Kara A. Dyckman

Neurophysiology and neuroanatomy of reflexive and volitional saccades: Evidence from studies of humans

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human (e.g., single-unit recordings) and human (e.g., lesions and neuroimaging) primates. Considerable knowledge of this systems functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in pro-saccade generation (by definition largely exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields) structures. Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g., anti-saccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution.

An effect of context on saccade-related behavior and brain activity

The present study evaluated the effect of context on behavior and brain activity during saccade tasks. FMRI and eye movement data were collected while 36 participants completed three runs in a block design: (1) fixation alternating with pro-saccades, (2) fixation alternating with anti-saccades, and (3) pro- alternating with anti-saccades. Two task-related data-driven regressors, identified using independent component analysis, were used in GLM analyses. Brain activity associated with anti- and pro-saccades were compared under both single (runs 1 and 2) and mixed saccade (run 3) conditions. Brain areas consistently associated with anti-saccades in previous studies, including striatum, thalamus, cuneus, precuneus, lateral and medial frontal eye fields (FEF), supplementary eye fields (SEF), and prefrontal cortex (PFC) showed significantly greater percent signal change during the fixation/anti- compared with the fixation/pro-saccade run. During the pro/anti run, however, only precuneus, SEF and FEF showed greater activation during the anti-saccade trials. This is a clear demonstration that the saccade-related neural circuitry is affected by context. Behavioral results suggest that performance on saccade tasks is also affected by context. Participants made more direction errors on pro-trials that followed anti-trials than on pro-trials that followed fixation. Results from this study indicate that precuneus, SEF and FEF, which showed anti-saccade-related activity during both comparisons, may be more important for supporting this complex behavioral response. Other brain regions, such as PFC, however, which showed anti-saccade-related activity during only the single task comparison, may be more involved in response selection and/or context updating.

Multimodal neuroimaging dissociates hemodynamic and electrophysiological correlates of error processing

Recognizing errors and adjusting responses are fundamental to adaptive behavior. The error-related negativity (ERN) and error-related functional MRI (fMRI) activation of the dorsal anterior cingulate cortex (dACC) index these processes and are thought to reflect the same neural mechanism. In the present study, we evaluated this hypothesis. Although errors elicited robust dACC activation using fMRI, combined electroencephalography and magnetoencephalography data localized the ERN to the posterior cingulate cortex (PCC). ERN amplitude correlated with fMRI activation in both the PCC and dACC, and these two regions showed coordinated activity based on functional connectivity MRI. Finally, increased microstructural integrity of the posterior cingulum bundle, as measured by diffusion tensor imaging, predicted faster error correction. These findings suggest that the PCC generates the ERN and communicates with the dACC to subserve error processing. They challenge current models that view fMRI activation of the dACC as the hemodynamic reflection of the ERN.

Electroencephalography/magnetoencephalography study of cortical activities preceding prosaccades and antisaccades

The temporal and spatial characteristics of brain activity preceding prosaccades and antisaccades were investigated using source reconstructions of 64-channel electroencephalography and 148-channel magnetoencephalography data. Stimulus-locked data showed early cuneus activity was stronger during antisaccades, and later occipital gyrus activity was stronger preceding prosaccades, which suggests a top-down influence on early visual processing. Response-locked data showed that supplementary eye field, prefrontal cortex, and medial frontal eye field activity was greater for antisaccades than for prosaccades prior to saccade generation. Lateral frontal eye field activity appeared to be inhibited prior to antisaccade response generation. The spatial and temporal resolution of combined electroencephalography/magnetoencephalography data allows the evaluation of specific cortical activities preceding saccades and for demonstration of how activities differ as a function of response contingencies.

Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during delayed response tasks.

BACKGROUND Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. METHODS The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. RESULTS Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. CONCLUSIONS These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.

Common neural circuitry supporting volitional saccades and its disruption in schizophrenia patients and relatives

BACKGROUND People with schizophrenia and their biological relatives have deficits in executive control processes such as inhibition and working memory as evidenced by performance abnormalities on antisaccade (AS) and ocular motor delayed response (ODR) tasks. METHODS The present functional magnetic resonance imaging (fMRI) study was conducted to investigate brain activity associated with these putative indices of schizophrenia risk by: 1) directly comparing neural functioning in 15 schizophrenia patients, 13 of their first-degree biological relatives (primarily siblings), and 14 healthy participants; and 2) assessing executive function associated with volitional saccades by using a combination of AS and ODR tasks. RESULTS Behavioral data showed that patients and relatives both made more volitional saccade errors. Imaging data demonstrated that within the context of preserved activity in some neural regions in patients and relatives, there were two distinct patterns of disruptions in other regions. First, there were deficits observed only in the schizophrenia group (decreased activity in lateral frontal eye field and supplementary eye field), suggesting a change associated with disease manifestation. Second, there were deficits observed in both patients and relatives (decreased activity in middle occipital gyrus, insula, cuneus, anterior cingulate, and Brodmann area 10 in prefrontal cortex), indicating a potential association with disease risk. CONCLUSIONS Results indicate that decreased brain activation in regions involved in managing and evaluating early sensory and attention processing might be associated with poor volitional saccade control and risk for developing schizophrenia.

