Brain activation predicts treatment improvement in patients with major depressive disorder

Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.     

Default mode network dysfunction in adults with prenatal alcohol exposure

Prenatal alcohol exposure (PAE) is known to cause significant cognitive and attentional dysfunction. Given the relationship between default mode network (DMN) activity and task-related attentional modulation, it is possible that PAE affects activity of this network. In the present study, task-related deactivation as well as structural and resting state functional connectivity of the DMN were examined using diffusional tensor imaging and functional magnetic resonance imaging in non-dysmorphic and dysmorphic PAE populations and compared to healthy controls. The dysmorphic PAE group was found to have reduced DMN deactivation as compared to controls, indicating poorer attentional modulation during the cognitive task. Additionally, structural connectivity and baseline functional connectivity were lower in both PAE groups as compared to controls. Primarily the findings suggest that learning problems seen with PAE may be a combination of general attentional and specific cognitive deficits. A secondary implication is that DMN activity is affected to varying extents depending on the degree of PAE.     

Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22–55 years) with paroxetine 20–50 mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [¹²³I]β-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.     

Children with reading disorder show modality independent brain abnormalities during semantic tasks

Neuroimaging studies have suggested that left inferior frontal gyrus, left inferior parietal lobule and left middle temporal gyrus are critical for semantic processing in normal children. The goal of the present functional magnetic resonance imaging (fMRI) study was to determine whether these regions are systematically related to semantic processing in children (9- to 15-year-old) diagnosed with reading disorders (RD). Semantic judgments required participants to indicate whether two words were related in meaning. The strength of semantic association varied continuously from higher association pairs (e.g., king-queen) to lower association pairs (e.g. net-ship). We found that the correlation between association strength and activation was significantly weaker for RD children compared to controls in left middle temporal gyrus and left inferior parietal lobule for both the auditory and the visual modalities and in left inferior frontal gyrus for the visual modality. These results suggest that the RD children have abnormalities in semantic search/retrieval in the inferior frontal gyrus, integration of semantic information in the inferior parietal lobule and semantic lexical representations in the middle temporal gyrus. These deficits appear to be general to the semantic system and independent of modality.     

Selective attention to sound location or pitch studied with fMRI

We used 3-T functional magnetic resonance imaging to compare the brain mechanisms underlying selective attention to sound location and pitch. In different tasks, the subjects (N = 10) attended to a designated sound location or pitch or to pictures presented on the screen. In the Attend Location conditions, the sound location varied randomly (left or right), while the pitch was kept constant (high or low). In the Attend Pitch conditions, sounds of randomly varying pitch (high or low) were presented at a constant location (left or right). Both attention to location and attention to pitch produced enhanced activity (in comparison with activation caused by the same sounds when attention was focused on the pictures) in widespread areas of the superior temporal cortex. Attention to either sound feature also activated prefrontal and inferior parietal cortical regions. These activations were stronger during attention to location than during attention to pitch. Attention to location but not to pitch produced a significant increase of activation in the premotor/supplementary motor cortices of both hemispheres and in the right prefrontal cortex, while no area showed activity specifically related to attention to pitch. The present results suggest some differences in the attentional selection of sounds on the basis of their location and pitch consistent with the suggested auditory "what" and "where" processing streams.     

Diminished rostral anterior cingulate activity in response to threat-related events in posttraumatic stress disorder

