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Biomedical subjects

Turhan Canli

Publications and source records attributed to Turhan Canli.

At least 19 recordsLinked to original sources
PubMed2006

Neural correlates of epigenesis.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Adult↗
PubMed2006

Additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on emotional processing.

Prior studies reported that functional variants of both the serotonin transporter (5-HTT) and tryptophan hydroxylase-2 genes (TPH2), 2 key regulators of the serotonergic signaling pathway, modulate amygdala activation during emotional processing. We addressed the question whether these 2 gene variants modulate each other, using an emotional picture-processing task. Specifically, we measured event-related potentials (ERPs) during a passive emotional picture perception task, focusing on ERPs for the early posterior negativity (EPN) around 240 ms and for the slow wave starting at 315 ms. We found evidence for increased neural activity at 240 ms in individuals who carried 1 or 2 copies of the low-expression short variant of the 5-HTT. Carriers of T variant of the TPH2 also showed a tendency toward increased neural activity at 240 ms. Moreover, we observed an additive effect of both genotypes for EPN, with highest neural activity to emotional stimuli in individuals carrying combination of both short variant of 5-HTT and T variant of TPH2. Our results indicate that both the 5-HTT and the TPH2 genotypes modulate the sensory encoding of affective stimuli during early steps of visual processing and reveal additive effects of 2 genes in the serotonergic control of emotion regulation.

Adult↗
PubMed2006

Effects of estrogen variation on neural correlates of emotional response inhibition.

Despite behavioral evidence that variation in ovarian hormones is associated with changes in affect, the neural basis of these processes is poorly understood. We combined functional magnetic resonance imaging (fMRI) with quantitative analysis of ovarian hormones in a within-subject design to investigate brain activation patterns during affective response inhibition, comparing activation between the early follicular (low estrogen and progesterone) and mid-luteal (high estrogen and progesterone) phases of the menstrual cycle in healthy women. There was significantly increased activation in the anterior cingulate and dorsolateral prefrontal cortex (DLPFC) while inhibiting response to positive words during the luteal, compared to the follicular phase. Furthermore, luteal phase estradiol level positively correlated with DLPFC activation while inhibiting response to positive words and negatively correlated with activation in several structures while inhibiting response to negative words, supporting estrogen's modulation of affective processing.

Adult↗
PubMed2006

Interference produced by emotional conflict associated with anterior cingulate activation.

The anterior cingulate cortex (ACC) is involved in cognition and emotion. In the classic Stroop task, presentation of stimuli that are in response conflict with one another produces activation in the caudal ACC. In the emotional Stroop task, presentation of emotionally salient stimuli produces activation in the rostral ACC. Presentation of stimuli that are emotionally conflicting should activate the caudal ACC; stimuli that are emotionally salient should activate the rostral ACC. We tested this prediction using functional magnetic resonance imaging while subjects made emotional valence judgments of words overlaid on emotional faces (word-face Stroop task). Emotionally incongruent pairs were responded to more slowly than emotionally congruent pairs. Emotionally incongruent trials were associated with increased activation within the caudal ACC, whereas no ACC activation was found in response to emotional saliency. These results support the conflict-monitoring model of caudal ACC and extend this function to conflict within the domain of emotional stimuli.

Adolescent↗
PubMed2005

Amygdala gray matter concentration is associated with extraversion and neuroticism.

Using high-resolution magnetic resonance imaging and voxel-based morphometry in 41 healthy individuals, this study evaluated the association between the personality traits of extraversion and neuroticism, on the one hand, and individual differences in localized brain volume and gray matter concentration, on the other, with a special focus on the amygdala. Extraversion was positively correlated with gray matter concentration in the left amygdala, whereas neuroticism was negatively correlated with gray matter concentration in the right amygdala. Given that neuroticism is a risk factor for depression, our finding offers one explanation as to why prior structural imaging studies of depressed patients (which did not control for personality) produced conflicting findings. Furthermore, our data are consistent with the view that amygdala reduction seen in depressed patients precedes the onset of the disease, rather than being a consequence of the illness.

