Large-scale distributed networks and cerebral hemispheres.

The two main large-scale distributed networks, Central Executive (CEN) and Default Mode (DMN) have been extensively studied, but their relationship to hemispheric specialization has not been comprehensively addressed. We present evidence that they are neuroanatomically asymmetric: the CEN components are volumetrically larger in the right hemisphere, and DMN components are volumetrically larger in the left hemisphere. Based on this, the possibility that CEN and DMN are also functionally asymmetric is introduced and implications of the putative functional asymmetry of large-scale distributed networks for refining our understanding of hemispheric specialization are examined.

Policy stringency and mental health during the COVID-19 pandemic: a longitudinal analysis of data from 15 countries.

BACKGROUND: To date, public health policies implemented during the COVID-19 pandemic have been evaluated on the basis of their ability to reduce transmission and minimise economic harm. We aimed to assess the association between COVID-19 policy restrictions and mental health during the COVID-19 pandemic. METHODS: In this longitudinal analysis, we combined daily policy stringency data from the Oxford COVID-19 Government Response Tracker with psychological distress scores and life evaluations captured in the Imperial College London-YouGov COVID-19 Behaviour Tracker Global Survey in fortnightly cross-sections from samples of 15 countries between April 27, 2020, and June 28, 2021. The mental health questions provided a sample size of 432 642 valid responses, with an average of 14 918 responses every 2 weeks. To investigate how policy stringency was associated with mental health, we considered two potential mediators: observed physical distancing and perceptions of the government's handling of the pandemic. Countries were grouped on the basis of their response to the COVID-19 pandemic as those pursuing an elimination strategy (countries that aimed to eliminate community transmission of SARS-CoV-2 within their borders) or those pursuing a mitigation strategy (countries that aimed to control SARS-CoV-2 transmission). Using a combined dataset of country-level and individual-level data, we estimated linear regression models with country-fixed effects (ie, dummy variables representing the countries in our sample) and with individual and contextual covariates. Additionally, we analysed data from a sample of Nordic countries, to compare Sweden (that pursued a mitigation strategy) to other Nordic countries (that adopted a near-elimination strategy). FINDINGS: Controlling for individual and contextual variables, higher policy stringency was associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients ß=0·014 [95% CI 0·005 to 0·023] for psychological distress; ß=-0·010 [-0·015 to -0·004] for life evaluation). Pandemic intensity (number of deaths per 100 000 inhabitants) was also associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients ß=0·016 [0·008 to 0·025] for psychological distress; ß=-0·010 [-0·017 to -0·004] for life evaluation). The negative association between policy stringency and mental health was mediated by observed physical distancing and perceptions of the government's handling of the pandemic. We observed that countries pursuing an elimination strategy used different policy timings and intensities compared with countries pursuing a mitigation strategy. The containment policies of countries pursuing elimination strategies were on average less stringent, and fewer deaths were observed. INTERPRETATION: Changes in mental health measures during the first 15 months of the COVID-19 pandemic were small. More stringent COVID-19 policies were associated with poorer mental health. Elimination strategies minimised transmission and deaths, while restricting mental health effects. FUNDING: None.

Mental Health During the First Year of the COVID-19 Pandemic: A Review and Recommendations for Moving Forward.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Multiple Neuroinvasive Pathways in COVID-19.

COVID-19 is a highly infectious viral disease caused by the novel coronavirus SARS-CoV-2. While it was initially regarded as a strictly respiratory illness, the impact of COVID-19 on multiple organs is increasingly recognized. The brain is among the targets of COVID-19, and it can be impacted in multiple ways, both directly and indirectly. Direct brain infection by SARS-CoV-2 may occur via axonal transport via the olfactory nerve, eventually infecting the olfactory cortex and other structures in the temporal lobe, and potentially the brain stem. A hematogenous route, which involves viral crossing of blood-brain barrier, is also possible. Secondary mechanisms involve hypoxia due to respiratory failure, as well as aberrant immune response leading to various forms of encephalopathy, white matter damage, and abnormal blood clotting resulting in stroke. Multiple neurological symptoms of COVID-19 have been described. These involve anosmia/ageusia, headaches, seizures, mental confusion and delirium, and coma. There is a growing concern that in a number of patients, long-term or perhaps even permanent cognitive impairment will persist well after the recovery from acute illness. Furthermore, COVID-19 survivors may be at increased risk for developing neurodegenerative diseases years or decades later. Since COVID-19 is a new disease, it will take months or even years to characterize the exact nature, scope, and temporal extent of its long-term neurocognitive sequelae. To that end, rigorous and systematic longitudinal follow-up will be required. For this effort to succeed, appropriate protocols and patient registries should be developed and put in place without delay now.

