Jyrki Liesivuori

Serotonergic modulation of mismatch negativity

Neurochemical mechanisms mediating the interaction between emotional and cognitive processing are not yet fully understood. Here, we utilized acute tryptophan depletion (ATD) to reduce the brain synthesis of serotonin (5-HT), which is thought to have a central role in regulation of emotions and mood in humans. ATD effects on event-related potentials and magnetic fields were studied using a passive odd-ball paradigm in a randomized, double-blinded, controlled, cross-over design. Auditory responses were recorded simultaneously with high-resolution magnetoencephalography (MEG) and electroencephalography (EEG) in 14 healthy subjects, 5 h after ATD or a control condition. ATD significantly increased depressed mood and lowered plasma tryptophan concentration (total tryptophan decreased by 75%, free tryptophan decreased by 39%). As compared with the control condition, ATD increased the amplitudes of mismatch negativity (MMN) to duration and frequency changes and decreased the latencies of magnetic MMN to frequency changes in the hemisphere ipsilateral to the ear stimulated. Further, ATD modulated N1m latencies and decreased P2m source activity. ATD increased the interhemispheric latency difference of MMNm to frequency changes. No effects on P50 were observed. The present results suggest serotonergic modulation of preattentive auditory change detection, suggested to initiate involuntary attention shifting in the human brain.

Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans.

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21-30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.

Auditory selective attention modulated by tryptophan depletion in humans

To elucidate serotonin modulation of selective attention, 13 volunteers (21-30 years) were studied in two sessions, 5 h after either acute tryptophan depletion (ATD) that decreases brain serotonin synthesis, or control-mixture ingestion (randomized, double-blind, cross-over design). Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of standard and deviant tones. Subjects counted the deviants presented to one ear and ignored those presented to the other ear. ATD lowered plasma total tryptophan by 75% and free tryptophan by 39%. ATD suppressed the amplitude enhancement of P50 and N1 to selectively attended tones, but did not affect the later aspects of processing negativity. The P50 latencies were increased after ATD, irrespective of attention. In conclusion, serotonin may regulate attentional modulation of early cortical stimulus processing.

Serotonin modulates early cortical auditory processing in healthy subjects: evidence from MEG with acute tryptophan depletion.

We studied the effects of acute tryptophan depletion (ATD) on early cortical auditory processing. Middle-latency auditory evoked fields (MAEF) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a randomized, double-blinded, controlled cross-over design study. MAEFs to monaural click stimuli (0.1-ms duration) were recorded with a 122-channel neuromagnetometer. Total plasma tryptophan (Trp), free Trp, and large neutral amino acid (LNAA) concentrations were determined by using high-performance liquid chromatography. ATD lowered the total plasma Trp levels by 75%, free Trp level by 47%, and the ratio Trp/ΣLNAA by 92%. The control mixture increased total Trp level by 45% and free Trp by 32%, and decreased the ratio Trp/ΣLNAA by 35%. The ratio tyrosine/ΣLNAA did not differ between ATD and control experiment. ATD resulted in a significant main effect on Pam latencies and a near-significant main effect on Pam amplitudes. A significant Mixture ingestion X Sex interaction on Nbm amplitude and a significant Mixture ingestion X Sex X Hemisphere interaction on Pam latency were observed. ATD did not affect the MAEF source dipoles. The Pam latencies in both hemispheres had a significant negative relationship with the extent of ATD. The results suggest that the neurotransmitter serotonin is involved in early auditory cortical processing. Further, the serotonin modulation may be different in males and females.

A controlled study of tryptophan and cortisol in violent offenders

Summary.Changes in the metabolism of tryptophan, other amino acids, and steroid hormones have been implicated in aggression. We compared tryptophan, competing long amino acids (CAAs), and cortisol in serum (S) and CSF in 22 violent offenders and 15 healthy controls. Offenders had significantly increased S-L-tryptophan, S-free tryptophan, S-CAAs, S-cortisol and CSF-cortisol, indicating abnormal neurophysiological processes. Larger studies on the interplay between violence, serotonin precursors, and stress hormones need to integrate personality traits, life situations, and physiological adaptation.

Gas chromatographic determination of some alkoxysilanes for use in occupational exposure assessment

The manufacture and application of organosilicon compounds, especially silanes, have increased dramatically during recent decades. This has led to an increase in the number of exposed workers in different areas of industry. Therefore, there is an urgent need for an analytical method which can assess exposure to these compounds. A capillary column gas chromatographic (GC) method was developed for detecting 3-methacryloxypropyltrimethoxysilane, 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane. The silanes diluted in heptane were analysed by GC using flame ionisation detection. Gas chromatography-mass spectrometry was used to confirm the identity of the GC peaks. The analytical range of the method varied from 1 or 5 micrograms ml-1 to 500 micrograms ml-1 depending on the silane being studied. The detection limits were 1 microgram ml-1 for 3-methacryloxypropyltrimethoxysilane and 3-glycidoxypropyltrimethoxysilane and 5 micrograms ml-1 for 3-aminopropyltriethoxysilane. The mean recovery of silanes tested with patch samples was > 95% for all of the silanes. The repeatability of the patch sample method for silanes varied from 6.5 to 10.1%. This new GC method allows the simultaneous determination of three organosilicon compounds for occupational exposure assessment.

Occupational Exposure to Indoor Allergens in Finnish Trained Home-Helpers:

Occupational Exposure to Indoor Allergens in Finnish Trained Home‐Helpers: a Pilot Study: Sirpa Pennanen, et al. Kuopio Regional Institute of Occupational Health—The presence of allergies, respiratory symptoms and skin‐prick reactions was evaluated in trained home‐helpers (THH), and indoor allergen levels were measured at their work sites. A questionnaire was answered by 118 THHs and forty THHs consented to skin‐prick tests. The indoor allergen levels in the settled house dust from the clients’ homes of 17 prick tested THHs were determined by two‐site monoclonal antibody ELISA methods. Forty‐ eight percent of the THHs had one or more symptoms at least weekly. The presence of respiratory symptoms and atopy was not particularly high in THHs. Prick tests revealed that 11 THHs (28%) had positive reactions to one or more of the allergens tested. A significant correlation was observed between the frequency of reported symptoms and positive prick reactions. Fel d 1 was found in 98% and Can f 1 in 96% of the dust samples, but Der p 1 in only 21% of the samples, though the levels remained rather low. The sensitization threshold suggested for cat allergen (1 μ g/g) was exceeded in 26%, and that for dog allergen (2 μg/g) in 32% of the sites studied. These results showed that THHs are occupationally exposed to allergen levels sufficient to result in sensitization.

Serotonin modulates human involuntary attention

INTRODUCTION Unexpected, novel changes in the environment trigger involuntary attention shifting and orienting to the novel stimuli. Impaired control of involuntary attention, and subsequent distractibility and impulsiveness, may be associated with a variety of psychopathologic conditions. Psychopharmacological studies have associated such disorders with low brain serotonin (5-HT) levels and function (Higley & Linnoila 1997). In healthy human brain, the serotonin function can be studied with a dietary challenge termed acute tryptophan depletion (ADT), which decreases brain serotonin synthesis (Reilly et al. 1997). We investigated the role of the serotonin system in involuntary attention using ADT, and event-related potential (ERP) components reflecting different phases of detection and orienting to stimulus changes.