WHERE DID OUR LOVE GO? Serotonergic drugs weaken insula and amplify ventromedial prefrontal cortex

[kpavel]

In this topic I will put relevant research to prove the statement in the title. Feelings of lust and love lost because of SSRI 'antidepressants' mode of action. Then other aspects of PSSD in the context and my thoughts on technical details and what could possibly be done. Your thoughts, critics and ideas are welcome.

Selective decision-making deficit in love following damage to the anterior insula
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222039/
Neuroimaging studies have found a correlation between activation in the anterior insula and love, and a correlation between activation in the posterior insula and lust. The present control-case study describes a neurological male patient, with a rare, circumscribed lesion in the anterior insula, whom we tested using a decision task that required he judge whether each of a series of attractive individuals could be the object of his love or lust. The patient, in contrast with neurologically typical participants matched on age, gender, and ethnicity, performed normally when making decisions about lust but showed a selective deficit when making decisions about love. These results provide the first clinical evidence indicating that the anterior insula may play an instrumental role in love but not lust more generally. These data support the notion of a posterior-to-anterior insular gradient, from sensorimotor to abstract representations, in the evaluation of anticipatory rewards in interpersonal relationships.

So what do fluoxetine etc specifically do to insula? They limit its acitivity, probably reducing it or reducing blood flow there and they may change functional connectivity to other brain parts, such as amygdala.

LOVE

Effects of an antidepressant on neural correlates of emotional processing in patients with major depression
https://pubmed.ncbi.nlm.nih.gov/22954751/
We measured brain activation in patients with major depressive disorder when exposed to emotional pictures before and after antidepressant treatment. The participants included 18 first-episode unmedicated patients with current major depressive disorder and 18 age- and gender-matched control subjects. All subjects performed an emotional task during functional magnetic resonance imaging scanning at baseline and after 8 weeks of fluoxetine treatment. Unmedicated depressed patients showed lower accuracy rates (0.53±0.26) than did subjects in the control group (0.71±0.18) while viewing positive pictures. During exposure to positive stimuli, decreased activations were seen in the right insula (BA13) and left anterior cingulate cortex (BA32) in patients after antidepressant treatment. After antidepressant treatment, patients exhibited greater activation in the right middle frontal gyrus (BA8,9) in response to negative stimuli. Our results suggest that the prefrontal cortex, anterior cingulate cortex and insula may play key roles as biological markers for treatment response and as predictors of therapeutic success.
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Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis
https://pubmed.ncbi.nlm.nih.gov/29560920/
Background: Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples.
Methods: We conducted a meta-analysis of studies reporting changes in brain activity (e.g., as indexed by positron emission tomography) following treatments with selective serotonin reuptake inhibitors (SSRIs), electroconvulsive therapy (ECT), or transcranial magnetic stimulation. Additionally, we examined the statistical reliability of overlap among thresholded meta-analytic SSRI, ECT, and transcranial magnetic stimulation maps as well as a map of abnormal neural function in MDD.
Results: Our meta-analysis revealed that 1) SSRIs decrease activity in the anterior insula, 2) ECT decreases activity in central nodes of the default mode network, 3) transcranial magnetic stimulation does not result in reliable neural changes, and 4) regional effects of these modes of treatment do not significantly overlap with each other or with regions showing reliable functional abnormality in MDD.
Conclusions: SSRIs and ECT produce neurally distinct effects relative to each other and to the functional abnormalities implicated in depression. These treatments therefore may exert antidepressant effects by diminishing neural functions not implicated in depression but that nonetheless impact mood. We discuss how the distinct neural changes resulting from SSRIs and ECT can account for both treatment effects and side effects from these therapies as well as how to individualize these treatments.

