Dorsal Lateral Prefrontal Cortex Research Articles

Study of a PST-trained voice-enabled artificial intelligence counselor for adults with emotional distress (SPEAC-2): Design and methods

BackgroundNovel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms. MethodsTo further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen after the trial period. Participants will be assessed at baseline and 18 weeks. The primary aim is to confirm neural target engagement by testing whether compared with waitlist controls, Lumen participants will show significantly greater improvements from baseline to 18 weeks in the a priori neural target for cognitive control, right dorsal lateral prefrontal cortex engaged by the go/nogo task (primary superiority hypothesis). A secondary hypothesis will test whether compared with human-coached PST participants, Lumen participants will show equivalent improvements (i.e., noninferiority) in the same neural target from baseline to 18 weeks. The second aim is to examine (1) treatment effects on depression and anxiety symptoms, psychosocial functioning, and quality of life outcomes, and (2) relationships of neural target engagement to these patient-reported outcomes. ConclusionsThis study offers potential to improve the reach and impact of psychotherapy, mitigating access, cost, and stigma barriers for people with depression and/or anxiety.Clinicaltrials.gov #: NCT05603923

Bilingual Language Control in the Brain: Evidence from Structural and Effective Functional Brain Connectivity.

Experience in bilingual language control is often accompanied by changes in the structure and function of the brain. Brain structural changes are also often closely related to changes in functions. Previous studies, however, have not directly explored the relationship between structural connectivity and effective functional connectivity of the brain during bilingual language control, and whether the two types of connectivity are associated with behavioral performance of language control. Using behavioral performance, functional, and diffusion imaging techniques, we found that: (1) during language control, the left dorsal lateral prefrontal cortex (dlPFC), left caudate nucleus (CN), inferior parietal lobe, precuneus, and dorsal anterior cingulate cortex (dACC)/pre-SMA were significantly activated. (2) In the language control model with left dlPFC, dACC/pre-SMA, and left CN as ROIs (selected based on activation results and language control models from previous studies), stimuli first enter dACC/pre-SMA and then to left CN. At the left CN, a bidirectional effective connectivity is formed with left dlPFC. (3) There is a nonlinear relationship between effective connectivity during language control and the structural connectivity of the second language learners' brains. Specifically, the fiber density between dACC/pre-SMA and left dlPFC has a positive influence on the bidirectional effective connectivity between left dlPFC and left CN. Findings of the present study contribute evidence toward functional effective connectivity during bilingual language control; toward structural connectivity in the brains of second language learners; as well as toward nonlinear relationships between functional effective connectivity, structural connectivity, and behavioral performance in relation to bilingual language control.

Glycoproteome-Wide Discovery of Cortical Glycoproteins That May Provide Cognitive Resilience in Older Adults.

