Kristina Visscher

Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia.

Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment. Using resting-state functional MRI, we examined the functional connectivity of the ventral tegmental area (VTA), the origin of the mesocorticolimbic dopamine projections, in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline (pre-treatment) and after 1 week of treatment with the antipsychotic drug risperidone (1-week post-treatment). Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups’ participant-level functional connectivity maps. We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response. Compared with controls, patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions, including the dorsal anterior cingulate cortex (dACC) and thalamus. After 1 week of treatment, VTA/midbrain connectivity to bilateral regions of the thalamus was re-established. Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone, whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated. Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response.

Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone.

Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the groups participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity.

Modulations of ongoing alpha oscillations predict successful short-term visual memory encoding

Alpha-frequency band oscillations have been shown to be one of the most prominent aspects of neuronal ongoing oscillatory activity, as reflected by electroencephalography (EEG) recordings. First thought to reflect an idling state, a recent framework indicates that alpha power reflects cortical inhibition. In the present study, the role of oscillations in the upper alpha-band (12 Hz) was investigated during a change-detection test of short-term visual memory. If alpha oscillations arise from a purely inhibitory process, higher alpha power before sample stimulus presentation would be expected to correlate with poorer performance. Instead, participants with faster reaction-times showed stronger alpha power before the sample stimulus in frontal and posterior regions. Additionally, faster participants showed stronger alpha desynchronization after the stimulus in a group of right frontal and left posterior electrodes. The same pattern of electrodes showed stronger alpha with higher working-memory load, so that when more items were processed, alpha power desynchronized faster after the stimulus. During memory maintenance, alpha power was greater when more items were held in memory, likely due to a faster resynchronization. These data are consistent with the hypothesis that the level of suppression of alpha power by stimulus presentation is an important factor for successfully encoding visual stimuli. The data are also consistent with a role for alpha as actively participating in attentional processes.

Cortical thickness in human V1 associated with central vision loss.

Better understanding of the extent and scope of visual cortex plasticity following central vision loss is essential both for clarifying the mechanisms of brain plasticity and for future development of interventions to retain or restore visual function. This study investigated structural differences in primary visual cortex between normally-sighted controls and participants with central vision loss due to macular degeneration (MD). Ten participants with MD and ten age-, gender-, and education-matched controls with normal vision were included. The thickness of primary visual cortex was assessed using T1-weighted anatomical scans, and central and peripheral cortical regions were carefully compared between well-characterized participants with MD and controls. Results suggest that, compared to controls, participants with MD had significantly thinner cortex in typically centrally-responsive primary visual cortex – the region of cortex that normally receives visual input from the damaged area of the retina. Conversely, peripherally-responsive primary visual cortex demonstrated significantly increased cortical thickness relative to controls. These results suggest that central vision loss may give rise to cortical thinning, while in the same group of people, compensatory recruitment of spared peripheral vision may give rise to cortical thickening. This work furthers our understanding of neural plasticity in the context of adult vision loss.

Tasks Driven by Perceptual Information Do Not Recruit Sustained BOLD Activity in Cingulo-Opercular Regions

Sustained blood oxygen level dependent (BOLD) signal in the dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) is found in a broad majority of tasks examined and is believed to function as a putative task set maintenance signal. For example, a meta-analysis investigating task-control signals identified the dorsal anterior cingulate cortex and anterior insula as exhibiting sustained activity across a variety of task types. Re-analysis of tasks included in that meta-analysis showed exceptions, suggesting that tasks where the information necessary to determine a response was present in the stimulus (i.e., perceptually driven) does not show strong sustained cingulo-opercular activity. In a new experiment, we tested the generality of this observation while addressing alternative explanations about sustained cingulo-opercular activity (including task difficulty and verbal vs. non-verbal task demands). A new, difficult, perceptually driven task was compared with 2 new tasks that depended on information beyond that provided by the stimulus. The perceptually driven task showed a lack of cingulo-opercular activity in contrast to the 2 newly constructed tasks. This finding supports the idea that sustained cingulo-opercular activity contributes to maintenance of task set in only a subset of tasks.

Retinotopic patterns of background connectivity between V1 and fronto-parietal cortex are modulated by task demands

Attention facilitates the processing of task-relevant visual information and suppresses interference from task-irrelevant information. Modulations of neural activity in visual cortex depend on attention, and likely result from signals originating in fronto-parietal and cingulo-opercular regions of cortex. Here, we tested the hypothesis that attentional facilitation of visual processing is accomplished in part by changes in how brain networks involved in attentional control interact with sectors of V1 that represent different retinal eccentricities. We measured the strength of background connectivity between fronto-parietal and cingulo-opercular regions with different eccentricity sectors in V1 using functional MRI data that were collected while participants performed tasks involving attention to either a centrally presented visual stimulus or a simultaneously presented auditory stimulus. We found that when the visual stimulus was attended, background connectivity between V1 and the left frontal eye fields (FEF), left intraparietal sulcus (IPS), and right IPS varied strongly across different eccentricity sectors in V1 so that foveal sectors were more strongly connected than peripheral sectors. This retinotopic gradient was weaker when the visual stimulus was ignored, indicating that it was driven by attentional effects. Greater task-driven differences between foveal and peripheral sectors in background connectivity to these regions were associated with better performance on the visual task and faster response times on correct trials. These findings are consistent with the notion that attention drives the configuration of task-specific functional pathways that enable the prioritized processing of task-relevant visual information, and show that the prioritization of visual information by attentional processes may be encoded in the retinotopic gradient of connectivty between V1 and fronto-parietal regions.

