Nathan A. Parks

Frontal Theta Cordance Predicts 6-Month Antidepressant Response to Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression: A Pilot Study

Deep brain stimulation (DBS) of subcallosal cingulate white matter (SCC) may be an effective approach for treatment-resistant depression (TRD) that otherwise fails to respond to more conventional therapies, but DBS is invasive, costly, and has potential for adverse effects. Therefore, it is important to identify potential biomarkers for predicting antidepressant response before intervention. Resting-state EEG was recorded from 12 TRD patients at pre-treatment baseline, after 4 weeks SCC DBS, and after 24 weeks SCC DBS. Lower frontal theta cordance (FTC) at baseline (and higher FTC after 4 weeks) predicted lower depression severity scores after 24 weeks. Greater FTC increases (baseline–4 weeks) predicted greater decreases in depression severity scores subsequently (4–24 weeks) and over the course of the study (baseline–24 weeks). Predictive relationships were topographically specific to theta cordance for frontal electrodes. Thus, results from this pilot study suggest that baseline FTC and changes early in treatment each have utility as biomarkers for predicting 6-month clinical response to SCC DBS for TRD.

Steady-state signatures of visual perceptual load, multimodal distractor filtering, and neural competition

The perceptual load theory of attention posits that attentional selection occurs early in processing when a task is perceptually demanding but occurs late in processing otherwise. We used a frequency-tagged steady-state evoked potential paradigm to investigate the modality specificity of perceptual load-induced distractor filtering and the nature of neural-competitive interactions between task and distractor stimuli. EEG data were recorded while participants monitored a stream of stimuli occurring in rapid serial visual presentation (RSVP) for the appearance of previously assigned targets. Perceptual load was manipulated by assigning targets that were identifiable by color alone (low load) or by the conjunction of color and orientation (high load). The RSVP task was performed alone and in the presence of task-irrelevant visual and auditory distractors. The RSVP stimuli, visual distractors, and auditory distractors were “tagged” by modulating each at a unique frequency (2.5, 8.5, and 40.0 Hz, respectively), which allowed each to be analyzed separately in the frequency domain. We report three important findings regarding the neural mechanisms of perceptual load. First, we replicated previous findings of within-modality distractor filtering and demonstrated a reduction in visual distractor signals with high perceptual load. Second, auditory steady-state distractor signals were unaffected by manipulations of visual perceptual load, consistent with the idea that perceptual load-induced distractor filtering is modality specific. Third, analysis of task-related signals revealed that visual distractors competed with task stimuli for representation and that increased perceptual load appeared to resolve this competition in favor of the task stimulus.

Competitive interaction degrades target selection: an ERP study.

Localized attentional interference (LAI) occurs when attending to a visual object degrades processing of nearby objects. Competitive interaction accounts of LAI explain the phenomenon as the result of competition among objects for representation in extrastriate cortex. Here, we examined the N2pc component of the event-related potential (ERP) as a likely neural correlate of LAI. In Experiment 1, participants responded to the orientation of a target while ignoring a nearby decoy. At small target-decoy separations, N2pc amplitude was attenuated whereas the amplitude of a later, positive component (Ptc) was potentiated. Experiment 2 ruled out sensory explanations of these effects. The N2pc results are consistent with the idea that spatially mediated competition for representation in extrastriate cortex degrades target selection. Moreover, the Ptc may reflect a bias signal needed to resolve the competition at smaller target-decoy separations.

Dynamics of target and distractor processing in visual search: Evidence from event-related brain potentials

When multiple objects are present in a visual scene, salient and behaviorally relevant objects are attentionally selected and receive enhanced processing at the expense of less salient or less relevant objects. Here we examined three lateralized components of the event-related potential (ERP) - the N2pc, Ptc, and SPCN - as indices of target and distractor processing in a visual search paradigm. Participants responded to the orientation of a target while ignoring an attentionally salient distractor and ERPs elicited by the target and the distractor were obtained. Results indicate that both the target and the distractor elicit an N2pc component which may index the initial attentional selection of both objects. In contrast, only the distractor elicited a significant Ptc, which may reflect the subsequent suppression of distracting or irrelevant information. Thus, the Ptc component appears to be similar to another ERP component - the Pd - which is also thought to reflect distractor suppression. Furthermore, only the target elicited an SPCN component which likely reflects the representation of the target in visual short term memory.