Molecular omics studies have identified proteins related to cognitive resilience but unrelated to Alzheimer disease and Alzheimer disease-related dementia (AD/ADRD) pathologies. Posttranslational modifications of proteins with glycans can modify protein function. In this study, we identified glycopeptiforms associated with cognitive resilience. We studied brains from adults with annual cognitive testing with postmortem indices of 10 AD/ADRD pathologies and proteome-wide data from dorsal lateral prefrontal cortex (DLPFC). We quantified 11, 012 glycopeptiforms from DLPFC using liquid chromatography with tandem mass spectrometry. We used linear mixed-effects models to identify glycopeptiforms associated with cognitive decline correcting for multiple comparisons (p < 5 × 10-6). Then, we regressed out the effect of AD/ADRD pathologies to identify glycopeptiforms that may provide cognitive resilience. We studied 366 brains, average age at death 89 years, and 70% female with no cognitive impairment = 152, mild cognitive impairment = 93, and AD = 121 cognitive status at death. In models adjusting for age, sex and education, 11 glycopeptiforms were associated with cognitive decline. In further modeling, 8 of these glycopeptiforms remained associated with cognitive decline after adjusting for AD/ADRD pathologies: NPTX2a (Est., 0.030, SE, 0.005, p = 1 × 10-4); NPTX2b (Est.,0.019, SE, 0.005, p = 2 × 10-4) NECTIN1(Est., 0.029, SE, 0.009, p = 9 × 10-4), NPTX2c (Est., 0.015, SE, 0.004, p = 9 × 10-4), HSPB1 (Est., -0.021, SE, 0.006, p = 2 × 10-4), PLTP (Est., -0.027, SE, 0.009, p = 4.2 × 10-3), NAGK (Est., -0.027, SE, 0.008, p = 1.4 × 10-3), and VAT1 (Est., -0.020, SE, 0.006, p = 1.1 × 10-3). Higher levels of 4 resilience glycopeptiforms derived through glycosylation were associated with slower decline and higher levels of 4 derived through glycation were related to faster decline. Together, these 8 glycopeptiforms accounted for an additional 6% of cognitive decline over the 33% accounted for the 10 brain pathologies and demographics. All 8 resilience glycopeptiforms remained associated with cognitive decline after adjustments for the expression level of their corresponding protein. Exploratory gene ontology suggested that molecular mechanisms of glycopeptiforms associated with cognitive decline may involve metabolic pathways including pyruvate and NADH pathways and highlighted the importance of molecular mechanisms involved in glucose metabolism. Glycopeptiforms in aging brains may provide cognitive resilience. Targeting these glycopeptiforms may lead to therapies that maintain cognition through resilience.

Transcranial Direct Current Stimulation (tDCS) as a Therapeutic Tool for Chronic Insomnia

&#x0D; &#x0D; &#x0D; &#x0D; Background and Objective: Insomnia is the most common sleep problem which is associated with cortical over- excitation. Transcranial direct-current stimulation (tDCS) potentially modifies insomnia-related cortical state. There- fore, we tested the hypothesis that insomnia severity can be modulated by tDCS.&#x0D; Materials and Methods: The current study was conducted with a pretest-posttest design and a control group. A total of 32 women with insomnia were randomly categorized into an intervention group (active stimulation) and a control group (sham stimulation). In the intervention group, tDCS ‎was used with an intensity of 2mA for 20 to 30 minutes during 12 sessions (3 times a week). Anodal stimulation was performed‎on the left primary motor cortex (M1) and cathodal stimulation was performed‎on the right dorsal lateral prefrontal cortex (DLPFC). The control group received sham stim- ulation for 20 to 30 minutes during 12 sessions (3 times a week). All participants were evaluated before and after the intervention using the Insomnia Severity Index (ISI) and Positive Affect and Negative Affect Schedule (PANAS).&#x0D; Results: The results of univariate analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) showed a significant difference between the tDCS group and the sham group in terms of reduction in the severity of insomnia. We also observed that positive affect increased and negative affect decreased following insomnia treatment (P ≤ 0.005).&#x0D; Conclusion: The results of our study indicated that performing our designed tDCS protocol for treating insomnia can be effective in treating insomnia and improving positive and negative affect.&#x0D; &#x0D; &#x0D; &#x0D;

Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain. Nonhuman primates provide more relevant models than rodents for human stroke and PSCI. This study investigated the effects of NBP on PSCI and secondary neurodegeneration in cynomolgus monkeys after permanent left middle cerebral artery occlusion (MCAO). Thirteen adult male cynomolgus monkeys were randomly assigned to sham (n=4), MCAO+placebo (n=5), and MCAO+NBP groups (n=4). The MCAO+placebo and MCAO+NBP groups received saline and NBP injections intravenously, respectively, starting at 6-hour postsurgery for 2 weeks, followed by soybean oil and NBP orally, respectively, for 10 weeks after MCAO. Infarct size was assessed at week 4 by magnetic resonance imaging. Working memory and executive function were evaluated dynamically using the delayed response task and object retrieval detour task, respectively. Neuron loss, glia proliferation, and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex, thalamus, and hippocampus were analyzed by immunostaining 12 weeks after MCAO. Infarcts were located in the left middle cerebral artery region, apart from the ipsilateral dorsal lateral prefrontal cortex, thalamus, or hippocampus, with no significant difference between the MCAO+placebo and MCAO+NBP group. Higher success in delayed response task was achieved at weeks 4, 8, and 12 after NBP compared with placebo treatments (P<0.05), but not in the object retrieval detour task (all P>0.05). More neurons and less microglia, astrocytes, CD68-positive microglia, tumor necrosis factor-α, and inducible NO synthase were observed in the ipsilateral dorsal lateral prefrontal cortex and thalamus after 12 weeks of NBP treatment (P<0.05), but not in the hippocampus (P>0.05). Our findings indicate that NBP improves working memory by alleviating remote secondary neurodegeneration and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex and thalamus after MCAO in cynomolgus monkeys.

