Brain functional connectivity correlates of anomalous interaction between sensorily isolated monozygotic twins.

This study examined brain functional connectivity (FC) changes associated with possible anomalous interactions between sensorily isolated monozygotic (MZ) twins. Brain FC was estimated using the Steady State Visual Evoked Potential-Event Related Partial Coherence (SSVEP-ERPC) methodology. Five twin pairs served twice as participants, with an average interval between sessions of 67 days. In each recording session, one twin, the Sender, viewed a randomized set of 50 general images and 50 personally relevant images, while the other twin, the Receiver, viewed a static personally relevant image for the entire duration of the session. Images appeared on the Sender screen for 1.0 s, with the interval between successive images varied randomly between 4.0 and 8.0 s. Receiver FC changes were calculated based on the appearance times of the images as viewed by the Sender. It was hypothesized that anomalous interactions would be indicated by statistically significant Receiver FC changes when those changes are determined using the Sender image appearance times. For each twin serving as Receiver, FC components were separately analyzed for the 50 general and the 50 personal images, yielding 38 observations (19 twin pairs by 2 conditions). The hypothesis was confirmed in that 11 of the 38 observations yielded statistically significant Receiver FC increases or decreases at the p < 0.01 level only when trials were synchronized to the Sender image appearance times. Overall, this effect was significant at the p = 4 × 10-8 Df = 175. To the best of our knowledge, this is the first study reporting statistically significant FC changes indicative of anomalous interactions between two sensorily isolated individuals.

Homocysteine Modulates Brain Functional Connectivity in a Memory Retrieval Task.

BACKGROUND: Homocysteine, a methionine metabolite, is a recognized risk factor for accelerated age-related cognitive decline and dementia. OBJECTIVE: In the light of studies indicating increases in brain activity and brain functional connectivity in the early stages of age-related cognitive decline, we undertook a study to examine the relationship between plasma homocysteine levels and brain functional connectivity in a group of late middle-aged males at risk of cognitive decline due to high body mass index and a sedentary lifestyle. METHODS: Brain functional connectivity was measured using the steady state visual evoked potential event related partial coherence while 38 participants performed a memory task where each trial comprised an object recognition task followed by a location memory task. RESULTS: We observed a significant transient peak in the correlation between plasma homocysteine levels and fronto-parietal brain functional connectivity immediately before the presentation of the memory location component of the task. Significantly, this correlation was only apparent if the participant pool included individuals with homocysteine concentrations above 11µmole/L. CONCLUSION: Our findings suggest that the increased brain functional connectivity observed in the earlier stages of age-related cognitive decline reflects pathognomonic changes in brain function and not compensatory changes engaged to enhance task performance. Our findings also suggest that homocysteine interferes with the inhibition of cortical networks where this inhibition is necessary for optimum task performance. Finally, we observed that the effect of homocysteine on brain functional connectivity is only apparent at concentrations above 11µmol/L.

Sex influences the brain functional connectivity correlates of originality.

Creative cognition is thought to involve two processes, the creation of new ideas and the selection and retention of suitable new ideas. Neuroimaging studies suggest that the Default Mode Network contributes to the creation of new ideas while left inferior frontal and parieto-temporal cortical networks mediate the selection/retention process. Higher levels of activity in the selection/retention have been shown to be associated with stricter criteria for selection and hence the expression of fewer novel ideas. In this study, we examined the brain functional connectivity correlates of an originality score while 27 males and 27 females performed a low and a high demand visual vigilance task. Brain functional connectivity was estimated from the steady state visual evoked potential event related partial coherence. In the male group, we observed a hypothesized left frontal functional connectivity that was negatively correlated with originality in both tasks. By contrast, in the female group no significant correlation between functional connectivity and originality was observed in either task. We interpret the findings to suggest that males and females engaged different functional networks when performing the vigilance tasks. We conclude with a consideration of the possible risks when data pooling across sex in studies of higher cortical function.

