Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover,double‐blind,sham‐controlled pilot study

Transcranial static magnetic field stimulation (tSMS) is a novel non‐invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double‐blind, sham‐controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty‐four right‐handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes‐closed, 2 min eyes‐open), during (10 min eyes‐open), and after (2 min eyes‐open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post‐stimulation fronto‐parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post‐stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post‐stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.     

GABA metabolism and its role in gamma‐band oscillatory activity during auditory processing: An MRS and EEG study

Gamma‐aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency‐specific synchronization of neuronal excitability within the gamma band (30–80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30–200 Hz) and time (?200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975–3987, 2017 . © 2017 Wiley Periodicals, Inc.     

The relationship between socioeconomic status and white matter microstructure in pre‐reading children: A longitudinal investigation

Reading is a learned skill crucial for educational attainment. Children from families of lower socioeconomic status (SES) tend to have poorer reading performance and this gap widens across years of schooling. Reading relies on the orchestration of multiple neural systems integrated via specific white‐matter pathways, but there is limited understanding about whether these pathways relate differentially to reading performance depending on SES background. Kindergarten white‐matter FA and second‐grade reading outcomes were investigated in an SES‐diverse sample of 125 children. The three left‐hemisphere white‐matter tracts most associated with reading, and their right‐hemisphere homologs, were examined: arcuate fasciculus (AF), superior longitudinal fasciculus (SLF), and inferior longitudinal fasciculus (ILF). There was a significant and positive association between SES and fractional anisotropy (FA) in the bilateral ILF in kindergarten. SES moderated the association between kindergarten ILF and second grade reading performance, such that it was positive in lower‐SES children, but not significant in higher‐SES children. These results have implications for understanding the role of the environment in the development of the neural pathways that support reading.     

Heritability of regional and global brain structure at the onset of puberty: A magnetic resonance imaging study in 9‐year‐old twin pairs

Puberty represents the phase of sexual maturity, signaling the change from childhood into adulthood. During childhood and adolescence, prominent changes take place in the brain. Recently, variation in frontal, temporal, and parietal areas was found to be under varying genetic control between 5 and 19 years of age. However, at the onset of puberty, the extent to which variation in brain structures is influenced by genetic factors (heritability) is not known. Moreover, whether a direct link between human pubertal development and brain structure exists has not been studied. Here, we studied the heritability of brain structures at 9 years of age in 107 monozygotic and dizygotic twin pairs (N = 210 individuals) using volumetric MRI and voxel‐based morphometry. Children showing the first signs of secondary sexual characteristics (N = 47 individuals) were compared with children without these signs, based on Tanner‐stages. High heritabilities of intracranial, total brain, cerebellum, and gray and white matter volumes (up to 91%) were found. Regionally, the posterior fronto‐occipital, corpus callosum, and superior longitudinal fascicles (up to 93%), and the amygdala, superior frontal and middle temporal cortices (up to 83%) were significantly heritable. The onset of secondary sexual characteristics of puberty was associated with decreased frontal and parietal gray matter densities. Thus, in 9‐year‐old children, global brain volumes, white matter density in fronto‐occipital and superior longitudinal fascicles, and gray matter density of (pre‐)frontal and temporal areas are highly heritable. Pubertal development may be directly involved in the decreases in gray matter areas that accompany the transition of our brains from childhood into adulthood. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre‐Bötzinger complex: a computational modelling study

The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre‐Bötzinger complex (pre‐BötC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre‐BötC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na⁺ current (I_NaP), and the other involving the voltage‐gated Ca²⁺ current (I_Ca) and the Ca²⁺‐activated nonspecific cation current (I_CAN), activated by intracellular Ca²⁺ accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na⁺‐dependent and Ca²⁺‐dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons with I_NaP and I_Ca randomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca²⁺ release, and the Na⁺/K⁺ pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on I_NaP and/or I_CAN, or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre‐BötC and other brainstem/spinal cord circuits under different experimental conditions.     