Behavioral plasticity of antisaccade performance following daily practice

The ability to change behavior to adapt to the environment, known as behavioral plasticity, is an important part of daily life. In the present study subjects’ performances on antisaccade tasks were manipulated by training them on one of three different eye movement tasks (antisaccade, prosaccade, and fixation). Thirty subjects were tested at three time points over a 2-week period and practiced their assigned task every day between test sessions. Subjects who trained on antisaccades significantly decreased their error rates, while maintaining their reaction time, suggesting that accuracy did not improve at the expense of speed. Subjects who practiced the prosaccade task made more errors on the antisaccade task on subsequent test sessions, while those who practiced the fixation task showed no change across test sessions. These results suggest that deliberate practice of eye movement tasks can alter antisaccade performance, and that the direction of the effect is dependent upon the type of practice in which the subject engages.

Preparatory Activations across a Distributed Cortical Network Determine Production of Express Saccades in Humans

Reaction time variability across trials to identical stimuli may arise from both ongoing and transient neural processes occurring before trial onset. These processes were examined with dense-array EEG as humans completed saccades in a “gap” paradigm known to elicit bimodal variability in response times, including separate populations of “express” and regular reaction time saccades. Results indicated that express reaction time trials could be differentiated from regular reaction time trials by (1) pretrial phase synchrony of occipital cortex oscillations in the 8–9 Hz (low alpha) frequency range (lower phase synchrony preceding express trials), (2) subsequent mid- and late-gap period cortical activities across a distributed occipital-parietal network (stronger activations preceding express trials), and (3) posttarget parietal activations locked to response generation (weaker preceding express trials). A post hoc path analysis suggested that the observed cortical activations leading to express saccades are best understood as an interdependent chain of events that affect express saccade production. These results highlight the importance of a distributed posterior cortical network, particularly in right hemisphere, that prepares the saccade system for rapid responding.

Reduced functional connectivity in a right-hemisphere network for volitional ocular motor control in schizophrenia

Patients with schizophrenia consistently show deficient performance on tasks requiring volitional saccades. We previously reported reduced fractional anisotropy in the white matter underlying right dorsal anterior cingulate cortex in schizophrenia, which, along with lower fractional anisotropy in the right frontal eye field and posterior parietal cortex, predicted longer latencies of volitional saccades. This suggests that reduced microstructural integrity of dorsal anterior cingulate cortex white matter disrupts connectivity in the right hemisphere-dominant network for spatial attention and volitional ocular motor control. To test this hypothesis, we examined functional connectivity of the cingulate eye field component of this network, which is located in dorsal anterior cingulate cortex, during a task comprising volitional prosaccades and antisaccades. In patients with schizophrenia, we expected to find reduced functional connectivity, specifically in the right hemisphere, which predicted prolonged saccadic latency. Twenty-seven medicated schizophrenia outpatients and 21 demographically matched healthy controls performed volitional saccades during functional magnetic resonance imaging. Based on task-related activation, seed regions in the right and left cingulate eye field were defined. In both groups, the right and left cingulate eye field showed positive correlations with the ocular motor network and negative correlations with the default network. Patients showed reduced positive functional connectivity of the cingulate eye field, specifically in the right hemisphere. Negative functional connectivity of the right cingulate eye field predicted faster saccades, but these relations differed by group, and were only present in controls. This pattern of relations suggests that the coordination of activity between ocular motor and default networks is important for efficient task performance and is disrupted in schizophrenia. Along with prior observations of reduced white matter microstructural integrity (fractional anisotropy) in schizophrenia, the present finding of reduced functional connectivity suggests that functional and structural abnormalities of the right cingulate eye field disrupt connectivity in the network for spatial attention and volitional ocular motor control. These abnormalities may contribute to deficits in overcoming prepotency in the service of directing eye gaze and attention to the parts of the environment that are the most behaviourally relevant.

A magnetoencephalography investigation of neural correlates for social exclusion and self-control

Abstract Past research indicates that social exclusion leads to self-control failure. The present research examined the neural substrates of this effect. Participants were randomly assigned to either a social exclusion (n=15) or control (n=15) condition. Self-control was assessed by having participants solve 180 moderately difficult math problems while measuring how quickly they identified a supplied answer as correct or incorrect. Magnetoencephalography (MEG) was used to assess neural activity during this task. Socially excluded participants showed lesser activity in occipital and parietal cortex from 100–350 ms after the presentation of the math problems. When presented with the answers, socially excluded participants showed lesser activity in several regions, including occipital, parietal, and right prefrontal cortex from 100–300 ms post-stimulus. Furthermore, activation in the parietal and right prefrontal cortex mediated exclusion-control performance differences on math problems. The findings suggest that social exclusion interferes with the executive control of attention, and this effect is manifest in specific aspects of cognitive performance and brain function.