Adult↗
PubMed2005

Subgenual anterior cingulate activation to valenced emotional stimuli in major depression.

Major depression has been associated with anomalous activation in the subgenual anterior cingulate cortex, but its response to emotional stimuli is poorly understood. The primary goal of this study was to compare levels of activation in the subgenual anterior cingulate cortex of diagnosed depressed and nondepressed participants in response to happy and sad facial expressions of affect. Whereas cognitive theories of depression predict increased activation to negative stimuli, depressed participants were found to exhibit increased activation to both types of stimuli in the subgenual anterior cingulate cortex. Importantly, the loci were in different regions of the subgenual anterior cingulate cortex, suggesting that there is functional specialization in the processing of negatively and positively valenced stimuli.

Adult↗
PubMed2005

Amygdala reactivity to emotional faces predicts improvement in major depression.

Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction. Using functional magnetic resonance imaging in a prospective study, we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later, controlling for initial depression severity and medication status. Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome.

Adolescent↗
PubMed2005

Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task.

Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes.

Analysis of Variance↗
PubMed2005

Effect of estrogen-serotonin interactions on mood and cognition.

Both the neurotransmitter serotonin and the ovarian steroid estrogen have been implicated in the modulation of mood and cognition. Although significant functional interactions between estrogen and serotonin are acknowledged, the nature of their relationship has not been fully elucidated. Research using ovariectomized animals has identified estrogen-induced changes in serotonin transmission, binding, and metabolism in brain regions implicated in the regulation of affect and cognition. Studies in humans, particularly of menopausal women undergoing estrogen treatment, have provided some support for these findings and identified instances in which change in mood or cognition is accompanied by alterations in serotonin function and hormonal status. However, it is apparent that further research is required to understand the neural processes involved in the interplay between estrogen and serotonin. By reviewing animal and human data regarding estrogen and serotonin's effects on mood and cognition, the authors aim to better define their relationship and highlight areas for further research.

Affect↗
PubMed2005

The endophenotype of impulsivity: reaching consilience through behavioral, genetic, and neuroimaging approaches.

Impulsivity is a multidimensional construct with implications for understanding the etiology and treatment of multiple forms of psychopathology. As a multidimensional construct, however, the processes underlying impulsivity, particularly behavioral inhibition, must be separated to allow for investigations into its neurogenetic bases. Evidence from both animal and human studies supports the role of dopamine in impulsivity, and neuroimaging research is elucidating brain regions involved in behavioral inhibition. Evidence is now emerging that suggests an interaction between dopamine system genes and frontal brain regions in underlying individual differences in behavioral inhibition. However, to reach a comprehensive understanding of the neurogenetic bases of behavioral inhibition, an appropriate framework is required. Therefore, it is proposed that by identifying intervening variables more sensitive to the effects of genetic variation, known as an endophenotype approach, we will be able to overcome many of the methodological limitations that prevent a better understanding at present.

Adult↗
PubMed2005

Variance maps as a novel tool for localizing regions of interest in imaging studies of individual differences.

Cognitive neuroimaging studies of individual differences seek to reveal brain mechanisms of cognition by associating intersubject variability in brain activation with other variables of interest, such as sex, personality trait, or mood state. The choice of a priori regions of interest (ROIs) raises problems, because the selection criterion is typically consistent activation across prior studies, suggesting little intersubject variability. Here, we introduce a novel approach for selecting regions that are defined on the basis of their variance characteristics, rather than on the basis of their location or because of theoretical expectations. These regions of variance (ROVs) constitute the search space with which to assess how much of the observed variance can be ascribed to specific variables of interest. We compare the ROI and ROV approaches by applying each to the same data set and suggest that the conjunction of both methods may yield the greatest likelihood of capturing the rich relation between brain and behavior, while limiting the search space for statistical analyses and minimizing false positive errors.

Adolescent↗
PubMed2004

Brain activation to emotional words in depressed vs healthy subjects.

Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with different cognitive or behavioral processes.