BDNF polymorphism in non-veridical decision making and differential effects of rTMS.

Making decisions when an objectively correct option is not obvious, involves different neurobiological mechanisms than "veridical" decision making. The dorsolateral prefrontal cortex (DLPFC) exhibits a distinct pattern of prefrontal activation in non-veridical cognition, but little is known about the role of underlying neurobiological endophenotypes. A functional polymorphism in the brain-derived neurotrophic factor (BDNF) gene, causing a valine (Val) to methionine (Met) amino acid substitution at codon 66, has been shown to be associated with structural and functional changes in DLPFC and affect veridical decision making. We hypothesized that the BDNF genotype may be related to non-veridical cognition. We explored whether the BDNF Val66Met polymorphism affected preferences in a cognitive task devoid of intrinsically correct or false choice, using the Cognitive Bias Task (CBT). We also studied if manipulating the right DLPFC with rTMS stimulation changes non-veridical preferences. Sixteen healthy adults, including 9 Val/Val and 7 Val/Met subjects, participated in the study. Participants with Val/Met genotype expressed a more context-independent, internally driven choice selection preference. Val/Val subjects' selection was more dependent on the context, driven by the properties of external stimuli. rTMS stimulation enhanced a preexisting bias in choice preferences. In Val/Val subjects, TMS stimulation shifted the non-veridical preference bias towards greater dependence on external context, while in Val/Met subjects the CBT score became more context-independent. Our study showed that BDNF genotype is associated with a bias in non-veridical preferences and that Val/Val and Val/Met subjects respond differently to right DLPFC rTMS stimulation, further enhancing their preexisting selection biases.

Effects of repetitive transcranial magnetic stimulation on non-veridical decision making.

We test the emerging hypothesis that prefrontal cortical mechanisms involved in non-veridical decision making do not overlap with those of veridical decision making. Healthy female subjects performed an experimental task assessing free choice, agent-centered decision making (The Cognitive Bias Task) and a veridical control task related to visuospatial working memory (the Moving Spot Task). Transcranial magnetic stimulation (TMS) was applied to the left and right dorsolateral prefrontal cortex (DLPFC) using 1 Hz and 10 Hz (intermittent) rTMS and sham protocols. Both 1 Hz and 10 Hz stimulation of the DLPFC triggered a shift towards a more context-independent, internal representations driven non-veridical selection bias. A significantly reduced preference for choosing objects based on similarity was detected, following both 1 Hz and 10 Hz treatment of the right as well as 1 Hz rTMS of the left DLPFC. 1 Hz rTMS treatment of the right DLPFC also triggered a significant improvement in visuospatial working memory performance on the veridical task. The effects induced by prefrontal TMS mimicked those of posterior lesions, suggesting that prefrontal stimulation influenced neuronal activity in remote cortical regions interconnected with the stimulation site via longitudinal fasciculi.

Schizophrenia and frontotemporal dementia: shared causation?

The relationship between specific genes and particular diseases in neuropsychiatry is unclear, and newer studies focus on shared domains of neurobiological and cognitive pathology across different disorders. This paper reviews the evidence for an association between schizophrenia and frontotemporal dementia, including symptom similarity, familial co-morbidity, and neuroanatomical changes. Genetic as well as epigenetic findings from both schizophrenia and frontotemporal dementia are also discussed. As a result, we introduce the hypothesis of a shared susceptibility for certain subgroups of schizophrenia and frontotemporal dementia. This common causation may involve the same gene(s) at different stages of life: early in schizophrenia and late in frontotemporal dementia. Additionally, we provide a rationale for future research that should emphasize both genetic and cognitive parallels between certain forms of schizophrenia and frontotemporal dementia in a synergistic, coordinated way, placing both in the context of aberrant lateralization patterns.

