery (Jung, 1943). In M’s experience the disappearance and non-retrieval of these flashbacks with further LSD trials strongly implies the complete erasure of the memory. It would follow from these two observations that REM sleep might be a natural (hallucinogenic) state of the sleep cycle that heals by inducing reticular activation (raphe suppression) to erase the burden of traumatic memory. Since REM occurs in almost all known mammals, it would represent the natural biological process that evolved for conserving energy, the coin of natural selection, by eliminating the energy needed for the constant firing of raphe neurons that keeps the memory hidden. Energy would be conserved, as well, by obviating trauma’s strenuous unconscious effects on behavior and on PTSD. Depriving a subject of REM sleep results in more erratic, irritating, hypersexual behavior and decreased cognitive ability, as if a process sorely needing completion has been interrupted. Notably, this same kind of “hangover” resulted from the deliberate experimental interruption of fetal movements in the adult on LSD (see Part 2.
As a nightly schedule for opening, releasing and erasing trauma (as defined here), REM sleep has certain attributes that are provocative with respect to its brainstem mechanisms and its similarity to some earmarks of the hallucinogenic state: 1) The REM state might be hallucinogenic, as it conforms to a well-known earmark of hallucinogenic state, i.e., reticular activation and alertness, well documented by the similarity of REM EEG tracings to the awake state. This alertness reflects thalamocortical activation seen in a REM-fMRI study (Wherie et al, 2007) and involves brainstem reticular activation with contributions from the orexin system of the hypothalamus, which is subject to 5-HT1a-ligand binding (Muraki et al, 2004). 2) The inability to move, as in REM atonia, is seen on occasion in human subjects on higher doses of both indole and phenethylamine hallucinogens. Muscle atonia is reported to be mediated by the "medullar" raphe nucleus (Hoffman et al, 2007; Brown et al, 2008; Chiu and Mishra, 1980). 3) Similarities are seen in brainstem neurotransmitter sites controlling both REM and the RaRN model (below). REM saccadic eye movements aren't seen in hallucinogenic trips, but originate also from the brainstem. While dream imagery certainly requires cerebral function, it is likely that some dreams originate from trauma and, by association, from the RaRN mechanism involving a 5-HT1a agonist to open the memory substrate in the cerebellum and/or the hippocampus for cortical dream imagery.
Furthermore, this conjecture of healing during sleep is not new. Carl Jung documented the gradual spontaneous disappearance of personal issues in sequential dreams long ago (Jung, 1943). Sir Francis Crick (of DNA fame) viewed REM sleep as a state in which memory traces are "forgotten" (Crick and Mitchison, 1983) as a nightly means to re-organize neural memory "nets" by "reverse learning" of unneeded "traces". The Crick-Mitchison theory was built upon and in agreement with earlier work with the same basic view (Newton and Evans, 1965; Gaarder, 1966). Francine Shapiro and Margot Forrest among others have taken the putative trauma-REM connection into practice as a successful therapeutic tool (EMDR) to alleviate trauma and its stressful effects (Shapiro and Forrest, 1997). Shapiro came upon this notion as she relieved uncomfotable mental states by moving her eyes rapidly. Here, the healing connection to REM arrives from a different and independent direction, the REM-flashback connection. As a function of REM sleep, the spontaneous and weakening persistence of flashbacks monitoring the progress of noxious memory erasure would take the altered form of repeated sequential dreaming. Testing of this REM-RaRN idea should be accessible with established neurobiological methods to provide the scientific support to answer criticisms of EMDR therapy and provide a sound basis for increasing its efficacy.
R2 The Brain Stem and REM Sleep.
If REM sleep is inaugurated by a 5-HT1a agonist, one obvious experimental expectation would be the prevention of the REM period with administration of a 5-HT1a antagonist, such as WAY 100 635 or its enhancement by the agonist. However, this experiment is not so simple. The first impression from a cursory look at the results of REM research is that REM sleep is suppressed, not enhanced, by serotonin re-uptake inhibitors (SSRIs) as well as 5-HT1a agonists, which is opposition to this proposed connection between flashbacks and the REM state (Gillin et al, 1996; Wilson et al, 2005). However, systemic application of agonists into humans may suffer from the same problem that occurs with similar administration of monoamine oxidase inhibitors to suppress REM sleep. As discussed below, the effect is paradoxical and is most likely due to the problem of access of the drug to specific brainstem sites from the circulatory system. Direct application of 5-HT1a agonists to the dorsal raphe nucleus does, indeed, increase the REM state (Monti and Monti, 2000). Also, the onset of the REM state is a complex affair involving cholinergic, GABAergic, noradrenergic and nitric oxide synthease action and depends on both pre- and post-synaptic receptors of the dorsal raphe (cf. Sorensen et al, 2001; Monti et al, 2001; Monti et al, 2002). While the dorsal raphe has a role in REM sleep, other raphe nuclei, perhaps having an opposite role are as well (Brown et al, 2008).
Earlier studies on REM neurophysiology pointed to its origin in the rostral or pons area of the brainstem (Jouvet 1962, McCarley & Hobson 1975). As already mentioned, application of agonists and antagonists to the dorsal raphe 5-HT1a receptor seems to be well established in initiating and stopping REM sleep (see below). The dorsal raphe nucleus is itself comprised of six to eight sub-nuclei and is the source of the great majority (ca. 90%) of serotonergic projections throughout the brain. Many attributes of REM sleep, e.g., changes in heart rate, blood pressure and body temperature are reproduced during non-REM sleep (NRM) with the application of raphe 5-HT1a agonist and reversed by 1a antagonists (Brown et al, 2007; Hoffman et al, 2008). NREM + 1a agonist = REM. Other neurotransmitter systems within the brainstem affect REM sleep by interacting with “REM-on” and REM-off neurons acting in reciprocal fashion. REM-on neurons are those that fire during REM sleep and REM-off neurons, e.g., the raphe 5-HT1a neurons, must remain inactive at the same time. The primary requirement for activating REM sleep is the cessation of firing of REM-OFF neurons (Pal and Mallick, 2007). The different locations of REM-on and REM-off neurons are shown in the table below:
TABLE LEGEND:
The headings, "REM-ON" and "REM-OFF" are the starting states before drug application.
ovlPAG ventrolateral periaqueductal gray (Sapin et al, 2009)
dDpMe dorsal part of the deep mesencephalic reticular nucleus immediately ventral to vlPAG (Sapin et al, 2009)
Med-RN medullary reticular nuclei known to generate muscle atonia during REM (Hoffman et al, 2007; Brown et al, 2008)
SLD is non-GABA
Pons Oralis A reticular nucleus in the pons region of the brainstem (Ming-Chu et al, 1999).
