Biology subjects

Holmes, E.

Publications and source records attributed to Holmes, E..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Microbe-derived indole tunes organ-function and links microbe metabolites to biological ageing

To investigate the underlying molecular mechanisms on how the gut microbe metabolite, indoles, regulate host organ growth and function, germ-free male mice were mono-colonized with indole-producing wildtype Escherichia coli or tryptophanase-encoding tnaA knockout mutant indole-non-producing E. coli. The indole mutant E. coli recipient mice exhibited significant multiorgan decline and growth retardation combined with catabolism and energy deficiency despite increased food intake compared to control mice. In addition, indole mutant mice displayed malfunctional intestine, enlarged caecum, reduced numbers of colonic enterochromaffin cells and reduced circulating serotonin levels, resulting in reduced gut motility, diminished digestion, and lower energy harvest. Furthermore, indole mutant mice also displayed decreased expression of Kcnj12 gene, suggesting reduced excitability of enteric neurons thus adding to intestinal dysfunctional phenotype. In conclusion, indoles are necessary to maintain adult metabolic homeostasis across multiple organs in vivo. Impairment of indole levels results in multiorgan functional decline suggesting a mechanism whereby gut microbe metabolites may regulate biological ageing and thus increase the risk for disease. Graphical summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/525337v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@182875dorg.highwire.dtl.DTLVardef@8525e9org.highwire.dtl.DTLVardef@17c24e3org.highwire.dtl.DTLVardef@159dff4_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

A switch in jaw form-function coupling during the evolution of mammals

The evolutionary shift from a single-element ear, multi-element jaw to a multi-element ear, single-element jaw during the transition to crown mammals marks one of the most dramatic structural transformations in vertebrates. Research on this transformation has focused on mammalian middle-ear evolution, but a mandible comprised of only the dentary is equally emblematic of this evolutionary radiation. Here we show that the remarkably diverse jaw shapes of crown mammals are coupled with surprisingly stereotyped jaw stiffness. This strength-based morphofunctional regime has a genetic basis and allowed mammalian jaws to effectively resist deformation as they radiated into highly disparate forms with markedly distinct diets. The main functional consequences for the mandible of decoupling hearing and mastication were a trade-off between higher jaw stiffness versus decreased mechanical efficiency and speed compared to non-mammals. This fundamental and consequential shift in jaw form-function underpins the ecological and taxonomic diversification of crown mammals.

evolutionary biology↗

bioRxiv2022

A mixed generative model of auditory word repetition

In this paper, we introduce a word repetition generative model (WORM), which--when combined with an appropriate belief updating scheme--is capable of inferring the word that should be spoken when presented with an auditory cue. Our generative model takes a deep temporal form, combining both discrete and continuous states. This allows a (synthetic) WORM agent to perform categorical inference on continuous acoustic signals, and--based on the same model--to repeat heard words at the appropriate time. From the perspective of word production, the model simulates how high-level beliefs about discrete lexical, prosodic and context attributes give rise to continuous acoustic signals at the sensory level. From the perspective of word recognition, it simulates how continuous acoustic signals are recognised as words and, how (and when) they should be repeated. We establish the face validity of our generative model by simulating a word repetition paradigm in which a synthetic agent or a human subject hears a target word and subsequently reproduces that word. The repeated word should be the target word but differs acoustically. The results of these simulations reveal how the generative model correctly infers what must be repeated, to the extent it can successfully interact with a human subject. This provides a formal process theory of auditory perception and production that can be deployed in health and disease. We conclude with a discussion of how the generative model could be scaled-up to include a larger phonetic and phonotactic repertoire, complex higher-level attributes (e.g., semantic, concepts, etc.), and produce more elaborate exchanges.

neuroscience↗

bioRxiv2021

Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in synaptic efficacy underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)--and its modulation by context predictability and musical expertise--are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)--typically related to gain control--or extrinsic connections between A1 and STG--typically related to propagation of prediction and error signals--better explained magnetoencephalography (MEG) responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing. Significance statementIn complex auditory contexts, being able to identify informative signals is of paramount importance. Such is the case of music listening, where surprising sounds play a fundamental role in its perceptual, aesthetical, and emotional experience. Crucially, surprising sounds in the pitch dimension are more easily detected and generate stronger cortical responses when melodies are predictable and when the listener is a musician. Using Dynamic Causal Modelling, here we show that such effects arise from a local increase in neural gain within auditory areas, rather than from passing of prediction and error signals between brain regions. Consistent with predictive processing theories, this suggests that the enhanced precision of auditory predictive models--through melodic predictability and musical training--up-regulates the processing of informative error signals in the brain.