Hemispheric asymmetries of cortical volume in the human brain.

Hemispheric asymmetry represents a cardinal feature of cerebral organization, but the nature of structural and functional differences between the hemispheres is far from fully understood. Using Magnetic Resonance Imaging morphometry, we identified several volumetric differences between the two hemispheres of the human brain. Heteromodal inferoparietal and lateral prefrontal cortices are more extensive in the right than left hemisphere, as is visual cortex. Heteromodal mesial and orbital prefrontal and cingulate cortices are more extensive in the left than right hemisphere, as are somatosensory, parts of motor, and auditory cortices. Thus, heteromodal association cortices are more extensively represented on the lateral aspect of the right than in the left hemisphere, and modality-specific cortices are more extensively represented on the lateral aspect of the left than in the right hemisphere. On the mesial aspect heteromodal association cortices are more extensively represented in the left than right hemisphere.

Neuropsychological assessment in traumatic brain injury.

Traumatic brain injury (TBI) is a neurological injury that can affect the cognitive, emotional, psychological, and physical functioning of an individual. The clinical neuropsychologist working with TBI patients must take a holistic approach when assessing and treating the patient and consider the patient in total, including premorbid and post-incident factors, to formulate a comprehensive and accurate picture of the patient. This approach will guide the clinician regarding multiple types of treatment the patient may require.

Alterations in theta activity associated with novelty and routinization processing in ADHD.

OBJECTIVE: Novelty and routinization-related information processing disturbances were examined in adolescent males with ADHD using an oddball paradigm and electrophysiological measurement of theta (4-7Hz) activity. METHODS: Fifty-four unmedicated adolescent males (12-18years) with Attention Deficit Hyperactivity Disorder (ADHD) and matched controls performed an auditory oddball task. Theta activity was sub-averaged, and Fourier Integrals with simultaneous measurement of electrodermal activity (EDA) was used to index response to stimulus novelty and routinization. RESULTS: ADHD participants showed an overall increase in theta activity to both novel and routine stimuli relative to controls. While controls showed increased theta activity in response to novel compared to routine targets across the brain, ADHD participants did not show this novelty-related increase in theta activity in the right anterior/frontal brain. CONCLUSIONS: The findings of this study are consistent with disturbances in theta activity and the brain substrates of novelty relative to routinization-related processing in ADHD. SIGNIFICANCE: These findings show that there are distinct alterations in theta activity related to stimulus novelty and routinization during an auditory oddball task in ADHD, and they highlight the value of using an event-related approach to elucidate the neural substrates of stimulus processing in ADHD.

Altered adaptive but not veridical decision-making in substance dependent individuals.

Drug addiction is associated with impaired judgment in unstructured situations in which success depends on self-regulation of behavior according to internal goals (adaptive decision-making). However most executive measures are aimed at assessing decision-making in structured scenarios, in which success is determined by external criteria inherent to the situation (veridical decision-making). The aim of this study was to examine the performance of Substance Abusers (SA, n = 97) and Healthy Comparison participants (HC, n = 81) in two behavioral tasks that mimic the uncertainty inherent in real-life decision-making: the Cognitive Bias Task (CB) and the Iowa Gambling Task (IGT) (administered only to SA). A related goal was to study the interdependence between performances on both tasks. We conducted univariate analyses of variance (ANOVAs) to contrast the decision-making performance of both groups; and used correlation analyses to study the relationship between both tasks. SA showed a marked context-independent decision-making strategy on the CB's adaptive condition, but no differences were found on the veridical conditions in a subsample of SA (n = 34) and HC (n = 22). A high percentage of SA (75%) also showed impaired performance on the IGT. Both tasks were only correlated when no impaired participants were selected. Results indicate that SA show abnormal decision-making performance in unstructured situations, but not in veridical situations.