The links between physical activity and prosocial behavior: an fNIRS hyperscanning study.

The prevalence of physically inactive lifestyles in modern society raises concerns about the potential association with poor brain health, particularly in the lateral prefrontal cortex, which is crucial for human prosocial behavior. Here, we explored the relationship between physical activity and prosocial behavior, focusing on potential neural markers, including intra-brain functional connectivity and inter-brain synchrony in the lateral prefrontal cortex. Forty participants, each paired with a stranger, completed two experimental conditions in a randomized order: (i) face-to-face and (ii) face stimulus (eye-to-eye contact with a face stimulus of a fictitious person displayed on the screen). Following each condition, participants played economic games with either their partner or an assumed person displayed on the screen. Neural activity in the lateral prefrontal cortex was recorded by functional near-infrared spectroscopy hyperscanning. Sparse multiset canonical correlation analysis showed that a physically inactive lifestyle was covaried with poorer reciprocity, greater trust, shorter decision-making time, and weaker intra-brain connectivity in the dorsal lateral prefrontal cortex and poorer inter-brain synchrony in the ventral lateral prefrontal cortex. These associations were observed exclusively in the face-to-face condition. Our findings suggest that a physically inactive lifestyle may alter human prosocial behavior by impairing adaptable prosocial decision-making in response to social factors through altered intra-brain functional connectivity and inter-brain synchrony.

TRANSCRANIAL DIRECT CURRENT STIMULATION MODULATES BRAIN ACTIVITY DURING DUAL-TASK STANDING IN OLDER ADULTS

Abstract In older adults, performing an attention-demanding cognitive task while standing comes with a ‘cost’ (i.e., decrement) to postural control. Transcranial direct current stimulation (tDCS) designed to facilitate the excitability of the left dorsal-lateral prefrontal cortex (L-DLPFC) and motor cortex (M1) mitigates this dual-task cost (DTC). The effects of tDCS on underlying brain activity measured by electroencephalography (EEG) during dual-tasking, however, is unknown. We hypothesized that tDCS would decrease the DTC of EEG-measured alpha and gamma power, as these frequencies have been linked to attentional processing and their attenuation is believed to reflect more efficient and/or effective postural control. Thirty participants received 20-minutes of tDCS targeting the L-DLPFC and M1, or sham (i.e., control) stimulation, in random order, on two separate visits. Before and immediately after each stimulation, EEG and postural sway area were recorded as participants completed trials of standing with and without verbalized serial subtractions. EEG alpha and gamma power were derived from channels corresponding to the L-DLPFC and M1 areas. The DTC (absolute change from single to dual-tasking) for both EEG and sway outcomes were calculated. tDCS, compared to sham, decreased the DTC to gamma power (p=0.04) and sway area (p=0.04). No pre-to-post stimulation changes were observed for alpha power (p=0.42). Participants who demonstrated a greater decrease in the DTC to gamma power after tDCS exhibited a greater reduction (improvement) in the DTC to sway area (r=0.66, p=0.002). The results suggest that the tDCS-induced changes in gamma-frequency activity were associated with improved dual-task standing balance in older adults.