Adult↗
PubMed2004

Individual differences in emotion processing.

Recent functional brain imaging studies of the neurobiology of emotion have investigated how individual differences among subjects modulate neural responses during emotion processing. Differences in personality, dispositional affect, biological sex, and genotype can all substantially modulate the neural bases of emotion processing in prefrontal, limbic, and other brain regions, across a variety of domains including emotional reactions, emotional memory, and emotion perception. Analysis of individual differences provides a new window into the neurobiology of emotion processing that complements traditional approaches.

Brain↗
PubMed2004

A double dissociation between mood states and personality traits in the anterior cingulate.

Neuroticism and extraversion are personality traits associated with negative and positive mood states, respectively, confounding trait and state factors that may affect brain responses to emotional stimuli. The authors dissociated these factors using fMRI and the emotional Stroop attention task: Anterior cingulate (AC) response to positive stimuli varied as a function of personality trait, but not mood state, whereas AC response to negative stimuli varied as a function of mood state, but not personality trait. Negative mood, but not personality trait, also increased the functional connectivity between AC and other regions. Variance in AC activation can thus be ascribed to an intersubject variable (extraversion) when responding to positive stimuli and an intrasubject variable (mood) when responding to negative stimuli. The former may explain stable differences between extraverts and introverts. The latter may provide an adaptive mechanism to expand an individual's dynamic range in response to potentially dangerous or threatening stimuli.

Adolescent↗
PubMed2004

Amygdala responses to emotionally valenced stimuli in older and younger adults.

As they age, adults experience less negative emotion, come to pay less attention to negative than to positive emotional stimuli, and become less likely to remember negative than positive emotional materials. This profile of findings suggests that, with age, the amygdala may show decreased reactivity to negative information while maintaining or increasing its reactivity to positive information. We used event-related functional magnetic resonance imaging to assess whether amygdala activation in response to positive and negative emotional pictures changes with age. Both older and younger adults showed greater activation in the amygdala for emotional than for neutral pictures; however, for older adults, seeing positive pictures led to greater amygdala activation than seeing negative pictures, whereas this was not the case for younger adults.

Adolescent↗
PubMed2004

Functional brain mapping of extraversion and neuroticism: learning from individual differences in emotion processing.

This review outlines how functional brain imaging, using an individual-differences approach in the processing of emotional stimuli, has begun to reveal the neural basis of extraversion (E) and neuroticism (N), two traits that are linked to both emotion and health. Studies using functional magnetic resonance imaging have shown that individual differences in participants' E and N scores are correlated with individual differences in brain activation in specific brain regions that are engaged during cognitive-affective tasks. Imaging studies using genotyped participants have begun to address the molecular mechanisms that may underlie these individual differences. The multidisciplinary integration of brain imaging and molecular genetic methods offers an exciting and novel approach for investigators who seek to uncover the biological mechanisms by which personality and health are interrelated.

Amygdala↗
PubMed2002

Sex differences in the neural basis of emotional memories.

Psychological studies have found better memory in women than men for emotional events, but the neural basis for this difference is unknown. We used event-related functional MRI to assess whether sex differences in memory for emotional stimuli is associated with activation of different neural systems in men and women. Brain activation in 12 men and 12 women was recorded while they rated their experience of emotional arousal in response to neutral and emotionally negative pictures. In a recognition memory test 3 weeks after scanning, highly emotional pictures were remembered best, and remembered better by women than by men. Men and women activated different neural circuits to encode stimuli effectively into memory even when the analysis was restricted to pictures rated equally arousing by both groups. Men activated significantly more structures than women in a network that included the right amygdala, whereas women activated significantly fewer structures in a network that included the left amygdala. Women had significantly more brain regions where activation correlated with both ongoing evaluation of emotional experience and with subsequent memory for the most emotionally arousing pictures. Greater overlap in brain regions sensitive to current emotion and contributing to subsequent memory may be a neural mechanism for emotions to enhance memory more powerfully in women than in men.

Behavior↗