Neurometabolite correlates with personality and stress in healthy emerging adults: A focus on sex differences.

Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p<0.05) negative correlates of stress with the NAA/Cr ratio in the pCC, and of extraversion with WM metabolite ratios. In regards of sex differences, a significantly higher NAA/Cho ratio in the pCC (p<0.05), the dACC (p<0.01), and in the left and right posterior WM matter (p<0.05), and a lower Cho/Cr ratio in the dACC (p<0.01) was detected in women. Moreover, the two sexes differed in regards of metabolite correlates of openness, conscientiousness, extraversion, agreeableness, neuroticism, stress, hopelessness, and self-esteem, and in multiple regression model predictions. Our results point to a role of the ACC in conscientiousness through its involvement in higher-order cognitive control as part of the salience network and internally directed thoughts as part of the default mode network (DMN). Furthermore, the two sexes differ in terms of metabolite correlates of openness and conscientiousness in the pCC, suggesting mental process involvement through the DMN, and of agreeableness in the dACC, possibly through involvement in social cognitive processes, particularly in women. Additionally, our results suggest that the ACC is linked to the so-called Alpha-factor of personality. Our findings on stress correlates contribute to the existing literature of the involvement of the ACC as part of the limbic system. In addition, our results suggest a possible role of the pCC in stress-regulatory processes through a possible co-involvement of stress, hopelessness, and self-esteem in the pCC in men, where higher self-esteem may help to cope with stress.

Sex matters: stress perception and the relevance of resilience and perceived social support in emerging adults.

The emerging adulthood represents a vulnerable and critical turning point for the beginning of mental illnesses and is therefore of particular interest for the study of risk and resilience. The present survey investigated the impact of sex on the associations between resilience and the perception of social support and stress in students. The Resilience Scale was used to assess resilience. Stress perception and social support perception were measured using the Perceived Stress Scale and the Social Support Questionnaire FSozU k-22, respectively. Between the ages of 18 and 30, 503 subjects (59.6% female) were included into the study. We detected a significant effect of sex with markedly lower resilience and a more pronounced perception of stress and social support among females. Significant correlations between resilience, stress perception, and social support perception were found in both sexes with women showing a stronger interrelationship between stress perception and both resilience and social support perception. Mediation analysis revealed that the relationship between the perception of social support and stress was fully mediated by resilience among men and partly mediated by resilience among women. Of note, the mediation of resilience on the interrelationship between the perception of social support and stress was much stronger in women than in men. These findings suggest that sex-specific, customized interventions focusing on the strengthening of resilience and the claiming of social support are needed to promote mental health in emerging adults.

Caffeine and cognition in functional magnetic resonance imaging.

Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

Neural substrates for episodic encoding and recognition of unfamiliar faces.

Functional MRI was used to investigate brain activation in healthy volunteers during encoding of unfamiliar faces as well as during correct recognition of newly learned faces (CR) compared to correct identification of distractor faces (CF), missed alarms (not recognizing previously presented faces, MA), and false alarms (incorrectly recognizing newly presented faces, FA). Encoding was associated with frontal, occipital/fusiform, thalamic, and cerebellar activation. CR produced activation in frontal and cerebellar regions, whereas CF activated frontal and occipitotemporal regions as well as the thalamus. In contrast, MA was associated with frontal and thalamic activation, and FA with frontal activation. The CR minus CF comparison showed left lateral prefrontal and parietal activation, while no suprathreshold positive signal changes were detected when subtracting the other conditions (CR minus MA, CR minus FA, and vice versa). These results support the view that the successful episodic retrieval of newly learned faces is based on a dorsal visual stream mechanism.

Sex differences in brain activation patterns during processing of positively and negatively valenced emotional words.

BACKGROUND: Previous studies have suggested that men and women process emotional stimuli differently. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences in regional cerebral activity during the perception of positive or negative emotions. METHOD: The experiment comprised two emotional conditions (positively/negatively valenced words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy volunteers (19 males, 19 females) were investigated. A direct comparison of brain activation between men and women revealed differential activation in the right putamen, the right superior temporal gyrus, and the left supramarginal gyrus during processing of positively valenced words versus non-words for women versus men. By contrast, during processing of negatively valenced words versus non-words, relatively greater activation was seen in the left perirhinal cortex and hippocampus for women versus men, and in the right supramarginal gyrus for men versus women. CONCLUSIONS: Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying the gender disparity of neuropsychiatric diseases such as mood disorders.

