Sympathetic nerve activity can be estimated from skin conductance responses - A comment on Henderson et al. (2012).

I read with great interest the paper by Henderson et al. (2012) on the relationship of skin sympathetic nerve activity (SSNA) and BOLD responses. The generation of the skin conductance response (SCR) via skin sympathetic nerve fibres remains an understudied topic despite the popularity of SCR as an indicator of sympathetic arousal in emotion neuroscience. However, in order to motivate their use of SSNA for fMRI analysis, Henderson et al. (2012) claim that SSNA cannot be retrieved from SCR. This is not supported by the literature

Psychophysiological modelling and the measurement of fear conditioning

Quantification of fear conditioning is paramount to many clinical and translational studies on aversive learning. Various measures of fear conditioning co-exist, including different observables and different methods of pre-processing. Here, we first argue that low measurement error is a rational desideratum for any measurement technique. We then show that measurement error can be approximated in benchmark experiments by how closely intended fear memory relates to measured fear memory, a quantity that we term retrodictive validity. From this perspective, we discuss different approaches commonly used to quantify fear conditioning. One of these is psychophysiological modelling (PsPM). This builds on a measurement model that describes how a psychological variable, such as fear memory, influences a physiological measure. This model is statistically inverted to estimate the most likely value of the psychological variable, given the measured data. We review existing PsPMs for skin conductance, pupil size, heart period, respiration, and startle eye-blink. We illustrate the benefit of PsPMs in terms of retrodictive validity and translate this into sample size required to achieve a desired level of statistical power. This sample size can differ up to a factor of three between different observables, and between the best, and the current standard, data pre-processing methods

A head-to-head comparison of SCRalyze and Ledalab, two model-based methods for skin conductance analysis.

Model-based analysis of skin conductance responses (SCR) can furnish less noisy estimates of sympathetic arousal (SA) than operational peak scoring approaches, as shown in previous work. Here, I compare two model-based methods for analysis of evoked (stimulus-locked) SCR, implemented in two software packages, SCRalyze and Ledalab, with respect to their sensitivity in recovering SA. Four datasets are analysed to compare predictive validity, i.e. the sensitivity to distinguish pairs of SA states that are known to be different. SCRalyze was significantly better able than Ledalab to recover this known difference in four out of five tested contrasts and comparable in the remaining one. SCRalyze performed significantly better than conventional analysis in all contrasts. I conclude that the model-based method engendered in SCRalyze is currently the best available approach to provide robust and sensitive estimates of sympathetic arousal

Beneath the surface:How social inhibition affects stress and emotion regulation

Sociale geremdheid is een persoonlijkheidskenmerk dat gekenmerkt wordt door angst voor, en het vermijden van, onbekende situaties. Sociaal geremde mensen zijn gevoeliger voor sociale dreiging en onderdrukken emotionele expressie, gedachten en gedragingen tijdens sociale interacties. Eerder onderzoek laat zien dat sociale geremdheid samen zou kunnen hangen met een verslechterde psychologische en lichamelijke gezondheid, maar hoe en waarom dit zo is bij sociaal geremde volwassenen is nog onduidelijk. Daarom was het doel van dit proefschrift om meer inzicht te krijgen in sociale geremdheid bij volwassenen, en kennis te vergaren over de lichamelijke en psychologische processen die gerelateerd zijn aan dit persoonlijkheidskenmerk. Onderzoeksmethoden De eerste stap was om een meetinstrument te ontwikkelen dat sociale geremdheid bij volwassenen betrouwbaar en valide kan meten. Met dit meetinstrument waren we in staat om te bekijken in hoeverre mensen met en zonder deze persoonlijkheidstrek van elkaar verschillen op bepaalde uitkomsten. Daarna hebben we een aantal stress- en emotieregulatie experimenten uitgevoerd in het Gedrags-fysiologisch Onderzoekslaboratorium (GO-Lab) om te bestuderen hoe sociaal geremde mensen reageren op stress en hoe ze omgaan met bepaalde emoties (verdriet, boosheid). Belangrijkste conclusies De uitkomsten van dit proefschrift laten zien dat sociaal geremde mensen meer psychologische en lichamelijke stress ervaren en minder goed kunnen omgaan met negatieve emoties, wat op den duur kan leiden tot stress-gerelateerde gezondheidsproblemen. Dit komt voornamelijk doordat sociaal geremde mensen sociale situaties als bedreigend ervaren en daardoor meer op hun hoede zijn, wat zorgt voor een herhaalde activatie van het stress-systeem. Daarnaast hebben sociaal geremde mensen de neiging om de (negatieve) gevoelens die ze ervaren te vermijden of onderdrukken, om niet te laten zien hoe ze zich echt voelen, uit angst voor afwijzing van anderen. Het vermijden en onderdrukken van emoties hangt samen met het ervaren van meer angst en stress, en zou een risico factor kunnen zijn voor het ontwikkelen van psychologische en lichamelijke aandoeningen. Belangrijkste aanbevelingen De bevindingen tonen aan dat het belangrijk is om sociaal geremde mensen te ondersteunen bij het managen van hun emotionele en lichamelijke welzijn. Het ontwikkelen en testen van interventies die gericht zijn op het emotionele en lichamelijke risicoprofiel van sociale remming is daarom essentieel

