Metabolic Dynamics in the Prefrontal Cortex during a Working Memory Task in Young Adult Smokers.

INTRODUCTION: Cigarette smoking is known to modulate brain metabolism and brain function. How the dynamics of these metabolic alterations influence the active performance of higher order cognitive tasks in smokers, compared to non-smokers, is still unclear. The present exploratory study sought to examine the impact of smoking on the "complete" metabolic profile while the participants performed a working memory (N-back) task. METHODS: The study sample consisted of 40 young male healthy participants (smokers [n = 20] and non-smokers [n = 20]). Functional magnetic resonance spectroscopy data were acquired using a 3 T whole-body MR system. Data analysis was performed using Java-based Magnetic Resonance User Interface software, and metabolite ratios with respect to creatine (Cr) were calculated. RESULTS: On a behavioural level, smokers showed worse performance (measured by d') than non-smokers. However, we observed significant differences in the metabolite concentrations in smokers compared to non-smokers, which also changed over the course of the N-back task. A significant effect of the group was observed with smokers showing lower glutamate/Cr (Glx/Cr) and choline/Cr (Cho/Cr) ratios than non-smokers. Further, N-acetyl aspartate (NAA/Cr) and Cho/Cr ratios were significantly different during the rest and the task conditions. In addition, our results demonstrated the metabolite interactions (NAA and Cho, Glx and myo-inositol [mI], and Cho and mI). CONCLUSION: Further studies are necessary to shed more light on the association between smoking behaviours and metabolic alterations. However, our preliminary findings would assist in this future research to have a complete understanding of the metabolite interactions not only in smoking but also in addiction research.

Human body odor increases familiarity for faces during encoding-retrieval task.

Odors can increase memory performance when presented as context during both encoding and retrieval phases. Since information from different sensory modalities is integrated into a unified conceptual knowledge, we hypothesize that the social information from body odors and faces would be integrated during encoding. The integration of such social information would enhance retrieval more so than when the encoding occurs in the context of common odors. To examine this hypothesis and to further explore the underlying neural correlates of this behavior, we have conducted a functional magnetic resonance imaging study in which participants performed an encoding-retrieval memory task for faces during the presentation of common odor, body odor or clean air. At the behavioral level, results show that participants were less biased and faster in recognizing faces when presented in concomitance with the body odor compared to the common odor. At the neural level, the encoding of faces in the body odor condition, compared to common odor and clean air conditions, showed greater activation in areas related to associative memory (dorsolateral prefrontal cortex), odor perception and multisensory integration (orbitofrontal cortex). These results suggest that face and body odor information were integrated and as a result, participants were faster in recognizing previously presented material.

When to collect resting-state data: The influence of odor on post-task resting-state connectivity.

The human brain networks at rest represent spontaneous activity that is highly correlated between different brain regions. Previous studies have shown that these resting-state networks are flexible and dynamic, and they can be affected by performance of different types of tasks. Moreover, it has been suggested that the re-activation of a task-related brain network during rest promotes learning and improves the expertise on that task. However, it is still unclear whether the presence of different sensory information in the on-task state affects functional connectivity in subsequent resting-state fMRI even though the perception of the sensory information did not induce significant behavioral effects. To clarify this issue, we compared pre- and post-task resting-state fMRI of two groups of participants performing the same task either with an odor context (ODOR group) or without an odor context (AIR group). Seed-based functional connectivity analyses were performed with orbitofrontal cortex, piriform cortex and working-memory core network as seeds. The results showed that an odor context presented during an encoding task induced significant changes in the functional connectivity only within the olfactory network of the post-task resting-state compared to the same post-task situation without previous odor context. No significant difference in functional connectivity were found for the working-memory core network. This evidence emphasizes how the sensory context, in which a task is performed, is relevant for understanding the observed changes of functional connectivity during rest.

Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers.

PURPOSE: Experimental investigations in rodents have contributed significantly to our current understanding of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behaviour. However, clinical evidence to support such interactions is still scarce. The present study used a double-blind, randomized, pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers. METHODS: Forty-five healthy volunteers were recruited for this study and were divided equally into three groups (PRP: probiotic, PLP: placebo, and CON: control). All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study, at the beginning (time point 1) and after 4 weeks (time point 2). MRI data were acquired using a 3T whole-body MR system (Magnetom Skyra, Siemens, Germany). RESULTS: Functional connectivity (FC) changes were observed in the default mode network (DMN), salience network (SN), and middle and superior frontal gyrus network (MFGN) in the PRP group as compared to the PLP and CON groups. PRP group showed a significant decrease in FC in MFGN (in frontal pole and frontal medial cortex) and in DMN (in frontal lobe) as compared to CON and PLP groups, respectively. Further, significant increase in FC in SN (in cingulate gyrus and precuneus cortex) was also observed in PRP group as compared to CON group. The significance threshold was set to p < 0.05 FWE corrected. No significant structural differences were observed between the three groups. CONCLUSIONS: This work provides new insights into the role of a multi-strain probiotic administration in modulating the behaviour, which is reflected as changes in the FC in healthy volunteers. This study motivates future investigations into the role of probiotics in context of major depression and stress disorders.