The neural regions sustaining episodic encoding and recognition of objects.

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

Contact force- and amplitude-controllable vibrating probe for somatosensory mapping of plantar afferences with fMRI.

PURPOSE: To study cerebral responses evoked from mechanoreceptors in the human foot sole using a computer-controlled vibrotactile stimulation system. MATERIALS AND METHODS: The stimulation system consisted of two stationary moving magnet actuators with indentors to gently contact and vibrate the foot sole during functional MRI (fMRI) experiments. To allow independent settings of contact force (0-20 N) and intensity of vibration (frequency range=20-100 Hz) the actuators were controlled by a digital servo loop. For fMRI experiments with complex stimulus protocols, both vibrating probes were further operated under supervisory control. RESULTS: The MR compatibility of this electromagnetic system was tested in a 1.5T scanner with an actively shielded magnet (Siemens Magnetom Sonata). Blood oxygenation level-dependent (BOLD) responses were detected in the contralateral left pre- and postcentral gyrus, bilaterally within the secondary somatosensory cortex, bilaterally within the supplementary motor cortex, and bilaterally within the anterior cingular gyrus. CONCLUSION: This stimulation device provides a new tool for identifying cerebral structures that convey sensory information from the foot region, which is of promising diagnostic value, particularly for assessing sensorimotor deficits resulting from brain lesions.

Gender differences in regional cerebral activity during the perception of emotion: a functional MRI study.

Whether men activate different brain regions during various emotions compared to women or whether gender differences exist in transient emotional states has been the subject of only few studies. We used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences during the perception of positive or negative emotions. The experiment comprised two emotional conditions (pleasant/unpleasant visual stimuli) during which fMRI data were acquired. Altogether, 38 healthy volunteers (19 males, 19 females) were investigated. When subtracting the activation values of men from those of women, suprathreshold positive signal changes were detected in the right posterior cingulate, the left putamen and the left cerebellum during positive mood induction, and in bilateral superior temporal gyri and cerebellar vermis during negative mood induction. The subtraction of activation values of women from those of men yielded no significant differences. Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying gender-related vulnerability of the prevalence and severity of neuropsychiatric disorders.

Human brain structures related to plantar vibrotactile stimulation: a functional magnetic resonance imaging study.

The purpose of this study was to investigate the sensorimotor cortex response to plantar vibrotactile stimulation using a newly developed MRI compatible vibration device. Ten healthy subjects (20-45 years) were investigated. Vibrotactile stimulation of the sole of the foot with a frequency of 50 Hz and a displacement of 1 mm was performed during fMRI (echo-planar imaging sequence at 1.5 T) using an MRI compatible moving magnet actuator that is able to produce vibration frequencies between 0 and 100 Hz and displacement amplitudes between 0 and 4 mm. The fMRI measurement during vibrotactile stimulation of the right foot revealed brain activation contralaterally within the primary sensorimotor cortex, bilaterally within the secondary somatosensory cortex, bilaterally within the superior temporal, inferior parietal, and posterior insular region, bilaterally within the anterior and posterior cingular gyrus, bilaterally within the thalamus and caudate nucleus, contralaterally within the lentiform nucleus, and bilaterally within the anterior and posterior cerebellar lobe. The advantages of the new MRI compatible vibration device include effective transmission of the stimulus and controlled vibration amplitudes, frequencies, and intensities. The results indicate that plantar vibration can be a suitable paradigm to observe activation within the sensorimotor network in fMRI. Furthermore, the method may be used to determine the optimal responsiveness of the individual sensorimotor network.

Laser acupuncture induced specific cerebral cortical and subcortical activations in humans.

As recent studies demonstrated, acupuncture can elicit activity in specific brain areas. This study aims to explore further the central effect using laser acupuncture. We investigated the cerebral effects of laser acupuncture at both acupoints GB43 with functional magnetic resonance imaging (fMRI). As a control condition the laser was mounted at the same acupoints but without application of laser stimulation. The group results showed significant brain activations within the thalamus, nucleus subthalamicus, nucleus ruber, the brainstem, and the Brodmann areas 40 and 22 for the acupuncture condition. No significant brain activations were observed within the placebo condition. The activations we observed were laser acupuncture-specific and predominantly ipsilateral. This supports the assumption that acupuncture is mediated by meridians, since meridians do not cross to the other side. Furthermore, we could show that laser acupuncture allows one to design a pure placebo condition.

Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

OBJECTIVE: Memory impairment has been well documented in schizophrenia. In a previous study, the authors investigated patterns of brain activity during episodic encoding and recognition of words in remitted, stable schizophrenia outpatients being treated with novel antipsychotics. The same procedure was used in this study to investigate unmedicated patients during an acute episode of schizophrenia. METHOD: Functional magnetic resonance imaging was used to study regional brain activation in 10 unmedicated patients experiencing an acute episode of schizophrenia and 10 healthy comparison subjects during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite intact recognition performance, patients with schizophrenia showed reduced activation of anterior prefrontal, posterior cingulate, and retrosplenial areas relative to comparison subjects during word encoding. During word recognition, reduced activation was found in the patients' dorsolateral prefrontal and limbic/paralimbic regions. On the other hand, higher metabolism in bilateral anterior prefrontal cortices was observed. CONCLUSIONS: The results suggest that different neural pathways are engaged during episodic encoding and recognition of words in patients experiencing an acute episode of schizophrenia relative to healthy comparison subjects. Furthermore, acute psychosis may prevent practice effects, reflected in a failure to engage brain regions associated with successful episodic memory retrieval in healthy subjects.

An FMRI study of episodic encoding and recognition of words in patients with schizophrenia in remission.

OBJECTIVE: Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia. METHOD: Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test. RESULTS: Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices. CONCLUSIONS: Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.

Functional magnetic resonance imaging of the human sensorimotor cortex using a novel vibrotactile stimulator.

The purpose of this study was to investigate the fMRI response of the sensorimotor cortex to a vibration paradigm produced by a novel vibrotactile stimulator. Fifteen contiguous slices covering the sensorimotor cortex parallel to the anterior (AC) and posterior commissure (PC) line were obtained with echoplanar magnetic resonance imaging at 1.5T. Cortical activity in ten healthy subjects (20-45 years) was investigated during vibration (50 Hz) of the palm of the right hand and compared to a finger-to-thumb tapping paradigm. For the vibration paradigm a mechanically driven vibration head was mounted on the palm of the right hand. The new vibration device produces vibration frequencies (1-130 Hz) and displacement amplitudes (0.5-4 mm) suitable to elicit the tonic vibratory reflex. The fMRI measurement during vibratory stimulation revealed activation in the pre- and postcentral gyrus in all subjects. These activations were comparable to the finger-to-thumb tapping paradigm. The advantages of the new MR compatible vibration device include effective transmission of the stimulus and controlled vibration frequencies and intensities. These preliminary fMRI results indicate that vibration can be an alternative paradigm for the evaluation of sensory and motor functions in patients unable to perform active motor paradigms.

Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans.

The aim of this study was to investigate the effect of laser acupuncture on cerebral activation. Using functional magnetic imaging (fMRI) cortical activations during laser acupuncture at the left foot (Bladder 67) and dummy acupuncture, were compared employing a block design in ten healthy male volunteers. All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil. During laser acupuncture, we found activation in the cuneus corresponding to Brodmann Area (BA) 18 and the medial occipital gyrus (BA 19) of the ipsilateral visual cortex. Placebo stimulation did not show any activation. We could demonstrate that laser acupuncture of a specific acupoint, empirically related to ophthalmic disorders, leads to activation of visual brain areas, whereas placebo acupuncture does not. These results indicate that fMRI has the potential to elucidate effects of acupuncture on brain activity.

A new pneumatic vibrator for functional magnetic resonance imaging of the human sensorimotor cortex.

The aim of the study was to implement a vibrotactile stimulator using functional magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting of a pneumatically driven dual membrane pump was developed. Brain activation during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers. The vibration paradigm showed a comparable activation pattern with respect to finger-to-thumb-tapping in the contralateral perirolandic region. The advantage of the new vibration device is the possibility to elicit the vibratory-tonic-reflex due to the higher amplitude in context with the high frequency than established devices. This reflex is considered to be responsible for the activation in the primary motor cortex and the current paradigm might prove useful in future neurosurgical planning in patients with perirolandic lesions.