FC2: The effect of Maintenance phase of Transcranial Direct Current Stimulation (tDCS) in Alzheimer’s Dementia

Introduction:Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. In pathology, the amyloid deposits in AD disrupts the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. An increasing number of studies have been concluded a positive therapeutic effect on cognition in AD. In brain stimulation, dorsolateral prefrontal cortex (DLPFC) was associated with improvements in memory enhancement, language, processing speed, global cognitive symptoms, and apathy over a period of treatment. Theoretically, the aftereffect of tDCS would need to be re-stimulated by tDCS to maintain its delayed plastic response benefits. In this pilot study, we investigate the maintenance effects of continuing tDCS at three different times, weekly, every two weeks, and every four weeks, for 12 weeks.Method:Twenty-eight AD participants aged 55-90 years were enrolled (mean age 72.7, 77.3, and 76.2 in the three groups - maintained weekly (7 cases), biweekly (9 cases) and every 4 weeks (12 cases)). The anodal electrode was placed over the left dorsal lateral prefrontal cortex and the cathodal electrode was placed over the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at (1) baseline, (2) post-10sessions of tDCS (in 2weeks), and (3) post-maintenance phase (total of 12 weeks). Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess differences in participant demographic characteristics and to compare differences in test scores between groups.Results:After 10 sessions of tDCS stimulations, the total CASI scores in the 1-week group improved significantly from baseline to 2 weeks. However, there are no significant difference in MMSE, CASI or WCST between baseline and after maintain phase stimulations in each group.Conclusion:Although tDCS has a positive effect in AD, it is recommended to prolong the number of tDCS stimulations, such as 20 sessions in 4 weeks.

Sex differences in marmoset neurocognitive aging, a nonhuman primate model for brain aging and age‐related neurodegenerative diseases

AbstractBackgroundNonhuman primate models of human aging are necessary to understand functional decline and identify vulnerabilities to aging pathologies. Longitudinal studies are critical and common marmosets (Callithrix jacchus) are ideal as they have a short lifespan (∼12 yr) and naturally develop neuropathology relevant to Alzheimer’s disease (AD).MethodWe studied 28 marmosets (14 females) from midlife (∼5 yr old) to old age across four years. Simple discrimination and reversal learning was used to evaluate cognitive performance. Additional yearly tests included motor, stress reactivity, and social behavior assessments. A subset of animals (n = 17, 9 females) were studied for AD‐relevant neuropathology in post‐mortem tissue of the dorsal lateral prefrontal cortex (dlPFC) and CA1 of the hippocampus.ResultMultilevel models revealed age‐related changes for cognitive performance with improved reversal learning during the first three years due to practice followed by decline in the final year with the onset of old age. Cognitive decline was steeper and began earlier for females compared to males. Based on cognitive trajectories which were highly variable across individuals, we categorized marmosets as cognitively impaired or non‐impaired. Mild amyloid β (Aβ) deposition was observed in the dlPFC and CA1 but did not differ between males and females. Aβ burden was higher in cognitively impaired compared to non‐impaired marmosets, but this difference did not reach statistical significance. However, cognitively impaired marmosets showed signs of accelerated brain aging including higher astrogliosis associated with Aβ deposits and dendritic spine loss, both in the dlPFC and hippocampus. In addition, increased activation and changes in microglial phenotypes were observed in the dlPFC.ConclusionLike humans, aging marmosets displayed intra‐individual variability in cognitive decline, neurodegeneration and neuronal aging. Female marmosets showed greater vulnerability to cognitive impairment, which is translationally relevant to the higher prevalence of AD in women. While trajectories of cognitive decline did not strongly map onto Aβ burden for females or males, evidence of accelerated brain aging was found in the impaired marmosets. This study highlights the value of marmosets as a nonhuman primate model of AD to identify vulnerabilities to aging pathologies, such as sex differences.