RPO nucleus reticularis pontis oralis (Sanford, et al, 2003)
RPC nucleus reticularis pontis caudalis (Sanford, et al, 2003)
Ld/pp/t Laterodorsal/pedunculopontine tegmentum (Pal and Mallick 2007)
Locus ceruleus (Pal and Mallick 2007)
A brain buster: The insertion of "Medllar raphe" as a REM-ON site in the table was made by this author and may be, as the French say, gauche. The placement as REM-on refers to the stopping of REM sleep in piglets with the application of the 5-HT1a agonist, 8-OH DPAT ,to the medullar raphe (Brown et al, 2008). This result seems to contradict a similar experiment by these workers of agonist action on this same medullar nucleus to produce muscular paralysis or atonia. Since atonia is a classic sign of REM sleep, the implication is that the REM state during atonia is being shut down by the same agonist simultaneously. Also, the validity of the Brown, et al observation demands that the dorsal and "medullar" raphe nuclei have opposite functions: inhibiting the serotonergic neurons of the dorsal and "medullar" raphe turns REM on and off, respectively. Consequently, either nightly secretion of the agonist is in a state of conflict or there's a timed protocol. Paradoxes abound, as seen below.
R3 The Opposition: NERUOPHYSIOLOGY
1) Some studies have eliminated the raphe nuclei altogether as mediating the REM state on the basis of retrograde dye transfer to trace the origins of 5-HT neurons in the brainstem (Rodrigo-Argulo, 2000). These serotonergic fibers originate from a different source in a location other than the brainstem.
2) In possible consistency with the Rodrigo-Argulo results, attention is called to the fact that 5-HT1a receptors that do not originate from 5-HT neurons share space within raphe nuclei and. too, are found elsewhere (Hoffman et al, 2007; Brown et al, 2008 see above table legend).
3) Shutting off 5-HT neurons in the medullar raphe of the piglets by the 5-HT1a agonist eliminates REM sleep. The specific binding of agonists and antagonists even in the presence of high 5-HT levels expected in the cooling stress for the animal would support this observation. However, this observation is questionable, as explained above.
Thus, the opening of brainstem memory substrates by a powerful 5-HT1a receptor agonist is a fact (M's LSD recall), but the involvement of raphe nuclei per se is weakened by the discovery of this same 1a receptor elsewhere. However, REM sleep enhancement by the agonist applied directly to the dorsal raphe nucleus encourages the RaRN model as a means to open the memory. There is one more problem.
Another area of conflict is the difference between the hypothesis of the RaRN model and human experimentation on REM sleep. It is proposed here that both DMT trauma recall and REM sleep, as well as the approach to PTSD therapy, begin with the suppression of raphe 5-HT neuron firing by agonist action at the 5-HT1a receptor. However, as mentioned above, REM sleep is suppressed with systemic administration of several 1a agonists of different molecular structures. Consistent with this is the suppression of REM sleep by systemic administration of monoamine oxidase inhibitors (MAOIs), which would be expected to increase the level of monoamines within the blood supply to the brainstem (Wyatt et al, 1969; Vogel et al, 1990). On the other hand, direct application of 1a agonists to the dorsal raphe nucleus promote REM sleep and antagonists suppress this period in animal studies.
A plausable way out of this dilemma is to call forth the argument that the onset of both REM sleep and flashbacks involves a highly localized system of DMT delivery to the brainstem raphe nuclei, which is largely inaccessible to the effects of drugs within the circulatory system. The plausibility of this argument lies in the proximity of the pineal source of DMT to the brainstem (see 1.9 "What is the endogenous hallucinogen?"). Secretion of DMT or DMT+ and their fast delivery to the brainstem would shorten the time of exposure to MAO(a). However, this argument is seriously opposed by the effective treatment of PTSD by systemic administration of serotonin congeners and, notably, MDMA as discussed in the page of this site, "Raphe --- Trauma Therapy" (PTSD is proposed to be accessible therapeutically via the RaRN model). The most likely answer to this is that systemic administration produces drug levels high enough to survive the effects of MAO and overcome the circulatory barriers between the DMT source and the brainstem. The spontaneous secretion of the 5-HT1a agonist for inducing the experienced flashbacks or REM sleep would be impossible without a rapid system for its delivery to the brainstem. This issue will be encountered again in the rebuttal to the claims of Vertes and Marshall (below). Yet, the effects of astonishingly small amounts of (systemic) LSD remains to be explained. This might be answered by the proposal that systemic access of drugs to brainstem functional neurons depends on their relative resistance to MAOa (for the indoles) and MAOb (for the phenethylamines). A comparison of these drugs as to their MAO resistance and their inebriation time would be illuminating. The lifetime of systemic DMT effects are short-lived (Strassman and Qualis, 1994), but is lengthened greatly by MAO inhibitors (Schultes et al, 2001). As the LSD effect averages around nine hours, it's likely that its access and that of other drugs to the raphe nuclei depends mainly upon resistance to MAO oxidation.
If REM sleep is inaugurated by a 5-HT1a agonist, one obvious experimental expectation would be the prevention of the REM period with administration of a 5-HT1a antagonist, such as WAY 100 635 or its enhancement by the agonist. However, this experiment is not so simple. The first impression from a cursory look at the results of REM research is that REM sleep is suppressed, not enhanced, by serotonin re-uptake inhibitors (SSRIs) as well as 5-HT1a agonists, which is opposition to this proposed connection between flashbacks and the REM state (Gillin et al, 1996; Wilson et al, 2005). However, systemic application of agonists into humans may suffer from the same problem that occurs with similar administration of monoamine oxidase inhibitors to suppress REM sleep. As discussed below, the effect is paradoxical and is most likely due to the problem of access of the drug to specific brainstem sites from the circulatory system. Direct application of 5-HT1a agonists to the dorsal raphe nucleus does, indeed, increase the REM state (Monti and Monti, 2000). Also, the onset of the REM state is a complex affair involving cholinergic, GABAergic, noradrenergic and nitric oxide synthease action and depends on both pre- and post-synaptic receptors of the dorsal raphe (cf. Sorensen et al, 2001; Monti et al, 2001; Monti et al, 2002). While the dorsal raphe has a role in REM sleep, other raphe nuclei, perhaps having an opposite role are as well (Brown et al, 2008).
