Activity In Frontal Cortex Research Articles

Prenatal Caffeine Exposure Is Linked to Elevated Sugar Intake and BMI, Altered Reward Sensitivity, and Aberrant Insular Thickness in Adolescents: An ABCD Investigation.

Prenatal caffeine exposure (PCE) has been positively associated with elevated body mass index (BMI) in children. Why this association occurs is unclear, but it is possible that PCE alters the in utero development of brain structures associated with food preference, leading to more total sugar intake (TSI, grams) later in childhood. To test this hypothesis, we investigated if PCE (daily/weekly/<weekly vs. no exposure) and elevated BMI are associated with increased TSI, neural activation during large reward anticipation (monetary incentive delay task—functional MRI) and structural changes (thickness, mm) in taste processing regions of children (n = 5534; 9−11 years) from the large-scale Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effect models, after covariate adjustments, identified a positive association (p < 0.05, all |βs| > 0.01) of excessive PCE (vs. no exposure) with elevated BMI (daily/weekly/daily limit; consistent in boys and girls), increased TSI (daily) and insular thickness (daily/weekly), as well as low middle frontal cortex (MFC) activation (daily). Our sub-analysis revealed an association of daily/weekly PCE (vs. no exposure) with increased gram sugar intake from soft drinks. We also identified a positive relationship of excessive PCE with elevated TSI and increased insular thickness (a key gustatory region), while in a Sobel test, reward sensitivity (reduced brain reactivity to reward anticipation in MFC; tracks reward outcomes) mediated (Test statistic = 2.23; p = 0.02) the PCE-linked BMI changes in adolescents. Our findings suggest that excessive PCE might be detrimental to frontal lobe development and altered reward sensitivity to food, thereby increasing risk for elevated TSI and obesity. Our results support recommendations to limit caffeine intake during pregnancy.

Progression of regional cortical cholinergic denervation in Parkinson's disease.

Cortical cholinergic deficits contribute to cognitive decline and other deficits in Parkinson's disease. Cross-sectional imaging studies suggest a stereotyped pattern of posterior-to-anterior cortical cholinergic denervation accompanying disease progression in Parkinson's disease. We used serial acetylcholinesterase PET ligand imaging to characterize the trajectory of regional cholinergic synapse deficits in Parkinson's disease, testing the hypothesis of posterior-to-anterior progression of cortical cholinergic deficits. The 16 Parkinson's disease subjects (4 females/12 males; mean age: 64.4 ± 6.7 years; disease duration: 5.5 ± 4.2 years; Hoehn & Yahr stage: 2.3 ± 0.6 at entry) completed serial 11C-methyl-4-piperidinyl propionate acetylcholinesterase PET scans over a 4-8 year period (median 5 years). Three-dimensional stereotactic cortical surface projections and volume-of-interest analyses were performed. Cholinergic synapse integrity was assessed by the magnitude, k 3, of acetylcholinesterase hydrolysis of 11C-methyl-4-piperidinyl propionate. Based on normative data, we generated Z-score maps for both the k 3 and the k 1 parameters, the latter as a proxy for regional cerebral blood flow. Compared with control subjects, baseline scans showed predominantly posterior cortical k 3 deficits in Parkinson's disease subjects. Interval change analyses showed evidence of posterior-to-anterior progression of cholinergic cortical deficits in the posterior cortices. In frontal cortices, an opposite gradient of anterior-to-posterior progression of cholinergic deficits was found. The topography of k 3 changes exhibited regionally specific disconnection from k 1 changes. Interval-change analysis based on k 3/k 1 ratio images (k 3 adjustment for regional cerebral blood flow changes) showed interval reductions (up to 20%) in ventral frontal, anterior cingulate and Brodmann area 6 cortices. In contrast, interval k 3 reductions in the posterior cortices, especially Brodmann areas 17-19, were largely proportional to k 1 changes. Our results partially support the hypothesis of progressive posterior-to-cortical cholinergic denervation in Parkinson's disease. This pattern appears characteristic of posterior cortices. In frontal cortices, an opposite pattern of anterior-to-posterior progression of cholinergic deficits was found. The progressive decline of posterior cortical acetylcholinesterase activity was largely proportional to declining regional cerebral blood flow, suggesting that posterior cortical cholinergic synapse deficits are part of a generalized loss of synapses. The disproportionate decline in regional frontal cortical acetylcholinesterase activity relative to regional cerebral blood flow suggests preferential loss or dysregulation of cholinergic synapses in these regions. Our observations suggest that cortical cholinergic synapse vulnerability in Parkinson's disease is mediated by both diffuse processes affecting cortical synapses and processes specific to subpopulations of cortical cholinergic afferents.