BACKGROUND: Previous brain imaging studies have reported hyperactivation of the amygdala and hypoactivation of the anterior cingulate in posttraumatic stress disorder (PTSD) patients, which is believed to be an underlying neural mechanism of the PTSD symptoms. The current study specifically focuses on the abnormal activity of the rostral anterior cingulate, using a paradigm which elicits an unexpected processing conflict caused by salient emotional stimuli. METHODS: Twelve survivors (seven men and five women) of the Taegu subway fire in 2003, who later developed PTSD, agreed to participate in this study. Twelve healthy volunteers (seven men and five women) were recruited for comparison. Functional brain images of all participants were acquired using functional magnetic resonance imaging while performing a same-different judgment task, which was modified to elicit an unexpected emotional processing conflict. RESULTS: PTSD patients, compared to comparison subjects, showed a decreased rostral anterior cingulate functioning when exposed to situations which induce an unexpected emotional processing conflict. Moreover, PTSD symptom severity was negatively correlated to the level of decrease in the rostral anterior cingulate activity. CONCLUSIONS: The results of this study provide evidence that the rostral anterior cingulate functioning is impaired in PTSD patients during response-conflict situations that involve emotional stimuli.     

Intrinsic connectivity networks from childhood to late adolescence: Effects of age and sex

There is limited evidence on the effects of age and sex on intrinsic connectivity of networks underlying cognition during childhood and adolescence. Independent component analysis was conducted in 113 subjects aged 7–18; the default mode, executive control, anterior salience, basal ganglia, language and visuospatial networks were identified. The effect of age was examined with multiple regression, while sex and ‘age × sex’ interactions were assessed by dividing the sample according to age (7–12 and 13–18 years). As age increased, connectivity in the dorsal and ventral default mode network became more anterior and posterior, respectively, while in the executive control network, connectivity increased within frontoparietal regions. The basal ganglia network showed increased engagement of striatum, thalami and precuneus. The anterior salience network showed greater connectivity in frontal areas and anterior cingulate, and less connectivity of orbitofrontal, middle cingulate and temporoparietal regions. The language network presented increased connectivity of inferior frontal and decreased connectivity within the right middle frontal and left inferior parietal cortices. The visuospatial network showed greater engagement of inferior parietal and frontal cortices. No effect of sex, nor age by sex interactions was observed. These findings provide evidence of strengthening of cortico-cortical and cortico-subcortical networks across childhood and adolescence.     

The Potential for New Understandings of Normal and Abnormal Cognition by Integration of Neuroimaging and Behavioral Data: Not an Exercise in Carrying Coals to Newcastle

Discovering the means to prevent and cure schizophrenia is a vision that motivates many scientists. But in order to achieve this goal, we need to understand its neurobiological basis. The emergent metadiscipline of cognitive neuroscience fields an impressive array of tools that can be marshaled towards achieving this goal, including powerful new methods of imaging the brain (both structural and functional) as well as assessments of perceptual and cognitive capacities based on psychophysical procedures, experimental tasks and models developed by cognitive science. We believe that the integration of data from this array of tools offers the greatest possibilities and potential for advancing understanding of the neural basis of not only normal cognition but also the cognitive impairments that are fundamental to schizophrenia. Since sufficient expertise in the application of these tools and methods rarely reside in a single individual, or even a single laboratory, collaboration is a key element in this endeavor. Here, we review some of the products of our integrative efforts in collaboration with our colleagues on the East Coast of Australia and Pacific Rim. This research focuses on the neural basis of executive function deficits and impairments in early auditory processing in patients using various combinations of performance indices (from perceptual and cognitive paradigms), ERPs, fMRI and sMRI. In each case, integration of two or more sources of information provides more information than any one source alone by revealing new insights into structure-function relationships. Furthermore, the addition of other imaging methodologies (such as DTI) and approaches (such as computational models of cognition) offers new horizons in human brain imaging research and in understanding human behavior.

Visual search for feature conjunctions: an fMRI study comparing alcohol-related neurodevelopmental disorder (ARND) to ADHD

Background

Alcohol-related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD). Diagnosis of ARND is difficult because individuals do not demonstrate the characteristic facial features associated with fetal alcohol syndrome (FAS). While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying impairment in attention pathways may be different.

Methods

Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was conducted at 3 T. Sixty-three children aged 10 to 14 years diagnosed with ARND, ADHD, and typically developing (TD) controls performed a single-feature and a feature-conjunction visual search task.