neuroscience↗

bioRxiv2021

Simulating lesion-dependent functional recovery mechanisms

Functional recovery after brain damage varies widely and depends on many factors, including lesion site and extent. When a neuronal system is damaged, recovery may occur by engaging residual (e.g., perilesional) components. When damage is extensive, recovery depends on the availability of other intact neural structures that can reproduce the same functional output (i.e., degeneracy). A systems response to damage may occur rapidly, require learning or both. Here, we simulate functional recovery from four different types of lesions, using a generative model of word repetition that comprised a default premorbid system and a less used alternative system. The synthetic lesions (i) completely disengaged the premorbid system, leaving the alternative system intact, (ii) partially damaged both premorbid and alternative systems, and (iii) limited the experience-dependent plasticity of both. The results, across 1000 trials, demonstrate that (i) a complete disconnection of the premorbid system naturally invoked the engagement of the other, (ii) incomplete damage to both systems had a much more devastating long-term effect on model performance and (iii) the effect of reducing learning capacity within each system. These findings contribute to formal frameworks for interpreting the effect of different types of lesions.

neuroscience↗

bioRxiv2020

Host age shapes virome abundance and diversity in birds

Host age influences the ecology of many microorganisms. This is evident in one-host - one virus systems, such as influenza A virus in Mallards, but also in community studies of parasites and microbiomes. We used a meta-transcriptomic approach to assess whether host age is associated with differences in the abundance and diversity of avian viromes. We used samples from cohabiting Ruddy Turnstones (Arenaria interpres) across three age groups, collected at two contrasting points in their annual migratory cycle. Overall, we identified 14 viruses that likely infect birds, 11 of which were novel, including members of the Reoviridae, Astroviridae, Picornaviridae, and Phenuiviridae. Strikingly, 12 of the viruses identified were from juvenile birds sampled in the first year of their life, compared to only two viruses in adult birds. Similarly, both viral abundance and alpha diversity were higher in juvenile than adult birds. Notably, time of sampling had no association with virome structure such that the migratory period may not play a major role in structuring avian viromes. As well as informing studies of virus ecology, that host age impacts viral assemblages is a critical consideration for the future surveillance of novel and emerging viruses.

microbiology↗

bioRxiv2020

Arabidopsis UGT76B1 glycosylates N-hydroxy-pipecolic acid and inactivates systemic acquired resistance in tomato

Systemic acquired resistance (SAR) is a mechanism that plants utilize to connect a local pathogen infection to global defense responses. N-hydroxy-pipecolic acid (NHP) and a glycosylated derivative are produced during SAR, yet their individual roles in the response have not yet been elucidated. Here we report that Arabidopsis thaliana UGT76B1 can generate glycosylated NHP (NHP-Glc) in vitro and when transiently expressed alongside Arabidopsis NHP biosynthetic genes in two Solanaceous plants. During infection, Arabidopsis ugt76b1 mutants do not accumulate NHP-Glc and accumulate less glycosylated salicylic acid (SA-Glc) than wild type plants. The metabolic changes in ugt76b1 mutant plants are accompanied by enhanced defense to the bacterial pathogen Pseudomonas syringae, suggesting that glycosylation of SAR molecules NHP and SA by UGT76B1 plays an important role in defense modulation. Transient expression of Arabidopsis UGT76B1 with the Arabidopsis NHP biosynthesis genes ALD1 and FMO1 in tomato increases NHP-Glc production and reduces NHP accumulation in local tissue, and abolishes the systemic resistance seen when expressing NHP-biosynthetic genes alone. These findings reveal that the glycosylation of NHP by UGT76B1 alters defense priming in systemic tissue and provide further evidence for the role of the NHP aglycone as the active metabolite in SAR signaling.

plant biology↗

bioRxiv2020

Active Listening

This paper introduces active listening, as a unified framework for synthesising and recognising speech. The notion of active listening inherits from active inference, which considers perception and action under one universal imperative: to maximise the evidence for our (generative) models of the world. First, we describe a generative model of spoken words that simulates (i) how discrete lexical, prosodic, and speaker attributes give rise to continuous acoustic signals; and conversely (ii) how continuous acoustic signals are recognised as words. The active aspect involves (covertly) segmenting spoken sentences and borrows ideas from active vision. It casts speech segmentation as the selection of internal actions, corresponding to the placement of word boundaries. Practically, word boundaries are selected that maximise the evidence for an internal model of how individual words are generated. We establish face validity by simulating speech recognition and showing how the inferred content of a sentence depends on prior beliefs and background noise. Finally, we consider predictive validity by associating neuronal or physiological responses, such as the mismatch negativity and P300, with belief updating under active listening, which is greatest in the absence of accurate prior beliefs about what will be heard next.