Dissociation of Writing Processes: A Functional Magnetic Resonance Imaging Study on the Neural Substrates for the Handwritten Production of Chinese Characters.

Writing is an important way to communicate in everyday life because it can convey information over time and space, but its neural substrates remain poorly known. Although the neural basis of written language production has been investigated in alphabetic scripts, it has rarely been examined in nonalphabetic languages such as Chinese. The present functional magnetic resonance imaging study explored the neural substrates of handwritten word production in Chinese and identified the brain regions sensitive to the psycholinguistic factors of word frequency and syllable frequency. To capture this, we contrasted neural activation in "writing" with "speaking plus drawing" and "watching plus drawing." Word frequency (high, low) and syllable frequency (high, low) of the picture names were manipulated. Contrasts between the tasks showed that writing Chinese characters was mainly associated with brain activation in the left frontal and parietal cortex, whereas orthographic processing and the motor procedures necessary for handwritten production were also related to activation in the right frontal and parietal cortex as well as right putamen/thalamus. These results demonstrate that writing Chinese characters requires activation in bilateral cortical regions and the right putamen/thalamus. Our results also revealed no brain activation associated with the main effects of word frequency and syllable frequency as well as their interaction, which implies that word frequency and syllable frequency may not affect the writing of Chinese characters on a neural level.

Dissociable neural mechanisms of cognition and well-being in youth versus healthy aging.

Mental health, cognition, and their underlying neural processes in healthy aging are rarely studied simultaneously. Here, in a sample of healthy younger (n = 62) and older (n = 54) adults, we compared subjective mental health as well as objective global cognition across several core cognitive domains with simultaneous electroencephalography (EEG). We found significantly greater symptoms of anxiety, depression, and loneliness in youth and in contrast, greater mental well-being in older adults. Yet, global performance across core cognitive domains was significantly worse in older adults. EEG-based source imaging of global cognitive task-evoked processing showed reduced suppression of activity in the anterior medial prefrontal default mode network (DMN) region in older adults relative to youth. Global cognitive performance efficiency was predicted by greater activity in the right dorsolateral prefrontal cortex in younger adults and in contrast, by greater activity in right inferior frontal cortex in older adults. Furthermore, greater mental well-being in older adults related to lesser global task-evoked activity in the posterior DMN. Overall, these results suggest dissociated neural mechanisms underlying global cognition and mental well-being in youth versus healthy aging. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neural correlates of affective task switching and asymmetric affective task switching costs.

The control of emotions is of potentially great clinical relevance. Accordingly, there has been increasing interest in understanding the cognitive mechanisms underlying the ability to switch efficiently between the processing of affective and non-affective information. Reports of asymmetrically increased switch costs when switching toward the more salient emotion task indicate specific demands in the flexible control of emotion. The neural mechanisms underlying affective task switching, however, are so far not fully understood. Using functional Magnetic Resonance Imaging (MRI) (N = 57), we observed that affective task switching was accompanied by increased activity in domain-general fronto-parietal control systems. Blood-oxygen-level-dependent (BOLD) activity in the posterior medial frontal and anterolateral prefrontal cortex was directly related to affective switch costs, indicating that these regions play a particular role in individual differences in (affective) task-switching ability. Asymmetric switch costs were associated with increased activity in the right inferior frontal and dorsal anterior medial prefrontal cortex, two brain regions critical for response inhibition. This suggests that asymmetric switch costs might-to a great extent-reflect higher demands on inhibitory control of the dominant emotion task. These results contribute to a refined understanding of brain systems for the flexible control of emotions and thereby identify valuable target systems for future clinical research.

Exploration of cortical inhibition and habituation in insomnia: Based on CNV and EEG.