Results

Dorsal and ventral attention pathways were activated during both attention tasks in all groups. Significantly greater activation was observed in ARND subjects during a single-feature search as compared to TD and ADHD groups, suggesting ARND subjects require greater neural recruitment to perform this simple task. ARND subjects appear unable to effectively use the very efficient automatic perceptual ‘pop-out’ mechanism employed by TD and ADHD groups during presentation of the disjunction array. By comparison, activation was lower in ARND compared to TD and ADHD subjects during the more difficult conjunction search task as compared to the single-feature search. Analysis of DTI data using tract-based spatial statistics (TBSS) showed areas of significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the right inferior longitudinal fasciculus (ILF) in ARND compared to TD subjects. Damage to the white matter of the ILF may compromise the ventral attention pathway and may require subjects to use the dorsal attention pathway, which is associated with effortful top-down processing, for tasks that should be automatic. Decreased functional activity in the right temporoparietal junction (TPJ) of ARND subjects may be due to a reduction in the white matter tract’s ability to efficiently convey information critical to performance of the attention tasks.

Conclusions

Limited activation patterns in ARND suggest problems in information processing along the ventral frontoparietal attention pathway. Poor integrity of the ILF, which connects the functional components of the ventral attention network, in ARND subjects may contribute to the attention deficits characteristic of the disorder.     

Altered relationship between electrophysiological response to errors and gray matter volumes in an extended network for error‐processing in pediatric obsessive‐compulsive disorder

Pediatric patients with obsessive‐compulsive disorder (OCD) show an increased electrophysiological response to errors that is thought to be localized to the posterior medial prefrontal cortex (pMFC). However, the relation of this response, the error‐related negativity (ERN), to underlying brain structures remains unknown. In an examination of 20 pediatric OCD patients and 20 healthy youth, we found that more negative ERN amplitude was correlated with lower gray matter (GM) density in pMFC and orbital frontal cortex. The association of the ERN with pMFC gray matter volume was driven by the patient group. In addition, a group difference in the association of ERN with gray matter in right insula was observed, showing an association of these measures in healthy youth (more negative ERN amplitude was associated with lower GM density in insula), but not in patients. These findings provide preliminary evidence linking gray matter volumes in an extended network for error processing to the ERN, and suggest that structural alterations in this network may underlie exaggeration of the ERN in pediatric OCD. Hum Brain Mapp 35:1143–1153, 2014. © 2013 Wiley Periodicals, Inc.     

Enhancing the representation of functional connectivity networks by fusing multi‐view information for autism spectrum disorder diagnosis

Functional connectivity network provides novel insights on how distributed brain regions are functionally integrated, and its deviations from healthy brain have recently been employed to identify biomarkers for neuropsychiatric disorders. However, most of brain network analysis methods utilized features extracted only from one functional connectivity network for brain disease detection and cannot provide a comprehensive representation on the subtle disruptions of brain functional organization induced by neuropsychiatric disorders. Inspired by the principles of multi‐view learning which utilizes information from multiple views to enhance object representation, we propose a novel multiple network based framework to enhance the representation of functional connectivity networks by fusing the common and complementary information conveyed in multiple networks. Specifically, four functional connectivity networks corresponding to the four adjacent values of regularization parameter are generated via a sparse regression model with group constraint ( l_2,1 ‐norm), to enhance the common intrinsic topological structure and limit the error rate caused by different views. To obtain a set of more meaningful and discriminative features, we propose using a modified version of weighted clustering coefficients to quantify the subtle differences of each group‐sparse network at local level. We then linearly fuse the selected features from each individual network via a multi‐kernel support vector machine for autism spectrum disorder (ASD) diagnosis. The proposed framework achieves an accuracy of 79.35%, outperforming all the compared single network methods for at least 7% improvement. Moreover, compared with other multiple network methods, our method also achieves the best performance, that is, with at least 11% improvement in accuracy.