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.     

A network approach to response inhibition: dissociating functional connectivity of neural components involved in action restraint and action cancellation

The ability to inhibit action tendencies is vital for adaptive human behaviour. Various paradigms are supposed to assess action inhibition and are often used interchangeably. However, these paradigms are based on different conceptualizations (action restraint vs. action cancellation) and the question arises as to what extent different conceptualizations of inhibitory processing are mirrored in a distinct neural activation pattern. We used functional magnetic resonance imaging to investigate the neural correlates of action restraint vs. action cancellation. Analyses of local activity changes as well as network connectivity measures revealed a strong overlap of activation within a common action inhibition network including inferior frontal, pre‐supplementary motor and thalamic brain areas as well as the anterior cingulate cortex. Furthermore, our findings pointed to additional neural networks that are distinct for action restraint (i.e. right superior frontal gyrus, left middle frontal gyrus, and bilateral anterior cingulate cortex) and action cancellation (i.e. right middle frontal gyrus, posterior cingulate cortex, and parietal regions). Our connectivity analyses showed that different inhibitory modalities largely relied on a task‐independent global inhibition network within the brain. Furthermore, they suggested that the conceptually distinct inhibitory aspects of action restraint vs. action cancellation also activated additional specific brain regions in a task‐dependent manner. This has implications for the choice of tasks in an empirical setting, but is also relevant for various clinical contexts in which inhibition deficits are considered a diagnostic feature.     

The eye contact effect in request and emblematic hand gestures

Request and emblematic gestures, despite being both communicative gestures, do differ in terms of social valence. Indeed, only the former are used to initiate/maintain/terminate an actual interaction. If such a difference is at stake, a relevant social cue, i.e. eye contact, should have different impacts on the neuronal underpinnings of the two types of gesture. We measured blood oxygen level‐dependent signals, using functional magnetic resonance imaging, while participants watched videos of an actor, either blindfolded or not, performing emblems, request gestures, or meaningless control movements. A left‐lateralized network was more activated by both types of communicative gestures than by meaningless movements, regardless of the accessibility of the actor's eyes. Strikingly, when eye contact was taken into account as a factor, a right‐lateralized network was more strongly activated by emblematic gestures performed by the non‐blindfolded actor than by those performed by the blindfolded actor. Such modulation possibly reflects the integration of information conveyed by the eyes with the representation of emblems. Conversely, a wider right‐lateralized network was more strongly activated by request gestures performed by the blindfolded than by those performed by the non‐blindfolded actor. This probably reflects the effect of the conflict between the observed action and its associated contextual information, in which relevant social cues are missing.     

Decoding the individual finger movements from single‐trial functional magnetic resonance imaging recordings of human brain activity

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non‐invasively recorded human brain activation is crucial for implementing a brain–machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single‐trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor‐related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial–temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non‐invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI‐based brain–machine interface for finger movement.     

Abnormal cingulum bundle development in autism: A probabilistic tractography study

There is now considerable evidence that white matter abnormalities play a role in the neurobiology of autism. Little research has been directed, however, at understanding (a) typical white matter development in autism and how this relates to neurocognitive impairments observed in the disorder. In this study we used probabilistic tractography to identify the cingulum bundle in 21 adolescents and young adults with Autism Spectrum Disorder (ASD), and 21 age- and sex-matched healthy volunteers. We investigated group differences in the relationships between age and fractional anisotropy, a putative measure of white matter integrity, within the cingulum bundle. Moreover, in a preliminary investigation, we examined the relationship between cingulum fractional anisotropy and executive functioning using the Behavior Rating Inventory of Executive Function (BRIEF). The ASD participants demonstrated significantly lower fractional anisotropy within the cingulum bundle compared to the typically developing volunteers. There was a significant group-by-age interaction such that the ASD group did not show the typical age-associated increases in fractional anisotropy observed among healthy individuals. Moreover, lower fractional anisotropy within the cingulum bundle was associated with worse BRIEF behavioral regulation index scores in the ASD group. The current findings implicate a dysregulation in cingulum bundle white matter development occurring in late adolescence and early adulthood in ASD, and suggest that greater disturbances in this trajectory are associated with executive dysfunction in ASD.