Neurocomputations on dual-brain signals underlie interpersonal prediction during a natural conversation

Prediction on the partner's speech plays a key role in a smooth conversation. However, previous studies on this issue have been majorly conducted at the single-brain rather than dual-brain level, leaving the interpersonal prediction hypothesis untested. To fill this gap, this study combined a neurocomputational modeling approach with a natural conversation paradigm in which two salespersons persuaded a customer to buy their product with their haemodynamic signals being collected using functional near-infrared spectroscopy hyperscanning. First, the results showed a cognitive hierarchy in a natural conversation, with the lower-level process (i.e., pragmatic representation of the persuasion) in the salesperson interacting with the higher-level process (i.e., value representation of the product) in the customer. Next, we found that the right dorsal lateral prefrontal cortex (rdlPFC) and temporoparietal junction (rTPJ) were associated with the representation of the product's value in the customer, while the right inferior frontal cortex (rIFC) was associated with the representation of the pragmatic processes in the salesperson. Finally, neurocomputational modeling results supported the prediction of the salesperson's lower-level brain activity based on the customer's higher-level brain activity. Moreover, the updating weight of the prediction model based on the neural computation between the rIFC of the salesperson and the rTPJ of the customer was closely associated with the interaction context, whereas that based on the rIFC-rdlPFC was not. In summary, these findings provide initial support for the interpersonal prediction hypothesis at the dual-brain level and reveal a hierarchy for the interpersonal prediction process.

Multisite rTMS combined with cognitive training modulates effective connectivity in patients with Alzheimer's disease.

To investigate the effective connectivity (EC) changes after multisite repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG). We selected 51 patients with mild or moderate Alzheimer's disease (AD) and delivered 10 Hz rTMS over the left dorsal lateral prefrontal cortex (DLPFC) and the lateral temporal lobe (LTL) combined with COG or sham stimulation for 4 weeks. The selected AD patients were divided into real (real rTMS+COG, n = 11) or sham (sham rTMS+COG, n = 8) groups to undergo neuropsychological assessment, resting-state fMRI, and 3D brain structural imaging before (T0), immediately at the end of treatment (T4), and 4 weeks after treatment (T8). A 2 × 3 factorial design with "time" as the within-subjects factor (three levels: T0, T4, and T8) and "group" as the between-subjects factor (two levels: real and sham) was used to investigate the EC changes related to the stimulation targets in the rest of the brain, as well as the causal interactions among seven resting-state networks based on Granger causality analysis (GCA). At the voxel level, the EC changes from the left DLPFC out to the left inferior parietal lobe and the left superior frontal gyrus, as well as from the left LTL out to the left orbital frontal cortex, had a significant group × time interaction effect. At the network level, a significant interaction effect was identified in the increase in EC from the limbic network out to the default mode network. The decrease in EC at the voxel level and the increase in EC at the network level were both associated with the improved ability to perform activities of daily living and cognitive function. Multisite rTMS combined with cognitive training can modulate effective connectivity in patients with AD, resulting in improved ability to perform activities of daily living and cognitive function.

Effect of Repetitive Transcranial Magnetic Stimulation on the Working Memory of Patients with Alzheimer’s Disease

Background and Aims Alzheimer’s disease (AD) is a common neurological disorder that begins with mild memory loss and progresses to severe impairment of executive and cognitive functions. This study aims to investigate the effect of repeated transcranial magnetic stimulation (rTMS) on the working memory of patients with AD. Methods In this quasi-experimental study with a pre-test/post-test design, 30 patients with AD aged 55-75 years referred to neurology clinics in Yazd, Iran participated, who were selected using a convenience sampling method and divided into two groups of intervention (n=15) and control (n=15). Active memory was measured by a computerized n-back test, both in terms of reaction time and percentage of accuracy before and after treatment. In the control group, each patient received 10 sessions of inactive rTMS for 20 minutes, while the intervention group received 10 sessions of active rTMS for 20 minutes at a frequency of 10 Hz over the left dorsal lateral prefrontal cortex. Data analysis was performed using analysis of covariance. Results Data analysis results showed that the reaction time significantly decreased, and the percentage of accuracy significantly increased in the n-back test in the intervention group after receiving rTMS compared to the control group (P= 0.001). Conclusion It seems that rTMS over the left dorsal lateral prefrontal cortex can improve the working memory in patients with AD.