neuroscience↗

bioRxiv2020

Speech-evoked brain activity is more robust to competing speech when it is spoken by someone familiar

People are much better at understanding speech when it is spoken by a familiar talker--such as a friend or partner--than when the interlocutor is unfamiliar. This provides an opportunity to examine the substrates of intelligibility and familiarity, independent of acoustics. Is the familiarity effect evident as early as primary auditory cortex, or only at later processing stages? Here, we presented sentences spoken by naturally familiar talkers (the participants friend or partner) and unfamiliar talkers (the friends or partners of other participants). We compared multivariate activity in speech-sensitive regions of cortex between conditions in which target sentences were presented alone and conditions in which the same target sentences were presented at the same time as a competing sentence. Using representational similarity analysis (RSA), we demonstrate that the pattern of activity evoked by a spoken sentence is less degraded by the presence of a competing sentence when it is spoken by a friend or partner than by someone unfamiliar; the results cannot be explained by acoustic differences since familiar and unfamiliar talkers were nearly identical across the group. This familiar-voice advantage is most prominent in nonprimary auditory cortical areas, along the posterior superior and middle temporal gyri. Across participants, the magnitude of the familiar-unfamiliar RSA difference correlates with the familiar-voice benefit to intelligibility. Overall, our results demonstrate that experience-driven improvements in intelligibility are associated with enhanced patterns of neural activity in nonprimary auditory cortical areas. Significance statementSpeech is a complex signal, and we do not yet fully understand how the content of a spoken sentence is encoded in cortex. Here, we used a novel approach based on analysing multivariate activity: we compared activity evoked by highly intelligible sentences presented alone and by the same sentences presented with a competing masker. The distributed pattern of activity in speech-sensitive regions of the brain was more similar between the alone and masker conditions when the target sentence was spoken by someone familiar--the participants friend or partner--than someone unfamiliar. This metric correlated with the intelligibility of the familiar voice. These results imply that the spatial pattern of activity in speech-sensitive regions reflects the intelligibility of a spoken sentence.

neuroscience↗

bioRxiv2020

Simultaneous auditory agnosia: Systematic description of a new type of auditory segregation deficit following a right hemisphere lesion

We investigated auditory processing in a young patient who experienced a single embolus causing an infarct in the right middle cerebral artery territory. This lead to damage to auditory cortex including planum temporale that spared medial Heschls gyrus, and included damage to the posterior insula and inferior parietal lobule. She first reported difficulty hearing all sounds, which fully recovered within days, but she subsequently reported chronic difficulties with segregating speech from noise and segregating elements of music. Clinical tests showed no evidence for abnormal cochlear function. Follow-up tests confirmed difficulties with auditory segregation in her left ear that spanned multiple domains, including speech-in-noise and music streaming. Testing with a stochastic figure-ground task--a way of estimating generic acoustic foreground and background segregation--demonstrated that this was also abnormal. This is the first demonstration of an acquired deficit in the segregation of complex acoustic patterns due to cortical damage, which we argue is a causal explanation for the symptomatic deficits in the segregation of speech and music. These symptoms are analogous to the visual symptom of simultaneous agnosia. Consistent with functional imaging studies on normal listeners, the work implicates non-primary auditory cortex. Further, the work demonstrates a (partial) lateralisation of the necessary anatomical substrate for segregation that has not been previously highlighted. HighlightsO_LIRare case of auditory agnosia in a young patient with a right-hemisphere infarct C_LIO_LIDamage affecting non-primary auditory cortex, but sparing primary auditory cortex C_LIO_LIGeneralised auditory segregation deficit, revealed by auditory figure-ground task C_LIO_LIThis explains segregation deficits for speech-in-noise and music streaming C_LIO_LIThe deficit affects stimuli presented on the left C_LI

neuroscience↗

bioRxiv2020

Speech-in-noise detection is related to auditory working memory precision for frequency

