Deactivation of the default mode network, specifically the medial prefrontal cortex and the posterior cingulate cortex, appears to be a function of mindfulness meditation as this review from Nature Reviews Neuroscience points out:
The neuroscience of mindfulness meditation
Abstract: Research over the past two decades broadly supports the claim that mindfulness meditation - practiced widely for the reduction of stress and promotion of health - exerts beneficial effects on physical and mental health, and cognitive performance. Recent neuroimaging studies have begun to uncover the brain areas and networks that mediate these positive effects. However, the underlying neural mechanisms remain unclear, and it is apparent that more methodologically rigorous studies are required if we are to gain a full understanding of the neuronal and molecular bases of the changes in the brain that accompany mindfulness meditation.
From article: fMRI studies have investigated activity in the DMN in association with mindfulness practice. Regions of the DMN (the medial PFC and PCC) showed relatively little activity in meditators compared to controls across different types of meditation, which has been interpreted as indicating diminished self-referential processing.
Tang YY, Hölzel BK, Posner MI.
Nat Rev Neurosci. 2015 Apr;16(4):213-25. doi: 10.1038/nrn3916. Epub 2015 Mar 18. Review.
PMID: 25783612
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An article from 2014 points to the posterior cingulate cortex as a primary target of meditation:
The posterior cingulate cortex as a plausible mechanistic target of meditation: findings from neuroimaging
Brewer JA, Garrison KA.
Ann N Y Acad Sci. 2014 Jan;1307:19-27.
PMID: 24033438
There has been an increased interest in mindfulness and meditation training over the past decade. As evidenced by exponential growth in the number of publications since the beginning of the 21st century, progressively more is becoming known about both the clinical efficacy and underlying neurobiological mechanisms of mindfulness training. This paper briefly highlights psychological models of stress that converge between ancient and modern day (e.g., operant conditioning); identifies key brain regions that, with these models, are biologically plausible targets for mindfulness (e.g., posterior cingulate cortex); and discusses recent and emerging findings from neuroimaging studies of meditation therein, including new advances using real-time functional magnetic resonance imaging neurofeedback in neurophenomenological studies.
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A related article from 2011 explains how mindfulness meditation deactivates the default mode network, specifically the medial prefrontal and posterior cingulate cortex:
Meditation experience is associated with differences in default mode network activity and connectivity.
Many philosophical and contemplative traditions teach that "living in the moment" increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.
Brewer JA, Worhunsky PD, Gray JR, Tang YY, Weber J, Kober H.
Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20254-9.
PMID: 22114193
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A 2012 article from PNAS describes a similar decrease in medial prefrontal and posterior cingulate cortex activity with psilocybin:
Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.
Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ.
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2138-43.
PMID: 22308440
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Finally a 2014 article from Neuropsychologia in which part of the PCC was resected in a patient, his post-surgical experience appears to have a mindfulness component to it:
Disrupting posterior cingulate connectivity disconnects consciousness from the external environment.
A patient with low-grade diffuse glioma had his posterior and ventral part of the left precuneus totally resected. Part of the left cingulate cortex and retrosplenial areas was also resected. Following surgery, the patient was asked to describe retrospectively his subjective experience. He reported experiencing no rumination and no negative thought for almost a month after the surgery. He described himself in a kind of contemplative state, with a subjective feeling of absolute happiness and timelessness.
Herbet G, Lafargue G, de Champfleur NM, Moritz-Gasser S, le Bars E, Bonnetblanc F, Duffau H.
Neuropsychologia. 2014 Apr;56:239-44. Epub 2014 Feb 4.
PMID: 24508051
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Saturday, June 20, 2015
Three new articles in European Psychiatry journal
The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making
K.H. Preller, T. Pokorny, R. Krähenmann, I. Dziobek, P. Stämpfli, F.X. Vollenweider
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 22
Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.
In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.
The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.
These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.
5HT2a Receptors – a New Target for Depression?
D. Nutt
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 35
Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic druds psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.
The Effect of Serotonin Receptor Manipulation On Brain Networks and Its Impact On Emotion Regulation
R. Krähenmann
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 21
Hallucinogenic substances have been used for millenia. Still, the scientific investigation into the effects and mechanisms of classical hallucinogens in humans has only commenced with the discovery of LSD by Albert Hofmann in 1943. In the 1960’s, there were more than a thousand clinical studies that reported promising therapeutic effects of LSD and psilocybin in psychiatric patients. Only recently, however, the neuropharmacological and neurobiological underpinnings of hallucinogenic drugs have undergone systematic investigations. Despite having different chemical structures, classical hallucinogens produce striking similar subjective and behavioral effects in both animals and humans. Activation of the serotonin 2A (5-HT2A) receptor is a core feature in hallucinogenic pharmacology. Recent neuroimaging studies have begun to elucidate the brain mechanisms underlying hallucinogen-induced changes of thought, perception, and mood. Among the many networks involved in hallucinogen-related states of consciousness, the prefrontal cortex and the limbic regions appear to be especially relevant to the putative antidepressant effects of classical hallucinogens. Furthermore, hallucinogens may foster neuroplastic adaptations within cortico-subcortical brain networks. This appears to be a promising mechanism with regard to future clinical studies into the effects of classical hallucinogens in depression and anxiety.
K.H. Preller, T. Pokorny, R. Krähenmann, I. Dziobek, P. Stämpfli, F.X. Vollenweider
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 22
Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.
In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.
The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.
These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.
5HT2a Receptors – a New Target for Depression?
D. Nutt
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 35
Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic druds psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.
The Effect of Serotonin Receptor Manipulation On Brain Networks and Its Impact On Emotion Regulation
R. Krähenmann
European Psychiatry March 28–31, 2015; Volume 30, Supplement 1, Page 21
Hallucinogenic substances have been used for millenia. Still, the scientific investigation into the effects and mechanisms of classical hallucinogens in humans has only commenced with the discovery of LSD by Albert Hofmann in 1943. In the 1960’s, there were more than a thousand clinical studies that reported promising therapeutic effects of LSD and psilocybin in psychiatric patients. Only recently, however, the neuropharmacological and neurobiological underpinnings of hallucinogenic drugs have undergone systematic investigations. Despite having different chemical structures, classical hallucinogens produce striking similar subjective and behavioral effects in both animals and humans. Activation of the serotonin 2A (5-HT2A) receptor is a core feature in hallucinogenic pharmacology. Recent neuroimaging studies have begun to elucidate the brain mechanisms underlying hallucinogen-induced changes of thought, perception, and mood. Among the many networks involved in hallucinogen-related states of consciousness, the prefrontal cortex and the limbic regions appear to be especially relevant to the putative antidepressant effects of classical hallucinogens. Furthermore, hallucinogens may foster neuroplastic adaptations within cortico-subcortical brain networks. This appears to be a promising mechanism with regard to future clinical studies into the effects of classical hallucinogens in depression and anxiety.
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