Serotonergic modulation of population receptive fields

The population receptive field (pRF) is the region of visual and somatosensory
space that elicits a response from a specific population of neurons [1]. FMRI
measurements at ultra-high field enable the sampling of these populations of
neurons over large scales in the living human brain, and allow the
investigation of neural computations with high sensitivity and specificity [2].
Like our cognitive processes, PRFs are not static but dynamic: an important
open question concerns the degree and mechanisms underlying flexibility of pRFs
[3]. Multiple lines of evidence implicate the serotonergic system in the
modulation of brain responses to visual and tactile stimuli [4,5]; however,
analysis of the effects of serotonergic manipulation on human visual and
somatosensory cortex pRF responses
is lacking. We hypothesise that neuropharmacological manipulation of the
serotonergic system will alter pRF properties in a systematic and robust way,
and have developed a computational model that allows us to investigate these
changes. The aim of the proposed study is to provide evidence for this
hypothesis, and hence for the first time provide evidence in humans of the role
of the serotonergic system in visuospatial and somatosensory pRF computations.


References

[1] Dumoulin, Serge O., and Brian A. Wandell. "Population receptive field
estimates in human visual cortex." Neuroimage 39.2 (2008): 647-660.
[2] Dumoulin, Serge O., et al. "Ultra-high field MRI: Advancing systems
neuroscience towards mesoscopic human brain function." Neuroimage 168 (2018):
345-357.
[3] Dumoulin, Serge O., and Tomas Knapen. "How visual cortical organization is
altered by ophthalmologic and neurologic disorders." Annual Review of Vision
Science 4 (2018): 357-379.
[4] Kometer, Michael, and Franz X. Vollenweider. "Serotonergic
hallucinogen-induced visual perceptual alterations." Behavioral neurobiology of
psychedelic drugs (2016): 257-282.
[5] Azimi, Zohre, et al. "Separable gain control of ongoing and evoked activity
in the visual cortex by serotonergic input." Elife 9 (2020): e53552.

The primary objective is to determine the effects of serotonergic stimulation,
via the administration of psilocybin, on population receptive fields in
different modalities and to relate these effect to specific computational
aspects of the divisive normalization pRF model. The secondary objective is to
draw relations between these changes and low-level visual and somatosensory
perceptual processes (measured with psychometry) and subjective experience
(measured with questionnaires).

The proposed study consists two study parts. Both will have a
within-participant double-blind placebo-controlled randomised crossover design,
and will consist of one preliminary data collection session and three
experimental sessions. For each study part, twenty healthy male and female
English and/or Dutch speaking participants between 21-55 years old will be
recruited. Participants will visit the laboratory site four times. During the
first visit, informed consent will be collected, as well as preliminary data
(structural MRI). During the three experimental sessions, participants will
receive either placebo, or a low dose of psilocybin (5mg), or a medium dose of
psilocybin (10mg). After the administration, each experimental session
encompasses an fMRI scan in a 7T Philips scanner, and behavioural psychophysics
tests of visual perception (study part 1) or visual and somatosensory
perception (study part 2).

Participants will visit the laboratory site 4 times. The first time informed
consent and preliminary data will be collected (anatomical MRI). On each of the
following visit, participant will receive placebo or a dose of psilocybin
orally, before an fMRI scan and psychometric tests. In the week before
experimental sessions all participants will have to adhere to some simple
restrictions regarding medication, alcohol and drug intake, as this may affect
the response to neuropharmacological manipulation. The most common adverse
effects of psilocybin include uncomfortable feelings of cognitive impairment,
anxiety, fear, nausea [6]. Adverse effects are strongly dose-dependent, and
subside within at most few hours from administration (see Figures 3-4 in
Document C1, section 12.1). We also remark that our highest dose is
approximately one third of the highest dose used in previous neuroimaging
studies involving psilocybin administration [8]. Considering the relatively low
doses involved in our study, exclusion criteria, screening procedure and
constant monitoring of the participants, no serious side effects are expected.
MRI is a safe method with no long-term side effects. Though the participants of
this study will have no direct benefits from participating, the results
contribute to new insights into the highly promising field of
neuropharmacological modulation of information encoding in the human brain. The
overall nature and extent of the added risk associated with participation in
the current study is to be classified as negligible and the burden can be
considered minimal. References [6] Studerus, Erich, et al. "Acute, subacute and
long-term subjective effects of psilocybin in healthy humans: a pooled analysis
of experimental studies." Journal of psychopharmacology 25.11 (2011):
1434-1452. [7] Brown, Randall T., et al. "Pharmacokinetics of escalating doses
of oral psilocybin in healthy adults." Clinical pharmacokinetics 56.12 (2017):
1543-1554. [8] Dos Santos, Rafael G., et al. "Classical hallucinogens and
neuroimaging: A systematic review of human studies: Hallucinogens and
neuroimaging." Neuroscience & Biobehavioral Reviews 71 (2016): 715-728.