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1.
Influence of tDCS over right inferior frontal gyrus and pre-supplementary motor area on perceptual decision-making and response inhibition: A healthy ageing perspective.
Fujiyama, H, Tan, J, Puri, R, Hinder, MR
Neurobiology of aging. 2022;:11-21
Abstract
A wide body of literature suggests that transcranial direct current stimulation (tDCS) administered over the prefrontal cortex can improve executive function - including decision-making and inhibitory control - in healthy young adults. However, the effects of tDCS in older adults are largely unknown. Here, using a double-blind, sham-controlled approach, changes in a combined perceptual decision-making and inhibitory control task were assessed before and after the application of tDCS (1 mA, 20 minute) targeting the right inferior frontal gyrus (rIFG) or pre-supplementary motor area (preSMA) in 42 young (18-34 years) and 41 older (60-80 years) healthy adults. Compared to sham stimulation, anodal tDCS over the preSMA improved decision-making speed for both age groups. Furthermore, the inhibitory control performance of older and younger adults was improved by preSMA and rIFG stimulation, respectively. This study provides evidence that tDCS can improve both perceptual decision-making and inhibitory control in healthy older adults, with the causal role of the preSMA and rIFG regions in cognitive control appearing to vary as a function of healthy ageing.
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2.
Cortical Oxygenation Changes during Gastric Tube Feeding in Moderate- and Late-Preterm Babies: A NIRS Study.
Muelbert, M, Alexander, T, Pook, C, Jiang, Y, Harding, JE, Bloomfield, FH
Nutrients. 2021;(2)
Abstract
Smell and taste of food can trigger physiological responses facilitating digestion and metabolism of nutrients. Controlled experimental studies in preterm babies have demonstrated that smell activates the orbitofrontal cortex (OFC) but none have investigated the effect of taste stimulation. Using cotside Near-Infrared Spectroscopy (NIRS), we measured changes in OFC cerebral oxygenation in response to gastric tube feeds five and 10 days after birth in 53 assessments of 35 moderate- to late-preterm babies enrolled in a randomized trial. Babies were randomly assigned to receive smell and taste of milk before gastric tube feeds (intervention group, n = 16) or no exposure (control group, n = 19). The majority of babies were born at 33 weeks of gestation (range 32-34) and 69% were boys. No differences in OFC cerebral oxygenation were observed between control and intervention groups. Gastric tube feeds induced activation of the OFC (p < 0.05), but sensory stimulation alone with smell and taste did not. Boys, but not girls, showed activation of the OFC following exposure to smell of milk (p = 0.01). The clinical impact of sensory stimulation prior to tube feeds on nutrition of preterm babies, as well as the impact of environmental inputs on cortical activation, remains to be determined.
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3.
Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial.
Fassini, PG, Das, SK, Magerowski, G, Marchini, JS, da Silva Junior, WA, da Silva, IR, de Souza Ribeiro Salgueiro, R, Machado, CD, Suen, VMM, Alonso-Alonso, M
International journal of obesity (2005). 2020;(6):1279-1290
Abstract
BACKGROUND/OBJECTIVES Obesity is associated with reduced neurocognitive performance. Individuals with obesity show decreased activation in the left dorsolateral prefrontal cortex (DLPFC), a key brain region relevant to the regulation of eating behavior. Transcranial direct current stimulation (tDCS) has emerged as a potential technique to correct these abnormalities. However, there is limited information to date, particularly in clinical settings and regarding long-term effects of tDCS. This study aimed to investigate the effects of DLPFC-targeted tDCS in young women with obesity. SUBJECT/METHODS Randomized, double-blind, sham-controlled parallel-design clinical trial conducted in 38 women, aged 20-40 years, with BMI 30-35 kg/m2. STUDY DESIGN Phase I: target engagement (immediate effects of tDCS on working memory performance), Phase II: tDCS only (ten sessions, 2 weeks), Phase III: tDCS + hypocaloric diet (six sessions, 30% energy intake reduction, 2 weeks, inpatient), Phase IV: follow-up at 1, 3, and 6 months. PRIMARY OUTCOME change in body weight. SECONDARY OUTCOMES change in eating behavior and appetite. Additional analyses: effect of Catechol-O-methyl transferase (COMT) gene variability. Data were analyzed as linear mixed models. RESULTS There was no group difference in change in body weight during the tDCS intervention. At follow-up, the active group lost less weight than the sham group. In addition, the active group regained weight at 6-month follow-up, compared with sham. Genetic analysis indicated that COMT Met noncarriers were the subgroup that accounted for this paradoxical response in the active group. CONCLUSION Our results suggest that in young women with class I obesity, tDCS targeted to the DLPFC does not facilitate weight loss. Indeed, we found indications that tDCS could have a paradoxical effect in this population, possibly connected with individual differences in dopamine availability. Future studies are needed to confirm these findings.
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4.
Meta-analysis of human prefrontal cortex reveals activation of GFAP and decline of synaptic transmission in the aging brain.