Diabetes mellitus type 2; The incretin effect and interaction with the autonomic nervous system

Bakgrunn: Inkretineffekten er kroppens evne til økt insulinsekresjon når glukose inntas peroralt sammenliknet med administrert intravenøst, utløst av spesifikke hormoner fra tarmen. En redusert inkretineffekt leder til forhøyet blodsukker etter måltid, og er et tidlig fenomen ved diabetes type 2, også påvist i forstadier til diabetes, såkalt prediabetes, og ved fedme. En bevart inkretineffekt ser delvis ut til å være avhengig av et intakt autonomt nervesystem. Autonom nevropati har vært betraktet som en sen komplikasjon til diabetes mellitus, men det er økende evidens for at nevropati også kan oppstå tidlig i forløpet. Kjennskap til disse faktorene ledet oss til en hypotese om at tidlig autonom nevropati kan bidra til den reduserte inkretineffekten ved diabetes type 2. Mål: Vårt primære mål var å undersøke om det var assosiasjon mellom inkretineffekt og grad av autonom nevropati. Sekundære mål var å se på inkretineffekten relatert til grad av hyperglykemi og varighet av diabetes, og sammenlikne en ny test som innebærer ballongdilatasjon i rektum, som mål for tarmens sensitivitet og videre signaloverføring, med mer etablerte tester for nevropati. Et siste sekundærmål var å undersøke gjennomførbarheten av en norsk versjon av spørreskjemaet, «Composite Autonomic Symptom Score» (COMPASS) 31, som kan påvise mulige symptomer fra autonom dysfunksjon, og vi testet om dette var assosiert med øvrige nerveundersøkelser. Metode: Tre grupper ble inkludert; en gruppe med diabetes type 2 varighet >10 år, en gruppe med nyoppdaget type 2 diabetes siste året, uten behov for medikamentell behandling, og en kontrollgruppe matchet for alder, kjønn og kroppsmasseindeks. Inkretineffekten ble kalkulert fra c-peptid (areal under kurven) ved oral glukosebelastning sammenliknet med intravenøs isoglykemisk glukose infusjon. Gastrointestinal glukose-håndtering (GIGD) ble kalkulert fra glukose gitt oralt sammenliknet med glukose tilført intravenøst. Tester for nevropati inkluderte kardiovaskulære reflekstester, hjertefrekvensvariabilitet, svettefunksjon, nerveledningshastighet i nervus suralis og monofilament test. Som mål på gastrointestinal visceral nervefunksjon utførte vi rektal ballongdilatasjon med registrering av trykk for første følelse av dilatasjon og ubehagelig følelse av dilatasjon. Evokerte hjernepotensial ble målt som respons på ballongdilatasjon ved gjentatte stimuli av nevnte trykk. Spørreskjemaet COMPASS 31 ble besvart digitalt. Resultat: Deltakerne med diabetes trengte høyere trykk for å oppnå første følelse av ballongdilatasjon i rektum, uavhengig av diabetesvarighet. Økt behov for trykk korrelerte med nedsatt GIGD, men ikke med inkretineffekt. Økt behov for trykk korrelerte også med nedsatt følelse på monofilament test. GIGD og inkretineffekt korrelerte signifikant med både grad av hyperglykemi og diabetesvarighet. Det ble funnet få tilfeller av nevropati totalt sett, og få forskjeller mellom gruppene. Det var en tendens til at lenger latenstid og mindre amplituder på evokerte hjernepotensial var assosiert med lavere hjertefrekvensvariabilitet og kardiovaskulære reflekstester, sural nerveledning og monofilament test, men ikke statistisk signifikant etter korreksjon for multippel testing. Høyere score på COMPASS 31 ble funnet hos dem med langvarig diabetes og hos kvinner, med best sensitivitet og negativ prediktiv verdi for score <10. Konklusjon: Vi fant rektal hyposensitivitet både ved langvarig og tidlig type 2 diabetes og dette var assosiert med redusert GIGD, men ikke med redusert inkretineffekt. Dette kan tyde på at adekvat nervefunksjon i tarmen er viktig for andre faktorer enn inkretineffekten i håndteringen av glukose. Redusert GIGD og inkretineffekt er assosiert med økende hyperglykemi og varighet av diabetes, som viser et kontinuum i tarmens glukosehåndtering fra normo- til hyperglykemi. Vi fant klinisk plausible tegn på at sentral nerveledning er assosiert med perifer nervefunksjon, men resultatene må tolkes med forsiktighet, gitt multippel testing. Rektal ballongdilatasjon med måling av sensitivitet og evokerte hjernepotensial synes å være en lovende metode for undersøkelse av nervefunksjon i tarmen, også når øvrige autonome tester er normale. Til sist finner vi spørreskjemaet COMPASS 31 lovende til bruk både i forskning, men også i den kliniske hverdag, hvor autonome symptomer ofte er neglisjert. I