Alter Brain Physiology Research Articles

Neural complexity through a nonextensive statistical–mechanical approach of human electroencephalograms

The brain is a complex system whose understanding enables potentially deeper approaches to mental phenomena. Dynamics of wide classes of complex systems have been satisfactorily described within q-statistics, a current generalization of Boltzmann-Gibbs (BG) statistics. Here, we study human electroencephalograms of typical human adults (EEG), very specifically their inter-occurrence times across an arbitrarily chosen threshold of the signal (observed, for instance, at the midparietal location in scalp). The distributions of these inter-occurrence times differ from those usually emerging within BG statistical mechanics. They are instead well approached within the q-statistical theory, based on non-additive entropies characterized by the index q. The present method points towards a suitable tool for quantitatively accessing brain complexity, thus potentially opening useful studies of the properties of both typical and altered brain physiology.

The Effect of Probiotic Supplementation on the Gut-Brain Axis in Psychiatric Patients.

The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic-pituitary-adrenal (HPA) axis and metabolic pathways. Variations in how these effects present themselves may be connected to individual variances in clinical symptoms and treatment responses, such as the observation that a significant fraction of participants do not respond to current antipsychotic drugs. A bidirectional signaling pathway between the central nervous system and the gastrointestinal tract is known as the microbiota-gut-brain axis. The large and small intestines contain more than 100 trillion microbial cells, contributing to the intestinal ecosystem's incredible complexity. Interactions between the microbiota and intestinal epithelium can alter brain physiology and affect mood and behavior. There has recently been a focus on how these relationships impact mental health. According to evidence, intestinal microbiota may play a role in neurological and mental illnesses. Intestinal metabolites of microbial origin, such as short-chain fatty acids, tryptophan metabolites, and bacterial components that might stimulate the host's immune system, are mentioned in this review. We aim to shed some on the growing role of gut microbiota in inducing/manipulating several psychiatric disorders, which may pave the way for novel microbiota-based therapies.

Why won’t it stop? The dynamics of benzodiazepine resistance in status epilepticus

Status epilepticus is a life-threatening neurological emergency that affects both adults and children. Approximately 36% of episodes of status epilepticus do not respond to the current preferred first-line treatment, benzodiazepines. The proportion of episodes that are refractory to benzodiazepines is higher in low-income and middle-income countries (LMICs) than in high-income countries (HICs). Evidence suggests that longer episodes of status epilepticus alter brain physiology, thereby contributing to the emergence of benzodiazepine resistance. Such changes include alterations in GABAA receptor function and in the transmembrane gradient for chloride, both of which erode the ability of benzodiazepines to enhance inhibitory synaptic signalling. Often, current management guidelines for status epilepticus do not account for these duration-related changes in pathophysiology, which might differentially impact individuals in LMICs, where the average time taken to reach medical attention is longer than in HICs. In this Perspective article, we aim to combine clinical insights and the latest evidence from basic science to inspire a new, context-specific approach to efficiently managing status epilepticus.

Emotional Modulation of Frontal Alpha Asymmetry - a Novel Biomarker of Mild Traumatic Brain Injury.

Objective findings of brain injury or dysfunction are typically lacking in mild traumatic brain injury (MTBI) despite prolonged post-concussion symptoms in some patients. Thus, there is a need for objective biomarkers of MTBI that reflect altered brain physiology underlying subjective symptoms. We have previously reported increased attention to threat-related stimuli in subjects with MTBI, suggesting a physiological vulnerability to depression. Vulnerability to depression has been linked with relatively greater activity of the right than left frontal cortex reflected in inverse pattern in frontal alpha with greater power on the left than right. We investigated whether patients with previous MTBI show this pattern of frontal activity reflected in more negative frontal alpha asymmetry (FAA) scores. Furthermore, in search for potential biomarkers of MTBI, we created a novel index, emotional modulation of FAA (eFAA) and investigated whether it correlates with subjective symptoms. EEG was recorded while subjects with previous MTBI and controls performed a computer-based reaction time task integrating different cognitive executive functions and containing either threat-related or emotionally neutral visual stimuli. Post-concussion symptoms and depression were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Beck’s depression inventory (BDI). Task-induced FAA was assessed and eFAA calculated by subtracting FAA in the context of neutral stimuli from FAA in the context of emotional stimuli. The MTBI group showed FAA scores reflecting relatively greater right-sided frontal activity compared to healthy controls. eFAA differentiated the symptomatic MTBI from non-symptomatic MTBI group and from healthy controls. eFAA also correlated with RPQ and BDI scores. In conclusion, FAA pattern previously linked with vulnerability to depression, was observed in patients with previous MTBI. Furthermore, eFAA has potential as a biomarker of altered affective brain functions in MTBI.

