Maureen McHugo

Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans and D2-like (D2/D3) receptor availability in the substantia nigra/ventral tegmental area. Based on the rodent literature we predicted that novelty seeking would be characterized by lowered levels of D2-like (auto)receptor availability in the midbrain. Thirty-four healthy adults (18 men, 16 women) completed the Tridimensional Personality Questionnaire-Novelty-Seeking Scale and PET scanning with the D2/D3 ligand [18F]fallypride. Novelty-Seeking personality traits were inversely associated with D2-like receptor availability in the ventral midbrain, an effect that remained significant after controlling for age. We speculate that the lower midbrain (auto)receptor availability seen in high novelty seekers leads to accentuated dopaminergic responses to novelty and other conditions that induce dopamine release.

Meta-Analytic Connectivity Modeling Reveals Differential Functional Connectivity of the Medial and Lateral Orbitofrontal Cortex

The orbitofrontal cortex (OFC) is implicated in a broad range of behaviors and neuropsychiatric disorders. Anatomical tracing studies in nonhuman primates reveal differences in connectivity across subregions of the OFC, but data on the connectivity of the human OFC remain limited. We applied meta-analytic connectivity modeling in order to examine which brain regions are most frequently coactivated with the medial and lateral portions of the OFC in published functional neuroimaging studies. The analysis revealed a clear divergence in the pattern of connectivity for the medial OFC (mOFC) and lateral OFC (lOFC) regions. The lOFC showed coactivations with a network of prefrontal regions and areas involved in cognitive functions including language and memory. In contrast, the mOFC showed connectivity with default mode, autonomic, and limbic regions. Convergent patterns of coactivations were observed in the amygdala, hippocampus, striatum, and thalamus. A small number of regions showed connectivity specific to the anterior or posterior sectors of the OFC. Task domains involving memory, semantic processing, face processing, and reward were additionally analyzed in order to identify the different patterns of OFC functional connectivity associated with specific cognitive and affective processes. These data provide a framework for understanding the human OFCs position within widespread functional networks.

Heightened attentional capture by threat in veterans with PTSD.

Although an attentional bias for threat-relevant cues has been theorized in posttraumatic stress disorder (PTSD), to date empirical demonstration of this phenomenon has been at best inconsistent. Furthermore, the nature of this bias in PTSD has not been clearly delineated. In the present study, veterans with PTSD (n = 20), trauma-exposed veterans without PTSD (n = 16), and healthy nonveteran controls (n = 22) completed an emotional attentional blink task that measures the extent to which emotional stimuli capture and hold attention. Participants searched for a target embedded within a series of rapidly presented images. Critically, a combat-related, disgust, positive, or neutral distracter image appeared 200 ms, 400 ms, 600 ms, or 800 ms before the target. Impaired target detection was observed among veterans with PTSD relative to both veterans without PTSD and healthy nonveteran controls after only combat-related threat distracters when presented 200 ms, 400 ms, or 600 ms before the target, indicating increased attentional capture by cues of war and difficulty disengaging from such cues for an extended period. Veterans without PTSD and healthy nonveteran controls did not significantly differ from each other in target detection accuracy after combat-related threat distracters. These data support the presence of an attentional bias toward combat related stimuli in PTSD that should be a focus of treatment efforts.

The emotional attentional blink: what we know so far

The emotional attentional blink (EAB), also known as emotion-induced blindness, refers to a phenomenon in which the brief appearance of a task-irrelevant, emotionally arousing image captures attention to such an extent that individuals cannot detect target stimuli for several hundred ms after the emotional stimulus. The EAB allows for mental chronometry of stimulus-driven attention and the time needed to disengage and refocus goal-directed attention. In this review, we discuss current evidence for the mechanisms through which the EAB occurs. Although the EAB shares some similarities to both surprise-induced blindness (SiB) and other paradigms for assessing emotion-attention interactions, it possesses features that are distinct from these paradigms, and thus appears to provide a unique measure of the influence of emotion on stimulus-driven attention. The neural substrates of the EAB are not completely understood, but neuroimaging and neuropsychological data suggest some possible neural mechanisms underlying the phenomenon. The importance of understanding the EAB is highlighted by recent evidence indicating that EAB tasks can detect altered sensitivity to disorder relevant stimuli in psychiatric conditions such as post-traumatic stress disorder (PTSD).

Enhanced Visual Cortical Activation for Emotional Stimuli is Preserved in Patients with Unilateral Amygdala Resection

Emotionally arousing pictures induce increased activation of visual pathways relative to emotionally neutral images. A predominant model for the preferential processing and attention to emotional stimuli posits that the amygdala modulates sensory pathways through its projections to visual cortices. However, recent behavioral studies have found intact perceptual facilitation of emotional stimuli in individuals with amygdala damage. To determine the importance of the amygdala to modulations in visual processing, we used functional magnetic resonance imaging to examine visual cortical blood oxygenation level-dependent (BOLD) signal in response to emotionally salient and neutral images in a sample of human patients with unilateral medial temporal lobe resection that included the amygdala. Adults with right (n = 13) or left (n = 5) medial temporal lobe resections were compared with demographically matched healthy control participants (n = 16). In the control participants, both aversive and erotic images produced robust BOLD signal increases in bilateral primary and secondary visual cortices relative to neutral images. Similarly, all patients with amygdala resections showed enhanced visual cortical activations to erotic images both ipsilateral and contralateral to the lesion site. All but one of the amygdala resection patients showed similar enhancements to aversive stimuli and there were no significant group differences in visual cortex BOLD responses in patients compared with controls for either aversive or erotic images. Our results indicate that neither the right nor left amygdala is necessary for the heightened visual cortex BOLD responses observed during emotional stimulus presentation. These data challenge an amygdalo-centric model of emotional modulation and suggest that non-amygdalar processes contribute to the emotional modulation of sensory pathways.