Continuous performance task in ADHD: Is reaction time variability a key measure?

OBJECTIVE: To compare the use of the Continuous Performance Task (CPT) reaction time variability (intraindividual variability or standard deviation of reaction time), as a measure of vigilance in attention-deficit hyperactivity disorder (ADHD), and stimulant medication response, utilizing a simple CPT X-task vs an A-X-task. METHOD: Comparative analyses of two separate X-task vs A-X-task data sets, and subgroup analyses of performance on and off medication were conducted. RESULTS: The CPT X-task reaction time variability had a direct relationship to ADHD clinician severity ratings, unlike the CPT A-X-task. Variability in X-task performance was reduced by medication compared with the children's unmedicated performance, but this effect did not reach significance. When the coefficient of variation was applied, severity measures and medication response were significant for the X-task, but not for the A-X-task. CONCLUSION: The CPT-X-task is a useful clinical screening test for ADHD and medication response. In particular, reaction time variability is related to default mode interference. The A-X-task is less useful in this regard.

First-Dose Methylphenidate-Induced Changes in Brain Functional Connectivity Are Correlated With 3-Month Attention-Deficit/Hyperactivity Disorder Symptom Response.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms are most commonly treated with stimulant medication such as methylphenidate (MPH); however, approximately 25% of patients show little or no symptomatic response. We examined the extent to which initial changes in brain functional connectivity (FC) associated with the first MPH dose in boys newly diagnosed with ADHD predict MPH-associated changes in ADHD inattentiveness and hyperactivity symptoms at 3 months. METHODS: Brain FC was estimated using steady-state visual evoked potential partial coherence before and 90 minutes after the administration of the first MPH dose to 40 stimulant drug-naïve boys newly diagnosed with ADHD while they performed the AX version of the continuous performance task. The change in parent-rated inattention and hyperactivity scores over the first 3 months of MPH medication was correlated with the initial 90-minute MPH-mediated FC changes. RESULTS: Hyperactivity improvements at 3 months were associated with first-dose MPH-mediated FC reductions restricted to frontal-prefrontal sites following the appearance of the "A" and at frontal and right temporal sites during the appearance of the "X." Corresponding 3-month inattention score improvement was associated with initial MPH-mediated FC reductions restricted to occipitoparietal sites following the appearance of the "A." CONCLUSIONS: These findings are discussed in the context of MPH effects on the default mode network and the possible role of the default mode network in MPH-mediated improvements in inattention and hyperactivity symptom scores.

Dopaminergic modulation of default mode network brain functional connectivity in attention deficit hyperactivity disorder.

INTRODUCTION: Recent evidence suggests that attention deficit hyperactivity disorder (ADHD) is associated with a range of brain functional connectivity abnormalities, with one of the most prominent being reduced inhibition of the default mode network (DMN) while performing a cognitive task. In this study, we examine the effects of a methylphenidate dose on brain functional connectivity in boys diagnosed with ADHD while they performed a cognitive task. METHOD: Brain functional connectivity was estimated using steady-state visual evoked potential partial coherence before and 90 min after the administration of a methylphenidate dose to 42 stimulant drug-naïve boys newly diagnosed with ADHD while they performed the A-X version of the continuous performance task (CPT A-X). RESULTS: Methylphenidate robustly reversed the transient functional connectivity increase in the A-X interval seen premedication to a postmedication decrease during this interval. In addition, methylphenidate-induced reductions in individual reaction time were correlated with corresponding reductions in functional connectivity. CONCLUSION: These findings suggest that methylphenidate suppresses the increased functional connectivity observed in ADHD and that such suppression is associated with improved performance. Our findings support the suggestion that the increased functional connectivity we have observed in ADHD is associated with abnormal DMN activity. In addition, we comment on the significance of specific frequency channels mediating top-down communication within the cortex and the extent to which our findings are selectively sensitive to top-down intracortical communication.