Speech-in-noise (SiN) perception is a critical aspect of natural listening, deficits in which are a major contributor to the hearing handicap in cochlear hearing loss. Studies suggest that SiN perception correlates with cognitive skills, particularly phonological working memory: the ability to hold and manipulate phonemes or words in mind. We consider here the idea that SiN perception is linked to a more general ability to hold sound objects in mind, auditory working memory, irrespective of whether the objects are speech sounds. This process might help combine foreground elements, like speech, over seconds to aid their separation from the background of an auditory scene. We investigated the relationship between auditory working memory precision and SiN thresholds in listeners with normal hearing. We used a novel paradigm that tests auditory working memory for non-speech sounds that vary in frequency and amplitude modulation (AM) rate. The paradigm yields measures of precision in frequency and AM domains, based on the distribution of participants estimates of the target. Across participants, frequency precision correlated significantly with SiN thresholds. Frequency precision also correlated with the number of years of musical training. Measures of phonological working memory did not correlate with SiN detection ability. Our results demonstrate a specific relationship between working memory for frequency and SiN. We suggest that working memory for frequency facilitates the identification and tracking of foreground objects like speech during natural listening. Working memory performance for frequency also correlated with years of musical instrument experience suggesting that the former is potentially modifiable.

neuroscience↗

bioRxiv2019

Difficulties with speech-in-noise perception related to fundamental grouping processes in auditory cortex

In our everyday lives, we are often required to follow a conversation when background noise is present (\"speech-in-noise\" perception). Speech-in-noise perception varies widely--and people who are worse at speech-in-noise perception are also worse at fundamental auditory grouping, as assessed by figure-ground tasks. Here, we examined the cortical processes that link difficulties with speech-in-noise perception to difficulties with figure-ground perception using functional magnetic resonance imaging (fMRI). We found strong evidence that the earliest stages of the auditory cortical hierarchy (left core and belt areas) are similarly disinhibited when speech-in-noise and figure-ground tasks are more difficult (i.e., at target-to-masker ratios corresponding to 60% than 90% thresholds)--consistent with increased cortical gain at lower levels of the auditory hierarchy. Overall, our results reveal a common neural substrate for these basic (figure-ground) and naturally relevant (speech-in-noise) tasks--which provides a common computational basis for the link between speech-in-noise perception and fundamental auditory grouping.

neuroscience↗

bioRxiv2019

Identification and evolution of avian endogenous foamy viruses

A history of long-term co-divergence means that foamy viruses (family Retroviridae) provide an ideal framework to understanding virus-host evolution over extended time periods. Endogenous foamy viruses (EndFVs) are rare, and to date have only been described in a limited number of mammals, amphibians, reptiles and fish genomes. By screening 414 avian genomes we identified EndFVs in two bird species: the Maguari Stork (Ciconia maguari) and the Oriental Stork (C. boyciana). Analyses of phylogenetic relationships, genome structures and flanking sequences revealed a single origin of EndFVs in Ciconia species. In addition, the marked incongruence between the virus and host phylogenies suggested that this integration event occurred independently in birds. In sum, by providing evidence that birds can be infected with foamy viruses, we fill the last major gap in the taxonomic distribution of foamy viruses and their animal hosts.

microbiology↗

bioRxiv2019

‘Normal’ hearing thresholds and fundamental auditory grouping processes predict difficulties with speech-in-noise perception

Understanding speech when background noise is present is a critical everyday task that varies widely among people. A key challenge is to understand why some people struggle with speech-in-noise perception, despite having clinically normal hearing. Here, we developed new figure-ground tests that require participants to extract a coherent tone pattern from a stochastic background of tones. These tests dissociated variability in speech-in-noise perception related to mechanisms for detecting static (same-frequency) patterns and those for tracking patterns that change frequency over time. In addition, elevated hearing thresholds that are widely considered to be normal explained significant variance in speech-in-noise perception, independent of figure-ground perception. Overall, our results demonstrate that successful speech-in-noise perception is related to audiometric thresholds, fundamental grouping of static acoustic patterns, and tracking of acoustic sources that change in frequency. Crucially, measuring both peripheral (audiometric thresholds) and central (grouping) processes is required to adequately assess speech-in-noise deficits.

neuroscience↗

bioRxiv2019

Novel hepatitis D-like agents in vertebrates and invertebrates

Hepatitis delta virus (HDV) is the smallest known RNA virus and encodes a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians and invertebrates. Notably, the novel viruses identified here share HDV-like genomic features such as a small genome size of ~1.7kb in length, circular genomes, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human HDAgs. Notably, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV-HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV in non-human species, but shed light on its origin and evolutionary history.

