Jurriaan Witteman

Postprandial triglyceride response in young adult men and familial risk for coronary atherosclerosis.

Atherosclerosis starts early in life [1, 2]. Postprandial lipoprotein metabolism is proposed to be involved in this process [3]. Cholesteryl ester-rich remnants of triglyceride-rich lipoproteins may directly promote accumulation of cholesteryl esters in the arterial wall [4-6]. Further, it has been reported [7, 8] that the protective effect of increased levels of high-density lipoprotein (HDL) cholesterol on the risk for coronary artery disease may not only be explained by their role in reverse cholesterol transport but also by the relation between HDL and triglyceride metabolism [9]. Plasma triglycerides have an effect on HDL composition and HDL cholesterol levels [10]; an inverse relation between HDL2 levels and postprandial triglyceride levels has been shown [11]. Levels and composition of HDL could thus be a reflection of the effectiveness of triglyceride-rich lipoprotein catabolism. A deranged metabolism of triglyceride-rich lipoproteins in plasma has been reported in familial dysbetalipoproteinemia [12, 13], a disease associated with premature coronary atherosclerosis. Studies comparing patients with coronary artery disease and persons without the disease have shown that differences with respect to postprandial hypertriglyceridemia [14-16] and postprandial retinyl palmitate concentrations (a marker of chylomicrons and their remnants) are detectable after an oral lipid load [14, 15]. These results suggest a delayed clearance of these lipoproteins in patients with coronary artery disease. Thus, accumulating evidence indicates that postprandial lipemia plays an important role in causing coronary artery disease, and the implications with respect to treatment and primary prevention are increasingly being recognized [17]. Postprandial lipoprotein metabolism has not yet been studied in children and young adults with an increased risk for coronary atherosclerosis. In our study, male offspring of men with clinical manifestations of and angiographically proven coronary atherosclerosis were compared with male offspring of men who did not have coronary atherosclerosis (negative result after angiography). This approach enabled us to study a group of healthy young adults at high familial risk for developing clinical manifestations of coronary artery disease later in life. We assessed whether changes in the triglyceride response to a standardized oral lipid load, as reported in patients with coronary artery disease, can also be measured in healthy young male offspring of such patients. Methods Participants Men with very severe coronary artery disease (patients), defined as more than 70% occlusion in at least three major coronary vessels, were selected from coronary angiography databases of cardiology departments of the Zuiderziekenhuis Rotterdam (1988 to 1991), the University Hospital Rotterdam (1988 to 1989), the Refaja Ziekenhuis in Dordrecht (1990 to 1991), and the Antonius Ziekenhuis in Nieuwegein (1992), all hospitals situated in the Netherlands. Simultaneously, a reference group of men [controls] was selected who at coronary angiography had no or, at most, only minor lesions, defined as 20% stenosis or less in all coronary vessels. Further, participants were selected according to the following additional criteria: 1) age between 45 and 65 years; 2) blood pressure not exceeding 160/100 mm Hg; 3) absence of liver disease, diabetes mellitus, thyroid disease, and renal disease; 4) first coronary angiography within 2 years before examination for our study; and 5) first consultation of a physician for cardiac symptoms within 5 years before the examination for our study. Eligible participants were sent a letter asking whether they had a son 15 to 30 years of age and, if so, whether the son was willing to participate in the study. These sons (identified by their fathers) received a separate letter inviting them to have an oral lipid loading test. Participants also received a short questionnaire about smoking habits, alcohol intake, physical activity, and fat intake. We screened medical files of 629 patients whose coronary angiographic data met the criteria. Of these patients, 19 had died, 46 had diabetes mellitus, 6 had renal disease, 2 had thyroid disease, 183 had either no son or sons outside the required age range, 58 could not be contacted, 17 had no contact with their children, 78 had a cardiac history exceeding 5 years, and 63 could not be invited for other reasons (hospitalization, other serious diseases). Of 157 families (fathers and sons) who met all the criteria, 55 (either father or son) refused to participate in the study (response, 65%), leaving 102 fathers and 139 sons. The latter had oral lipid loading tests. The study protocol was approved by the medical ethics committees of the Zuiderziekenhuis Rotterdam and the University Hospital Rotterdam. Informed consent forms were obtained from all participants in the study. Baseline