Feasibility and Safety of Sequential Transcranial Direct Current Stimulation and Physical Therapy in Older Adults at Risk of Falling: A Randomized Pilot Study

ObjectiveTo establish the feasibility and safety of administering transcranial direct current stimulation (tDCS) immediately prior to physical therapy (PT) sessions in older adults at risk of falls. DesignA pilot randomized controlled study. SettingOutpatient geriatric physical therapy clinic. ParticipantsTen older adults living within supportive housing facilities (86.8±7.9 y/o, 8F) were enrolled in the study. InterventionsParticipants received tDCS or sham stimulation targeting the left dorsal lateral prefrontal cortex for 20 minutes, immediately prior to up to 10 of their PT visits. Main Outcome MeasuresFeasibility, safety, and functional outcomes were reported to inform the design of a larger and more definitive trial. ResultsSix fallers (88.8±5.0 y/o, 5F) completed the study and received 82.3% of the possible stimulation sessions, suggesting adding a 20-minute session of stimulation immediately prior to PT training sessions, along with pre- and post-assessments is feasible. The blinding strategy was successful and all reported side effects were expected and transient. While feasible and safe, the trial was met with numerous challenges, including selection bias, time and energy commitment, and large variation in functional performance, that must be considered when designing and implementing larger more definitive trials. ConclusionThis study provides preliminary evidence about the feasibility, safety, and challenges to combine PT and tDCS in very frail older adults.

Beyond Broca's and Wernicke's: Functional Mapping of Ancillary Language Centers Prior to Brain Tumor Surgery.

Functional MRI is a well-established tool used for pre-surgical planning to help the neurosurgeon have a roadmap of critical functional areas that should be avoided, if possible, during surgery to minimize morbidity for patients with brain tumors (though this also has applications for surgical resection of epileptogenic tissue and vascular lesions). This article reviews the locations of secondary language centers within the brain along with imaging findings to help improve our confidence in our knowledge on language lateralization. Brief overviews of these language centers and their contributions to the language networks will be discussed. These language centers include primary language centers of "Broca's Area" and "Wernicke's Area". However, there are multiple secondary language centers such as the dorsal lateral prefrontal cortex (DLPFC), frontal eye fields, pre- supplemental motor area (pre-SMA), Basal Temporal Language Area (BTLA), along with other areas of activation. Knowing these foci helps to increase self-assurance when discussing the nature of laterality with the neurosurgeon. By knowing secondary language centers for language lateralization, via fMRI, one can feel confident on providing neurosurgeon colleagues with appropriate information on the laterality of language in preparation for surgery.

Excitatory Dorsal Lateral Prefrontal Cortex Transcranial Magnetic Stimulation Increases Social Anxiety.

Social exclusion refers to the experience of rejection by one or more people during a social event and can induce pain-related sensations. Cyberball, a computer program, is one of the most common tools for analyzing social exclusion. Regions of the brain that underlie social pain include networks linked to the dorsal lateral prefrontal cortex (DLPFC). Specifically, self-directed negative socially induced exclusion is associated with changes in DLPFC activity. Direct manipulation of this area may provide a better understanding of how the DLPFC can influence the perception of social exclusion and determine a causal role of the DLPFC. Transcranial magnetic stimulation (TMS) was applied to both the left and right DLPFC to gauge different reactions to the Cyberball experience. It was found that there were elevated exclusion indices following right DLPFC rTMS; participants consistently felt more excluded when the right DLPFC was excited. This may relate to greater feelings of social pain when the right DLPFC is manipulated. These data demonstrate that direct manipulation of the DLPFC results in changes in responses to social exclusion.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Representing creative thought: A representational similarity analysis of creative idea generation and evaluation

