Peter Manza

A Prospective Study of Loss of Consciousness in Epilepsy Using Virtual Reality Driving Simulation and Other Video Games

Patients with epilepsy are at risk of traffic accidents when they have seizures while driving. However, driving is an essential part of normal daily life in many communities, and depriving patients of driving privileges can have profound consequences for their economic and social well-being. In the current study, we collected ictal performance data from a driving simulator and two other video games in patients undergoing continuous video/EEG monitoring. We captured 22 seizures in 13 patients and found that driving impairment during seizures differed in terms of both magnitude and character, depending on the seizure type. Our study documents the feasibility of a prospective study of driving and other behaviors during seizures through the use of computer-based tasks. This methodology may be applied to further describe differential driving impairment in specific types of seizures and to gain data on anatomical networks disrupted in seizures that impair consciousness and driving safety.

Alpha power gates relevant information during working memory updating.

Human working memory (WM) is inherently limited, so we must filter out irrelevant information in our environment or our mind while retaining limited important relevant contents. Previous work suggests that neural oscillations in the alpha band (8–14 Hz) play an important role in inhibiting incoming distracting information during attention and selective encoding tasks. However, whether alpha power is involved in inhibiting no-longer-relevant content or in representing relevant WM content is still debated. To clarify this issue, we manipulated the amount of relevant/irrelevant information using a task requiring spatial WM updating while measuring neural oscillatory activity via EEG and localized current sources across the scalp using a surface Laplacian transform. An initial memory set of two, four, or six spatial locations was to be memorized over a delay until an updating cue was presented indicating that only one or three locations remained relevant for a subsequent recognition test. Alpha amplitude varied with memory maintenance and updating demands among a cluster of left frontocentral electrodes. Greater postcue alpha power was associated with the high relevant load conditions (six and four dots cued to reduce to three relevant) relative to the lower load conditions (four and two dots reduced to one). Across subjects, this difference in alpha power was correlated with condition differences in performance accuracy. In contrast, no significant effects of irrelevant load were observed. These findings demonstrate that, during WM updating, alpha power reflects maintenance of relevant memory contents rather than suppression of no-longer-relevant memory traces.

Resting-state functional connectivity of the striatum in early-stage Parkinson's disease: Cognitive decline and motor symptomatology.

Parkinsons disease is a neurodegenerative disorder characterized by changes to dopaminergic function in the striatum and a range of cognitive and motor deficits. Neuroimaging studies have repeatedly shown differences in activation and functional connectivity patterns of the striatum between symptomatic individuals with Parkinsons disease and healthy controls. However, the presence and severity of cognitive and motor symptoms seem to differ dramatically among individuals with Parkinsons disease at the early‐stages. To investigate the neural basis of such heterogeneity, we examined the resting state functional connectivity patterns of caudate and putamen subdivisions in relation to cognitive and motor impairments among 62 early‐stage individuals with Parkinsons disease (21 females, 23 drug naive, ages 39–77 years, average UPDRS motor scores off medication = 18.56, average H&Y stage = 1.66). We also explored how changes in striatal connectivity relate to changes in symptomatology over a year. There are two main findings. First, higher motor deficit rating was associated with weaker coupling between anterior putamen and midbrain including substantia nigra. Intriguingly, steeper declines in functional connectivity between these regions were associated with greater declines in motor function over the course of 1 year. Second, decline in cognitive function, particularly in the memory and visuospatial domains, was associated with stronger coupling between the dorsal caudate and the rostral anterior cingulate cortex. These findings remained significant after controlling for age, medication, gender, and education. In sum, our findings suggest that cognitive decline and motor deficit are each associated with a differentiable pattern of functional connectivity of striatal subregions. Hum Brain Mapp 37:648–662, 2016.

