Symmetry and Artistic Elongation of the Human Form: Exploring the Attainment of Aesthetic Appeal

Although typically associated with the Mannerist artistic style of the Renaissance, artists throughout history have created pictures and sculptures of humans depicted in an unrealistic and abnormally elongated form. The scientific basis for adopting this form of distortion is discussed here. First, probably subconsciously, artists have appreciated that the human form displays a symmetry which is often aesthetically pleasing. Second, perceived beauty is enhanced when the symmetrical image is elongated. There is evidence that the appeal of artworks which feature these characteristics can be attributed to their ease of cerebral processing, a view supported by functional MRI studies indicating there is an overlap between regions of the brain devoted to processing of symmetry and those devoted to appreciation of beauty.

Neural Correlates of Anti-appetite Medications: an fMRI Meta-analysis

: Food craving is a health issue for a considerable proportion of the general population. Medications have been introduced to alleviate the craving or reduce the appetite via a neuropharmacological approach. However, the underlying cerebral processing of the medications was largely unknown. This study aimed to meta-analyze existing neuroimaging findings. We searched PubMed, Web of Science, and Scopus to identify relevant publications. Original studies that reported brain imaging findings using functional magnetic resonance imaging (fMRI) were initially included. The reported coordinates of brain activation available from the studies were extracted and meta-analyzed with the activation likelihood estimation (ALE) approach via the software GingerALE. The overall analysis pooling data from 24 studies showed that the right claustrum and insula were the targeted sites of altered cerebral processing of food cues by the medications. Subgroup analysis pooling data from 11 studies showed that these sites had reduced activity level under medications compared to placebo. The location of this significant cluster partially overlapped with that attributable to affective value processing of food cue in a prior meta-analysis. No brain regions were found to have increased activity level by medications. These neural correlates may help explain the physiological effect of food consumption by anti-appetite and anti-obesity medications.

Serotonergic gene-to-gene interaction is associated with mood and GABA concentrations but not with pain-related cerebral processing in fibromyalgia subjects and healthy controls

The neurotransmitter serotonin, involved in the regulation of pain and emotion, is critically regulated by the 5‐HT1A autoreceptor and the serotonin transporter (5-HTT). Polymorphisms of these genes affect mood and endogenous pain modulation, both demonstrated to be altered in fibromyalgia subjects (FMS). Here, we tested the effects of genetic variants of the 5‐HT1A receptor (CC/G-carriers) and 5-HTT (high/intermediate/low expression) on mood, pain sensitivity, cerebral processing of evoked pain (functional MRI) and concentrations of GABA and glutamate (MR spectroscopy) in rostral anterior cingulate cortex (rACC) and thalamus in FMS and healthy controls (HC). Interactions between serotonin-relevant genes were found in affective characteristics, with genetically inferred high serotonergic signalling (5-HT1A CC/5-HTThigh genotypes) being more favourable across groups. Additionally, 5‐HT1A CC homozygotes displayed higher pain thresholds than G-carriers in HC but not in FMS. Cerebral processing of evoked pressure pain differed between groups in thalamus with HC showing more deactivation than FMS, but was not influenced by serotonin-relevant genotypes. In thalamus, we observed a 5‐HT1A-by-5-HTT and group-by-5-HTT interaction in GABA concentrations, with the 5-HTT high expressing genotype differing between groups and 5‐HT1A genotypes. No significant effects were seen for glutamate or in rACC. To our knowledge, this is the first report of this serotonergic gene-to-gene interaction associated with mood, both among FMS (depression) and across groups (anxiety). Additionally, our findings provide evidence of an association between the serotonergic system and thalamic GABA concentrations, with individuals possessing genetically inferred high serotonergic signalling exhibiting the highest GABA concentrations, possibly enhancing GABAergic inhibitory effects via 5-HT.