Dual process theories of creativity suggest that creative thought is supported by both a generation phase, where unconstrained ideas are generated and combined in novel ways, and an evaluation phase, where those ideas are filtered for usefulness in context. Neurocognitively, both the default mode network (DMN) and the executive control network (ECN) have been implicated in generation and evaluation, respectively. Importantly, generating and evaluating ideas implies that the same information, reflected in patterns of neural activity, must be present in both phases, suggesting that information should be ‘reinstated’ (i.e. multidimensional patterns must reappear) within and/or between network nodes. In the present study, we used representational similarity analysis (RSA) to investigate the extent to which nodes of the DMN and ECN reinstate information between a generation phase, in which participants generated novel or appropriate word associations to single nouns, and an evaluation phase, where we presented the associations back to participants to evaluate them. We showed strong evidence for reinstatement within the ECN dorsal lateral prefrontal cortex during the novel association task, and within the DMN medial prefrontal cortex during the appropriate association task. We additionally showed between network reinstatement between the ECN dorsal lateral prefrontal cortex and the DMN posterior parietal cortex during the novelty task. These results demonstrate the importance of both within- and between-informational reinstatement for generating and evaluating ideas, and implicate both the DMN and ECN in dual process models of creativity.

Binge drinking is associated with higher cortisol and lower hippocampal and prefrontal gray matter volume: Prospective association with future alcohol intake

BackgroundCortisol is a significant driver of the biological stress response that is potently activated by acute alcohol intake and increased with binge drinking. Binge drinking is associated with negative social and health consequences and risk of developing alcohol use disorder (AUD). Both cortisol levels and AUD are also associated with changes in hippocampal and prefrontal regions. However, no previous research has assessed structural gray matter volume (GMV) and cortisol concurrently to examine BD effects on hippocampal and prefrontal GMV and cortisol, and their prospective relationship to future alcohol intake. MethodsIndividuals who reported binge drinking (BD: N = 55) and demographically matched non-binge moderate drinkers (MD: N = 58) were enrolled and scanned using high-resolution structural MRI. Whole brain voxel-based morphometry was used to quantify regional GMV. In a second phase, 65% of the sample volunteered to participate in prospective daily assessment of alcohol intake for 30 days post-scanning. ResultsRelative to MD, BD showed significantly higher cortisol and smaller GMV in regions including hippocampus, dorsal lateral prefrontal cortex (dlPFC), prefrontal and supplementary motor, primary sensory and posterior parietal cortex (FWE, p < 0.05). GMV in bilateral dlPFC and motor cortices were negatively associated with cortisol levels, and smaller GMV in multiple PFC regions was associated with more subsequent drinking days in BD. ConclusionThese findings indicate neuroendocrine and structural dysregulation associated with BD relative to MD. Notably, BD-associated lower GMV regions were those involved in stress, memory and cognitive control, with lower GMV in cognitive control and motor regions also predicting higher levels of future alcohol intake in BD.

Lower Dorsal Lateral Prefrontal Cortex Functional Connectivity in Late-Life Depression With Suicidal Ideation

The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

A Systematic Review of the Effect of Short Term Transcranial Direct Current Stimulation Therapy in Methamphetamine Use Disorder

Background: Methamphetamine use disorder (MUD) has become more and more common. Some studies have shown that Transcranial Direct Current stimulation (tDCS) may reduce craving when stimulating the dorsal lateral prefrontal cortex. Objectives: The aim of this systematic review was to evaluate the effect of transcranial direct current stimulation (tDCS) on MUD. Databases were searched through May 2022. Randomized Controlled Trials (RCT) and pre-post studies investigating the efficacy of tDCS in MUD were included. The Cochrane Manual of Systematic Evaluation 6.3 bias risk assessment tool was used to assess the risk of bias. For each article, where possible, we extracted the population(s), standardized mean differences (SMD), standard deviations, and other study metrics (design, year, randomization, and details) on efficacy and tolerability outcomes. We assessed each article’s quality via the GRADE assessment protocol. Results: Six studies involving 220 patients were included. All six studies included reported continuous data on craving. Results from craving favored active tDCS over sham tDCS at the end of treatment (SMD −0.58, 95% CI −0.85 to −0.30; studies = 6, participants = 220; I2 = 60%). Tolerability data showed that tDCS does not cause more tingling or itching sensation compared to sham tDCS. Conclusions: Further trials with larger sample sizes and longer durations are needed to determine whether tDCS is a valuable tool in treating MUD.