Earlier studies on REM neurophysiology pointed to its origin in the rostral or pons area of the brainstem (Jouvet 1962, McCarley & Hobson 1975). As already mentioned, application of agonists and antagonists to the dorsal raphe 5-HT1a receptor seems to be well established in initiating and stopping REM sleep (see below). The dorsal raphe nucleus is itself comprised of six to eight sub-nuclei and is the source of the great majority (ca. 90%) of serotonergic projections throughout the brain. Many attributes of REM sleep, e.g., changes in heart rate, blood pressure and body temperature are reproduced during non-REM sleep (NRM) with the application of raphe 5-HT1a agonist and reversed by 1a antagonists (Brown et al, 2007; Hoffman et al, 2008). NREM + 1a agonist = REM. Other neurotransmitter systems within the brainstem affect REM sleep by interacting with “REM-on” and REM-off neurons acting in reciprocal fashion. REM-on neurons are those that fire during REM sleep and REM-off neurons, e.g., the raphe 5-HT1a neurons, must remain inactive at the same time. The primary requirement for activating REM sleep is the cessation of firing of REM-OFF neurons (Pal and Mallick, 2007). The different locations of REM-on and REM-off neurons are shown in the table below:
TABLE LEGEND:
The headings, "REM-ON" and "REM-OFF" are the starting states before drug application.
ovlPAG ventrolateral periaqueductal gray (Sapin et al, 2009)
dDpMe dorsal part of the deep mesencephalic reticular nucleus immediately ventral to vlPAG (Sapin et al, 2009)
Med-RN medullary reticular nuclei known to generate muscle atonia during REM (Hoffman et al, 2007; Brown et al, 2008)
SLD is non-GABA
Pons Oralis A reticular nucleus in the pons region of the brainstem (Ming-Chu et al, 1999).
RPO nucleus reticularis pontis oralis (Sanford, et al, 2003)
RPC nucleus reticularis pontis caudalis (Sanford, et al, 2003)
Ld/pp/t Laterodorsal/pedunculopontine tegmentum (Pal and Mallick 2007)
Locus ceruleus (Pal and Mallick 2007)
A brain buster: The insertion of "Medllar raphe" as a REM-ON site in the table was made by this author and may be, as the French say, gauche. The placement as REM-on refers to the stopping of REM sleep in piglets with the application of the 5-HT1a agonist, 8-OH DPAT ,to the medullar raphe (Brown et al, 2008). This result seems to contradict a similar experiment by these workers of agonist action on this same medullar nucleus to produce muscular paralysis or atonia. Since atonia is a classic sign of REM sleep, the implication is that the REM state during atonia is being shut down by the same agonist simultaneously. Also, the validity of the Brown, et al observation demands that the dorsal and "medullar" raphe nuclei have opposite functions: inhibiting the serotonergic neurons of the dorsal and "medullar" raphe turns REM on and off, respectively. Consequently, either nightly secretion of the agonist is in a state of conflict or there's a timed protocol. Paradoxes abound, as seen below.
R3 The Opposition: NERUOPHYSIOLOGY
1) Some studies have eliminated the raphe nuclei altogether as mediating the REM state on the basis of retrograde dye transfer to trace the origins of 5-HT neurons in the brainstem (Rodrigo-Argulo, 2000). These serotonergic fibers originate from a different source in a location other than the brainstem.
2) In possible consistency with the Rodrigo-Argulo results, attention is called to the fact that 5-HT1a receptors that do not originate from 5-HT neurons share space within raphe nuclei and. too, are found elsewhere (Hoffman et al, 2007; Brown et al, 2008 see above table legend).
3) Shutting off 5-HT neurons in the medullar raphe of the piglets by the 5-HT1a agonist eliminates REM sleep. The specific binding of agonists and antagonists even in the presence of high 5-HT levels expected in the cooling stress for the animal would support this observation. However, this observation is questionable, as explained above.
Thus, the opening of brainstem memory substrates by a powerful 5-HT1a receptor agonist is a fact (M's LSD recall), but the involvement of raphe nuclei per se is weakened by the discovery of this same 1a receptor elsewhere. However, REM sleep enhancement by the agonist applied directly to the dorsal raphe nucleus encourages the RaRN model as a means to open the memory. There is one more problem.
Another area of conflict is the difference between the hypothesis of the RaRN model and human experimentation on REM sleep. It is proposed here that both DMT trauma recall and REM sleep, as well as the approach to PTSD therapy, begin with the suppression of raphe 5-HT neuron firing by agonist action at the 5-HT1a receptor. However, as mentioned above, REM sleep is suppressed with systemic administration of several 1a agonists of different molecular structures. Consistent with this is the suppression of REM sleep by systemic administration of monoamine oxidase inhibitors (MAOIs), which would be expected to increase the level of monoamines within the blood supply to the brainstem (Wyatt et al, 1969; Vogel et al, 1990). On the other hand, direct application of 1a agonists to the dorsal raphe nucleus promote REM sleep and antagonists suppress this period in animal studies.