Lateralized Cerebral Processing of Abstract Linguistic Structure in Clear and Degraded Speech

Human cortical activity measured with magnetoencephalography (MEG) has been shown to track the temporal regularity of linguistic information in connected speech. In the current study, we investigate the underlying neural sources of these responses and test the hypothesis that they can be directly modulated by changes in speech intelligibility. MEG responses were measured to natural and spectrally degraded (noise-vocoded) speech in 19 normal hearing participants. Results showed that cortical coherence to “abstract” linguistic units with no accompanying acoustic cues (phrases and sentences) were lateralized to the left hemisphere and changed parametrically with intelligibility of speech. In contrast, responses coherent to words/syllables accompanied by acoustic onsets were bilateral and insensitive to intelligibility changes. This dissociation suggests that cerebral responses to linguistic information are directly affected by intelligibility but also powerfully shaped by physical cues in speech. This explains why previous studies have reported widely inconsistent effects of speech intelligibility on cortical entrainment and, within a single experiment, provided clear support for conclusions about language lateralization derived from a large number of separately conducted neuroimaging studies. Since noise-vocoded speech resembles the signals provided by a cochlear implant device, the current methodology has potential clinical utility for assessment of cochlear implant performance.

Inferring the infant pain experience: a translational fMRI-based signature study

BackgroundIn the absence of verbal communication it is challenging to infer an individual’s sensory and emotional experience. In adults, fMRI has been used to develop multivariate brain activity signatures, which reliably capture elements of human pain experience. We translate whole-brain fMRI signatures that encode pain perception in adults to the newborn infant brain, to advance understanding of functional brain development and pain perception in early life.MethodsA cohort of adults (n=10; mean age=28.3 years) and 2 cohorts of healthy infants (Cohort A: n=15; Cohort B: n=22; mean postnatal age=3 days) were stimulated with low intensity nociceptive stimuli (64-512mN) during acquisition of functional MRI data. fMRI pain signatures were applied directly to the adult data and transformed such that they could be applied to the infant brain. In each cohort, we assessed the concordance of the signatures with the brain responses using cosine-similarity scores, and we assessed stimulus intensity encoding of the signature responses using Spearman rank correlation. Brain activity in ‘pro-pain’ and ‘anti-pain’ brain regions were also examined.FindingsThe Neurologic Pain Signature (NPS), which reflects aspects of nociceptive pain experience, was activated in both the adults and infants, and reliably encoded stimulus intensity. However, the Stimulus Intensity Independent Pain Signature (SIIPS1), which reflects higher-level cognitive modulation of nociceptive input, was only expressed in adults. ‘Pro-pain’ brain regions showed similar activation patterns in adults and infants, whereas, ‘anti-pain’ brain regions exhibited divergent responses.InterpretationBasic intensity encoding of nociceptive information is similar in adults and infants. However, translation of adult brain signatures into infants reveals significant differences in infant cerebral processing of nociceptive information, which may reflect their lack of expectation, motivation and contextualisation. This study expands the use of brain activity pain signatures to non-verbal patients and provides a potential approach to assess analgesic interventions in infancy.FundingThis work was funded by Wellcome (Senior Research Fellowship awarded to Prof. Rebeccah Slater) and SSNAP “Support for Sick and Newborn Infants and their Parents” Medical Research Fund (University of Oxford Excellence Fellowship awarded to Dr Eugene Duff).Research in contextEvidence before this studyWe searched PubMed for research articles published prior to March 2020 using terms including ‘fMRI’, ‘infant or neonate’, and ‘pain or nociception’ in the title or abstract. Due to the relatively new emergence of this field, and the experimental and analytical challenges involved in studying cerebral processing of pain in the MRI environment in healthy newborn infants, only five fMRI studies have examined infant brain responses to nociceptive input.In a foundational pilot study, Williams et al., applied an experimental noxious stimulus to a single infant, evoking widespread brain activity that included several brain regions involved in pain processing in adults. Goksan et al., subsequently performed an observational cohort study and used regional analyses to compare active brain regions in infants (n=10) and adults (n=10), concluding that the evoked patterns of brain activity were broadly similar in infants and adults. Further follow-up analysis in the infant cohort revealed that the functional connectivity of brain regions involved in descending pain modulation influences the magnitude of pain-related brain activity. Two further studies focused on methodological advances, providing evidence-based recommendations for fMRI acquisition parameters and image processing in order to maximise the quality of infant data, and these methods have been implemented in this study.Added value of this studyThis study translates validated adult pain fMRI brain signatures to a nonverbal patient population in which the assessment and management of pain presents a significant clinical challenge. Application of fMRI brain signatures to newborn infants expands on previous fMRI studies that provided only qualitative evidence that noxious stimulation commonly activates brain regions in the adult and infant brain. Here we demonstrate that the basic encoding of the sensory discriminative aspects of pain, as represented by the Neurologic Pain Signature (NPS), occurs in both adults and infants, whereas higher-level cognitive modulation of pain, represented by the Stimulus Intensity Independent Pain Signature (SIIPS1) is only present in adults and not observed in infants. The differences in how the immature infant brain processes pain, relative to the mature adult brain, are likely to reflect differences in their expectation, motivation and contextualisation of external events rather than differences in their core nociceptive cerebral processing of pain. This work allows us to use quantitative fMRI observations to make stronger inferences related to pain experience in nonverbal infants.Implications of all the available evidenceBehavioural pain scores used in neonatal clinical care offer limited sensitivity and specificity to pain. Neonatal clinical trials that use these scores as outcome measures frequently report a lack of efficacy of common analgesic interventions, resulting in few evidence-based drugs for treating pain. The value of using brain-based neuroimaging markers of pain as a means of providing objective evidence of analgesic efficacy in early proof of concept studies is well recognised in adults, even in the absence of behavioural pain modulation. Similarly, in infants EEG-based measures of noxious-evoked brain activity have been used as outcome measures in clinical trials of analgesics to overcome some of the inherent limitations of using behavioural observations to quantify analgesic efficacy. Considering the successful translation of the Neurologic Pain Signature (NPS) and its sensitivity to analgesic modulation in adults, this novel methodology represents an objective brain-based fMRI approach that could be used to advance the discovery and assessment of analgesic interventions in infancy.