The experience of Trauma Center-Trauma Sensitive Yoga training on professional practice of mental health professionals and yoga instructors

Background and purposeTraumatic psychological events are thought to alter brain physiology, notably regions such as the thalamus and the limbic system, affecting personal choice, autonomy, and behavior. Innovative therapies are needed to address the diverse, mental and physical consequences of these changes. Trauma Center–Trauma Sensitive Yoga (TC-TSY) has shown promising results in clinical trials among individuals experiencing posttraumatic symptomatology. Materials and methodsUsing a qualitative, descriptive design, we examined the impact of TC-TSY training on the professional practice of seven practitioners who were certified yoga instructors and/or registered psychologists. ResultsThe findings suggest TC-TSY training enriched their practices, chiefly through its choice-based, widely applicable approach; invitation- and mindfulness-based language; and building of therapeutic trust and attunement. Some participants questioned the accessibility and suitability of the training, as well as the rigidity of TC-TSY terminology. ConclusionMore research is needed to examine potential outcomes of TC-TSY practice related to self-efficacy, coping, quality of life, and stress reduction among traumatized individuals.

Association of microbiota-derived propionic acid and Alzheimer's disease; bioinformatics analysis.

Microbiota-derived metabolites could alter the brain tissue toward the neurodegeneration disease. This study aims to select the genes associated with Propionic acid (PPA) and compromise Alzheimer's disease (AD) to find the possible roles of PPA in AD pathogenesis. Microbiota-derived metabolites could alter the brain tissue toward the neurodegeneration disease. This study aims to select the genes associated with Propionic acid (PPA) and compromise Alzheimer's disease (AD) to find the possible roles of PPA in AD pathogenesis. Amongst all genes associated with PPA and AD, 284 genes to be shared by searching databases and were subjected to further analysis. AD-PPA genes mainly involved in cancer, bacterial and virus infection, and neurological and non-neurological diseases. Gene Ontology and pathway analysis covered the most AD hallmark, such as amyloid formation, apoptosis, proliferation, inflammation, and immune system. Network analysis revealed hub and bottleneck genes. MCODE analysis also indicated the seed genes represented in the significant subnetworks. ICAM1 and CCND1 were the hub, bottleneck, and seed genes. PPA interacted genes implicated in AD act through pathways initiate neuronal cell death. In sum up, AD-PPA shared genes exhibited evidence that supports the idea PPA secreted from bacteria could alter brain physiology toward the emerging AD signs. This idea needs to confirm by more future investigation in animal models.

Physiology of Transcranial Direct Current Stimulation.

Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation.

The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized by Gnotobiotic Mice.

A growing body of experimental data suggests that microbes in the gut influence behavior and can alter brain physiology and neurochemistry. Although promising, researchers are only starting to understand the potential of the gut microbiota for use in neurological disease. Recent evidence demonstrated that gastrointestinal activities are linked to mood disorders such as anxiety, depression, and most recently, cognitive functions in age-related neurodegenerative disorders. Studies from our group and others are uncovering new evidence suggesting that the gut microbiota plays a crucial role in the metabolism and bioavailability of certain dietary compounds and synthetic drugs. Based on this evidence, this review article will discuss the implications of the gut microbiota in mechanisms of bioavailability and biotransformation with an emphasis on dietary polyphenol compounds. This will be followed by a survey of ongoing innovative research identifying the ability of individual gut bacteria to enhance the bioavailability of gut-derived, brain-penetrating, bioactive polyphenol metabolites that ultimately influence mechanisms associated with the promotion of resilience against psychological and cognitive impairment in response to stress. Lastly, current research initiatives aimed at promoting the generation of brain bioactive polyphenol metabolites by specialized gut microbes will be discussed, specifically the use of gnotobiotic mice to develop bioengineered second generation probiotics. We propose that leveraging the gut microbial ecosystem to generate brain targeted bioactive metabolites from dietary polyphenols can attenuate lifestyle risk factors and promote resilience against age-related cognitive decline.