evolutionary biology↗

bioRxiv2019

Conservation of N-hydroxy-pipecolic acid-mediated systemic acquired resistance in crop plants

Signal propagation and the coordination of whole-organism responses in plants rely heavily on small molecules. Systemic acquired resistance (SAR) is one such process in which long-distance signaling activates immune responses in uninfected tissue as a way to limit the spread of a primary, localized infection. Recently, N-hydroxy pipecolic acid (NHP) was discovered and shown to coordinate SAR in Arabidopsis. Here, we provide metabolic and biochemical evidence that NHP is conserved across the plant kingdom and demonstrate a role for NHP in mediating SAR responses in tomato and pepper. We reconstituted the NHP biosynthetic pathway in planta and show that transient expression of two NHP biosynthetic genes in tomato induces enhanced resistance to a bacterial pathogen in distal tissue. Our results suggest engineering strategies to induce NHP-mediated SAR are a promising route to improve broad-spectrum pathogen resistance in crops. IN BRIEFEngineering NHP production is a promising strategy to enhance disease resistance in crops. HIGHLIGHTSO_LIArabidopsis N-hydroxy-pipecolic acid (NHP) pathway is conserved across the plant kingdom C_LIO_LIApplication of NHP to tomato and pepper plants induces a robust SAR response C_LIO_LIMetabolic engineering of the Arabidopsis NHP pathway in Solanum lycopersicum leads to enhanced NHP production and defense priming C_LIO_LIGenetic engineering for enhanced NHP production is a promising strategy to protect crop plants from multiple pathogens C_LI

plant biology↗

bioRxiv2019

Virome heterogeneity and connectivity in waterfowl and shorebird communities

Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two well described multi-host virus species (avian coronavirus and influenza A virus) and a novel Rotavirus species that were shared among some Anseriform species, while heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, within avian host families there was no significant relationship between either host taxonomy or foraging ecology and virome composition, although Anseriform species positive for influenza A virus harboured more additional viruses than those negative for influenza virus. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.

ecology↗

bioRxiv2018

Emotional recognition training modifies neural response to emotional faces but does not improve mood in healthy volunteers with high levels of depressive symptoms

IMPORTANCEDepression is a debilitating and highly prevalent mental health disorder. There is a need for new, effective, and scalable treatments for depression, and cognitive bias modification (CBM) of negative emotional processing biases has been suggested as one possibility. Such treatments may form the basis of digital therapeutics, that could be administered remotely and at low cost, should they prove to be effective.\n\nOBJECTIVESStudy one was designed to determine neural correlates of a recently developed CBM technique for emotion recognition training; specifically, our aim was to compare the effects of training vs placebo on pre-specified regions of interest involved in emotion processing that are known to be sensitive to antidepressant treatment. Study two aimed to investigate efficacy of training on mood measures at 2 and 6-week follow-up and was powered to replicate and extend earlier findings.\n\nDESIGN, SETTING, AND PARTICIPANTSBoth studies were double blind RCTs, in which participants completed five sessions of emotion recognition training or sham training, in the laboratory, over a one-week period. In study one (N=37), following this training, participants completed a novel emotion recognition task whilst undergoing fMRI. In study two (N=190), measures of mood were assessed post training, and at 2-week and 6-week follow-up. Both studies recruited analogue samples of healthy volunteers with high levels of depressive symptoms (BDI-ii > 14).\n\nMAIN OUTCOMES AND MEASURESIn study one, our primary outcome was neural activation in the following pre-specified regions of interest: the bilateral amygdala, the mPFC, bilateral dlPFC, and the occipital cortex. In study two, our primary outcome was depressive symptoms over the last 2 weeks assessed using the BDI-ii at 6-week follow-up. Secondary outcomes included depressive symptoms measured using the HAM-D, and positive and negative affect assessed using the PANAS.\n\nRESULTSIn both studies, CBM resulted in a change in emotion recognition bias, which (in study two) persisted for 6 weeks after the end of the CBM phase. In study one, CBM resulted in increases neural activation to happy faces compared to sad faces, with this effect driven by an increase in neural activity for happy faces. We saw this increase in activation for this contrast at both the whole brain level and among our a priori ROIs, specifically the mPFC and bilateral amygdala. In study two, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias.\n\nCONCLUSIONS AND RELEVANCECBM of emotion recognition appears to have effects on neural activity that are similar in some respects to those induced by SSRI administration (study one), but we find no evidence that this has any effect on self-reported mood in an analogue sample of healthy volunteers with low mood (study two).

neuroscience↗