Attentional capture by emotional stimuli is preserved in patients with amygdala lesions

The importance of cues signaling reward, threat or danger would suggest that they receive processing privileges in the neural systems underlying perception and attention. Previous research has documented enhanced processing of motivationally salient cues, and has pointed to the amygdala as a candidate neural structure underlying the enhancements. In the current study, we examined whether the amygdala was necessary for this emotional modulation of attention to occur. Patients with unilateral amygdala lesions and matched controls completed an emotional attentional blink task in which emotional distractors impair the perception of subsequent targets. Emotional images proved more distracting across all participant groups, including those with right or left amygdala lesions. These data argue against a central role for the amygdala in mediating all types of attentional capture by emotional stimuli.

Fear-enhanced visual search persists after amygdala lesions

Previous research has indicated that the amygdala is a critical neural substrate of the emotional modulation of attention. However, a recent case study suggests that the amygdala may not be essential for all types of emotion-attention interactions. In order to test this hypothesis, we assessed the visual-search performance of patients with unilateral amygdala lesions, matched controls, and medication-matched epilepsy patients with intact amygdalae. All participants completed a visual-search task consisting of trials in which (1) an emotional target was embedded among neutral distractors, (2) a neutral target was embedded among emotional distractors, or (3) a neutral target was embedded among neutral distractors. All participant groups, including those with amygdala lesions, detected emotional targets more efficiently than neutral targets. These data indicate that the amygdala is not necessary for emotion-guided visual search and suggest that other mechanisms beyond the amygdala help guide attention toward threatening stimuli.

Increased Amplitude of Low Frequency Fluctuations but Normal Hippocampal-Default Mode Network Connectivity in Schizophrenia.

Background Clinical and preclinical studies have established that the hippocampus is hyperactive in schizophrenia, making it a possible biomarker for drug development. Increased hippocampal connectivity, which can be studied conveniently with resting state imaging, has been proposed as a readily accessible corollary of hippocampal hyperactivity. Here, we tested the hypothesis that hippocampal activity and connectivity are increased in patients with schizophrenia. Methods Sixty-three schizophrenia patients and 71 healthy control subjects completed a resting state functional magnetic resonance imaging scan. We assessed hippocampal activity with the amplitude of low frequency fluctuations. We analyzed hippocampal functional connectivity with the default mode network using three common methods: group and single subject level independent component analysis, and seed-based functional connectivity. Results In patients with schizophrenia, we observed increased amplitude of low frequency fluctuations but normal hippocampal connectivity using independent component and seed-based analyses. Conclusion Our results indicate that although intrinsic hippocampal activity may be increased in schizophrenia, this finding does not extend to functional connectivity. Neuroimaging methods that directly assess hippocampal activity may be more promising for the identification of a biomarker for schizophrenia.

Personality traits predicting quality of life and overall functioning in schizophrenia

INTRODUCTION Clinical symptoms and sociodemographic variables predict level of functioning and quality of life in patients with schizophrenia. However, few studies have examined the effect of personality traits on quality of life and overall functioning in schizophrenia. Personality traits are premorbid to illness and may predict the way patients experience schizophrenia. The aim of this study was to examine the individual and additive effects of two core personality traits-neuroticism and extraversion-on quality of life and functioning. METHODS Patients with schizophrenia-spectrum disorders (n=153) and healthy controls (n=125) completed personality and quality of life questionnaires. Global functioning was assessed during a clinician-administered structured interview. Neuroticism and extraversion scores were analyzed both as continuous variables and as categorical extremes (High versus Normal Neuroticism, Low versus Normal Extraversion). RESULTS Quality of life was significantly associated with neuroticism, extraversion, and the neuroticism×diagnosis and extraversion×diagnosis interactions. For patients, a lower neuroticism score (in the normal range) was associated with quality of life scores comparable to controls; whereas high neuroticism scores in patients were associated with the lowest quality of life. For overall functioning, only diagnosis had a significant effect. CONCLUSION Neuroticism modulates quality of life and may provide an important key to improving the life of patients with schizophrenia.

Multi-scale hippocampal parcellation improves atlas-based segmentation accuracy

Known for its distinct role in memory, the hippocampus is one of the most studied regions of the brain. Recent advances in magnetic resonance imaging have allowed for high-contrast, reproducible imaging of the hippocampus. Typically, a trained rater takes 45 minutes to manually trace the hippocampus and delineate the anterior from the posterior segment at millimeter resolution. As a result, there has been a significant desire for automated and robust segmentation of the hippocampus. In this work we use a population of 195 atlases based on T1-weighted MR images with the left and right hippocampus delineated into the head and body. We initialize the multi-atlas segmentation to a region directly around each lateralized hippocampus to both speed up and improve the accuracy of registration. This initialization allows for incorporation of nearly 200 atlases, an accomplishment which would typically involve hundreds of hours of computation per target image. The proposed segmentation results in a Dice similiarity coefficient over 0.9 for the full hippocampus. This result outperforms a multi-atlas segmentation using the BrainCOLOR atlases (Dice 0.85) and FreeSurfer (Dice 0.75). Furthermore, the head and body delineation resulted in a Dice coefficient over 0.87 for both structures. The head and body volume measurements also show high reproducibility on the Kirby 21 reproducibility population (R2 greater than 0.95, p < 0.05 for all structures). This work signifies the first result in an ongoing work to develop a robust tool for measurement of the hippocampus and other temporal lobe structures.