Processing speed training increases the efficiency of attentional resource allocation in young adults.

Cognitive training has been shown to improve performance on a range of tasks. However, the mechanisms underlying these improvements are still unclear. Given the wide range of transfer effects, it is likely that these effects are due to a factor common to a wide range of tasks. One such factor is a participants efficiency in allocating limited cognitive resources. The impact of a cognitive training program, Processing Speed Training (PST), on the allocation of resources to a set of visual tasks was measured using pupillometry in 10 young adults as compared to a control group of a 10 young adults (n = 20). PST is a well-studied computerized training program that involves identifying simultaneously presented central and peripheral stimuli. As training progresses, the task becomes increasingly more difficult, by including peripheral distracting stimuli and decreasing the duration of stimulus presentation. Analysis of baseline data confirmed that pupil diameter reflected cognitive effort. After training, participants randomized to PST used fewer attentional resources to perform complex visual tasks as compared to the control group. These pupil diameter data indicated that PST appears to increase the efficiency of attentional resource allocation. Increases in cognitive efficiency have been hypothesized to underlie improvements following experience with action video games, and improved cognitive efficiency has been hypothesized to underlie the benefits of PST in older adults. These data reveal that these training schemes may share a common underlying mechanism of increasing cognitive efficiency in younger adults.

Would the field of cognitive neuroscience be advanced by sharing functional MRI data

During the past two decades, the advent of functional magnetic resonance imaging (fMRI) has fundamentally changed our understanding of brain-behavior relationships. However, the data from any one study add only incrementally to the big picture. This fact raises important questions about the dominant practice of performing studies in isolation. To what extent are the findings from any single study reproducible? Are researchers who lack the resources to conduct a fMRI study being needlessly excluded? Is pre-existing fMRI data being used effectively to train new students in the field? Here, we will argue that greater sharing and synthesis of raw fMRI data among researchers would make the answers to all of these questions more favorable to scientific discovery than they are today and that such sharing is an important next step for advancing the field of cognitive neuroscience.

Cortical thickness in frontoparietal and cingulo-opercular networks predicts executive function performance in older adults.

OBJECTIVE This study examined the relationship between cortical thickness in executive control networks and neuropsychological measures of executive function. METHOD Forty-one community-dwelling older adults completed an MRI scan and a neuropsychological battery including 5 measures of executive function. RESULTS Factor analysis of executive function measures revealed 2 distinct factors: (a) Complex Attention Control (CAC), comprised of tasks that required immediate response to stimuli and involved subtle performance feedback; and (b) Sustained Executive Control (SEC), comprised of tasks that involved maintenance and manipulation of information over time. Neural networks of interest were the frontoparietal network (F-P) and cingulo-opercular network (C-O), which have previously been hypothesized to relate to different components of executive function, based on functional MRI studies, but not neuropsychological factors. Linear regression models revealed that greater cortical thickness in the F-P network, but not the C-O network, predicted better performance on the CAC factor, whereas greater cortical thickness in the C-O network, but not the F-P network, predicted better performance on the SEC factor. CONCLUSIONS The relationship between cortical thickness and performance on executive function measures was characterized by a double dissociation between the thickness of cortical regions hypothesized to be involved in executive control and distinct executive processes. Results indicate that fundamentally different executive processes may be predicted by cortical thickness in distinct brain networks.

Alpha-band EEG activity in perceptual learning.

In studies of perceptual learning (PL), subjects are typically highly trained across many sessions to achieve perceptual benefits on the stimuli in those tasks. There is currently significant debate regarding what sources of brain plasticity underlie these PL-based learning improvements. Here we investigate the hypothesis that PL, among other mechanisms, leads to task automaticity, especially in the presence of the trained stimuli. To investigate this hypothesis, we trained participants for eight sessions to find an oriented target in a field of near-oriented distractors and examined alpha-band activity, which modulates with attention to visual stimuli, as a possible measure of automaticity. Alpha-band activity was acquired via electroencephalogram (EEG), before and after training, as participants performed the task with trained and untrained stimuli. Results show that participants underwent significant learning in this task (as assessed by threshold, accuracy, and reaction time improvements) and that alpha power increased during the pre-stimulus period and then underwent greater desynchronization at the time of stimulus presentation following training. However, these changes in alpha-band activity were not specific to the trained stimuli, with similar patterns of posttraining alpha power for trained and untrained stimuli. These data are consistent with the view that participants were more efficient at focusing resources at the time of stimulus presentation and are consistent with a greater automaticity of task performance. These findings have implications for PL, as transfer effects from trained to untrained stimuli may partially depend on differential effort of the individual at the time of stimulus processing.