en liknende populasjon som vår vil en score på 10 poeng eller mindre nærmest utelukke kardiovaskulær autonom nevropati.Background: The incretin effect refers to the amplified insulin response when glucose is administered orally compared to intravenously. A reduced incretin effect is found at early stages of type 2 diabetes, even in prediabetes and obesity, but the mechanisms behind are unknown. Evidence suggests that part of the effect of incretin hormones are mediated through vagal nerve transmission. Diabetic autonomic neuropathy is considered a late complication of diabetes mellitus, but there is an increasing awareness that neuropathy can exist in both prediabetes and early stages of diabetes. This led us to the hypothesis that the incretin effect could be affected by early autonomic neuropathy because of a reduced transmission of signals. Aims: Our main objective was to explore whether a reduced incretin effect could be associated with autonomic neuropathy. Secondarily, we aimed to explore the incretin effect in relation to degree of dysglycemia and the duration of diabetes. Other secondary objectives were to explore a novel test of gut visceral sensitivity and central transmission of peripheral signals, and to compare it with established tests for diabetic neuropathy, including assessment of symptoms using the Composite Autonomic Symptom Score (COMPASS) 31. Methods: This was case-control study including three groups of participants: People with type 2 diabetes for >10 years (longstanding), people with newly discovered type 2 diabetes within the last year, without the need for antidiabetic medication (early), and a group of matched controls in age, sex, and body mass index. An oral glucose tolerance test followed by an intravenous isoglycemic glucose infusion were performed to calculate the incretin effect (from c-peptide area under the curve). Gastrointestinal-mediated glucose disposal (GIGD) was calculated as an estimate of the body’s ability to cope with the challenge of a carbohydrate ingestion. Neuropathy tests included cardiovascular reflex tests, heart rate variability, sudomotor function, sural nerve, and the monofilament test. Rapid rectal balloon distention measuring visceral sensitivity and evoked potentials was performed as a proxy for gut autonomic nerve function. The COMPASS 31 questionnaire was distributed and answered online. Results: Both groups of diabetes were hyposensitive to first sensation performing rapid rectal balloon distention. Also, those with reduced sensation performing the monofilament test showed hyposensitivity. A correlation was found between rectal hyposensitivity at the first sensation and reduced GIGD, but not with the incretin effect. Both GIGD and the incretin effect were found to correlate with degree of dysglycaemia and duration of diabetes, and were comparable to previous studies. Overall, few cases of confirmed neuropathy were detected, and there were few differences between groups regarding established neuropathy tests. Longer evoked potential latencies and smaller amplitudes plausibly correlated with lower heart rate variability and cardiovascular reflex test score, reduced parameters in the sural nerve test and monofilament sensation, but not statistically significant considering multiple testing. Higher scores in COMPASS 31 were correlated with longstanding diabetes and female sex. We found an acceptable negative predictive value for cardiovascular autonomic neuropathy at a 10-point cut-off . Conclusions: Rectal hyposensitivity may be an early manifestation of type 2 diabetes, and associated with GIGD, but not with the incretin effect. GIGD and the incretin effect are associated with degree of dysglycemia and duration of diabetes, indicating a continuum in the diminished effect. Central neuronal signal processing appears to be affected in parallel with peripheral neuronal function, but the results must be interpreted with caution. In general, we found that investigating evoked potentials following rapid rectal balloon distention may be a useful research tool for evaluating gut autonomic neuropathy, also when other autonomic neuropathy tests are normal. The Norwegian version of COMPASS 31 was easy to use and for assessing autonomic neuropathy in diabetes, and we suggest a cut off at ten points for screening purposes. Symptoms of autonomic neuropathy seems to be more frequent in people with longstanding diabetes and in women.Doktorgradsavhandlin