A plausable way out of this dilemma is to call forth the argument that the onset of both REM sleep and flashbacks involves a highly localized system of DMT delivery to the brainstem raphe nuclei, which is largely inaccessible to the effects of drugs within the circulatory system. The plausibility of this argument lies in the proximity of the pineal source of DMT to the brainstem (see 1.9 "What is the endogenous hallucinogen?"). Secretion of DMT or DMT+ and their fast delivery to the brainstem would shorten the time of exposure to MAO(a). However, this argument is seriously opposed by the effective treatment of PTSD by systemic administration of serotonin congeners and, notably, MDMA as discussed in the page of this site, "Raphe --- Trauma Therapy" (PTSD is proposed to be accessible therapeutically via the RaRN model). The most likely answer to this is that systemic administration produces drug levels high enough to survive the effects of MAO and overcome the circulatory barriers between the DMT source and the brainstem. The spontaneous secretion of the 5-HT1a agonist for inducing the experienced flashbacks or REM sleep would be impossible without a rapid system for its delivery to the brainstem. This issue will be encountered again in the rebuttal to the claims of Vertes and Marshall (below). Yet, the effects of astonishingly small amounts of (systemic) LSD remains to be explained. This might be answered by the proposal that systemic access of drugs to brainstem functional neurons depends on their relative resistance to MAOa (for the indoles) and MAOb (for the phenethylamines). A comparison of these drugs as to their MAO resistance and their inebriation time would be illuminating. The lifetime of systemic DMT effects are short-lived (Strassman and Qualis, 1994), but is lengthened greatly by MAO inhibitors (Schultes et al, 2001). As the LSD effect averages around nine hours, it's likely that its access and that of other drugs to the raphe nuclei depends mainly upon resistance to MAO oxidation.
On the whole, the functions of the raphe activity appear to be inhibitory and protective to the organism’s homeostasis by preventing sensory overload and untoward activation of specialized brain areas. The suppression of their 5-HT neurons provides a selective dis-inhibition of these specialized areas needed at a particular time. Three properties of REM dreaming associated with protection are: 1) Atonia during the REM state would protect the dreamer from harm by violent movement, which testifies to the high intensity possible in REM dreams, 2) After dreaming, there is a mechanism that militates against recall of the dream that is consistent with the re-closing of the memory substrate as the raphe restore normal activity and 3) Recurring dreams of noxious events imply that, like flashbacks, the release of traumatic material is metered in a sequential, stepwise manner each REM cycle to avoid the release of stored impulses too noxious to bear all at once. This speculation is visited again later in a discussion of the RaRN model’s suitability as a means for re-consolidating noxious flashbacks. This stepwise activation of trauma as recurring (REM) dreams of a particular noxious insult would prevent the reconsolidation of the total insult and provide for sequential erasure of the memory as seen in M’s flashbacks.
These conjectures give rise to two considerations, one about the role of REM dreaming and the other, the relation between REM sleep and depression. First, is the proposal that the REM state that occurs nightly involves the same spontaneous brainstem process for resolving trauma seen here in the occurrence and disappearance of flashbacks. Second, depression is a form of PTSD, i.e., chronic depression is the autonomic expression of unfinished subcortical attempts to complete the erasure of trauma memory that remains as a residue of interrupted trauma resolution by the same proposed mechanism in REM sleep. The argument for this second hypothesis is derived from the success in alleviating depression by methods that increase “REM pressure” to produce REM rebound.
To begin, the hypothetical description of the REM state is as follows: The REM state begins with the 5 –HT1a mediated suppression of serotonergic neurons in response to the nightly secretion of the endogenous hallucinogen (EH), in concert with supporting noradrenalin action at the locus ceruleus and cholinergic and glutaminergic actions at various other brainstem sites (see table). As in M’s recall and flashbacks, subcortical (and hippocampal) memory substrates are opened via the RaRN mechanism to release stored noxious impulses (trauma) into the cerebral cortical areas for conscious interpretation as physical sensation and dream imagery. Anatomical details of the RaRN mechanism are shown in Figures 9a,b and c for a particular case of pain recall. Associated hippocampal memories are released by the same RaRN model involving suppression of 5-HT neurons of the dorsal and medial raphe nuclei. The resulting cerebral imagery creates a special kind of dream initiated by the release of the noxious components of the hidden traumatic memory. Accordingly, the hypothesis demands the proposal that dreams are not all alike: There are trauma dreams (TDs) that arise from brainstem activity in the REM state and non-trauma dreams (NTDs) that could originate from both REM and non-REM states. NTDs can arise during the non-REM state, or perhaps even the REM state, but TDs arise only from the REM state.
Here, as discussed throughout this monograph, trauma is defined as stored noxious impulses generated by a broad spectrum of viscerally associated incidents that occur during the opening of a sub-cortical memory substrate in response to the secretion of endogenous hallucinogens. Other similar or more intense insults not stored by this process would not qualify as trauma (see 1.5.3 and 1.5.3.1 in the section on Twilight sleep). Stored noxious impulses can take the form of any incident associated with pain of one kind or another. Examples could be in the form of stomach twinges or bradycardia during an incident associated with an urgent mental conflict or global physiological activation from a war injury.
In approaching the question of whether REM sleep might be involved in spontaneous healing, some of its voluminous and confusing history will be confronted, much of which is contrary to this notion. Accordingly, three points will be referenced: 1) REM, though not the only sleep state for dreaming, is postulated to be associated with the kind of dreams that are related to trauma, 2) Earmarks of a REM traumatic dream are the diffuse presence of noxious body sensations arising from sub-cortical storage and the recognition of a specific symbol from the past of the dreamer and 3) REM dreams of the traumatic kind originate from the same brainstem condition of raphe inhibition by the bi-directional RaRN model for opening and closing memory substrates.
More on this second point will be discussed at some length under the section on Twilight Sleep birth, and in the description of Jung’s dream progressions in the page, “Afterwords”. Briefly, the popular clinical therapeutic description of PTSD as “psychological trauma” with its semantic implication of cerebral exclusivity tends to draw attention away from the importance of visceral and somatic pain stored sub-cortically. Yet, brainstem-generated memory may be the primary association for this therapeutic and empirical approach. The pristine physicality of M’s LSD memory recall is from a sub-cortical domain and likely represents a key stimulation for dreams of this kind. Perhaps a better name for “psychological trauma” would be “CNS trauma”.
REM sleep or not, it is generally agreed that dreams do not include recapitulation of physical discomforts or intense emotional states that one would expect from released trauma; they are not an actual re-living of traumatic insults as in M’s case. Apparently, the associations expressed in dreams are exclusive to or minimize visceral somatic sensations and form imagery mainly from cerebral cortical areas. Yet, their bizarre imagery serving as theatre set to distorted plots are much more than the mere recall of the incident as declarative or cognitive memory. Within this fantasyland certain objects and symbols appear that were players in the real incident leading to the memory and are recognizable by the dreamer soon after awakening (Jung, 1943). At this time, some visceral sensations will be felt as details of the real incident are remembered. Indeed, it is often realized after awakening that a rather unpleasant dream occurred during a physical discomfort during the night. These global characteristics identify the dream as one initiated by the release of noxious memory from brainstem memory substrates. These dreams are manifestations of accumulated hidden memories, whose consolidation and release require neural activation within the brainstem.