Measurements Fathers were asked to visit the hospital at 9:00 a.m. after fasting for at least 12 hours. Fathers responded to a questionnaire about the number of first-degree relatives who had had myocardial infarctions and about medication use at the time of the examination (medication was taken to the hospital where the examination took place). Systolic blood pressure and diastolic blood pressure were measured using a random zero sphygmomanometer (Hawksley, Lancing, United Kingdom). Fasting serum blood samples were drawn by antecubital venipuncture for measurement of levels of triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, and HDL cholesterol (and its subfractions HDL2 and HDL3). Height and weight were measured without shoes and without heavy clothing. The sons were invited to come to the hospital, after the same period of fasting, on a separate day to have an oral lipid loading test. For sons, questionnaires were used to obtain data about use of medication, fat intake, alcohol intake, and smoking habits, referring to a 1-month period before the examination for this study. Daily total fat intake was calculated from an 81-item semiquantitative food frequency questionnaire by using a computerized food-composition table [18]. In the sons, blood samples were taken by antecubital venipuncture for measurement of baseline levels of serum triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol (and its subfractions HDL2 and HDL3), apoprotein A-1, apoprotein A-2, apoprotein B, and retinyl palmitate concentrations. This baseline measurement of lipid levels was taken as the starting point (t0) for the oral lipid loading test. In all of the sons, apolipoprotein E was phenotyped. Oral Lipid Loading Test Sons of patients and sons of controls came to the hospital at 7:45 a.m. after an overnight fasting of 12 hours. Height and weight were measured first to calculate body surface area. Five minutes after the venipuncture for obtaining baseline lipid levels (at t0), all participants received a liquid lipid load, which consisted of a mixture of dairy cream (40% fat), egg yolk, milk powder, and retinyl palmitate (in aqueous solution) [15]. Participants received the lipid load in a dose based on their individual body surface area (77.5 g fat, 0.5 g cholesterol, and 27 000 IU of retinyl palmitate per square meter of body surface area). The mixture was consumed within 15 minutes. The participants received an antecubital venous catheter (Venflon Viggo AB, Helsingborg, Sweden), which was kept open during the test period by means of disposable obturators (Venflon). Through this catheter, blood samples were drawn at 2 (t2), 4 (t4), 5 (t5), 6 (t6), 7 (t7), 8 (t8), 10 (t10), and 12 (t12) hours after starting consumption of the oral lipid load. Total cholesterol, triglyceride, and retinyl palmitate concentrations were determined in serum isolated from these samples. During the 12-hour period, other sources of calories were withheld from participants. Because postprandial exercise has been reported to decrease postprandial lipemia [19], participants stayed in the hospital and were asked to refrain from heavy physical activity during the test period. Laboratory Analyses Serum total cholesterol levels were measured using an automated enzymatic method (Boehringer Mannheim, Mannheim, Germany) CHOD-PAP reagent kit [20]. Levels of HDL cholesterol and LDL cholesterol were measured by the same method after precipitation. For HDL cholesterol, the phosphotungstate method according to Burstein [21], with a minor modification as described by Grove [22], was used. For LDL cholesterol, precipitation was carried out with polyvinylsulfate (Boehringer Mannheim). Throughout the entire study period, results of total cholesterol and HDL cholesterol determinations were within limits of the quality control program of the World Health Organization Regional Lipid Reference Centre (Prague, Czechoslovakia). Levels of apoprotein A-1 and B were assayed using an automated immunoturbidimetric method (Kone Diagnostics, Espoo, Finland). Levels of apoprotein A-2 were determined by radial immunodiffusion against specific antiserum (Boehringer Mannheim, Germany) according to Cheung and Albers [23], with slight modifications. All automated analyses were carried out on the Kone Specific Analyzer (Kone Instruments) using frozen ( 20C) serum samples. High-density lipoprotein2 and HDL3 in serum were assayed as described by Gidez and colleagues [24] with slight modifications. High-density lipoprotein2 and HDL3 were separated using stepwise precipitation of apoprotein B containing lipoproteins with heparin/Mn2+ and HDL2 with dextran sulfate. Apolipoprotein E phenotyping was done by isoelectric focusing of delipidated serum followed by immunoblotting, using apolipoprotein E antiserum as first antibodies [25]. Retinyl palmitate analyses were done as described previously by Groot and colleagues [15]. Statistical Analysis Means SDs were calculated for baseline characteristics of all family members. The total cholestero