Cognitive dysfunction with abnormal cortical inhibition and habituation has frequently been found in patients with insomnia. And the so-called contingent negative variation (CNV) and EEG power spectral density (FFT) may be the best choice to explore the underlining pathophysiology. We used polysomnography (PSG) to record such objective PSG parameters. The amplitudes, latencies, areas of different CNV components such as oCNV, iCNV and tCNV, PINV have been selected and analyzed. Behavioral data such as manual reaction time (RT) has been analyzed. Spectral analysis was performed with fast Fourier transformation (FFT) on all channels to make a spectral analyses of EEG datas. The A-latency located in CZ or PZ were statistically longer in insomnia group than control group, the iCNV-latency located in insomnia group were statistically shorter than control group. The iCNV-amplitude located in insomnia group was lower than control group. The oCNV-amplitude or the tCNV-amplitude located in insomnia group was higher than control group. The oCNV-square, tCNV-square, or PINV-square located in insomnia group were significant larger than control group. β1 or β2 activity distributed in bilateral hemisphere were significantly increased in insomnia group than control group with different distributions. Our study revealed varied attentional and information processing in insomnia patients. Above all, we made a hypothesis with ceiling theory: Frontal lobe play an important role in maintaining cognitive processing, which needs much more energy consumption and leads to decreased fast EEG activity in frontal cortex, which contributes to reduced cortical inhibition, represented as abnormal CNV.

Winners and losers in brain computer interface competitive gaming: directional connectivity analysis

Objective. To characterize the direction within and between brain connectivity in winning and losing players in a competitive brain-computer interface game. Approach. Ten dyads (26.9 ± 4.7 yr old, eight females and 12 males) participated in the study. In a competitive game based on neurofeedback, they used their relative alpha (RA) band power from the electrode location Pz, to control a virtual seesaw. The players in each pair were separated into winners (W) and losers (L) based on their scores. Intrabrain connectivity was analyzed using multivariate Granger causality (GC) and directed transfer function, while interbrain connectivity was analyzed using bivariate GC. Main results. Linear regression analysis revealed a significant relationship (p < 0.05) between RA and individual scores. During the game, W players maintained a higher RA than L players, although it was not higher than their baseline RA. The analysis of intrabrain GC indicated that both groups engaged in general social interactions, but only the W group succeeded in controlling their brain activity at Pz. Group L applied an inappropriate metal strategy, characterized by strong activity in the left frontal cortex, indicative of collaborative gaming. Interbrain GC showed a larger flow of information from the L to the W group, suggesting a higher capability of the W group to monitor the activity of their opponent. Significance. Both innate neurological indices and gaming mental strategies contribute to game outcomes. Future studies should investigate whether there is a causal relationship between these two factors.

Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms.

Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism. To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16). We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio= 9.43, p< .001) and an independent generalization sample (odds ratio= 4.64, p= .003). Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.

Short- and Long-term Central Action of Botulinum Neurotoxin Treatment in Laryngeal Dystonia.

Background and ObjectivesLaryngeal dystonia (LD) is isolated task-specific focal dystonia selectively impairing speech production. The first choice of LD treatment is botulinum neurotoxin (BoNT) injections into the affected laryngeal muscles. However, whether BoNT has a lasting therapeutic effect on disorder pathophysiology is unknown. We investigated short-term and long-term effects of BoNT treatment on brain function in patients with LD.MethodsA total of 161 participants were included in the functional MRI study. Statistical analyses examined central BoNT effects in patients with LD who were stratified based on the effectiveness and duration of treatment.ResultsPatients with LD who were treated and benefited from BoNT injections had reduced activity in the left precuneus compared with BoNT-naive and treatment nonbenefiting patients. In addition, BoNT-treated patients with adductor LD had decreased activity in the right thalamus, whereas BoNT-treated abductor patients with LD had reduced activity in the left inferior frontal cortex. No statistically significant differences in brain activity were found between patients with shorter (1–5 years) and longer (13–28 years) treatment durations. However, patients with intermediate treatment duration of 6–12 years showed reduced activity in the right cerebellum compared with patients with both shorter and longer treatment durations and reduced activity in the right prefrontal cortex compared with patients with shorter treatment duration.DiscussionOur findings suggest that the left precuneus is the site of short-term BoNT central action in patients with LD, whereas the prefrontal-cerebellar axis is engaged in the BoNT response in patients with intermediate treatment duration of 6–12 years. Involvement of these structures points to indirect action of BoNT treatment on the dystonic sensorimotor network through modulation of motor sequence planning and coordination.