Quantitative microglia analyses reveal diverse morphologic responses in the rat cortex after diffuse brain injury

Determining regions of altered brain physiology after diffuse brain injury is challenging. Microglia, brain immune cells with ramified and dynamically moving processes, constantly surveil the parenchyma for dysfunction which, when present, results in a changed morphology. Our purpose was to define the spatiotemporal changes in microglia morphology over 28 days following rat midline fluid percussion injury (mFPI) as a first step in exploiting microglia morphology to reflect altered brain physiology. Microglia morphology was quantified from histological sections using Image J skeleton and fractal analysis procedures at three time points and in three regions post-mFPI: impact site, primary somatosensory cortex barrel field (S1BF), and a remote region. Microglia ramification (process length/cell and endpoints/cell) decreased in the impact and S1BF but not the remote region (p < 0.05). Microglia complexity was decreased in the S1BF (p = 0.003) and increased in the remote region (p < 0.02). Rod-shaped microglia were present in the S1BF and had a 1.8:1.0 length:width ratio. An in-depth quantitative morphologic analysis revealed diverse and widespread changes to microglia morphology in the cortex post-mFPI. Due to their close link to neuronal function, changes in microglia morphology, summarized in this study, likely reflect altered physiology with diverse and widespread impact on neuronal and circuit function.

Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging.

The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

Multidisciplinary approach to psychiatric symptoms in mild traumatic brain injury: Complex sequelae necessitate a cadre of treatment providers

Multidisciplinary approach to psychiatric symptoms in mild traumatic brain injury: Complex sequelae necessitate a cadre of treatment providers

Physiological Evidence Consistent with Reduced Neuroplasticity in Human Adolescents Born Preterm

Preterm-born children commonly experience motor, cognitive, and learning difficulties that may be accompanied by altered brain microstructure, connectivity, and neurochemistry. However, the mechanisms linking the altered neurophysiology with the behavioral outcomes are unknown. Here we provide the first physiological evidence that human adolescents born preterm at or before 37 weeks of completed gestation have a significantly reduced capacity for cortical neuroplasticity, the key overall mechanism underlying learning and memory. We examined motor cortex neuroplasticity in three groups of adolescents who were born after gestations of ≤32 completed weeks (early preterm), 33-37 weeks (late preterm), and 38-41 weeks (term) using a noninvasive transcranial magnetic brain stimulation technique to induce long-term depression (LTD)-like neuroplasticity. Compared with term-born adolescents, both early and late preterm adolescents had reduced LTD-like neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels. We also compared neuroplasticity in term-born adolescents with that in term-born young adults, finding that the motor cortex retains a relatively enhanced neuroplastic capacity in adolescence. These findings provide a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent associated behavioral deficits, particularly in learning and memory. They also suggest that altered hypothalamic-pituitary-adrenal axis function due to preterm birth may be a significant modulator of this altered neuroplasticity. This latter finding may offer options in the development of possible therapeutic interventions.

Sleep EEG alterations: effects of different pulse‐modulated radio frequency electromagnetic fields

Previous studies have observed increases in electroencephalographic power during sleep in the spindle frequency range (approximately 11-15 Hz) after exposure to mobile phone-like radio frequency electromagnetic fields (RF EMF). Results also suggest that pulse modulation of the signal is crucial to induce these effects. Nevertheless, it remains unclear which specific elements of the field are responsible for the observed changes. We investigated whether pulse-modulation frequency components in the range of sleep spindles may be involved in mediating these effects. Thirty young healthy men were exposed, at weekly intervals, to three different conditions for 30 min directly prior to an 8-h sleep period. Exposure consisted of a 900-MHz RF EMF, pulse modulated at 14 Hz or 217 Hz, and a sham control condition. Both active conditions had a peak spatial specific absorption rate of 2 W kg(-1) . During exposure subjects performed three different cognitive tasks (measuring attention, reaction speed and working memory), which were presented in a fixed order. Electroencephalographic power in the spindle frequency range was increased during non-rapid eye movement sleep (2nd episode) following the 14-Hz pulse-modulated condition. A similar but non-significant increase was also observed following the 217-Hz pulse-modulated condition. Importantly, this exposure-induced effect showed considerable individual variability. Regarding cognitive performance, no clear exposure-related effects were seen. Consistent with previous findings, our results provide further evidence that pulse-modulated RF EMF alter brain physiology, although the time-course of the effect remains variable across studies. Additionally, we demonstrated that modulation frequency components within a physiological range may be sufficient to induce these effects.

Cognitive Performance Measures in Bioelectromagnetic Research - Critical Evaluation and Recommendations

