Exposure to Patterned Auditory Stimuli during Acute Stress Prevents Despair-Like Behavior in Adult Mice That Were Previously Housed in an Enriched Environment in Combination with Auditory Stimuli.

Several interventions have been shown to counteract the effects of stress that may be related to improved neuroplasticity and neuronal activation. In this sense, environmental enrichment (ENR) protects against acute stress and increases neuroplasticity. It has been suggested that the use of patterned auditory stimuli (PAS) may be beneficial in increasing the effectiveness of ENR on disorders related to stress, such as depression and anxiety. Examples of PAS are classical music compositions that have interesting effects at both clinical and preclinical levels. Thus, we analyzed the effects of the exposure to PAS, represented in this study by Mozart's compositions, during ENR housing for 35 days in adult male Balb/C mice to evaluate depression-associated behavior using the forced-swim test (FST) paradigm with an additional short exposure to PAS. We found that the ENR mice that were exposed to PAS during both housing and behavioral task (ENR + PAS/FST + PAS) show decreased immobility and the number of despair episodes within a higher latency to show the first bout of immobility. Additionally, we found increased neuronal activation evaluated by the identification of activity-regulated cytoskeleton-associated protein- (Arc-) labeled cells in the prefrontal cortex (PFC) in mice exposed to PAS during housing and in the absence or presence of PAS during FST. Moreover, we found increased neuronal activation in the auditory cortex (AuCx) of mice exposed to PAS during FST. Our study suggests that the exposure to PAS during an emotional challenge decreases despair-like behavior in rodents that were previously housed in an enriched environment in combination with auditory stimuli. Thus, our data indicate that the role of the exposure to PAS as an intervention or in combination with positive environment to aid in treating neuropsychiatric disorders is worth pursuing.

Differential alpha coherence hemispheric patterns in men and women during pleasant and unpleasant musical emotions.

Potential sex differences in EEG coherent activity during pleasant and unpleasant musical emotions were investigated. Musical excerpts by Mahler, Bach, and Prodromidès were played to seven men and seven women and their subjective emotions were evaluated in relation to alpha band intracortical coherence. Different brain links in specific frequencies were associated to pleasant and unpleasant emotions. Pleasant emotions (Mahler, Bach) increased upper alpha couplings linking left anterior and posterior regions. Unpleasant emotions (Prodromidès) were sustained by posterior midline coherence exclusively in the right hemisphere in men and bilateral in women. Combined music induced bilateral oscillations among posterior sensory and predominantly left association areas in women. Consistent with their greater positive attributions to music, the coherent network is larger in women, both for musical emotion and for unspecific musical effects. Musical emotion entails specific coupling among cortical regions and involves coherent upper alpha activity between posterior association areas and frontal regions probably mediating emotional and perceptual integration. Linked regions by combined music suggest more working memory contribution in women and attention in men.

Metabolic and electric brain patterns during pleasant and unpleasant emotions induced by music masterpieces.

Brain correlates comparing pleasant and unpleasant states induced by three dissimilar masterpiece excerpts were obtained. Related emotional reactions to the music were studied using Principal Component Analysis of validated reports, fMRI, and EEG coherent activity. A piano selection by Bach and a symphonic passage from Mahler widely differing in musical features were used as pleasing pieces. A segment by Prodromidès was used as an unpleasing stimulus. Ten consecutive 30 s segments of each piece alternating with random static noise were played to 19 non-musician volunteers for a total of 30 min of auditory stimulation. Both brain approaches identified a left cortical network involved with pleasant feelings (Bach and Mahler vs. Prodromidès) including the left primary auditory area, posterior temporal, inferior parietal and prefrontal regions. While the primary auditory zone may provide an early affective quality, left cognitive areas may contribute to pleasant feelings when melodic sequences follow expected rules. In contrast, unpleasant emotions (Prodromidès vs. Bach and Mahler) involved the activation of the right frontopolar and paralimbic areas. Left activation with pleasant and right with unpleasant musical feelings is consistent with right supremacy in novel situations and left in predictable processes. When all musical excerpts were jointly compared to noise, in addition to bilateral auditory activation, the left temporal pole, inferior frontal gyrus, and frontopolar area were activated suggesting that cognitive and language processes were recruited in general responses to music. Sensory and cognitive integration seems required for musical emotion.

Immunomodulatory Effects Mediated by Dopamine.

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

Immunomodulation and anti-inflammatory effects of garlic compounds.

The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.