Frontal cortical activation during emotional and non-emotional verbal fluency tests

There has been growing recognition of the utility of combining the verbal fluency test and functional near-infrared spectroscopy (fNIRS) to assess brain functioning and to screen for psychiatric disorders. Recently, an emotional analogue of the semantic fluency test (SFT) has been developed that taps partly different processes from conventional verbal fluency tests. Nevertheless, neural processing during the emotional SFT remains elusive. Here, fNIRS was used to compare frontal cortical activation during emotional and non-emotional SFTs. The goal was to determine whether the emotional SFT activated overlapping yet distinct frontal cortical regions compared with the conventional, non-emotional SFT. Forty-three healthy young adults performed the emotional and non-emotional SFTs while hemodynamic changes in the bilateral frontopolar, dorsomedial, dorsolateral, ventrolateral, and posterolateral frontal cortices were measured by fNIRS. There were significant increases in oxyhemoglobin concentration and significant decreases in deoxyhemoglobin concentration (i.e., activation) in frontopolar, dorsolateral, and ventrolateral frontal regions during both the non-emotional and emotional SFTs. Also, complementary analyses conducted on changes in the two chromophores using classical and Bayesian hypothesis testing suggested that comparable frontal cortical regions were activated while performing the two tests. This similarity in activation occurred in a context where non-emotional and emotional SFT performances exhibited differential relationships with the overall level of negative mood symptoms. In conclusion, frontal cortical activation during the emotional SFT is similar to that during the conventional, non-emotional SFT. Given that there is evidence for discriminant validity for the emotional SFT, the neural mechanisms underlying the uniqueness of this test warrant further investigation.

Stay or Go? Neuronal Activity in Medial Frontal Cortex During a Voluntary Tactile Preference Task in Head-fixed Mice

The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant sensation in the cortex involves multiple brain regions, although the specific role of the brain areas involved in voluntary, rather than reflexive movement away from unpleasant stimuli is not well understood. Here, we focused on the medial subdivision of secondary motor cortex, which is proposed to link sensory and contextual cues to motor action, and tested its role in controlling voluntary movement in the context of an aversive tactile cue. We designed a novel, 3D-printed tactile platform consisting of innocuous (grid) and mildly noxious (spiked) surfaces (50:50 % of total area), which enabled monitoring neuronal activity in the medial frontal cortex by two-photon imaging during a sensory preference task in head-fixed mice. We found that freely moving mice spent significantly less time on a spiked-surface, and that this preference was eliminated by administration of a local anesthetic. At the neuronal level, individual neurons were differentially modulated specific to the tactile surface encountered. At the population level, the neuronal activity was analyzed in relation to the events where mice chose to "stop-on" or "go-from" a specific tactile surface and when they "switched" surfaces without stopping. Notably, each of these three scenarios showed population activity that differed significantly between the grid and spiked tactile surfaces. Collectively, these data provide evidence that tactile quality is encoded within medial frontal cortex. The task pioneered in this study provides a valuable tool to better evaluate mouse models of nociception and pain, using a voluntary task that allows simultaneous recording of preference and choice. Grant support from NS109287 (G.A.), NS096246 (Y.U.), DK116624 (Y.U.) and NS113189 (Y.U.), the Iowa Neuroscience Institute, and the Williams- Cannon faculty fellowship (G.A). A.K. was supported by a predoctoral fellowship through NIH T32 Grant GM067795.

Longitudinal changes of motor cortex function during motor recovery after stroke

ABSTRACT Background and purpose Functional magnetic resonance imaging (fMRI) combined with behavioral assessments was used in our study to investigate the dynamic process of motor cortical functional reorganization after infarction. Therefore, we could provide a theoretical basis and build a useful evaluation system for rehabilitation after stroke and various other cerebral injuries. Methods Acute stroke patients with a single lesion in the middle cerebral artery supply area and age- and sex-matched healthy volunteers were recruited. A longitudinal observational study involving 20 patients with stroke was conducted using repeated fMRI. Task-based fMRI data were acquired 3 times over a period of 3 months. The behavioral assessment included dynamometer and finger-tapping tests to evaluate the strength and dexterity of each upper arm. Results Behavioral results: The behavioral assessments demonstrated large improvements in session 2 and session 3. fMRI results: The healthy group showed activation in the contralateral primary sensory-motor cortex (S1M1) when executing tasks with either the left or right hand. Compared with the healthy subjects, the patients demonstrated greater activation in the ipsilateral frontal and parietal cortices and supplementary motor areas (SMAs). Across all sessions, more motor activation was observed in the left infarction group. Conclusions Our results show that motor cortical activation induced by moving the paretic hand changes over time. There were differences in motor functional recovery and motor cortex compensation between the dominant hemisphere and nondominant hemisphere after stroke.