Mapping language with resting‐state functional magnetic resonance imaging: A study on the functional profile of the language network

Resting‐state functional magnetic resonance imaging (rsfMRI) is a promising technique for language mapping that does not require task‐execution. This can be an advantage when language mapping is limited by poor task performance, as is common in clinical settings. Previous studies have shown that language maps extracted with rsfMRI spatially match their task‐based homologs, but no study has yet demonstrated the direct participation of the rsfMRI language network in language processes. This demonstration is critically important because spatial similarity can be influenced by the overlap of domain‐general regions that are recruited during task‐execution. Furthermore, it is unclear which processes are captured by the language network: does it map rather low‐level or high‐level (e.g., syntactic and lexico‐semantic) language processes? We first identified the rsfMRI language network and then investigated task‐based responses within its regions when processing stimuli of increasing linguistic content: symbols, pseudowords, words, pseudosentences and sentences. The language network responded only to language stimuli (not to symbols), and higher linguistic content elicited larger brain responses. The left fronto‐parietal, the default mode, and the dorsal attention networks were examined and yet none showed language involvement. These findings demonstrate for the first time that the language network extracted through rsfMRI is able to map language in the brain, including regions subtending higher‐level syntactic and semantic processes.     

Occipital blood‐brain barrier permeability is an independent predictor of visual outcome in type 2 diabetes,irrespective of the retinal barrier: A longitudinal study

Blood‐brain barrier (BBB) permeability in type 2 diabetic patients has been previously shown to be altered in certain brain regions such as the basal ganglia and the hippocampus. Because of the histological and functional similarities between the BBB) and the blood‐retinal barrier (BRB), we aimed to investigate how the permeability of both barriers predicts visual outcome. We included 2 control groups (acute unilateral stroke patients, n = 9; type 2 diabetics without BRB leakage n = 10) and a case study group of type 2 diabetics with established BRB leakage (n = 17). We evaluated sex, age, disease duration, metabolic impairment, retinopathy grade and BBB permeability as predictors of visual acuity at baseline, 12  and 24 months in the type 2 diabetics without BRB leakage group and the case study group. We have also explored differences in BBB permeability in the occipital lobe and frontal lobe in the 3 different groups. K^trans (volume transfer coefficient) and V_p (fractional plasma volume) were estimated. The BBB permeability parameter V_p was higher in the case study group compared to the unaffected hemisphere of the stroke patient control group, suggesting vascular dynamics were changed in the occipital lobe of type 2 diabetics with established BRB leakage. These patients showed a significant correlation between glycated hemoglobin (HbA1C) levels and occipital and frontal K^trans. We report for the first time that occipital BBB permeability is an independent predictor of visual acuity at baseline, as well as at 12 and 24 months, in type 2 diabetics with established BRB leakage. Our results suggest that occipital BBB permeability might be an independent biomarker for visual impairment in patients with established BRB leakage.     

Acute white matter changes following sport‐related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study

Recent neuroimaging studies have suggested that following sport‐related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow‐up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post‐injury, the concussed group reported significantly more concussion symptoms than a well‐matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8‐day follow‐up. Similarly, within 24‐hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821–3834, 2016. © 2016 Wiley Periodicals, Inc .     

Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: A diffusion tensor imaging study using voxel‐based approaches

The early prediction of consciousness recovery from traumatic brain injury (TBI) is crucial to make decisions about the appropriate use of prolonged intensive care. Diffusion tensor imaging (DTI) has been proposed as a biomarker of white matter injury that could be used in a classification purpose. Instead of region‐of‐interest‐based approach, we applied voxel‐based approaches (voxel‐based DTI and tract‐based spatial statistics) on 30 patients with TBI to identify, without any prior, the brain regions that were specifically damaged in unfavorable 1‐year outcome group compared to the favorable one. DTI were acquired at mean 23 days (5–53 days) and two DTI‐derived indices, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were tested. Our results showed that (1) ADC is not a relevant biomarker for early 1‐year outcome prognosis; (2) FA measured in inferior longitudinal fasciculus, in cerebral peduncle, in posterior limb of the internal capsule, and in posterior corpus callosum is specifically decreased in unfavorable outcome group compare to the favorable one; (3) a linear discriminant analysis using the FA measured in these four regions showed good classification performance (sensitivity = 86% and specificity = 86%). These findings confirm the relevance of the use of DTI as biomarkers for consciousness recovery after TBI and support the possible use of these biomarkers for early classification of patients. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Association between the scores of the Japanese version of the Brief Assessment of Cognition in Schizophrenia and whole‐brain structure in patients with chronic schizophrenia: A voxel‐based morphometry and diffusion tensor imaging study