Effects of Subcallosal Cingulate Deep Brain Stimulation on Negative Self-bias in Patients With Treatment-resistant Depression

BACKGROUND The cognitive neuropsychological model states that antidepressant treatment alters emotional biases early in treatment, and after this initial change in emotional processing, environmental and social interactions allow for long-term/sustained changes in mood and behavior. OBJECTIVE Changes in negative self-bias after chronic subcallosal cingulate (SCC) deep brain stimulation (DBS) were investigated with the hypothesis that treatment would lead to changes in emotional biases followed by changes in symptom severity. METHODS Patients (N = 7) with treatment-resistant depression were assessed at three time points: pre-treatment; after one month stimulation; and after six months stimulation. The P1, P2, P3, and LPP (late positive potential) components of the event-related potential elicited by positive and negative trait adjectives were recorded in both a self-referential task and a general emotion recognition task. RESULTS Results indicate that DBS reduced automatic attentional bias toward negative words early in treatment, as indexed by the P1 component, and controlled processing of negative words later in treatment, as indexed by the P3 component. Reduction in negative words endorsed as self-descriptive after six months DBS was associated with reduced depression severity after six months DBS. Change in emotional processing may be restricted to the self-referential task. CONCLUSIONS Together, these results suggest that the cognitive neuropsychological model, developed to explain the time-course of monoamine antidepressant treatment, may also be used as a framework to interpret the antidepressant effects of SCC DBS.

Examining cortical dynamics and connectivity with simultaneous single-pulse transcranial magnetic stimulation and fast optical imaging

Transcranial magnetic stimulation (TMS) is a widely used experimental and clinical technique that directly induces activity in human cortex using magnetic fields. However, the neural mechanisms of TMS-induced activity are not well understood. Here, we introduce a novel method of imaging TMS-evoked activity using a non-invasive fast optical imaging tool, the event-related optical signal (EROS). EROS measures changes in the scattering of near-infrared light that occur synchronously with electrical activity in cortical tissue. EROS has good temporal and spatial resolution, allowing the dynamics and spatial spread of a TMS pulse to be measured. We used EROS to monitor activity induced in primary motor cortex (M1) by a TMS pulse. Left- and right-hand representations were mapped using standard TMS procedures. Optical sources and detectors mounted on thin rubber patches were then centered on M1 hand representations. EROS was recorded bilaterally from motor cortex while unilateral TMS was simultaneously delivered. Robust ipsilateral EROS activations were apparent within 16 ms of a pulse for TMS delivered to both left and right hemispheres. Clear motor evoked potentials (MEPs) were also elicited by these TMS pulses. Movement artifacts could be excluded as a source of EROS, as no activation was present on short-distance optical channels. For left hemisphere TMS subsequent (40 ms) contralateral activity was also present, presumably due to trans-synaptic propagation of TMS-evoked activity. Results demonstrate that concurrent TMS/EROS is a viable and potentially powerful method for studying TMS-induced activity in the human brain. With further development, this technique may be applied more broadly in the study of the dynamics of causal cortico-cortical connectivity.

