Changes In Brain Organization Research Articles

Prenatal binge-like alcohol exposure alters brain and systemic responses to reach sodium and water balance

The aim of the present work is to analyze how prenatal binge-like ethanol exposure to a moderate dose (2.0g/kg; group Pre-EtOH) during gestational days (GD) 17–20 affects hydroelectrolyte regulatory responses. This type of exposure has been observed to increase ethanol consumption during adolescence (postnatal day 30–32). In this study we analyzed basal brain neural activity and basal-induced sodium appetite (SA) and renal response stimulated by sodium depletion (SD) as well as voluntary ethanol consumption as a function of vehicle or ethanol during late pregnancy. In adolescent offspring, SD was induced by furosemide and a low-sodium diet treatment (FURO+LSD). Other animals were analyzed in terms of immunohistochemical detection of Fra-like (Fra-LI-ir) protein and serotonin (5HT) and/or vasopressin (AVP). The Pre-EtOH group exhibited heightened voluntary ethanol intake and a reduction in sodium and water intake induced by SD relative to controls. Basal Na and K concentrations in urine were also reduced in Pre-EtOH animals while the induced renal response after FURO treatment was similar across prenatal treatments. However, the correlation between urine volume and water intake induced by FURO significantly varied across these treatments. At the brain level of analysis, the number of basal Fra-LI-ir was significantly increased in AVP magnocellular neurons of the paraventricular nucleus (PVN) and in 5HT neurons in the dorsal raphe nucleus (DRN) in Pre-EtOH pups. In the experimental group, we also observed a significant increase in Fra-LI along the nucleus of the solitary tract (NTS) and in the central extended amygdala nuclei. In summary, moderate Pre-EtOH exposure produces long-lasting changes in brain organization, affecting basal activity of central extended amygdala nuclei, AVP neurons and the inhibitory areas of SA such as the NTS and the 5HT-DRN. These changes possibly modulate the above described variations in basal-induced drinking behaviors and renal regulatory responses.

Changes in brain organization after TBI

Traumatic brain injury (TBI) is a problem of growing public health interest with high incidence. After injury, patients are at risk for several long-term sequelae that encompass a wide array of physical and behavioral symptoms. Since conventional imaging modalities are limited in their ability to assess axonal injury or functional network connectivity, resting-state (RS) fMRI has great potential to evaluate the traumatic effect on brain network function. This technique may be particularly powerful in patients with mild TBI, who typically have minimal or no structural changes on anatomic imaging. There are several different ways to assess RS-fMRI data in order to gain insight into brain networks and connections. Well-established intrinsic brain networks in the resting state include the default mode network (DMN),1 the anti-DMN dorsal attention network, and the sensorimotor and visual networks. There are a variety of changes in RS-fMRI in subjects after mild TBI, including changes in DMN1 and changes in thalamocortical connectivity.2

Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities

BackgroundNeurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification.MethodsWe studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1.ResultsSubcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions.ConclusionsThe neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype.

Morning-evening variation in human brain metabolism and memory circuits

It has been posited that a critical function of sleep is synaptic renormalization following a net increase in synaptic strength during wake. We hypothesized that wake would alter the resting-state functional organization of the brain and increase its metabolic cost. To test these hypotheses, two experiments were performed. In one, we obtained morning and evening resting-state functional MRI scans to assess changes in functional brain organization. In the second experiment, we obtained quantitative positron emission tomography measures of glucose and oxygen consumption to assess the cost of wake. We found selective changes in brain organization. Most prominently, bilateral medial temporal regions were locally connected in the morning but in the evening exhibited strong correlations with frontal and parietal brain regions involved in memory retrieval. We speculate that these changes may reflect aspects of memory consolidation recurring on a daily basis. Surprisingly, these changes in brain organization occurred without increases in brain metabolism.