Neuropsychologic assessment of frontal lobe dysfunction.

Given the pervasive nature of executive deficit, assessment of executive functions is of crucial importance in neuropsychiatry, child and adolescent psychiatry, geriatric psychiatry, and other related areas. A number of neuropsychologic tests of executive function commonly are used in assessing several clinical disorders, including but not limited to traumatic brain injury, schizophrenia, depression, attention deficit disorder/attention deficit hyperactivity disorder, and dementia. Because the concept of executive control in its current form constitutes an over arching construct, a construct that is based on the cognitive symptoms of the frontal lobe disorder caused by many disparate underlying conditions, no single measure of executive function can adequately tap the construct in its entirety.Therefore, it is necessary to administer several tests of executive function,each assessing a particular aspect of the executive function. An appropriate combination of such neuropsychologic tests and batteries, including the Wisconsin Card Sorting Test, Tower test, Stroop test, the D-KEFS, and the ECB, provides an adequate but relatively crude mechanism for assessing executive systems dysfunction. Neuroscientists continue to refine their understanding of the nature of executive control, and additional innovative procedures that reflect state-of-the-art insights of cognitive neuroscience have been introduced recently. Among a few first steps in that direction are nonveridical, actor-centered procedures such as the CBT and the Iowa Gambling Test.

Lateralization of the frontal lobe functions elicited by a cognitive bias task is a fundamental process. Lesion study.

Cognitive neuroscience researchers have hypothesized that context-dependent and context-independent response selection is associated with the left and right frontal lobe, respectively, in right-handed adult males. Patients with left frontal lobe lesions show context-independent reasoning in a cognitive bias task (CBT), while those with right frontal lesions show context-dependent reasoning. Young children show more context-independent responses in a modified CBT (mCBT), while adolescents and adults show more context-dependent responses. We investigated the cognitive bias of right-handed children with unilateral frontal lobe lesions/epileptic foci to explore the plasticity of lateralization in the frontal lobes. The study included eight children with left frontal lobe lesions/epileptic foci (LLF) and four children with right frontal lobe lesions/epileptic foci (RLF). Twenty-three right-handed age-matched males served as controls. A computer presented version of the original card-choice task that was simplified and modified for children was used (mCBT). Simple visual stimuli differed dichotomously in shape, color, number, and shading. A target object presented alone was followed by two choices from which subjects made selection based on preference. Considering all four characteristics, the degree of similarity between the target and the subjects' choice was scored for 30 trials. A high score indicated a context-dependent response selection bias and a low score indicated a context-independent bias. The RLF subjects had a higher converted score (mean: 26.8+/-2.2), while LLF subjects showed a lower converted score (mean: 7.75+/-6.3). There were highly significant differences between LLF subjects and the other groups (P<0.001 vs. controls or RLF subjects). No significant correlations were observed between the converted scores and the age at onset, time since insult, or IQ in either LLF or RLF subjects. These findings suggest that the lateralization of frontal lobe function elicited by mCBT is fundamental and independent of language lateralization, rather than secondary to it. Furthermore, these findings also indicate that the timetable for the development of lateralized frontal lobe functions depends upon biologic factors.

Age-dependent change in executive function and gamma 40 Hz phase synchrony.

Decline in cognitive function is well recognized, yet few neurophysiological correlates of age-related cognitive decline have been identified. In this study we examined the impact of age on neurocognitive function and Gamma phase synchrony among 550 normal subjects (aged 11-70). Gamma phase synchrony was acquired to targets in the auditory oddball paradigm. The two tasks of executive function were switching of attention and an electronic maze. Subjects were divided into four age groups, which were balanced for sex. We hypothesized that reduced cognitive performance among older healthy individuals would be associated with age-related changes in gamma phase synchrony. Results showed a significant decrease in executive function in the oldest (51-70 years) age group. ANOVAs of age-by-frontal Gamma synchrony also showed a significant effect of age on Gamma phase synchrony in the left frontal region that corresponded modestly to the age effect found on executive task performance, with reduced performance associated with increased gamma synchrony. The results indicate that age-related changes in cognitive function evident among elderly individuals may in part be related to decreased ability to integrate information and this may be reflected as a compensatory increase in gamma synchrony in frontal regions of the brain.