Brain functional connectivity abnormalities in attention-deficit hyperactivity disorder.

INTRODUCTION: Recent evidence suggests that attention-deficit hyperactivity disorder (ADHD) is associated with brain functional connectivity (FC) abnormalities. METHODS: In this study, we use steady-state visually evoked potential event-related partial coherence as a measure of brain FC to examine functional connectivity differences between a typically developing (TD) group of 25 boys and an age/IQ-matched group of 42 drug naive boys newly diagnosed with ADHD (ADHD group). Functional connectivity was estimated while both groups performed a low-demand reference task and the A-X version of the continuous performance task (CPT A-X). RESULTS: While the TD and ADHD groups exhibited similar prefrontal FC increases prior to the appearance of the target in the reference task, these groups demonstrated significant FC differences in the interval preceding the appearance of the target in the CPT A-X task. Specifically, the ADHD group exhibited robust prefrontal and parieto-frontal FC increases that were not apparent in the TD group. CONCLUSION: The FC differences observed in the ADHD group are discussed in the context of inadequate suppression of cortical networks that may interfere with task performance.

Measuring emotion in advertising research: prefrontal brain activity.

With the current interest in the role of emotion in advertising and advertising research, there has been an increasing interest in the use of various brain activity measures to access nonverbal emotional responses. One such approach relies on measuring the difference between left and right hemisphere prefrontal cortical activity to assess like and dislike. This approach is based on electroencephalography (EEG) and neuroimaging work, suggesting that the approach/withdrawal (frequently but not always associated with like/dislike) dimension of emotion is indicated by the balance of activity between the left and right prefrontal cortex. Much of this work was initiated by Richard Davidson in the early 1990s. An early study by Davidson et al. measured brain electrical activity to assess patterns of activation during the experience of happiness and disgust. The authors reported that disgust was found to be associated with increased right-sided activation in the frontal and anterior temporal regions compared with happiness. In contrast, happiness was found to be accompanied by left-sided activation in the anterior temporal region compared with disgust. Early reports suggested that frontal laterality indexes motivational valence with positive emotions (happy, like) associated with left greater than the right frontal activity and vice versa. Although these findings appear to be consistent with personality traits (e.g., optimism pessimism), state changes in frontal laterality appears to index approach withdraw rather than emotional valence. Interestingly, the behavioral and motivational correlates of prefrontal asymmetric activity are not restricted to humans or even primates but have been observed in numerous species such as birds and fish (see [4]). Henceforth, we use the term motivational valence (MV) rather than the more cumbersome term approach withdraw.

Brain oscillatory activity during spatial navigation: theta and gamma activity link medial temporal and parietal regions.

Brain oscillatory correlates of spatial navigation were investigated using blind source separation (BSS) and standardized low resolution electromagnetic tomography (sLORETA) analyses of 62-channel EEG recordings. Twenty-five participants were instructed to navigate to distinct landmark buildings in a previously learned virtual reality town environment. Data from periods of navigation between landmarks were subject to BSS analyses to obtain source components. Two of these cortical sources were found to exhibit significant spectral power differences during navigation with respect to a resting eyes open condition and were subject to source localization using sLORETA. These two sources were localized as a right parietal component with gamma activation and a right medial-temporal-parietal component with activation in theta and gamma bandwidths. The parietal gamma activity was thought to reflect visuospatial processing associated with the task. The medial-temporal-parietal activity was thought to be more specific to the navigational processing, representing the integration of ego- and allo-centric representations of space required for successful navigation, suggesting theta and gamma oscillations may have a role in integrating information from parietal and medial-temporal regions. Theta activity on this medial-temporal-parietal source was positively correlated with more efficient navigation performance. Results are discussed in light of the depth and proposed closed field structure of the hippocampus and potential implications for scalp EEG data. The findings of the present study suggest that appropriate BSS methods are ideally suited to minimizing the effects of volume conduction in noninvasive recordings, allowing more accurate exploration of deep brain processes.

Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation.

Dietary interventions may have the potential to counter age-related cognitive decline. Studies have demonstrated an improvement in age-related cognitive impairment in animals after supplementation with plant extracts containing flavonoids but there are few human studies. This double-blind, controlled study examined the effects on cognitive performance of a 5 week supplementation with Enzogenol Pinus radiata bark extract containing flavonoids, in 42 males aged 50-65 years, with a body mass index >25. Participants were supplemented for 5 weeks either with Enzogenol plus vitamin C, or with vitamin C only. A battery of computerized cognitive tests was administered, and cardiovascular and haematological parameters were assessed prior to and following supplementation. The speed of response for the spatial working memory and immediate recognition tasks improved after supplementation with Enzogenol plus vitamin C, whereas vitamin C alone showed no improvements. A trend in a reduction of systolic blood pressure was observed with Enzogenol plus vitamin C, but not with vitamin C alone. The blood safety parameters were unchanged. The findings suggest a beneficial effect of supplementation with Enzogenol on cognition in older individuals. Larger studies are needed to ascertain its potential as a preventive treatment for age-related cognitive decline.

Dynamic sculpting of brain functional connectivity and mental rotation aptitude.

Changes in long-range synchronization are considered a key mechanism for the integration and segregation of cortical regions mediating cognitive processes. Such synchronization or functional connectivity is reflected in human electroencephalographic (EEG) coherence and in steady-state visually evoked potential (SSVEP) coherence. In this chapter, the relationship between cognitive proficiency in the mental rotation task (MRT) and functional connectivity reflected in SSVEP event-related partial coherence is described. The capacity to estimate changing levels of functional connectivity with a relatively high temporal resolution makes it possible to examine the relationship between functional connectivity at various points in time and aptitude. In the current study, the relationships between functional connectivity and two mental rotation aptitude measures, mental rotation speed and mental rotation accuracy, are described. We observed that functional connectivity was correlated with proficiency and that this correlation was both positive and negative for various regions and points in time. It is suggested that cognitive aptitude is related to the brain's capacity to enhance functional connectivity or communication between cortical regions that are relevant to the cognitive demands while attenuating irrelevant communication. This capacity is termed functional connectivity sculpting, and it is proposed that functional connectivity sculpting may constitute an important functional component of the neural substrate of learning and aptitude.

Exploring the temporal dynamics of the spatial working memory n-back task using steady state visual evoked potentials (SSVEP).

The neural networks associated with spatial working memory (SWM) are well established. However, the temporal dynamics of SWM-related brain activity are less clear. This study examined changes in temporal neurophysiology during the spatial n-back task using steady state probe topography (SSPT) to record cortical steady state visual evoked potentials (SSVEPs) at 64 scalp locations. Twenty healthy male volunteers participated in the study. The findings identified three different time periods of significance during the spatial n-back task--an early perceptual/encoding period (approximately 0-500 ms), an early delay period just following the stimulus disappearing from view (approximately 850-1400 ms), and a late period lasting the final second of the delay and anticipation of the new stimulus (approximately 2500-3500 ms). The delay period was associated with increases in frontal and occipital region amplitude, consistent with previous findings in more basic working memory tasks. The two different SSVEP components during the delay appear reflective of the additional "executive" demands associated with the n-back and may suggest variable roles for the PFC during different stages of the delay. All three n-back levels demonstrated a relative consistent electrophysiological profile, indicating that this pattern is specific to the spatial n-back task. Nevertheless, these findings supported the hypothesis that memory load modulates activity within the networks identified, consistent with previous neuroimaging studies. The current findings may offer a framework in which to further investigate the temporal aspects of SWM.

Dynamic sculpting of brain functional connectivity is correlated with performance.