Altered Neuromagnetic Activity in Persistent Postural-Perceptual Dizziness: A Multifrequency Magnetoencephalography Study.

ObjectiveThe aim of our study was to investigate abnormal changes in brain activity in patients with persistent postural-perceptual dizziness (PPPD) using magnetoencephalography (MEG).MethodsMagnetoencephalography recordings from 18 PPPD patients and 18 healthy controls were analyzed to determine the source of brain activity in seven frequency ranges using accumulated source imaging (ASI).ResultsOur study showed that significant changes in the patterns of localization in the temporal-parietal junction (TPJ) were observed at 1–4, 4–8, and 12–30 Hz in PPPD patients compared with healthy controls, and changes in the frontal cortex were found at 1–4, 80–250, and 250–500 Hz in PPPD patients compared with controls. The neuromagnetic activity in TPJ was observed increased significantly in 1–4 and 4–8 Hz, while the neuromagnetic activity in frontal cortex was found increased significantly in 1–4 Hz. In addition, the localized source strength in TPJ in 1–4 Hz was positively correlated with DHI score (r = 0.7085, p < 0.05), while the localized source strength in frontal cortex in 1–4 Hz was positively correlated with HAMA score (r = 0.5542, p < 0.05).ConclusionOur results demonstrated that alterations in the TPJ and frontal cortex may play a critical role in the pathophysiological mechanism of PPPD. The neuromagnetic activity in TPJ may be related to dizziness symptom of PPPD patients, while the neuromagnetic activity in frontal lobe may be related to emotional symptoms of PPPD patients. In addition, frequency-dependent changes in neuromagnetic activity, especially neuromagnetic activity in low frequency bands, were involved in the pathophysiology of PPPD.

Perspective: Estrogen and the Risk of Cognitive Decline: A Missing Choline(rgic) Link?

ABSTRACTFactors that influence the risk of neurocognitive decline and Alzheimer's disease (AD) may provide insight into therapies for both disease treatment and prevention. Although age is the most striking risk factor for AD, it is notable that the prevalence of AD is higher in women, representing two-thirds of cases. To explore potential underlying biological underpinnings of this observation, the intent of this article is to explore the interplay between cognitive aging and sex hormones, the cholinergic system, and novel hypotheses related to the essential nutrient choline. Mechanistic evidence points toward estrogen's neuroprotective effects being strongly dependent on its interactions with the cholinergic system, a modulator of attentional functioning, learning, and memory. Estrogen has been shown to attenuate anticholinergic-induced impairments in verbal memory and normalize patterns of frontal and occipital cortex activation, resulting in a more “young adult” phenotype. However, similar to estrogen replacement's effect in cardiovascular diseases, its putative protective effects may be restricted to early postmenopausal women only, a finding supportive of the “critical window hypothesis.” Estrogen's impact on the cholinergic system may act both locally in the brain but also through peripheral tissues. Estrogen is critical for inducing endogenous choline synthesis via the phosphatidylethanolamine N-methyltransferase (PEMT) gene–mediated pathway of phosphatidylcholine (PC) synthesis. PEMT is dramatically induced in response to estrogen, producing not only a PC molecule and source of choline for the brain but also a key source of the long-chain ω-3 fatty acid, DHA. Herein, we highlight novel hypotheses related to hormone replacement therapy and nutrient metabolism aimed at directing future preclinical and clinical investigation.

Disrupted Choline Clearance and Sustained Acetylcholine Release In Vivo by a Common Choline Transporter Coding Variant Associated with Poor Attentional Control in Humans.