A clustering-based method to detect functional connectivity differences

Recently, resting-state functional magnetic resonance imaging (R-fMRI) has emerged as a powerful tool for investigating functional brain organization changes in a variety of neurological and psychiatric disorders. However, the current techniques may need further development to better define the reference brain networks for quantifying the functional connectivity differences between normal and diseased subject groups. In this study, we introduced a new clustering-based method that can clearly define the reference clusters. By employing group difference information to guide the clustering, the voxels within the reference clusters will have homogeneous functional connectivity changes above predefined levels. This method identified functional clusters that were significantly different between the amnestic mild cognitively impaired (aMCI) and age-matched cognitively normal (CN) subjects. The results indicated that the distribution of the clusters and their functionally disconnected regions resembled the altered memory network regions previously identified in task fMRI studies. In conclusion, the new clustering method provides an advanced approach for studying functional brain organization changes associated with brain diseases.

The Still Bay and Howiesons Poort, 77–59 ka

Variations in the material culture in Africa in the Late Pleistocene indicate that it was a period of rapid cultural change not previously observed in the Middle Stone Age. In southern Africa, two techno-traditions, the Still Bay and the Howiesons Poort, have raised interest because of their relatively early cultural complexity. What might have driven the development of the innovative practices and ideas between ca. 77,000 and 59,000 years ago? Explanations for the ascent and demise of these two entities must focus on analyses of recovered materials and in situ features such as hearths and spatial patterning. They must also consider whether these innovations are likely to have ensued from cognitive evolution in Homo sapiens and trace the changes in brain organization and cognitive functions that best explain them. This article presents an updated review of the Still Bay and Howiesons Poort industries and argues that innovations during the Late Pleistocene must be related to a previous expansion of the hig...

Recovery and Rehabilitation after Stroke

Most individuals survive stroke and age with its consequences. Rehabilitation becomes the dominant medical need soon after onset, and coordinated rehabilitation services using evidence-based interventions determined by patient need are of primary importance in affecting outcome and quality of life. This discussion will focus on the natural history of recovery after stroke and the changes in brain organization that support behavioral improvement during recovery, then review established and emerging therapeutic approaches directed at improving independent functional performance and quality of life.

The lives of the brain

Humans are generally curious about their origins, and most cultures have stories relating to this concern. Now we know that our species originated in Africa, approximately 200,000 years ago. Six million years earlier, an ape-like ancestor, who walked on two legs and had new eating habits and reduced dentition, led to subsequent hominin species that gradually acquired a very large brain of unprecedented functional capacity. In The Lives of the Brain, John S. Allen — a neuroanthropologist at the Dana and David Dornsife Cognitive Neuroscience Imaging Center and Brain and Creativity Institute at the University of Southern California — captures this history and expands on what we know about the human brain. The scope and scholarship of this book is impressive. Allen discusses relevant contributions from the past, such as those of 100 years ago by W.E. LeGros Clark and G. Elliott Smith on comparative aspects of brain anatomy, covers the major contributions of researchers over the last 60 years, and includes the most recent results and conclusions of current investigators. There is much to learn, even by the experienced investigator, from reading this book, which is also a treat for any science-loving reader. Each chapter deals with a different topic and a surprising number of subtopics. For example, an early chapter introduces us to the brain and its basic neuroanatomy, but it also covers early, and now discarded, theories of brain evolution, the recognition that neocortex is not really new, and the debate over the value of the lunate sulcus as a marker of the border of the primary visual cortex in the endocasts of the brains of now extinct hominins. In this chapter, Allen is more optimistic than some of us would be in concluding that the classic Brodmann areas of the brain “can be readily identified as homologous units across primate species.” Progress in understanding brain evolution would have been much greater if this were the case, and many present day controversies would have been resolved. In the same chapter, Allen discusses the growth of comparative neuroscience over the past several decades, methods of determining the functional divisions of the brain, including informative studies of patients with lesions, and Wilder Penfield’s electrical stimulation studies of human cortex. He concludes with the reflection that most neuroscientists today do not study brains directly but representations of brains on computer screens. Such has been the impact of functional brain-imaging techniques. Other chapters are equally broad and varied. A chapter on brain size contains a nice history of early investigations, a review of the cranial capacity of fossil hominins, the problem of giving birth to a baby with a large brain, and a discussion of the relative roles of brain size increases compared with changes in brain organization in human brain evolution. Subsequent chapters on brain evolution range from discussion of the modified position of the foramen magnum with the evolution of bipedality, the degeneration of the human olfactory system, the recently published views on the functions of spindle cells of the human brain, the lunate sulcus debate, and frontal lobe evolution. Allen also draws examples of brain evolution from nonhuman species. Thus, he draws attention to the larger hippocampus for the memory of hidden food in food-storing birds. A chapter on the plastic brain considers the relative roles of genetic and environmental factors in brain development and brain plasticity as a result of learning and experience. Molecular and genetic aspects of brain development and evolution are covered further in a subsequent chapter. Elsewhere, we are told about the energy costs of the brain and how changes in diet were necessary in order to allow the evolution of big human brains. We are reminded that humans live a very long time compared with other primates and given reasons why a long life may have been selected for in human evolution. We are reassured by the evidence that human brains can be expected to function fairly well for at least 70 years, although some regressive changes are expected. A thoughtful chapter on the evolution of language covers the last 20 years of intensive research and debate, as well as earlier contributions. For those outside the field of linguistics, this chapter provides a good introductory background. At the book’s conclusion, Allen clearly feels that there has been great recent progress in understanding the evolution and organization of the human brain, but there is so much more to learn. He concludes that the large human brain reflects the evolution of many different cognitive adaptations. Perhaps most important is the ability to look into the future and reflect on the past, a cognitive ability that is said to be unique to humans. We can do both while reading this book.