BackgroundThe steady increase of mobile phone usage has led to a rising concern about possible adverse health effects of radio frequency electromagnetic field (RF EMF) exposure at intensities even below the existing safety limits. Accumulating evidence suggests that pulse-modulated RF EMF may alter brain physiology. Yet, whereas effects on the human electroencephalogram in waking and sleep have repeatedly been shown in recent years, results on cognitive performance are inconsistent.MethodsThis review compares 41 provocation studies regarding the effects of RF EMF exposure similar to mobile telephones on cognitive performance measures in humans. The studies were identified via systematic searches of the databases Pub Med and ISI Web of Science and were published in peer-reviewed journals between 1998 and the end of 2009.ResultsBased on a critical discussion within the scope of methodological standards it is concluded that state-of-the-art-methods in bio-electromagnetic research on RF EMF effects and cognition have neither been specified nor fully implemented over the last 10-11 years. The lack of a validated tool, which reliably assesses changes in cognitive performance caused by RF EMF exposure, may contribute to the current inconsistencies in outcomes. The high variety of findings may also be due to methodological issues such as differences in sample size and the composition of study groups, experimental design, exposure setup as well as the exposure conditions, and emphasizes the need for a standardized protocol in bioelectromagnetic research.ConclusionsAt present, no underlying biological mechanism has been identified which mediates the effects on brain functioning as observed in electroencephalographic (EEG) studies. A future aim must be to identify this mechanism as well as a reliable exposure protocol in order to gain more insights into possible behavioral and related health consequences of high-frequency EMF exposure.

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn 2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn 2+ is a metabolic toxin and a competitive inhibitor for Ca 2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl 2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl 2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl 2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca 2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl 2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl 2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn 2+ administration protocol.

Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1 Hz rTMS in patients with juvenile myoclonic epilepsy

Objective The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. Methods Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. Results In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. Conclusions Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. Significance The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Transcriptome Differences Between the Frontal Cortex and Hippocampus of Wild-Type and Humanized Presenilin-1 Transgenic Mice

Objective The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin-1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)–linked ΔE9 hPS1 mutant mice. Methods Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and ΔE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions. Results The data revealed that in the wild-type mice, there are significant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or ΔE9 hPS1 mutation. Also, they provide evidence that a subset of genes show disturbed regional Fc–Hc gene-expression ratios in the transgenic mice carrying the ΔE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD. Conclusions Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology. The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin-1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)–linked ΔE9 hPS1 mutant mice. Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and ΔE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions. The data revealed that in the wild-type mice, there are significant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or ΔE9 hPS1 mutation. Also, they provide evidence that a subset of genes show disturbed regional Fc–Hc gene-expression ratios in the transgenic mice carrying the ΔE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD. Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology.

Transcriptome Differences Between the Frontal Cortex and Hippocampus of Wild-Type and Humanized Presenilin-1 Transgenic Mice

The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin-1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)-linked DeltaE9 hPS1 mutant mice. Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and DeltaE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions. The data revealed that in the wild-type mice, there are significant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or DeltaE9 hPS1 mutation. Also, they provide evidence that a subset of genes show disturbed regional Fc-Hc gene-expression ratios in the transgenic mice carrying the DeltaE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD. Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology.

Genetics and visual attention: selective deficits in healthy adult carriers of the epsilon 4 allele of the apolipoprotein E gene.

The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with altered brain physiology in healthy adults before old age, but concomitant deficits in cognition on standardized tests of cognitive function have not been consistently demonstrated. We hypothesized that sensitive and specific assessment of basic attentional functions that underlie complex cognition would reveal evidence of impairment in otherwise asymptomatic individuals. We found that as early as middle age, nondemented carriers of the varepsilon4 allele of the APOE gene showed deficits when visual attention was spatially directed by cues in tasks of visual discrimination and visual search, in comparison to those without the epsilon4 allele (epsilon2 and epsilon3 carriers). Two component attentional operations were selectively affected: (i) shifting spatial attention following invalid location cues, and (ii) adjusting the spatial scale of attention during visual search. These changes occurred only in the presence of the epsilon4 allele and without decline in other aspects of attention (vigilance), memory, or general cognition. The results show that specific components of visual attention are affected by APOE genotype and that the course of cognitive aging is subject to selective alteration by a genetic trait.

Different Neural Circuits Subserve Reading before and after Therapy for Acquired Dyslexia

Rehabilitative measures for stroke are not generally based on basic neurobiological principles, despite evidence from animal models that certain anatomical and pharmacological changes correlate with recovery. In this report, we use functional magnetic resonance imaging (fMRI) to study in vivo human brain reorganization in a right handed patient with an acquired reading disorder from stroke. With phonological dyslexia, her whole-word (lexical) reading approach included inability to read nonwords and poor reading of function words. Following therapy, she was able to read nonwords and function words, and preferred a decompositional (sub-lexical) strategy in general. fMRI was performed during a reading task before and after treatment. Prior to therapy, her main focus of brain activation was in the left angular gyrus (area 39). After therapy, it was instead in the left lingual gyrus (area 18). This result suggests first that it is possible to alter brain physiology with therapy for acquired language disorders, and second, that two reading strategies commonly used in normal reading use distinct neural circuits, possibly reconciling several conflicting neuroimaging studies of reading.