Neural synchrony and gray matter variation in human males and females: integration of 40 Hz gamma synchrony and MRI measures.

Coherent cognition requires activity to be brought together across diverse brain networks. Synchronous, in-phase oscillations in the high-frequency (40 Hz) Gamma range are thought to be one mechanism underlying the functional integration of brain networks. While sex differences have been observed across a range of cognitive functions, their role in normal cortical synchronization has not been elucidated. We recorded Gamma phase synchrony in 500 male and 500 female subjects during an auditory oddball task, which taps discrimination of task-relevant signals. Results revealed a marked sex-linked dissociation in the spatio-temporal pattern of cortical synchronization. Females showed increased Gamma synchrony in the frontal brain, while males showed enhanced synchrony in the parieto-occipital region. These differences were not accounted for by sex differences in whole brain MRI volume. However, there were positive associations between Gamma synchrony and gray matter for females, while these relationships were negative for males. Sex differences in the profile of cortical synchronization may reflect distinct aspects of evolutionary advantage.

Context-dependent reasoning in a cognitive bias task Part II. SPECT activation study.

A cognitive bias task (CBT) delineates two different cognitive selection mechanisms in the prefrontal cortex. To identify functional anatomy of context-dependent reasoning, we used technetium-99mhexamethyl- propyleneamine oxime (99mTc HM-PAO) single photon emission computed tomography (SPECT) and statistical parametric mapping. Twelve right-handed men 20-24 years old were instructed to look at a target card and then select the choice card (among two) that they preferred (modified CBT; mCBT). They also selected a choice card 2 weeks later without prior presentation of a target card (control task). In both tasks, 99mTc HM-PAO was injected intravenously about 15 s after initiation of the mCBT or control task. Brain images were obtained using a gamma camera and reconstructed by a UNIX-based workstation. Statistical analysis compared all activated images to control images. Results associated with P values of less than 0.01 (Z score > 2.36) were depicted on T1-weighted magnetic resonance images. All subjects preferred choices more similar to the target. SPECT activation occurred bilaterally in the dorsolateral prefrontal cortices and middle temporal gyri during performance of the CBT. Additionally, the left inferior prefrontal cortex and left fusiform gyrus showed significant activation compared with the control task. A neural network linking the temporal and prefrontal cortices prominently seen in the left hemisphere participates in context-dependent reasoning. Knowledge of such neural systems is essential for understanding prefrontal lobe function and dysfunction.

Age shifts frontal cortical control in a cognitive bias task from right to left: part I. Neuropsychological study.

Two functionally and neurally distinct cognitive selection mechanisms involve the prefrontal lobes: those based on internal representations (context dependent) and those involving exploratory processing of novel situations (context independent). We used a cognitive bias task (CBT) representing contextual reasoning to correlate lateralization with age in the frontal lobes. Subjects included 37 healthy right-handed male children and adolescents (age range, 5-18 years). Controls were 19 right-handed men from 20 to 30 years old. A computer-presented version of the original card-choice task simplified, modified for children was used (modified CBT; mCBT). Simple visual stimuli differed dichotomously in shape, color, number, and shading. A target object presented alone was followed by two choices from which subjects selected according to preference. Considering all four characteristics, similarity between target and subject choice was scored for 30 trials. A high score implied a context-dependent response selection bias and a low score, a context-independent bias. Similarity increased significantly with age. The youngest children (5-7 years) scored lower than ages from 11 years to adulthood. Between 7 and 9 years, scores began to increase with age to reach an adult level by age 13-16. Young children showed context-independent responses representing right frontal lobe function, while adolescents and adults showed context-dependent responses implicating left frontal lobe function. The locus of frontal cortical control in right-handed male subjects thus shifts from right to left as cognitive contextual reasoning develops.