OPEN Foundation

C. Orban

LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion

Abstract

The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced “psychedelic imagery” (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function “as if” there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs.

Roseman, L., Sereno, M. I., Leech, R., Kaelen, M., Orban, C., McGonigle, J., … & Carhart‐Harris, R. L. (2016). LSD alters eyes‐closed functional connectivity within the early visual cortex in a retinotopic fashion. Human Brain Mapping. http://dx.doi.org/10.1002/hbm.23224

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LSD modulates music-induced imagery via changes in parahippocampal connectivity

Abstract

Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75 µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC–visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.

Kaelen, M., Roseman, L., Kahan, J., Santos-Ribeiro, A., Orban, C., Lorenz, R., … & Wall, M. B. (2016). LSD modulates music-induced imagery via changes in parahippocampal connectivity. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.03.018
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Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution

Abstract

Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1]; however, because of LSD’s unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of “ego dissolution.” The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain’s modular and “rich-club” organization and, simultaneously, the perceptual boundaries between the self and the environment.

Tagliazucchi, E., Roseman, L., Kaelen, M., Orban, C., Muthukumaraswamy, S. D., Murphy, K., … & Bullmore, E. (2016). Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology. http://dx.doi.org/10.1016/j.cub.2016.02.010

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