Wruck, W, Adjaye, J
Acta neuropathologica communications. 2020;(1):26
Abstract
Despite ongoing research efforts, mechanisms of brain aging are still enigmatic and need to be elucidated for a better understanding of age-associated cognitive decline. The aim of this study is to investigate aging in the prefrontal cortex region of human brain in a meta-analysis of transcriptome datasets. We analyzed 591 gene expression datasets pertaining to female and male human prefrontal cortex biopsies of distinct ages. We used hierarchical clustering and principal component analysis (PCA) to determine the influence of sex and age on global transcriptome levels. In sex-specific analysis we identified genes correlating with age and differentially expressed between groups of young, middle-aged and aged. Pathways and gene ontologies (GOs) over-represented in the resulting gene sets were calculated. Potential causal relationships between genes and between GOs were explored employing the Granger test of gene expression time series over the range of ages. The most outstanding results were the age-related decline of synaptic transmission and activated expression of glial fibrillary acidic protein (GFAP) in both sexes. We found an antagonistic relationship between calcium/calmodulin dependent protein kinase IV (CAMK4) and GFAP which may include regulatory mechanisms involving cAMP responsive element binding protein (CREB) and mitogen-activated protein kinase (MAPK, alias ERK). Common to both sexes was a decline in synaptic transmission, neurogenesis and an increased base-level of inflammatory and immune-related processes. Furthermore, we detected differences in dendritic spine morphogenesis, catecholamine signaling and cellular responses to external stimuli, particularly to metal (Zinc and cadmium) ions which were higher in female brains.
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5.
Comparing the effects of multi-session anodal trans-cranial direct current stimulation of primary motor and dorsolateral prefrontal cortices on fatigue and quality of life in patients with multiple sclerosis: a double-blind, randomized, sham-controlled trial.
Mortezanejad, M, Ehsani, F, Masoudian, N, Zoghi, M, Jaberzadeh, S
Clinical rehabilitation. 2020;(8):1103-1111
Abstract
OBJECTIVE To compare the effects of anodal trans-cranial direct current stimulation (a-tDCS) over primary motor and dorsolateral prefrontal cortices on Fatigue Severity Scale and its lasting effect on fatigue reduction and improvement in quality of life in patients with multiple sclerosis. DESIGN A randomized, double-blinded, sham-controlled parallel clinical trial study. SETTING Neurological physiotherapy clinics. SUBJECTS Thirty-nine participants were randomly assigned to three groups: dorsolateral prefrontal cortex a-tDCS, primary motor a-tDCS (experimental groups) and sham a-tDCS. Finally, 36 participants completed the whole study (n = 12 in each group). INTERVENTIONS Participants in the experimental groups received six-session a-tDCS (1.5 mA, 20 minutes) during two weeks (three sessions per week). The sham group received six sessions of 20-minute sham stimulation. MAIN MEASURES The Fatigue Severity Scale and quality of life were assessed before, immediately and four weeks after the intervention. RESULTS Findings indicated a significant reduction in the Fatigue Severity Scale and a significant increase in the quality of life in both experimental groups, immediately after the intervention (P < 0.001), while Fatigue Severity Scale and quality of life changes were not significant in the sham a-tDCS group (P > 0.05). In addition, improvement of the variables remained four weeks after the intervention in dorsolateral prefrontal cortex a-tDCS (mean differences (95% confidence interval): 0.03 (-0.63 to 0.68) as compared to primary motor (-0.62 (-0.11 to -1.14) and sham a-tDCS groups (-0.47 (-1.37 to 0.43)). CONCLUSION Both primary motor and dorsolateral prefrontal cortex a-tDCS as compared to sham intervention can immediately improve fatigue and quality of life. However, the effects last up to four weeks only by the dorsolateral prefrontal cortex a-tDCS.
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6.
Prefrontal Cortex Neuromodulation Enhances Frontal Asymmetry and Reduces Caloric Intake in Patients with Morbid Obesity.
Forcano, L, Castellano, M, Cuenca-Royo, A, Goday-Arno, A, Pastor, A, Langohr, K, Castañer, O, Pérez-Vega, KA, Serra, C, Ruffini, G, et al
Obesity (Silver Spring, Md.). 2020;(4):696-705
Abstract
OBJECTIVE The objective of this study was to test the feasibility of a combined intervention involving transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (dlPFC) and cognitive training (CT). Short-term effects on food consumption, cognition, endocannabinoid (eCB) levels, and electroencephalogram (EEG) markers of future weight loss were explored. METHODS Eighteen healthy volunteers with morbid obesity were randomized in a double-blind, placebo-controlled, parallel trial. Participants received sham or active tDCS plus CT for four consecutive days. Cognitive performance, daily food intake, and eCB blood samples were collected before and after the intervention; EEG data were gathered before and after daily training. RESULTS The active tDCS + CT group reversed left-dominant frontal asymmetry and increased frontal coherence (FC) in the γ-band (30-45 Hz) after the intervention. The strength of the latter predicted BMI reduction. Additionally, a large intervention effect on food intake was shown in the active tDCS + CT group at follow-up (-339.6 ± 639 kcal on average), and there was a decrease of plasma eCB concentrations. CONCLUSIONS dlPFC modulation through tDCS + CT is an effective tool to restore right dominance of the dlPFC and enhance FC in patients with morbid obesity. Moreover, the effect of the strength of FC on BMI suggests that the interhemispheric FC at the dlPFC is functionally relevant for the efficient regulation of food choice.