R4 THE OPPOSITION: MEDICINE AND PSYCHOLOGY
The canons about REM sleep published in 2000 by Solms and those of Vertes and Eastman are found together as fully accessible texts in (http://bbsontime.org/Preprints/OldArchives/bbs.htm). These works provide valuable insights into the origins and functions of the REM state and dreaming, while rejecting the brainstem (the source of REM cycles) as a source of dreams (Solms) that have nothing to do with memory (Vertes and Eastman). These claims are placed into serious question rather neatly by parsing each from the perspective of REM state definitions presented here in the preceding text.
Solms
Solms’ argument that the basal forebrain in the cerebellum is not a passive actor as previously thought, but an active area for the generation of dreams may be an important piece in the puzzle for understanding of dreams, together with his finding of the parietal-occipital-temporal nexus as the area for dream interpretation. Just as Jouvet (Jouvet, 1962) rejects the forebrain in favor of the brainstem, Solms rejects the brainstem in favor of the forebrain as the source of dreams. The problem is the position that dreams, all being of the same kind, can’t originate in one area if they originate in another. Both Jouvet and Solms are correct, but it depends on the kind of dream they are referring to. As hypothesized here, not all dreams are alike. The facts of M’s recall and flashbacks establish the existence and modality of cerebral interpretation of impulses originating in the brainstem, even without the need to invoke the RaRN mechanism. Of course, the images within some sort of distorted plot of an original memory would all require exercise of the cortical areas in the cerebrum, but some dreams would carry associations that must originate from brainstem processes that specialize in the opening of memory substrates. These would be traumatic dreams (TDs), as opposed to non-traumatic dreams (NTDs), whose existence is not in question. NTDs could be unrelated to brainstem or hippocampal storage opening and, as Solms postulates, may well originate in the basal forebrain and even occur during the REM state. However, only the REM state established by brainstem processes shown here can give rise to TDs, whose imagery, again, is manifested in the cerebral cortical areas. Without the suggestion presented here that TDs exist, the conflation of all dreams under the same rubric becomes the central mistake in rejecting the brainstem or basal forebrain as a source in all cases. The possibility of dreams, both originating and not originating in the brainstem, continues as a problem for the following reports.
Vertes and Marshall.
Verdes and Marshall (V&M) may be quite correct in cutting the connection between REM (or NREM) dreaming and memory consolidation, but the evaluation of memory consolidation used in the cited references is incomplete. The survival of learning ability and memory in humans belongs to the category of declarative memory, which is willfully accessed and (apparently) independent of the brainstem (Kandel et al, 2001). Declarative or cognitive memory retrieval exercises cerebral functions and is accessed voluntarily by recalling associations stored in cortical areas under the control of the hippocampus. The maintenance of this kind of learning ability after absorbing different sorts of brainstem injury or living in the absence of REM sleep, even in someone without brainstem function, is not too surprising, since this is only a question of declarative memory that may operate independently of brainstem processes. The brainstem consolidates a different kind of memory defined in this monograph as trauma. Unlike declarative memory, trauma recall is not accessible voluntarily or by any means used in those experiments cited by V&M. What is needed for access to this hidden memory is the subcortical opening of a memory substrate by the interaction between a brainstem 5-HT1a receptor having a high affinity for an endogenous, highly specific agonist. This process would be immune to tricyclic antidepressives or to SSRIs that only encourage moderate increases in 5-HT. Also, the use of SSRIs, as opposed to adding 5-HT, is done in recognition that the sites at issue are highly localized and less accessible to systemic factors. For this same reason, their citation of experiments showing that monoamine oxidase inhibitors (MAOIs) completely abolish REM sleep does not jibe with the kind of parameter measured, i.e., evidence that the subject is unaffected in (declarative) memory or learning.
V&W’s reference to MAOI studies (Vogel et al, 1990; Wyatt et al, 1969) may be the most serious evidence questioning the REM-flashback mechanism proposed here for the nightly onset of the REM state and, indeed, the raphe mechanism itself. As previously discussed and referring to the table above, inhibition of MAO would produce an increase in the monoamines, catecholamine and the tertiary amine, acetylcholine that would not inhibit, but drive REM sleep at each of the REM-ON and REM-OFF sites. This paradox, created by the hypotheses presented in this monograph, would apply to the endogenous hallucinogens, DMT and it’s amine congeners as well, to induce a chronic REM or hallucinogenic state for months, since tolerance is not seen with these drugs (Section 1.9, “What is the endogenous hallucinogen”). Resolution of this koan by invoking the necessity for sequestering these REM-ON and REM-OFF sites away from access to a blood agent is a weaker argument, since other blood components, e.g., LSD do have access. The way out of this is to adopt the present view that the action of MAOI is very unbalanced with respect to the resulting ratios of psychoactive amines. REM sleep is reported to be attributed to noradrenergic and serotonergic blockade to produce this imbalance (Sharpley & Cowen, 1995). In either case, the implication made in the V&M citations, that MAOI action involves the brainstem sites, is questionable.
In summary, cited works within the claims of Vertes and Marshall showing that insults to the brainstem or loss of REM sleep don’t affect memory consolidation is dealt with by two arguments: 1) The criteria used for assessing the effects of REM or brainstem perturbations is not appropriate alone and 2) The results of this monograph reveal the consolidation hidden memory that can reach the cerebral cortex to manifest conscious sensation that might initiate a certain kind of (trauma) dream. There can be no question that a process is inaugurated spontaneously to erase the memory. In addition, evidence for healing a hidden memory is seen in the successful use of a 5-HT1a agonist in PTSD therapy (MAPS.com). This and the similarities between the REM and hallucinogenic states, together with the cerebral awareness of the flashbacks would have to be a consideration in the rejection of memory consolidation by Vertes and Marshall as a component of all dreams.