Modulation of resting-state network connectivity by verbal divergent thinking training.

A growing body of evidence suggests that creativity is associated with functional connectivity across widespread neural networks, including regions associated with executive processes and cognitive control, along with regions linked to the default mode network (DMN) of the brain. This study investigated whether a three-week verbal divergent thinking training modulates functional connectivity in networks that have been related to creativity. In a task-based functional imaging study (Fink et al., 2015), the employed creativity training was found to modulate brain activity in regions closely associated with semantic memory demands. Hence, the specific aim of this study was to assess whether the observed task-related brain changes relate to changes in functional connectivity patterns of the brain at rest, as assessed by independent component analysis. The participants were tested at three time points with an inter-test interval of four weeks each, and randomly assigned to two groups which received the verbal creativity training time-delayed. Findings revealed that successful training of verbal creativity was mirrored by functional connectivity changes in the DMN, sensorimotor and auditory network, and the attention network. These rather global changes in resting-state functional connectivity supplement the findings of task-based fMRI, where changes in more task specific brain regions were found.

Investigating Sex-Specific Characteristics of Nicotine Addiction Using Metabolic and Structural Magnetic Resonance Imaging.

Nicotine addiction is known to modulate neurotransmission and alter the brain structure. The detrimental effect of nicotine is more prominent in females as compared to males. This study sought to examine the sex-specific influence of nicotine addiction on gamma amino butyric acid (GABA) and the white matter (WM) microstructure. Sixty healthy subjects (smokers/non-smokers) underwent structural and metabolic magnetic resonance imaging scans. Results showed alterations in WM integrity (measured as changes in fractional anisotropy [FA] and GABA in smokers versus non-smokers and females versus males. No overall significant smoking and sex-specific interactions were observed in this study. However, on comparing female smokers with female non-smokers, significantly higher GABA and FA values were observed in female smokers. However, GABA and FA values did not differ significantly when male smokers were compared against male non-smokers. Our results provide a further rationale to investigate the impact of nicotine on central GABAergic function and WM integrity, in particular due to the potential risk for females to experience depressive/anxiety symptoms during smoking cessation.

Probiotics drive gut microbiome triggering emotional brain signatures.

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks' probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.

T2 relaxation time alterations underlying neurocognitive deficits in alcohol-use disorders (AUD) in an Indian population: A combined conventional ROI and voxel-based relaxometry analysis.

Long-term heavy alcohol consumption has traditionally been associated with impaired cognitive abilities, such as deficits in abstract reasoning, problem solving, verbal fluency, memory, attention, and visuospatial processing. The present study aimed at exploring these neuropsychological deficits in alcohol-use disorders (AUD) in an Indian population using the Postgraduate Institute Battery of Brain Dysfunction (PGIBBD) and their possible correlation with alterations in T2 relaxation times (T2-RT), using whole-brain voxel-based relaxometry (VBR) and conventional region of interest (ROI) approach. Multi-echo T2 mapping sequence was performed on 25 subjects with AUD and 25 healthy controls matched for age, education, and socioeconomic status. Whole-brain T2-RT measurements were conducted using VBR and conventional ROI approach. The study was carried out on a 3T whole-body MR scanner. Post processing for VBR and ROI analysis was performed using SPM 8 software and vendor-provided software, respectively. A PGIBBD test battery was conducted on all subjects to assess their cognitive abilities, and the results were reported as raw scores. VBR and ROI results revealed that AUD subjects showed prolonged T2-RTs in cerebellum bilaterally, parahippocampal gyrus bilaterally, right anterior cingulate cortex, left superior temporal gyrus, left middle frontal gyrus, and left calcarine gyrus. A significant correlation was also observed between the neuropsychological test raw scores and alterations in T2-RT in AUD subjects. Our results are consistent with previous studies suggesting tissue disruption or gliosis or demyelination as a possible reason for prolonged T2-RTs. This damage to brain tissue, which is evident as prolonged T2-RT, could possibly be associated with impaired cognitive abilities noticeable in AUD subjects.

Impaired visual information processing in alcohol-dependent subjects: a proton magnetic resonance spectroscopy study of the primary visual cortex.