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7.
Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms.
Dos Santos, RG, Hallak, JEC
Neuroscience and biobehavioral reviews. 2020;:423-434
Abstract
Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.
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8.
Neuromodulation of the prefrontal cortex facilitates diet-induced weight loss in midlife women: a randomized, proof-of-concept clinical trial.
Amo Usanos, C, Valenzuela, PL, de la Villa, P, Navarro, SM, Melo Aroeira, AE, Amo Usanos, I, Martínez Cancio, L, Cuesta Villa, L, Shah, H, Magerowski, G, et al
International journal of obesity (2005). 2020;(3):568-578
Abstract
BACKGROUND High body mass index (BMI) is associated with neurocognitive impairments that contribute to overeating and interfere with weight loss efforts. Overweight and obesity at midlife can accelerate neurodegenerative changes and increase the risk of late-life dementia. Noninvasive neuromodulation represents a novel, affordable and scalable approach to improve neurocognitive function in this context. The purpose of this proof-of-concept study was to examine whether transcranial direct current stimulation (tDCS) aimed at enhancing prefrontal cortex activity could enhance weight loss, in combination with a hypocaloric diet, and study underlying mechanisms. METHODS Overall, 38 women with BMI 25-35 kg/m2 underwent a 4 week randomized, double-blinded, sham-controlled, and parallel-design intervention, during which they received eight sessions of tDCS (n = 18 sham, n = 20 active) in combination with a diet (caloric goal of 20 kcal/kg/day). We evaluated longitudinal changes in body weight, appetite and food craving. In addition, we examined the contribution of cognitive-executive processes via food-modified computerized tasks. RESULTS We found that the active group had more reduction in body weight than the sham group throughout the study (p = 0.020) and significant weekly weight loss. At 4 weeks, the active group lost 2.32% of initial body weight (sham: 1.29%). Components of subjective appetite and food craving showed a trend toward more reduction in the active group. These changes were paralleled by significant improvements in task performance in the active group, particularly in a dual task that required inhibitory control and working memory (p = 0.007-0.031). Improvement in inhibitory control performance predicted reduction in lack of control overeating, explaining 43.5% of its variance at the end of the study (p = 0.003). No significant adverse effects were observed. CONCLUSIONS Our results provide proof-of-concept validation of prefrontal-targeted tDCS, combined with a diet, in midlife women with excess body weight, paving the way for larger studies evaluating clinical efficacy and long-term effects of this intervention.
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9.
Genome-wide DNA methylomic differences between dorsolateral prefrontal and temporal pole cortices of bipolar disorder.
Ho, AM, Winham, SJ, Armasu, SM, Blacker, CJ, Millischer, V, Lavebratt, C, Overholser, JC, Jurjus, GJ, Dieter, L, Mahajan, G, et al
Journal of psychiatric research. 2019;:45-54
Abstract
Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation - an epigenetic mechanism both heritable and sensitive to the environment - may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850 K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.
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10.
Neural markers of category-based selective working memory in aging.
Mok, RM, O'Donoghue, MC, Myers, NE, Drazich, EHS, Nobre, AC
NeuroImage. 2019;:163-173
Abstract
Working memory (WM) is essential for normal cognitive function, but shows marked decline in aging. The importance of selective attention in guiding WM performance is increasingly recognized. Studies so far are inconclusive about the ability to use selective attention during WM in aging. To investigate the neural mechanisms supporting selective attention in WM in aging, we tested a large group of older adults using functional magnetic resonance imaging whilst they performed a category-based (faces/houses) selective-WM task. Older adults were able to use attention to encode targets and suppress distractors to reach high levels of task performance. A subsequent, surprise recognition-memory task showed strong consequences of selective attention. Attended items in the relevant category were recognized significantly better than items in the ignored category. Neural measures also showed reliable markers of selective attention during WM. Purported control regions including the dorsolateral and inferior prefrontal and anterior cingulate cortex were reliably recruited for attention to both categories. Activation levels in category-sensitive visual cortex showed reliable modulation according to attentional demands, and positively correlated with subsequent memory measures of attention and WM span. Psychophysiological interaction analyses showed that activity in category-sensitive areas were coupled with non-sensory cortex known to be involved in cognitive control and memory processing, including regions in the prefrontal cortex and hippocampus. In summary, we found that older adults were able to recruit a network of brain regions involved in top-down attention during selective WM, and individual differences in attentional control corresponded to the degree of attention-related modulation in the brain.