Transport of choline via the neuronal high-affinity choline transporter (CHT; SLC5A7) is essential for cholinergic terminals to synthesize and release acetylcholine (ACh). In humans, we previously demonstrated an association between a common CHT coding substitution (rs1013940; Ile89Val) and reduced attentional control as well as attenuated frontal cortex activation. Here, we used a CRISPR/Cas9 approach to generate mice expressing the I89V substitution and assessed, in vivo, CHT-mediated choline transport, and ACh release. Relative to wild-type (WT) mice, CHT-mediated clearance of choline in male and female mice expressing one or two Val89 alleles was reduced by over 80% in cortex and over 50% in striatum. Choline clearance in CHT Val89 mice was further reduced by neuronal inactivation. Deficits in ACh release, 5 and 10 min after repeated depolarization at a low, behaviorally relevant frequency, support an attenuated reloading capacity of cholinergic neurons in mutant mice. The density of CHTs in total synaptosomal lysates and neuronal plasma-membrane-enriched fractions was not impacted by the Val89 variant, indicating a selective impact on CHT function. When challenged with a visual disruptor to reveal attentional control mechanisms, Val89 mice failed to adopt a more conservative response bias. Structural modeling revealed that Val89 may attenuate choline transport by altering conformational changes of CHT that support normal transport rates. Our findings support the view that diminished sustained cholinergic signaling capacity underlies perturbed attentional performance in individuals expressing CHT Val89. The CHT Val89 mouse serves as a valuable model to study heritable risk for cognitive disorders arising from cholinergic dysfunction.SIGNIFICANCE STATEMENT Acetylcholine (ACh) signaling depends on the functional capacity of the neuronal choline transporter (CHT). Previous research demonstrated that humans expressing the common CHT coding variant Val89 exhibit attentional vulnerabilities and attenuated fronto-cortical activation during attention. Here, we find that mice engineered to express the Val89 variant exhibit reduced CHT-mediated choline clearance and a diminished capacity to sustain ACh release. Additionally, Val89 mice lack cognitive flexibility in response to an attentional challenge. These findings provide a mechanistic and cognitive framework for interpreting the attentional phenotype associated with the human Val89 variant and establish a model that permits a more invasive interrogation of CNS effects as well as the development of therapeutic strategies for those, including Val89 carriers, with presynaptic cholinergic perturbations.

Electroencephalographic Signature of Negative Self Perceptions in Medical Students.

Frontal alpha asymmetry (fAA) is purported to be a neurophysiological marker for anxiety and depression. Higher left frontal alpha EEG voltage is associated with lower left and higher right frontal cerebral cortical activation, indicative of right-sided fAA. This pilot study tests the hypothesis that greater left-sided frontal alpha voltage is associated with negative thoughts about oneself. A group of eight healthy 28-41-year-old right-handed male medical students were subjected to an extensive interactive self-report inventory (ISI) evaluating perceptions of their psychosocial interactions. Quantitative EEG (qEEG) was performed with eyes closed. Computations of fAA and related parameters were based on measurements in the alpha bandwidth (8-13 Hz) at the left frontal F7 and right frontal F8 scalp electrodes. fAA was the percent difference between mean voltages at F8 minus that at F7. Significance of associations between fAA and the ISI scores was determined by Pearson’s product-moment correlation coefficient, at P≤0.05. “Depressed” scores were positively correlated with right-sided fAA (P=0.01). “Relaxed” (P=0.05), “regulated” (P=0.02), “cooperative” (P=0.05) and “dependent scores” (P=0.004) were negatively correlated with right-sided fAA. These findings imply that right-sided fAA may be associated with more perceptions of “depressed” psychosocial interactions involving negative thoughts about oneself, as well as, more reliance on others (“dependence” score), less sharing (“cooperative” ISI score), less trust (“regulated” ISI score) and less initiative (“relaxed” ISI score). These results support the hypothesis that right-sided fAA may identify individuals with a predilection for negative thoughts about themselves and other negatively-valenced perceptions of their psychosocial interactions.

Cortical Correlates of Gait Compensation Strategies in Parkinson Disease.

ObjectiveGait impairment in persons with Parkinson disease is common and debilitating. Compensation strategies (eg, external cues) are an essential part of rehabilitation, but their underlying mechanisms remain unclear. Using electroencephalography (EEG), we explored the cortical correlates of 3 categories of strategies: external cueing, internal cueing, and action observation.MethodsEighteen participants with Parkinson disease and gait impairment were included. We recorded 126‐channel EEG during both stance and gait on a treadmill under 4 conditions: (1) uncued, (2) external cueing (listening to a metronome), (3) internal cueing (silent rhythmic counting), and (4) action observation (observing another person walking). To control for the effects of sensory processing of the cues, we computed relative power changes as the difference in power spectral density between walking and standing for each condition.ResultsRelative to uncued gait, the use of all 3 compensation strategies induced a decrease of beta band activity in sensorimotor areas, indicative of increased cortical activation. Parieto‐occipital alpha band activity decreased with external and internal cueing, and increased with action observation. Only internal cueing induced a change in frontal cortical activation, showing a decrease of beta band activity compared to uncued gait.InterpretationThe application of compensation strategies resulted in changed cortical activity compared to uncued gait, which could not be solely attributed to sensory processing of the cueing modality. Our findings suggest there are multiple routes to control gait, and different compensation strategies seem to rely on different cortical mechanisms to achieve enhanced central motor activation in persons with Parkinson disease. ANN NEUROL 2022;91:329–341

Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing.