Human transsaccadic visual processing: Presaccadic remapping and postsaccadic updating

With every movement of the eye the visual field is drastically displaced in space. However, our visual experience is stable rather than constantly jittering with every saccade. One neural mechanism thought to underlie such spatial constancy across saccades is predictive remapping in which visual receptive fields remap to non-classical future locations in anticipation of a forthcoming saccade. We investigated mechanisms of predictive remapping in humans using a cross-hemispheric remapping paradigm. EEG was recorded while subjects performed a task requiring leftward and rightward horizontal saccades in the presence of salient peripheral stimuli. Saccades caused the peripheral stimuli to either shift between the two visual hemifields (Cross condition), necessitating remapping between cerebral hemispheres or to shift within a single visual hemifield (Within condition), requiring remapping only within a single hemisphere. Saccade-locked event-related potentials were calculated for each of these conditions. A baseline saccade-only condition was subtracted from experimental conditions to isolate remapping activity from activity related to saccade planning and generation. In a presaccadic time window difference waveforms were consistent with predictive remapping, exhibiting an ipsilateral positivity in the Cross condition and a contralateral positivity in the Within condition. This result is consistent with the occurrence of remapping in advance of a saccade. A similar pattern was also apparent in an intrasaccadic time window suggesting that predictive remapping persists during saccadic execution. Examination of postsaccadic visual responses revealed that hemispheric distributions of Cross and Within conditions matched the distribution of the corresponding presaccadic remapping response suggesting that the pressacadic response indeed reflects a shift of visual representations to match that of postsaccadic space.

Enhancement and suppression in the visual field under perceptual load

The perceptual load theory of attention proposes that the degree to which visual distractors are processed is a function of the attentional demands of a task—greater demands increase filtering of irrelevant distractors. The spatial configuration of such filtering is unknown. Here, we used steady-state visual evoked potentials (SSVEPs) in conjunction with time-domain event-related potentials (ERPs) to investigate the distribution of load-induced distractor suppression and task-relevant enhancement in the visual field. Electroencephalogram (EEG) was recorded while subjects performed a foveal go/no-go task that varied in perceptual load. Load-dependent distractor suppression was assessed by presenting a contrast reversing ring at one of three eccentricities (2, 6, or 11°) during performance of the go/no-go task. Rings contrast reversed at 8.3 Hz, allowing load-dependent changes in distractor processing to be tracked in the frequency-domain. ERPs were calculated to the onset of stimuli in the load task to examine load-dependent modulation of task-relevant processing. Results showed that the amplitude of the distractor SSVEP (8.3 Hz) was attenuated under high perceptual load (relative to low load) at the most proximal (2°) eccentricity but not at more eccentric locations (6 or 11°). Task-relevant ERPs revealed a significant increase in N1 amplitude under high load. These results are consistent with a center-surround configuration of load-induced enhancement and suppression in the visual field.

Anger management: age differences in emotional modulation of visual processing.

Although positive and negative images enhance the visual processing of young adults, recent work suggests that a life-span shift in emotion processing goals may lead older adults to avoid negative images. To examine this tendency for older adults to regulate their intake of negative emotional information, the current study investigated age-related differences in the perceptual boost received by probes appearing over facial expressions of emotion. Visually-evoked event-related potentials were recorded from the scalp over cortical regions associated with visual processing as a probe appeared over facial expressions depicting anger, sadness, happiness, or no emotion. The activity of the visual system in response to each probe was operationalized in terms of the P1 component of the event-related potentials evoked by the probe. For young adults, the visual system was more active (i.e., greater P1 amplitude) when the probes appeared over any of the emotional facial expressions. However, for older adults, the visual system displayed reduced activity when the probe appeared over angry facial expressions.

Attending to depth: electrophysiological evidence for a viewer-centered asymmetry.

It has been proposed that the configuration of visuospatial attention in depth is viewer-centered such that an attentional gradient is concentrated between an observer and attended depth, trailing off steeply beyond. To investigate this asymmetry, event-related potentials were recorded while participants attended to far or near depths in a pictorial scene. The attention-sensitive visual components, P1 (100–160 ms) and N1 (160–220 ms), were assessed for amplitude differences. Amplitude enhancement of the P1 component was present when participants attended far but not near depths. Reaction time facilitation also followed this pattern. Results are consistent with a viewer-centered asymmetry because such a configuration predicts the gradient of attention to distribute differentially to far depths but to remain constant for near depths.