OBJECTIVE: Chronic alcoholism is associated with impaired cognitive abilities, with a more severe deficit in visual than in verbal functions. The visual processing deficits have classically been associated with impaired function of the visual cortex, located in the occipital lobe. The present study sought to increase current understanding of the impaired visual processing abilities in alcohol-dependent subjects and their correlation with metabolic aberrations in the occipital lobe using in vivo proton magnetic resonance spectroscopy (¹H MRS). METHOD: To that end, ¹H MRS was carried out in the primary visual cortex on 35 alcohol-dependent subjects and 35 healthy controls. Neuropsychological tests for visual processing skills were performed on all the subjects, and the deficits were reported as raw dysfunction rating scores. RESULTS: The alcohol-dependent subjects showed a significant increase in choline/creatine (Cho/Cr) and myo-Inositol/creatine (mI/Cr) ratios, whereas N-acetyl-aspartate/creatine (NAA/Cr) and glutamate-glutamine/creatine (Glu-Gln)/Cr ratios were significantly decreased. Reductions in NAA levels might be attributed to neuronal loss, whereas reductions in Glu-Gln levels might reflect perturbation of the Glu-Gln system in alcohol-dependent individuals, which could represent a neuroprotective adaptation. Elevations in mI levels may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage, whereas a significant increase in Cho levels indicates altered cell membrane metabolism. Also, a significant inverse correlation between NAA/Cr and raw dysfunction scores (rDyS) on the Nahor-Benson (NB) test and Glu-Gln/Cr with rDyS of the NB and the Bender-Gestalt (BG) test was observed, whereas a positive correlation between rDyS of the BG and the NB test and Cho/Cr was observed. CONCLUSIONS: The results suggest that metabolic alterations in the primary visual cortex may contribute to the neuropsychological impairment in visual information processing observed in alcohol-dependent subjects.

Decreased white matter integrity in fronto-occipital fasciculus bundles: relation to visual information processing in alcohol-dependent subjects.

Chronic alcohol abuse is characterized by impaired cognitive abilities with a more severe deficit in visual than in verbal functions. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The present study sought to increase current understanding of the impairment of visual processing abilities in alcohol-dependent subjects, and its correlation with white matter microstructural alterations, using diffusion tensor imaging (DTI). To that end, a DTI study was carried out on 35 alcohol-dependent subjects and 30 healthy male control subjects. Neuropsychological tests were assessed for visual processing skills and deficits were reported as raw dysfunction scores (rDyS). Reduced FA (fractional anisotropy) and increased MD (mean diffusivity) were observed bilaterally in inferior and superior fronto-occipital fasciculus (FOF) fiber bundles. A significant inverse correlation in rDyS and FA values was observed in these fiber tracts whereas a positive correlation of these scores was found with the MD values. Our results suggest that FOF fiber bundles linking the frontal lobe to occipital lobe might be related to visual processing skills. This is the first report of an alteration of the white matter microstructure of FOF fiber bundles that might have functional consequences for visual processing in alcohol-dependent subjects who exhibit no neurological complications.

Assessment of abstract reasoning abilities in alcohol-dependent subjects: an fMRI study.

INTRODUCTION: Chronic alcohol abuse has been traditionally associated with impaired cognitive abilities. The deficits are most evident in higher order cognitive functions, such as abstract reasoning, problem solving and visuospatial processing. The present study sought to increase current understanding of the neuropsychological basis of poor abstract reasoning abilities in alcohol-dependent subjects using functional magnetic resonance imaging (fMRI). METHODS: An abstract reasoning task-based fMRI study was carried out on alcohol-dependent subjects (n = 18) and healthy controls (n = 18) to examine neural activation pattern. The study was carried out using a 3-T whole-body magnetic resonance scanner. Preprocessing and post processing was performed using SPM 8 software. RESULTS: Behavioral data indicated that alcohol-dependent subjects took more time than controls for performing the task but there was no significant difference in their response accuracy. Analysis of the fMRI data indicated that for solving abstract reasoning-based problems, alcohol-dependent subjects showed enhanced right frontoparietal neural activation involving inferior frontal gyrus, post central gyrus, superior parietal lobule, and occipito-temporal gyrus. CONCLUSIONS: The extensive activation observed in alcohol dependents as compared to controls suggests that alcohol dependents recruit additional brain areas to meet the behavioral demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting decreased neural efficiency of relevant brain networks or compensatory mechanisms for the execution of task for showing an equivalent performance.

White matter damage is associated with memory decline in chronic alcoholics: a quantitative diffusion tensor tractography study.

Neuroimaging studies have reported an association between white matter integrity and cognitive performance in normal aging and various neuropathological conditions. We compared alcoholics with controls and hypothesized that the degree of disconnection of white matter fibers would be negatively correlated with memory dysfunction scores. Diffusion tensor imaging (DTI) based tractography and PGI-memory scale (PGIMS) test was performed in 10 abstinent chronic alcoholic and 10 demographically equivalent control men. DTI measures [fractional anisotropy (FA), and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was done between patient group and controls. Spearman's rank correlation coefficient was computed between memory dysfunction score and DTI measures. Compared to controls alcoholic participants had significantly reduced FA in corpus callosum (CC), fornix (FX), and right hemispheric arcuate fasciculus (AF), anterior thalamic radiation (ATR) and inferior longitudinal fasciculus (ILF). A significant inverse correlation with memory dysfunction score was observed with right cingulum, right uncinate fasciculus, right ILF and left ILF. The inverse correlation of memory dysfunction score with FA of white matter tracts suggest that white matter deficit in these white matter fibers may contribute to underlying dysfunction in memory in alcoholism.