In this study, we examined the relationship between cortical coupling, reflected in event related partial coherence (ERPC) and cognitive processing speed while subjects performed a set of Raven's Progressive Matrices (RPM), a task used to measure IQ. Fifty-five participants (29 males) performed a computerized version of the RPM where they were required to identify the shape (probe) that is consistent with a matrix of displayed shapes. Participants indicated a match or non-match by pressing a micro-switch with either the right or left hand. The steady state visually evoked potential (SSVEP) was elicited by a 13 Hz uniform visual flicker superimposed over the visual fields and the SSVEP event-related coherence (SSVEP-ERPC) calculated for all 2016 unique electrode pairs. The linear correlation between SSVEP-ERPC and processing speed (the inverse of reaction time) was calculated for all electrode pairs for all time points during the 3 sec interval that the probes were on the screen. Using correlation coeffident thresholds corresponding to p=0.001 we identified those electrode pairs where SSVEP-ERPC or neural synchronization was significantly correlated with processing speed. At a point 0.8 sec before the appearance of the probe we observed that the synchronization between specific prefrontal, frontal and central sites was correlated with processing speed. We suggest that this relationship may reflect the efficiency of working memory processes and speed of information processing.

Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans.

The serotonergic system is one of the major systems targeted in the pharmacological treatment of a wide range of mood disorders including depression; however, little is known about the neurophysiological mechanisms underlying the effects of serotonin (5-HT) on affective phenomena including emotional behaviours, mood and emotional processing. The aim of the current study was to investigate how 5-HT acutely modulates steady-state visually evoked potentials (SSVEP), heart rate (HR) and verbal ratings associated with the viewing of differently valent emotional images. In a randomised double-blind, placebo-controlled design, 17 healthy subjects were tested under two acute treatment conditions: placebo and citalopram (20 mg) (a selective serotonin re-uptake inhibitor, or SSRI). Participants were tested 2 h post treatment whilst viewing 75 images (categorised as pleasant, neutral or unpleasant). Results indicate that under placebo treatment, processing of unpleasant valence [unpleasant (-) neutral images] was associated with decreases in SSVEP amplitude and latency in frontal and occipital cortices, whereas processing of pleasant valence [pleasant (-) neutral images] was associated with amplitude decreases and latency increases within frontal and left temporoparietal cortices. Decreases in both amplitude and latency are both interpreted as surrogate measures of cortical activation or excitation. Citalopram relative to placebo attenuated the electrophysiological activation to unpleasant valence within frontal and occipital cortices, but potentiated electrophysiological activation (amplitude only) to pleasant valence within parietooccipital cortices. Citalopram relative to placebo also suppressed differences in heart rate associated with the viewing of pleasant and unpleasant images, but did not alter subject's subjective responses to emotional images. Results suggest that responsiveness to pleasant and unpleasant stimuli following neurochemical modulation may vary across different response systems (i.e. self-report, HR and SSVEP). Electrophysiological findings suggest that acute serotonergic augmentation with citalopram modulates cortical processing of emotionally valent stimuli such that response to pleasant valence is potentiated and response to unpleasant valence is suppressed. The findings suggest a possible neurophysiological mechanism underlying antidepressant drug action on emotion.

Fronto-parietal evoked potential synchronization is increased during mental rotation.

We used steady state visually evoked potential event related partial coherence (SSVEP-ERPC) to examine the SSVEP synchronization between brain regions while 22 males undertook a sequential version of the Shepard and Metzler mental rotation task. Compared to the 60 degrees rotation, the 180 degrees rotation was associated with increased synchronization between bilateral prefrontal and parieto-occipital sites, between left frontal and right parietal sites and between bilateral parietal and occipital sites. We suggest that the increased synchronization between prefrontal and parieto-occipital regions may be associated with the working memory components of the task, while the left frontal to right parietal synchronization may represent the increased interaction between these regions thought to occur in a variety of visuo-motor tasks.