Exploring the cerebral substrate of voice perception in primate brains

One can consider human language to be the Swiss army knife of the vast domain of animal communication. There is now growing evidence suggesting that this technology may have emerged from already operational material instead of being a sudden innovation. Sharing ideas and thoughts with conspecifics via language constitutes an amazing ability, but what value would it hold if our conspecifics were not first detected and recognized? Conspecific voice (CV) perception is fundamental to communication and widely shared across the animal kingdom. Two questions that arise then are: is this apparently shared ability reflected in common cerebral substrate? And, how has this substrate evolved? The paper addresses these questions by examining studies on the cerebral basis of CV perception in humans' closest relatives, non-human primates. Neuroimaging studies, in particular, suggest the existence of a ‘voice patch system’, a network of interconnected cortical areas that can provide a common template for the cerebral processing of CV in primates. This article is part of the theme issue ‘What can animal communication teach us about human language?’

Direct Anterior Insular Cortex Stimulation Increases Heat Pain Threshold: A Case Report

INTRODUCTION The insular cortex is thought to be involved in the cerebral processing of three dissociable dimensions of pain: sensory-discriminative, affective-motivational, and cognitive-evaluative. The posterior portion of the insular cortex (pIC) has greater connectivity to the primary and secondary somatosensory cortices and is likely related to the sensory-discriminative dimension of pain. The anterior portion the of insular cortex (aIC) has greater connectivity to the ventrolateral prefrontal and orbitofrontal cortices and is involved in the affective-motivational and cognitive-evaluative aspects of pain. While direct pIC stimulation has been demonstrated to increase thermal pain threshold, direct aIC stimulation has never been attempted in humans. We hypothesize that direct aIC stimulation will induce an inhibitory effect upon cerebral processing of the affective components of pain and therefore will result in a significant increase in thermal pain threshold. METHODS A 31-yr-old female patient undergoing epileptic focus localization with depth electrodes implanted in the aIC was recruited for this study. The locations of the aIC electrodes were determined by postoperative T2-weighted MRI. Direct aIC stimulation was performed with the following settings: bipolar mode, 3 trains of 10 s stimulations at a frequency of 50 Hz, pulse width of 250 μs, and interstimulus train intervals of 5 s. The intensity of stimulation was set to 2 mA and 4 mA. Thermal pain thresholds were measured on the contralateral forearm following direct aIC stimulation. RESULTS Direct aIC stimulation increased the heat pain threshold by 2°C, and the magnitude of this effect was positively correlated with the intensity of stimulation (P = .011). No evoked sensations were reported. CONCLUSION This case suggests that direct aIC stimulation decreases thermal nociception and provides evidence that the aIC may be a neuromodulation target for chronic pain treatment.