Hemispheric Lateralization of Resting-State Functional Connectivity of the Anterior Insula: Association with Age, Gender, and a Novelty-Seeking Trait

Abstract Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The imaging literature has described lateralization of insula activations during cognitive and affective processing. Evidence appears to support a role of the right-hemispheric insula in attentional orientation to salient stimulus, interoception, and physiological arousal, and a role of the left-hemispheric insula in cognitive and affective control, as well as perspective taking. In this study, in a large data set of healthy adults, we examined lateralization of the rsFC of the anterior insula (AI) by computing a laterality index (LI) of connectivity with 54 regions from the Automated Anatomic Labeling atlas. At a corrected threshold (p < 0.001), the AI is left lateralized in connectivity with the dorsomedial prefrontal cortex, superior frontal gyrus, inferior frontal cortex, and posterior orbital gyrus and right lateralized in connectivity with the postcentral gyrus, supramarginal gyrus, and superior parietal lobule. In gender differences, women, but not men, showed right-lateralized connectivity to the thalamus. Furthermore, in a subgroup of participants assessed by the tridimensional personality questionnaire, novelty seeking is correlated with the extent of left lateralization of AI connectivity to the pallidum and putamen in men and with the extent of right lateralization of AI connectivity to the parahippocampal gyrus in women. These findings support hemispheric functional differentiation of the AI.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task.

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior.

A dual but asymmetric role of the dorsal anterior cingulate cortex in response inhibition and switching from a non-salient to salient action

Response inhibition and salience detection are among the most studied psychological constructs of cognitive control. Despite a growing body of work, how inhibition and salience processing interact and engage regional brain activations remains unclear. Here, we examined this issue in a stop signal task (SST), where a prepotent response needs to be inhibited to allow an alternative, less dominant response. Sixteen adult individuals performed two versions of the SST each with 25% (SST25) and 75% (SST75) of stop trials. We posited that greater regional activations to the infrequent trial type in each condition (i.e., to stop as compared to go trials in SST25 and to go as compared to stop trials in SST75) support salience detection. Further, successful inhibition in stop trials requires attention to the stop signal to trigger motor inhibition, and the stop signal reaction time (SSRT) has been used to index the efficiency of motor response inhibition. Therefore, greater regional activations to stop as compared to go success trials in association with the stop signal reaction time (SSRT) serve to expedite response inhibition. In support of an interactive role, the dorsal anterior cingulate cortex (dACC) increases activation to salience detection in both SST25 and SST75, but only mediates response inhibition in SST75. Thus, infrequency response in the dACC supports motor inhibition only when stopping has become a routine. In contrast, although the evidence is less robust, the pre-supplementary motor area (pre-SMA) increases activity to the infrequent stimulus and supports inhibition in both SST25 and SST75. These findings clarify a unique role of the dACC and add to the literature that distinguishes dACC and pre-SMA functions in cognitive control.

Response inhibition in Parkinson’s disease: a meta-analysis of dopaminergic medication and disease duration effects

Parkinson’s disease is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. Dopamine-replacement therapy ameliorates some of the hallmark motor symptoms of Parkinson’s disease, but whether these medications improve deficits in response inhibition, a critical executive function for behavioral control, has been questioned. Several studies of Parkinson’s disease patients “on” and “off” (12-h withdrawal) dopaminergic medications suggested that dopamine-replacement therapy did not provide significant response inhibition benefits. However, these studies tended to include patients with moderate-to-advanced Parkinson’s disease, when the efficacy of dopaminergic drugs is reduced compared to early-stage Parkinson’s disease. In contrast, a few recent studies in early-stage Parkinson’s disease report that dopaminergic drugs do improve response inhibition deficits. Based on these findings, we hypothesized that Parkinson’s disease duration interacts with medication status to produce changes in cognitive function. To investigate this issue, we conducted a meta-analysis of studies comparing patients with Parkinson’s disease and healthy controls on tests of response inhibition (50 comparisons from 42 studies). The findings supported the hypothesis; medication benefited response inhibition in patients with shorter disease duration, whereas “off” medication, moderate deficits were present that were relatively unaffected by disease duration. These findings support the role of dopamine in response inhibition and suggest the need to consider disease duration in research of the efficacy of dopamine-replacement therapy on cognitive function in Parkinson’s disease.

Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson's disease

Dopaminergic medications improve the motor symptoms of Parkinsons disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during functional magnetic resonance imaging. In contrast to previous studies reporting null effects in more advanced PD, levodopa significantly improved response inhibition performance in our sample. No significant group differences were found in brain activations to pure motor inhibition or error processing (stop success vs. error trials). However, relative to controls, the PD group showed weaker striatal activations to salient events (infrequent vs. frequent events: stop vs. go trials) and fronto-striatal task-residual functional connectivity; both were restored with levodopa. Thus, levodopa appears to improve an important executive function in early-stage PD via enhanced salient signal processing, shedding new light on the role of dopaminergic signaling in response inhibition.

Spontaneous but not voluntary eye blinks during spatial working memory are associated with successful performance

Spontaneous eye blink rate (SBR) has been associated with central dopamine (DA) levels, raising the intriguing possibility that SBR is related to cognitive functions dependent on DA, such as spatial working memory (WM). We tested this hypothesis in two behavioral experiments, examining the relationship between SBR, WM load and individual differences in spatial WM performance in 126 young adults. In Experiment 1, we examined the temporal profile of SBR during a spatial delayed recognition task requiring maintenance of 1, 2, 4, 6 or 7 dot locations. We observed a suppression in SBR during dot- and recognition probe-presentation, and a significant increase in SBR afterwards. High performers showed significantly lower SBR than low performers during the first 500 ms of the delay period. In Experiment 2, we used a similar spatial WM task as Experiment 1 to test whether an instructed voluntary blink during the early delay would directly dampen WM performance. While the temporal dynamics of SBR across task events were comparable to Experiment 1, WM performance was not significantly different between the voluntary blink and no blink conditions. Together, these results suggest that spontaneous but not voluntary eye blinking is closely linked to spatial WM, and that lower SBR during WM encoding and early phase of maintenance is associated with better WM task performance.

Abnormal frontostriatal tracts in young male tobacco smokers

&NA; Dysfunctions in frontostriatal circuits have been associated with craving and cognitive control in smokers. However, the relevance of white matter (WM) diffusion properties of the ventral and dorsal frontostriatal tracts for behaviors associated with smoking remains relatively unknown, especially in young adulthood, a critical time period for the development and maintenance of addiction. Here, diffusion tensor imaging (DTI) and probabilistic tractography were used to investigate the WM tracts of the ventral and dorsal frontostriatal circuits in two independent studies (Study1: 36 male smokers (21.3 ± 1.3 years) vs. 35 male nonsmokers (21.2 ± 1.3 years); Study2: 29 male smokers (21.4 ± 1.1 years) vs. 25 male nonsmokers (21.0 ± 1.4 years)). Subjective craving was measured by the Questionnaire on Smoking Urges (QSU) and cognitive control ability was assessed with the Stroop task. In both studies, smokers committed more response errors than nonsmokers during the incongruent condition of the Stroop task. Relative to controls, smokers showed lower fractional anisotropy (FA) and higher radial diffusivity in left medial orbitofrontal cortex‐to‐nucleus accumbens fiber tracts (ventral frontostriatal path) and also lower FA in right dorsolateral prefrontal cortex‐to‐caudate fiber tracts (dorsal frontostriatal path). The FA values of the right dorsal fibers were negatively correlated with incongruent response Stroop errors in smokers, whereas the mean diffusivity values of the left ventral fibers were positively correlated with craving in smokers. Thus, WM diffusion properties of the dorsal and ventral frontostriatal tracts were associated with cognitive control and craving, respectively, in young male tobacco smokers. These data highlight the importance of studying WM in relation to neuropsychological changes underlying smoking.