The nature of hemispheric specialization for linguistic and emotional prosodic perception: A meta-analysis of the lesion literature

It is unclear whether there is hemispheric specialization for prosodic perception and, if so, what the nature of this hemispheric asymmetry is. Using the lesion-approach, many studies have attempted to test whether there is hemispheric specialization for emotional and linguistic prosodic perception by examining the impact of left vs. right hemispheric damage on prosodic perception task performance. However, so far no consensus has been reached. In an attempt to find a consistent pattern of lateralization for prosodic perception, a meta-analysis was performed on 38 lesion studies (including 450 left hemisphere damaged patients, 534 right hemisphere damaged patients and 491 controls) of prosodic perception. It was found that both left and right hemispheric damage compromise emotional and linguistic prosodic perception task performance. Furthermore, right hemispheric damage degraded emotional prosodic perception more than left hemispheric damage (trimmed g=-0.37, 95% CI [-0.66; -0.09], N=620 patients). It is concluded that prosodic perception is under bihemispheric control with relative specialization of the right hemisphere for emotional prosodic perception.

Hearing feelings: A quantitative meta-analysis on the neuroimaging literature of emotional prosody perception

With the advent of neuroimaging considerable progress has been made in uncovering the neural network involved in the perception of emotional prosody. However, the exact neuroanatomical underpinnings of the emotional prosody perception process remain unclear. Furthermore, it is unclear what the intrahemispheric basis might be of the relative right-hemispheric specialization for emotional prosody perception that has been found previously in the lesion literature. In an attempt to shed light on these issues, quantitative meta-analyses of the neuroimaging literature were performed to investigate which brain areas are robustly associated with stimulus-driven and task-dependent perception of emotional prosody. Also, lateralization analyses were performed to investigate whether statistically reliable hemispheric specialization across studies can be found in these networks. A bilateral temporofrontal network was found to be implicated in emotional prosody perception, generally supporting previously proposed models of emotional prosody perception. Right-lateralized convergence across studies was found in (early) auditory processing areas, suggesting that the right hemispheric specialization for emotional prosody perception reported previously in the lesion literature might be driven by hemispheric specialization for non-prosody-specific fundamental acoustic dimensions of the speech signal.

Hearing Feelings: Affective Categorization of Music and Speech in Alexithymia, an ERP Study

Background Alexithymia, a condition characterized by deficits in interpreting and regulating feelings, is a risk factor for a variety of psychiatric conditions. Little is known about how alexithymia influences the processing of emotions in music and speech. Appreciation of such emotional qualities in auditory material is fundamental to human experience and has profound consequences for functioning in daily life. We investigated the neural signature of such emotional processing in alexithymia by means of event-related potentials. Methodology Affective music and speech prosody were presented as targets following affectively congruent or incongruent visual word primes in two conditions. In two further conditions, affective music and speech prosody served as primes and visually presented words with affective connotations were presented as targets. Thirty-two participants (16 male) judged the affective valence of the targets. We tested the influence of alexithymia on cross-modal affective priming and on N400 amplitudes, indicative of individual sensitivity to an affective mismatch between words, prosody, and music. Our results indicate that the affective priming effect for prosody targets tended to be reduced with increasing scores on alexithymia, while no behavioral differences were observed for music and word targets. At the electrophysiological level, alexithymia was associated with significantly smaller N400 amplitudes in response to affectively incongruent music and speech targets, but not to incongruent word targets. Conclusions Our results suggest a reduced sensitivity for the emotional qualities of speech and music in alexithymia during affective categorization. This deficit becomes evident primarily in situations in which a verbalization of emotional information is required.