The value of contributions by Solms, Vertes and Marshall is not diminished by the suggestion made here of more than one source giving rise to dreams. These authors may be correct if their reference is restricted to non-trauma related dreams in their respective positions about basal forebrain sources and memory consolidation. These authors have additional critics on similar issues (Bednar, 2003). Therefore, the extension of these experimental results of spontaneous flashbacks as signs of trauma erasure to the mechanism of REM sleep remains as an hypothesis worthy of testing. The appearance of the agonist in the blood as the REM state begins and ends could be managed (see "Testing the Hypothesis). Just as brainstem events documented here lead to conscious awareness of released memory impulses, the release of stored impulses by the same brainstem events in the REM state reach their conscious manifestation as dreams from cerebral processes. The confirmation or falsification of these predictions is possible by testing based on neurobiological methods with the 5-HT1a receptor as target and the use of functional imaging (fMRI) and PET, as outlined in the same section on testing. The anticipation is that REM dreams are evidence of a healing function repeated nightly to rid the dreamer of noxious impulses stored according to the RaRN model. Whether or not the 5-HT1a receptor really belongs to the raphe nuclei or to another thus far unknown source is a valid question, but irrelevant to the fact that cerebral transformation into conscious sensation or dream imagery can originate from 1a-ligand binding within the brainstem.
R5 A PROPOSED ETIOLOGY OF DEPRESSION
A major finding of this monograph is the evidence of a memory substrate controlled by a 5-HT1a agonist for consolidation or release of traumatic impulses. The model generated from this evidence has been exemplified by known anatomical and neural interactions and accounts for a number of general observations in the areas of hallucinogen research and, notably, in the area of posttraumatic stress disorder (PTSD). The RaRN model accounts for the frequent persistence of noxious flashbacks and PTSD in the clinical setting.
Thus, a natural outcome of combining the REM-flashback hypothesis with clinical studies on REM sleep is the proposal that chronic depression is an external manifestation of autonomic attempts to complete the resolution of a trauma memory whose resolution was not completed during REM sleep. In other words, the daytime condition of certain depressive individuals is a chronic form of posttraumatic stress disorder (PTSD). The basis for this hypothesis is the documented success of treating depression by methods that increase REM pressure to induce “REM rebound” (Bednar, 2003). In these cases, the patient is awakened each time the REM state is detected, either by EEG theta waves or by rapid eye movement. This awakening is repeated for one or two nights. If the patient is undisturbed the third night, his REM latency will be normal and dreams may be intense as the patient “catches up” on REM time. The next day the depression is gone. Although this approach does not produce lasting relief from depression, the observation is fairly reliable and was suggested by earlier observations that loss of sleep often produces an improvement in depression, while napping does the opposite. The rationale for using these clinical observations is as follows: In some depressives the brainstem mechanism of opening memory substrates containing noxious impulses is insufficient, owing to insufficient REM pressure to reach a threshold for agonist secretion or for the activation of second messengers as described in later sections to hyperpolarize functional target areas. Increasing REM pressure is required to reach this threshold and release the hidden memory into cortical dream interpretation. The question as to what neural processes give rise to REM pressure is an intriguing one. The autonomic system is keeping track of jobs unfinished. As mentioned in "Afterword," a "reference" is continually monitored and, as in M's flashbacks, personal issues in dreams diminish with time to some end-point (Jung, 1943).
These conjectures give rise to two considerations, one about the role of REM dreaming and the other, the relation between REM sleep and depression. First, is the proposal that the REM state that occurs nightly involves the same spontaneous brainstem process for resolving trauma seen here in the occurrence and disappearance of flashbacks. Second, depression is a form of PTSD, i.e., chronic depression is the autonomic expression of unfinished subcortical attempts to complete the erasure of trauma memory that remains as a residue of interrupted trauma resolution by the same proposed mechanism in REM sleep. The argument for this second hypothesis is derived from the success in alleviating depression by methods that increase “REM pressure” to produce REM rebound.
To begin, the hypothetical description of the REM state is as follows: The REM state begins with the 5 –HT1a mediated suppression of serotonergic neurons in response to the nightly secretion of the endogenous hallucinogen (EH), in concert with supporting noradrenalin action at the locus ceruleus and cholinergic and glutaminergic actions at various other brainstem sites (see table). As in M’s recall and flashbacks, subcortical (and hippocampal) memory substrates are opened via the RaRN mechanism to release stored noxious impulses (trauma) into the cerebral cortical areas for conscious interpretation as physical sensation and dream imagery. Anatomical details of the RaRN mechanism are shown in Figures 9a,b and c for a particular case of pain recall. Associated hippocampal memories are released by the same RaRN model involving suppression of 5-HT neurons of the dorsal and medial raphe nuclei. The resulting cerebral imagery creates a special kind of dream initiated by the release of the noxious components of the hidden traumatic memory. Accordingly, the hypothesis demands the proposal that dreams are not all alike: There are trauma dreams (TDs) that arise from brainstem activity in the REM state and non-trauma dreams (NTDs) that could originate from both REM and non-REM states. NTDs can arise during the non-REM state, or perhaps even the REM state, but TDs arise only from the REM state.
Here, as discussed throughout this monograph, trauma is defined as stored noxious impulses generated by a broad spectrum of viscerally associated incidents that occur during the opening of a sub-cortical memory substrate in response to the secretion of endogenous hallucinogens. Other similar or more intense insults not stored by this process would not qualify as trauma (see 1.5.3 and 1.5.3.1 in the section on Twilight sleep). Stored noxious impulses can take the form of any incident associated with pain of one kind or another. Examples could be in the form of stomach twinges or bradycardia during an incident associated with an urgent mental conflict or global physiological activation from a war injury.
In approaching the question of whether REM sleep might be involved in spontaneous healing, some of its voluminous and confusing history will be confronted, much of which is contrary to this notion. Accordingly, three points will be referenced: 1) REM, though not the only sleep state for dreaming, is postulated to be associated with the kind of dreams that are related to trauma, 2) Earmarks of a REM traumatic dream are the diffuse presence of noxious body sensations arising from sub-cortical storage and the recognition of a specific symbol from the past of the dreamer and 3) REM dreams of the traumatic kind originate from the same brainstem condition of raphe inhibition by the bi-directional RaRN model for opening and closing memory substrates.