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide a comprehensive account of the relationships between fluctuations in arousal and neuronal population activity across the human brain. Exploiting the established link between pupil size and central arousal systems, we performed concurrent magnetoencephalographic (MEG) and pupillographic recordings in a large number of participants, pooled across three laboratories. We found a cascade of effects relative to the peak timing of spontaneous pupil dilations: Decreases in low-frequency (2-8 Hz) activity in temporal and lateral frontal cortex, followed by increased high-frequency (>64 Hz) activity in mid-frontal regions, followed by monotonic and inverted U relationships with intermediate frequency-range activity (8-32 Hz) in occipito-parietal regions. Pupil-linked arousal also coincided with widespread changes in the structure of the aperiodic component of cortical population activity, indicative of changes in the excitation-inhibition balance in underlying microcircuits. Our results provide a novel basis for studying the arousal modulation of cognitive computations in cortical circuits.

Subdividing Stress Groups into Eustress and Distress Groups Using Laterality Index Calculated from Brain Hemodynamic Response.

A stress group should be subdivided into eustress (low-stress) and distress (high-stress) groups to better evaluate personal cognitive abilities and mental/physical health. However, it is challenging because of the inconsistent pattern in brain activation. We aimed to ascertain the necessity of subdividing the stress groups. The stress group was screened by salivary alpha-amylase (sAA) and then, the brain’s hemodynamic reactions were measured by functional near-infrared spectroscopy (fNIRS) based on the near-infrared biosensor. We compared the two stress subgroups categorized by sAA using a newly designed emotional stimulus-response paradigm with an international affective picture system (IAPS) to enhance hemodynamic signals induced by the target effect. We calculated the laterality index for stress (LIS) from the measured signals to identify the dominantly activated cortex in both the subgroups. Both the stress groups exhibited brain activity in the right frontal cortex. Specifically, the eustress group exhibited the largest brain activity, whereas the distress group exhibited recessive brain activity, regardless of positive or negative stimuli. LIS values were larger in the order of the eustress, control, and distress groups; this indicates that the stress group can be divided into eustress and distress groups. We built a foundation for subdividing stress groups into eustress and distress groups using fNIRS.

Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect

BackgroundThe negative symptoms of schizophrenia have been proposed to reflect prefrontal cortex dysfunction. However, this proposal has not been consistently supported in functional imaging studies, which have also used executive tasks that may not capture key aspects of negative symptoms such as lack of volition. MethodTwenty-four DSM-5 schizophrenic patients with high negative symptoms (HNS), 25 with absent negative symptoms (ANS) and 30 healthy controls underwent fMRI during performance of the Computerized Multiple Elements Test (CMET), a task designed to measure poor organization of goal directed behaviour or ‘goal neglect’. Negative symptoms were rated using the PANSS and the Clinical Assessment Interview for Negative Symptoms (CAINS). ResultsOn whole brain analysis, the ANS patients showed no significant clusters of reduced activation compared to the healthy controls. In contrast, the HNS patients showed hypoactivation compared to the healthy controls in the left anterior frontal cortex, the right dorsolateral prefrontal cortex (DLPFC), the anterior insula bilaterally and the bilateral inferior parietal cortex. When compared to the ANS patients, the HNS patients showed reduced activation in the left anterior frontal cortex, the left DLPFC and the left inferior parietal cortex. After controlling for disorganization scores, differences remained in clusters in the left anterior frontal cortex and the bilateral inferior parietal cortex. ConclusionsThis study provides evidence that reduced prefrontal activation, perhaps especially in the left anterior frontal cortex, is a brain functional correlate of negative symptoms in schizophrenia. The simultaneous finding of reduced inferior parietal cortex activation was unexpected, but could reflect this region’s involvement in cognitive control, particularly the ‘regulative’ component of this.