The nature of affective priming in music and speech

The phenomenon of affective priming has caught scientific interest for over 30 years, yet the nature of the affective priming effect remains elusive. This study investigated the underlying mechanism of cross-modal affective priming and the influence of affective incongruence in music and speech on negativities in the N400 time-window. In Experiment 1, participants judged the valence of affective targets (affective categorization). We found that music and speech targets were evaluated faster when preceded by affectively congruent visual word primes, and vice versa. This affective priming effect was accompanied by a significantly larger N400-like effect following incongruent targets. In this experiment, both spreading of activation and response competition could underlie the affective priming effect. In Experiment 2, participants categorized the same affective targets based on nonaffective characteristics. However, as prime valence was irrelevant to the response dimension, affective priming effects could no longer be attributable to response competition. In Experiment 2, affective priming effects were observed neither at the behavioral nor electrophysiological level. The results of this study indicate that both affective music and speech prosody can prime the processing of visual words with emotional connotations, and vice versa. Affective incongruence seems to be associated with N400-like effects during evaluative categorization. The present data further suggest a role of response competition during the affective categorization of music, prosody, and words with emotional connotations.

Blunted feelings: Alexithymia is associated with a diminished neural response to speech prosody

How we perceive emotional signals from our environment depends on our personality. Alexithymia, a personality trait characterized by difficulties in emotion regulation has been linked to aberrant brain activity for visual emotional processing. Whether alexithymia also affects the brains perception of emotional speech prosody is currently unknown. We used functional magnetic resonance imaging to investigate the impact of alexithymia on hemodynamic activity of three a priori regions of the prosody network: the superior temporal gyrus (STG), the inferior frontal gyrus and the amygdala. Twenty-two subjects performed an explicit task (emotional prosody categorization) and an implicit task (metrical stress evaluation) on the same prosodic stimuli. Irrespective of task, alexithymia was associated with a blunted response of the right STG and the bilateral amygdalae to angry, surprised and neutral prosody. Individuals with difficulty describing feelings deactivated the left STG and the bilateral amygdalae to a lesser extent in response to angry compared with neutral prosody, suggesting that they perceived angry prosody as relatively more salient than neutral prosody. In conclusion, alexithymia may be associated with a generally blunted neural response to speech prosody. Such restricted prosodic processing may contribute to problems in social communication associated with this personality trait.

The nature of hemispheric specialization for prosody perception

Recent evidence suggests a relative right-hemispheric specialization for emotional prosody perception, whereas linguistic prosody perception is under bilateral control. It is still unknown, however, how the hemispheric specialization for prosody perception might arise. Two main hypotheses have been put forward. Cue-dependent hypotheses, on the one hand, propose that hemispheric specialization is driven by specialization for the non-prosody-specific processing of acoustic cues. The functional lateralization hypothesis, on the other hand, proposes that hemispheric specialization is dependent on the communicative function of prosody, with emotional and linguistic prosody processing being lateralized to the right and left hemispheres, respectively. In the present study, the functional lateralization hypothesis of prosody perception was systematically tested by instructing one group of participants to evaluate the emotional prosody, and another group the linguistic prosody dimension of bidimensional prosodic stimuli in a dichotic-listening paradigm, while event-related potentials were recorded. The results showed that the right-ear advantage was associated with decreased latencies for an early negativity in the contralateral hemisphere. No evidence was found for functional lateralization. These findings suggest that functional lateralization effects for prosody perception are small and support the structural model of dichotic listening.