More on this second point will be discussed at some length under the section on Twilight Sleep birth, and in the description of Jung’s dream progressions in the page, “Afterwords”. Briefly, the popular clinical therapeutic description of PTSD as “psychological trauma” with its semantic implication of cerebral exclusivity tends to draw attention away from the importance of visceral and somatic pain stored sub-cortically. Yet, brainstem-generated memory may be the primary association for this therapeutic and empirical approach. The pristine physicality of M’s LSD memory recall is from a sub-cortical domain and likely represents a key stimulation for dreams of this kind. Perhaps a better name for “psychological trauma” would be “CNS trauma”.
REM sleep or not, it is generally agreed that dreams do not include recapitulation of physical discomforts or intense emotional states that one would expect from released trauma; they are not an actual re-living of traumatic insults as in M’s case. Apparently, the associations expressed in dreams are exclusive to or minimize visceral somatic sensations and form imagery mainly from cerebral cortical areas. Yet, their bizarre imagery serving as theatre set to distorted plots are much more than the mere recall of the incident as declarative or cognitive memory. Within this fantasyland certain objects and symbols appear that were players in the real incident leading to the memory and are recognizable by the dreamer soon after awakening (Jung, 1943). At this time, some visceral sensations will be felt as details of the real incident are remembered. Indeed, it is often realized after awakening that a rather unpleasant dream occurred during a physical discomfort during the night. These global characteristics identify the dream as one initiated by the release of noxious memory from brainstem memory substrates. These dreams are manifestations of accumulated hidden memories, whose consolidation and release require neural activation within the brainstem.
R4 THE OPPOSITION: MEDICINE AND PSYCHOLOGY
The canons about REM sleep published in 2000 by Solms and those of Vertes and Eastman are found together as fully accessible texts in (http://bbsontime.org/Preprints/OldArchives/bbs.htm). These works provide valuable insights into the origins and functions of the REM state and dreaming, while rejecting the brainstem (the source of REM cycles) as a source of dreams (Solms) that have nothing to do with memory (Vertes and Eastman). These claims are placed into serious question rather neatly by parsing each from the perspective of REM state definitions presented here in the preceding text.
Solms
Solms’ argument that the basal forebrain in the cerebellum is not a passive actor as previously thought, but an active area for the generation of dreams may be an important piece in the puzzle for understanding of dreams, together with his finding of the parietal-occipital-temporal nexus as the area for dream interpretation. Just as Jouvet (Jouvet, 1962) rejects the forebrain in favor of the brainstem, Solms rejects the brainstem in favor of the forebrain as the source of dreams. The problem is the position that dreams, all being of the same kind, can’t originate in one area if they originate in another. Both Jouvet and Solms are correct, but it depends on the kind of dream they are referring to. As hypothesized here, not all dreams are alike. The facts of M’s recall and flashbacks establish the existence and modality of cerebral interpretation of impulses originating in the brainstem, even without the need to invoke the RaRN mechanism. Of course, the images within some sort of distorted plot of an original memory would all require exercise of the cortical areas in the cerebrum, but some dreams would carry associations that must originate from brainstem processes that specialize in the opening of memory substrates. These would be traumatic dreams (TDs), as opposed to non-traumatic dreams (NTDs), whose existence is not in question. NTDs could be unrelated to brainstem or hippocampal storage opening and, as Solms postulates, may well originate in the basal forebrain and even occur during the REM state. However, only the REM state established by brainstem processes shown here can give rise to TDs, whose imagery, again, is manifested in the cerebral cortical areas. Without the suggestion presented here that TDs exist, the conflation of all dreams under the same rubric becomes the central mistake in rejecting the brainstem or basal forebrain as a source in all cases. The possibility of dreams, both originating and not originating in the brainstem, continues as a problem for the following reports.
Vertes and Marshall.
Verdes and Marshall (V&M) may be quite correct in cutting the connection between REM (or NREM) dreaming and memory consolidation, but the evaluation of memory consolidation used in the cited references is incomplete. The survival of learning ability and memory in humans belongs to the category of declarative memory, which is willfully accessed and (apparently) independent of the brainstem (Kandel et al, 2001). Declarative or cognitive memory retrieval exercises cerebral functions and is accessed voluntarily by recalling associations stored in cortical areas under the control of the hippocampus. The maintenance of this kind of learning ability after absorbing different sorts of brainstem injury or living in the absence of REM sleep, even in someone without brainstem function, is not too surprising, since this is only a question of declarative memory that may operate independently of brainstem processes. The brainstem consolidates a different kind of memory defined in this monograph as trauma. Unlike declarative memory, trauma recall is not accessible voluntarily or by any means used in those experiments cited by V&M. What is needed for access to this hidden memory is the subcortical opening of a memory substrate by the interaction between a brainstem 5-HT1a receptor having a high affinity for an endogenous, highly specific agonist. This process would be immune to tricyclic antidepressives or to SSRIs that only encourage moderate increases in 5-HT. Also, the use of SSRIs, as opposed to adding 5-HT, is done in recognition that the sites at issue are highly localized and less accessible to systemic factors. For this same reason, their citation of experiments showing that monoamine oxidase inhibitors (MAOIs) completely abolish REM sleep does not jibe with the kind of parameter measured, i.e., evidence that the subject is unaffected in (declarative) memory or learning.
V&W’s reference to MAOI studies (Vogel et al, 1990; Wyatt et al, 1969) may be the most serious evidence questioning the REM-flashback mechanism proposed here for the nightly onset of the REM state and, indeed, the raphe mechanism itself. As previously discussed and referring to the table above, inhibition of MAO would produce an increase in the monoamines, catecholamine and the tertiary amine, acetylcholine that would not inhibit, but drive REM sleep at each of the REM-ON and REM-OFF sites. This paradox, created by the hypotheses presented in this monograph, would apply to the endogenous hallucinogens, DMT and it’s amine congeners as well, to induce a chronic REM or hallucinogenic state for months, since tolerance is not seen with these drugs (Section 1.9, “What is the endogenous hallucinogen”). Resolution of this koan by invoking the necessity for sequestering these REM-ON and REM-OFF sites away from access to a blood agent is a weaker argument, since other blood components, e.g., LSD do have access. The way out of this is to adopt the present view that the action of MAOI is very unbalanced with respect to the resulting ratios of psychoactive amines. REM sleep is reported to be attributed to noradrenergic and serotonergic blockade to produce this imbalance (Sharpley & Cowen, 1995). In either case, the implication made in the V&M citations, that MAOI action involves the brainstem sites, is questionable.