Biological Correlates of Conduct Disorder and Callous-Unemotional Traits

Callous-unemotional (CU) traits have been proposed to identify a unique subgroup of children with conduct disorder (CD). Little is known, however, about the biological correlates of these traits. In addition, research into the biological correlates of CD has been mixed. This dissertation tested the hypothesis that CU traits moderate the relationship between CD and biological indicators of activity in the central nervous system, the autonomic nervous system, and the hypothalamic-pituitary-adrenal (HPA) axis. Specifically, CU traits were expected to be associated with decreased arousal at rest and in response to stress, whereas it was predicted that symptoms of CD would be associated with decreased arousal at rest and increased arousal in response to stress. These hypotheses were tested in a community sample of 11-12 year old children (N = 446). Symptoms of CD were assessed using child- and caregiver-report, and both the child and the caregiver reported on levels of CU traits using the Antisocial Process Screening Device (APSD). Section 1 focused on electroencephalography (EEG) recorded during an eyes-open rest period. CU traits were associated with a marginally significant increase in theta power in African American participants. In participants of other races, CU traits predicted significantly decreased theta, alpha, and beta power. CD was not significantly associated with EEG in any frequency band. Section 2 examined heart rate (HR) and skin conductance level (SCL) at rest and in response to a modified version of the Trier Social Stress Test (TSST). Heart rate was negatively associated with CU traits, but it was not significantly associated with symptoms of CD. CD symptoms and CU traits interacted to predict SCL such that CD was negatively associated with SCL, but only in the context of low levels of CU traits. Section 3 investigated cortisol response to the TSST. Results indicated that CD was positively associated with total cortisol production (as measured by area under the curve with respect to ground [AUCG]), whereas CU traits were negatively associated with AUCG at a trend level. Overall, these results suggest that the biological correlates of CU traits differ from those of CD as a whole, with CU traits being associated with hypoarousal and CD symptoms being associated with a pattern indicating impulsivity. These divergent results for CD and CU may imply that children with CD who are high in CU traits have different treatment needs compared to children with CD who are low in CU traits

Central and Peripheral Chemoreflex Function in the Supine and Upright Postures in Women throughout the Menstrual Cycle with a Comparison to Men

The primary purpose of the study was to examine sex differences and menstrual cycle time-points on chemoreflex function during supine and 70o upright (HUT) positions during: 1) normoxia, 2) hypercapnia (5% CO2), or 3) hyperoxia (100% O2). Women were tested during the early-follicular phase (EF; days 2-5) and the mid-luteal phase (ML; days 18-24). Compared to baseline, men and women had lower cardiac output index (Qi), mean arterial pressure (MAP), cerebrovascular resistance index, and respiratory rate during HUT. In response to hypercapnia during HUT (compared to supine), men had an augmented increase in MAP, while all groups had an augmented increase in ventilation suggesting sexually dimorphic interactions between the baroreflex and central chemoreflex. In response to hyperoxia during HUT, men and women displayed an attenuated increase of total peripheral resistance index and an attenuated decrease of Qi suggesting upright posture activated peripheral chemoreceptors