Procesamiento de la música en el primer episodio de trastorno depresivo mayor sin tratamiento / Music processing in major depressive disorder first episode without treatment

El propósito de este estudio fue registrar diferencias durante la audición de dos tipos diferentes de música en pacientes con Trastorno Depresivo Mayor (TDM), comparados con sujetos sanos, mediante imagen por resonancia magnética funcional (IRMf). La actividad cerebral con estímulos musicales ha sido investigada ampliamente en sujetos sanos, pero son escasos los estudios del procesamiento de la música en estados de patología mental, particularmente en el TDM. Los estudios en esta área interdisciplinaria proveen una nueva perspectiva de investigación para explorar los sustratos neurobiológicos del TDM. Participaron 20 sujetos de sexo masculino: 10 pacientes con TDM (34 ± 7 años) y 10 sujetos control (33 ± 7 años). Los pacientes se seleccionaron en el servicio de pre-consulta del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz (INPRFM) de la Ciudad de México, y los sujetos control entre los trabajadores del propio Instituto que respondieron a la invitación. Todos los participantes contestaron, con fines de confirmar el diagnóstico, las escalas de ansiedad y depresión de Hamilton, los inventarios de Beck para ansiedad y depresión y el SCL-90-R. A los pacientes se les aplicó además el MINI-mental test. Para la IRMf se usó un equipo Philips Achieva de tres Teslas en el INPRFM, el análisis se hizo con el formato SPM2 usando el sistema MRIcro. Los estímulos experimentales fueron una obra musical de JS Bach validada como tranquila y otra de J Prodromidès validada como inquietante. Los resultados muestran diferencias tanto entre los grupos de sujetos como entre los tipos de música: en todos los casos se activó el área parahipocampal, la cola del núcleo caudado y la corteza temporal auditiva. Concluimos que el procesamiento neurobiológico de la música es afectado por el TDM. Se discuten las implicaciones clínicas y cognoscitivas de estos hallazgos.

The purpose of this study is the assessment of the differences in brain activity when patients with major depressive disorder (MDD) listen to two different types of music, with healthy subjects as control, by using functional magnetic resonance imaging (fMRI). Brain activity in musical stimuli with healthy subjects has been investigated extensively, but there are few neurobiologic music studies in mental illness, particularly in MDD. Studies in this area provide a new perspective on interdisciplinary research to explore the neurobiological substrates of MDD. This study involved 20 male subjects: 10 patients (34 ± 7 years), and 10 control subjects (33 ± 7 years). The MDD :atients were selected in the pre-consultation service of the National Institute of :sychiatry Ramón de la Fuente Muñiz (IN:RFM) of Mexico City, and control subjects were selected among workers of the Institute who responded to the invitation. All participants completed the Hamilton scales for anxiety and depression, Beck inventories for depression and anxiety and, the SCL-90-R. The Mini-Mental State Examination test was also administered to patients for diagnostic purposes. The fMRI was obtained by Philips Achieva 3-Tesla in the INPRF; the analysis was done using S:M2 format MRIcro system. The experimental stimuli were two pieces of music: one by JS Bach validated as quiet and another one by J Prodromidès validated as disturbing. Results show differences between both groups of subjects and between types of music. In all cases, the parahippocampal area, the tail of the caudate nucleus and the auditory temporal cortex were activated. The neurobiological processing of music is affected by MDD. We discuss the clinical and cognitive implications of these findings.

La respuesta emocional a la música: atribución de términos de la emoción a segmentos musicales / The emotional response to music: attribution of emotions words to musical segments