Aim

The Brief Assessment of Cognition in Schizophrenia (BACS) is a concise tool designed to evaluate cognitive deficits in schizophrenia. We examined the possible association between BACS scores and whole‐brain structure, as observed using magnetic resonance imaging with a relatively large sample.

Methods

The study sample comprised 116 patients with schizophrenia (mean age, 39.3 ± 11.1 years; 66 men) and 118 healthy controls (HC; mean age, 40.0 ± 13.6 years; 58 men) who completed the Japanese version of the BACS (BACS‐J). All participants were of Japanese ethnicity. The magnetic resonance imaging volume and diffusion tensor imaging data were processed with voxel‐based morphometry and tract‐based spatial statistics, respectively.

Results

There were significant reductions in the regional gray matter volumes and white matter fractional anisotropy values in patients with schizophrenia compared to HC. For the gray matter areas, the working memory score had a significant positive correlation with the anterior cingulate and medial frontal cortices volumes in the patients. For the white matter areas, the motor speed score had a significant positive correlation with fractional anisotropy values in the corpus callosum, internal capsule, superior corona radiata, and superior longitudinal fasciculus in the patients. However, there was no significant correlation among either the gray or white matter areas in the HC.

Conclusion

Our results suggest that among the BACS‐J measures, the working memory and motor speed scores are associated with several structural alterations in the brains of patients with schizophrenia.     

Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

We used quantitative, coordinate‐based meta‐analysis to objectively synthesize age‐related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23–34 years) were matched to 20 studies with children (age means: 7–12 years). The separate meta‐analyses of these two sets showed a pattern of reading‐related brain activation common to children and adults in left ventral occipito‐temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta‐analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading‐related activation clusters in children and adults are provided. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. .     

Further evaluation of [11C]MP‐10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis

[¹¹C]MP‐10 is a potent and specific PET tracer previously shown to be suitable for imaging the phosphodiesterase 10A (PDE10A) in baboons with reversible kinetics and high specific binding. However, another report indicated that [¹¹C]MP‐10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood‐brain‐barrier (BBB) into the brain. This study was designed to address the discrepancies between the species by re‐evaluating [¹¹C]MP‐10 in vivo in rhesus monkey with baseline scans to assess tissue uptake kinetics and self‐blocking scans with unlabeled MP‐10 to determine binding specificity. Ex vivo studies with one rhesus monkey and 4 Sprague‐Dawley rats were also performed to investigate the presence of radiolabeled metabolites in the brain. Our results indicated that [¹¹C]MP‐10 displayed reversible uptake kinetics in rhesus monkeys, albeit slower than in baboons. Administration of unlabeled MP‐10 reduced the binding of [¹¹C]MP‐10 in a dose‐dependent manner in all brain regions including the cerebellum. Consequently, the cerebellum appeared not to be a suitable reference tissue in rhesus monkeys. Regional volume of distribution (V_T) was mostly reliably derived with the multilinear analysis (MA1) method. In ex vivo studies in the monkey and rats only negligible amount of radiometabolites was seen in the brain of either species. In summary, results from the present study strongly support the suitability of [¹¹C]MP‐10 as a radiotracer for PET imaging and quantification of PDE10A in nonhuman primates. Synapse 69:86–95, 2015. © 2014 Wiley Periodicals, Inc.