LUST

Subchronic SSRI administration reduces insula response during affective anticipation in healthy volunteers
https://pubmed.ncbi.nlm.nih.gov/19545475/
The anterior cingulate cortex (ACC) and insula are important neural substrates for the integration of cognitive, emotional, and physiological information, as well as the coordination of responses to anticipated stimuli. Increased neural activation within these structures has been observed in individuals with anxiety and depressive disorders. Selective serotonin reuptake inhibitors (SSRIs) are among the most effective and frequently prescribed anxiolytic agents, yet it is not known whether ACC or insula underlie the effects of these drugs. We examined whether subchronic administration of a SSRI to healthy volunteers attenuates activation in ACC or insula during anticipation, an important emotional process underlying anxiety. Support for this hypothesis would help to understand where and by what process SSRIs may exert beneficial effects as anxiolytics and would provide further mechanistic evidence for functional magnetic resonance imaging (fMRI) as a biomarker for the development of anxiolytics. Fifteen volunteers participated in a double-blind, placebo-controlled, randomized cross-over study. Participants completed a pleasant and aversive picture-cued anticipation task during fMRI after taking either escitalopram (10 mg) or placebo for 21 d. We found that escitalopram significantly decreased activation in bilateral posterior and middle insula during the anticipation condition irrespective of stimulus valence and in medial prefrontal and ACC during anticipation of aversive vs. pleasant images. Reduced insular and ACC activation in healthy controls during anticipation may be integral to the therapeutic efficacy of SSRIs and may provide a mechanistic approach for the use of pharmaco-fMRI in the identification of novel pharmacotherapeutic agents in patient populations.
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The insula has been suggested to play a key role in evaluating the impact that environmental stimuli may have on the interoceptive body state 15, 88. Activity in this region relates to anxiety during risk-taking decision making 103, is elevated in individuals with specific phobia when viewing fearful faces 104, is increased during anticipation of emotion face processing in those with high trait anxiety 23, 105, relates to anticipatory anxiety in those with social phobia 57, and is associated with increased perfusion in patients with panic disorder 106. Taken in combination, these studies suggest that altered insula activity may be a common denominator that could be used as a biomarker for treatment effects. The anterior subdivision of the insula has been highlighted as an important region for the integration of physiological and psychological self 32, 88, and is of particular importance in down-modulating the posterior insula 28. In the present study, activity in the posterior insula was reduced by the administration of escitalopram, suggesting that SSRIs may contribute to central reduction in physiological reactivity during emotional anticipation.

[kpavel]

This review study says that the affective pleasure from genital touch exclusively depends on activation of posterior insular cortex which can be deactivated by escitalopram (see the post above).

The cortical sensory representation of genitalia in women and men: a systematic review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357265/
Afferent neural pathways from the genitalia
The ratio of small to large axons seen in nerves originating from the dermis of the human glans penis show an overwhelming majority of axons of small diameter (A6- or C-fibers) and scant larger myelinated fibers (>2 µm in diameter) (Halata & Munger, 1986).
At this point, it is relevant to mention a line of work done on sensual touch applied to hairy skin, in regions other than the genitalia. Some C-fibers are exquisitely sensitive to light (sensual) touch (Vallbo, Olausson, & Wessberg, 1999), but that has been shown only for hairy skin, i.e. not for the glabrous skin of the penis or for the clitoral and vaginal mucosae. In addition, human tactile C (CT) afferent pathways ultimately target the insular cortex (Björnsdotter, Löken, Olausson, Vallbo, & Wessberg, 2009; Björnsdotter, Morrison, & Olausson, 2010; Olausson et al., 2002, 2008). It is important to note that there is now fairly compelling evidence that the posterior insular cortex mediates the perception of pleasant caress (Morrison, Björnsdotter, & Olausson, 2011). There may even exist a somatotopic organization of the posterior insular cortex, with gentle touch of forearm evoking activation anterior to the one recorded in response to gentle touch of thigh. Interestingly, it appears that the two systems are partially antagonistic as CT stimulation in a patient lacking large myelinated afferents induced activation of posterior insular cortex while evoking deactivation in somatosensory cortex (Olausson et al., 2008). This potential antagonism could be helpful to understand why meta-analyses of brain responses to visual sexual stimuli show activation in SII, but not in SI.