Even though music is usually considered a source of intense, diverse, and specific affective states, at the present time there is not a standardized scientific procedure that reveals with reliable confidence the emotional processes and events evoked by music. The progress in understanding musical emotion crucially depends in the development of reasonable secure methods to record and analyze such a peculiar and universally-sought affective process. In 1936 Kate Hevner published a pioneer study where she used a list of 66 adjectives commonly used to categorize musical compositions arranged in a circle of eight groups of similar emotions. The volunteers selected the terms that seemed appropriate to categorize their emotional experience while they listened to masterpieces by Debussy, Mendelssohn, Paganini, Tchaikovsky, and Wagner. The results were presented in histograms showing a different profile for each piece. Subsequent studies have advanced in the methods and techniques to assess the emotions produced by music but there are many still unresolved difficulties concerning the criteria to choose the musical pieces, the terms of emotion, the design of the experiment, the proper controls, and the relevant statistical tools to analyze the results. The present study was undertaken in order to test and advance an experimental technique designed to evaluate and study the human emotions evoked by music. Specifically, the study intends to prove if different musical excerpts evoke a significant agreement in the selection of previously organized emotion terms within a relatively homogeneous population of human subjects. Since music constitutes a form of acoustic language that has been selected and developed through millennia of human cultural evolution for the expression and communication of emotional states, it is supposed that there will be a significant agreement in the attribution of terms of emotion to musical segments among human evaluators belonging to a relatively homogeneous population. The attribution system allowed both to obtain objective responses derived from introspection and to analyze the data by means of an appropriate statistical processing of data obtained in groups of subjects submitted to carefully selected musical stimuli. Volunteer subjects were 108 college-level students of both sexes with a mean age of 22 years from schools and universities located in the central Mexico. The audition and attribution sessions lasted for 90 min and were conducted in a specially adapted classroom located in each institution. Four criteria were established for the selection of the musical excerpts: instrumental music, homogeneous melody and musical theme, clear and distinct affective tone, and samples of different cultures. The ten selected pieces were: 1. Mozart's piano concerto no. 1 7, K 453, third movement; 2. A sound of the magnetic spectra of an aurora borealis, a natural event; 3. Mussorgsky's Gnome, from Pictures at an Exhibition orchestrated by Ravel; 4. Andean folk music; 5. Tchaikovsky's Fifth Symphony, second movement; 6. << Through the Never>>, heavy metal music by Metallica; 7. Japanese Usagi folk music played with koto and shyakuhachi; 8. Mahler's Fifth Symphony, second movement; 9. Taqsim Sigah, Arab folk music played with kamandja, and 1 0. Bach's Inventions in three parts for piano, BMW 797. The selected fragments and their replicas were divided in two to five musically homogeneous segments (mean segment duration: 24 seconds) and were played in different order in each occasion. The segments were played twice during the test. During the first audition, the complete piece was played in order for the subjects to become familiar with the composition and freely express their reaction in writing. During the second hearing, the same piece was played in the separate selected segments and the volunteers were asked to choose those emotion-referring terms that more accurately identified their music-evoked feelings from an adjunct chart obtained and arranged from an original list of 328 Spanish words designing particular emotions. The terms had been previously arranged in 28 sets of semantically related terms located in 14 bipolar axes of opposing affective polarity in a circumflex model of the affective system. The recorded attributions from all the subjects were captured and transformed into ranks. The non-parametric Friedman test of rank bifactorial variance for k related samples was selected for the statistical analysis of agreement. All the data were gathered in the 28 categories or sets of emotion obtained in the previous taxonomy of emotion terms and the difference among the musical segments was tested. The difference was significant for 24 of the 28 emotional categories for α=0.05 and 33 degrees of freedom (Fr ≥43.88). In order to establish in which segments were the main significant differences, the extension of the Friedman test for comparison of groups to a control was undertaken. Thus, after applying the appropriate formula, a critical value of the difference - R1 - Ru - was established at ≥18.59. In this way it was possible to plot the significance level of all 28 emotion categories for each music segment and thereby to obtain the emotion profile of each selected music fragment. The differences obtained for the musical pieces were established both for the significant response of individual emotion, groups of emotions, and the global profile of the response. In all the pieces used, one or more terms showed significance. Sometimes as many as seven terms appear predominant (Mahler, Mozart). In contrast other segments produce only one or two responses (aurora borealis, Arab music). In most musical segments there were null responses implying that there was an agreement concerning not only the emotions that were present, but also those that did not occur. Concerning the global response, there were several profiles recognizable among different pieces. The histogram is slanted to the left when positive and vigorous emotions are reported (Tchaikovsky, Bach). The predominance of emotions in the center-right sector corresponds to negative and quiet emotions (Arab music) or in the fourth sector of negative and agitated emotions (Mahler). Sometimes a <> shaped profile was obtained when vigorous emotions predominated (Mahler, Metallica). A bell-shaped response was obtained when calm emotions were reported, both pleasant and unpleasant (Japanese music). There is also music that globally stimulates one of the four quadrants defined in the affective circle, such as pleasant (Mozart), unpleasant (Mussorgsky), exciting (Metallica) or relaxing emotions (Japanese music). The only segment that produced scattered responses in the four sectors of emotions was the aurora borealis. Very similar profiles were obtained with very different pieces, such as the identical responses to Mozart and Andean music. It is necessary to analyze the individual emotion terms to distinguish them. Several common characteristics can be detected in these two pieces, such as fast speed in tempo allegro, binary rhythm, counterpoint figures, and ascending melody, well known features in music composition. In contrast other segments evoked unpleasant responses (Mussorgsky), where fear, tension, doubt or pain was reported. The listener probably concedes a high value to a piece that evokes emotions that normally avoids in the context of a controlled artistic experience.