Solving the problem of double negation is not impossible : electrophysiological evidence for the cohesive function of sentential negation

ABSTRACT In natural languages, two negating elements that cancel each other out (as in not impossible) are logically equivalent to the non-negated word form (in this case, possible). It has been proposed that the function of sentential double negation is to create coherence between sentences containing opposing information. Thus, not impossible is functionally different from possible. The present ERP study tested this hypothesis in Dutch. Native speakers read sentences in which evoked negative expectations are cancelled by a second sentence including either a double negation or the corresponding non-negated word form. Results showed that non-negated word forms, such as possible, elicited a larger N400 effect than double negations, such as not impossible. We suggest that canceling out a negative expectation by a double negation compared to the non-negated word form, makes it easier for the reader to integrate the two sentences semantically and connect them to the present discourse.

Brain reactivity to alcohol and cannabis marketing during sobriety and intoxication

Drugs of abuse stimulate striatal dopamine release and activate reward pathways. This study examined the impact of alcohol and cannabis marketing on the reward circuit in alcohol and cannabis users while sober and intoxicated. It was predicted that alcohol and cannabis marketing would increase striatal activation when sober and that reward sensitivity would be less during alcohol and cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21) participated in a mixed factorial study involving administration of alcohol and placebo in the alcohol group and cannabis and placebo in the cannabis group. Non‐drug users (n = 20) served as between group reference. Brain activation after exposure to alcohol and cannabis marketing movies was measured using functional magnetic resonance imaging and compared between groups while sober and compared with placebo while intoxicated. Implicit alcohol and cannabis cognitions were assessed by means of a single‐category implicit association test. Alcohol and cannabis marketing significantly increased striatal BOLD activation across all groups while sober. Striatal activation however decreased during intoxication with alcohol and cannabis. Implicit associations with cannabis marketing cues were significantly more positive in alcohol and cannabis users as compared with non‐drug using controls. Public advertising of alcohol or cannabis use elicits striatal activation in the brains reward circuit. Reduction of marketing would reduce brain exposure to reward cues that motivate substance use. Conversely, elevated dopamine levels protect against the reinforcing potential of marketing.

Effects of vasopressin on neural processing of infant crying in expectant fathers

ABSTRACT In a randomized, double blind, placebo‐controlled, within‐subject magnetic resonance imaging study, we examined the effect of 20IU intranasal vasopressin on the neural processing of infant crying in 25 fathers‐to‐be. We explored whether familial background modulates vasopressin effects, and whether vasopressin differentially affects cry processing coupled with neutral or emotional contextual information. Participants listened to cries accompanied by neutral (‘this is an infant’) or emotional (‘this infant is sick/bored’) contextual information, and neutral control sounds (‘this is a saw’). Additionally, participants reported on their childhood experiences of parental love‐withdrawal and abuse. Infant crying (vs control sounds) was associated with increased activation in the bilateral auditory cortex and posterior medial cortex. No effects of vasopressin were found in this ‘cry network’. Exploratory whole‐brain analyses suggested that effects of vasopressin in the anterior cingulate cortex, paracingulate gyrus and supplemental motor area were stronger in fathers who experienced lower (vs higher) levels of love‐withdrawal. No interaction was observed for abuse. Vasopressin increased activation in response to cries accompanied by emotional vs neutral contextual information in several brain regions, e.g. the cerebellum, brainstem (midbrain), posterior medial cortex, hippocampus, putamen, and insula. Our results suggest that the experience of love‐withdrawal may modulate the vasopressin system, influencing effects of vasopressin administration on cry processing. Results further suggest a role for vasopressin in the processing of cry sounds with emotional contextual information. HIGHLIGHTSIn expectant fathers, infant crying activates auditory and posterior medial cortex.Effects of vasopressin are stronger in fathers who experienced lower love‐withdrawal.Vasopressin increased activation to cries with emotional contextual information.