In summary, cited works within the claims of Vertes and Marshall showing that insults to the brainstem or loss of REM sleep don’t affect memory consolidation is dealt with by two arguments: 1) The criteria used for assessing the effects of REM or brainstem perturbations is not appropriate alone and 2) The results of this monograph reveal the consolidation hidden memory that can reach the cerebral cortex to manifest conscious sensation that might initiate a certain kind of (trauma) dream. There can be no question that a process is inaugurated spontaneously to erase the memory. In addition, evidence for healing a hidden memory is seen in the successful use of a 5-HT1a agonist in PTSD therapy (MAPS.com). This and the similarities between the REM and hallucinogenic states, together with the cerebral awareness of the flashbacks would have to be a consideration in the rejection of memory consolidation by Vertes and Marshall as a component of all dreams.
The value of contributions by Solms, Vertes and Marshall is not diminished by the suggestion made here of more than one source giving rise to dreams. These authors may be correct if their reference is restricted to non-trauma related dreams in their respective positions about basal forebrain sources and memory consolidation. These authors have additional critics on similar issues (Bednar, 2003). Therefore, the extension of these experimental results of spontaneous flashbacks as signs of trauma erasure to the mechanism of REM sleep remains as an hypothesis worthy of testing. The appearance of the agonist in the blood as the REM state begins and ends could be managed (see "Testing the Hypothesis). Just as brainstem events documented here lead to conscious awareness of released memory impulses, the release of stored impulses by the same brainstem events in the REM state reach their conscious manifestation as dreams from cerebral processes. The confirmation or falsification of these predictions is possible by testing based on neurobiological methods with the 5-HT1a receptor as target and the use of functional imaging (fMRI) and PET, as outlined in the same section on testing. The anticipation is that REM dreams are evidence of a healing function repeated nightly to rid the dreamer of noxious impulses stored according to the RaRN model. Whether or not the 5-HT1a receptor really belongs to the raphe nuclei or to another thus far unknown source is a valid question, but irrelevant to the fact that cerebral transformation into conscious sensation or dream imagery can originate from 1a-ligand binding within the brainstem.
R5 A PROPOSED ETIOLOGY OF DEPRESSION
A major finding of this monograph is the evidence of a memory substrate controlled by a 5-HT1a agonist for consolidation or release of traumatic impulses. The model generated from this evidence has been exemplified by known anatomical and neural interactions and accounts for a number of general observations in the areas of hallucinogen research and, notably, in the area of posttraumatic stress disorder (PTSD). The RaRN model accounts for the frequent persistence of noxious flashbacks and PTSD in the clinical setting.
Thus, a natural outcome of combining the REM-flashback hypothesis with clinical studies on REM sleep is the proposal that chronic depression is an external manifestation of autonomic attempts to complete the resolution of a trauma memory whose resolution was not completed during REM sleep. In other words, the daytime condition of certain depressive individuals is a chronic form of posttraumatic stress disorder (PTSD). The basis for this hypothesis is the documented success of treating depression by methods that increase REM pressure to induce “REM rebound” (Bednar, 2003). In these cases, the patient is awakened each time the REM state is detected, either by EEG theta waves or by rapid eye movement. This awakening is repeated for one or two nights. If the patient is undisturbed the third night, his REM latency will be normal and dreams may be intense as the patient “catches up” on REM time. The next day the depression is gone. Although this approach does not produce lasting relief from depression, the observation is fairly reliable and was suggested by earlier observations that loss of sleep often produces an improvement in depression, while napping does the opposite. The rationale for using these clinical observations is as follows: In some depressives the brainstem mechanism of opening memory substrates containing noxious impulses is insufficient, owing to insufficient REM pressure to reach a threshold for agonist secretion or for the activation of second messengers as described in later sections to hyperpolarize functional target areas. Increasing REM pressure is required to reach this threshold and release the hidden memory into cortical dream interpretation. The question as to what neural processes give rise to REM pressure is an intriguing one. The autonomic system is keeping track of jobs unfinished. As mentioned in "Afterword," a "reference" is continually monitored and, as in M's flashbacks, personal issues in dreams diminish with time to some end-point (Jung, 1943).
1.4.5 SOME ADDITIONAL REFERENCES FOR REM SLEEP
Gillin JC, Sohn J-W, Stahl SM, Lardon M, Kelsoe J, Rapaport M, Ruiz C and Golsham S. (1996) Ipsapirone, a 5-HT1a agonist, suppresses REM sleep equally in unmidicated depressived patients and normal controls. Neuropharmacology 15, 109-15.
Wilson SJ, Bailey JE, Rich AS, Nash J, Adrover M, Tournoux A and Nutt DJ. (2005) The use of sleep measures to compare a neew 5HT1a agonist with buspirone in humans. J. Psychopharmacoogy 12, 609-13.
Monti JM and Monti D. (2000) Role of dorsal raphe nucleus serotonin 5-HT1a receptor in the regulation of REM sleep. Life Sciences 66, 1999-2012
See other citations in the REFERENCE page of this website.
Gillin JC, Sohn J-W, Stahl SM, Lardon M, Kelsoe J, Rapaport M, Ruiz C and Golsham S. (1996) Ipsapirone, a 5-HT1a agonist, suppresses REM sleep equally in unmidicated depressived patients and normal controls. Neuropharmacology 15, 109-15.
Wilson SJ, Bailey JE, Rich AS, Nash J, Adrover M, Tournoux A and Nutt DJ. (2005) The use of sleep measures to compare a neew 5HT1a agonist with buspirone in humans. J. Psychopharmacoogy 12, 609-13.
Monti JM and Monti D. (2000) Role of dorsal raphe nucleus serotonin 5-HT1a receptor in the regulation of REM sleep. Life Sciences 66, 1999-2012
See other citations in the REFERENCE page of this website.