What do comparisons between younger and older adult listeners tell us about speech processing?

The perception of speech, the recognition of words, and the understanding of spoken language involve the dynamic and interactive processing of cues provided by the incoming signal and information stored in memory. Even when accuracy is high, the relative contributions of bottom-up and top-down processes may explain variations in the speed and effort required when listening to speech. Listening is fast when the quality of the incoming signal is optimal, but it is slowed as signal quality is reduced. Likewise, listening can be speeded when expectations constrain the likely alternatives or when priming implicitly facilitates the recognition of the signal, whereas it can be slowed if the context is incongruent with the signal or if context is used to resolve ambiguities or repair misperceptions in a compensatory fashion. Within-subjects comparisons on off-line and on-line measures in different listening conditions, including simulations of auditory aging and hearing loss, are used to investigate how listening effort varies and how listening is speeded or slowed depending on signal-driven and knowledge-driven factors. Comparisons between younger and older participants are used to evaluate how long-standing reductions in auditory temporal processing and compensatory changes in brain organization may alter how signal-driven and knowledge-driven processes interact.

6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke

This case study contrasted two subjects with stroke who received 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) to the contralesional primary motor area (M1) to disinhibit ipsilesional M1. Functional magnetic resonance imaging (fMRI) showed that the intervention disrupted cortical activation at contralesional M1. Subject 1 showed decreased intracortical inhibition and increased intracortical facilitation following intervention during paired-pulse TMS testing of ipsilesional M1. Subject 2, whose precentral knob was totally obliterated and who did not show an ipsilesional motor evoked potential at pretest, still did not show any at posttest; however, her fMRI did show a large increase in peri-infarct zone cortical activation. Behavioral results were mixed, indicating the need for accompanying behavioral training to capitalize on the brain organization changes induced with rTMS.

Parasomnias and Movement Disorders of Sleep

Neurologists are often enlisted to help diagnose, evaluate, and manage a spectrum of abnormal spells during the night ranging from parasomnias to motor disturbance that span the sleep-wake cycle. Parasomnias are undesirable emotional or physical events that accompany sleep. These events typically occur during entry into sleep from wakefulness, or during arousals from sleep, and are often augmented by the sleep state. Some parasomnias, such as the rapid eye movement (REM) sleep behavior disorder may be extremely undesirable, while others such as somniloquy are often of little concern. The parasomnias include a spectrum of abnormal emotions, movements, behaviors, sensory perceptions, dream mentation, and autonomic activity. Basic physiologic drives, such as sex, hunger, and aggression, may manifest as sleep-related eating, sleep-related sexual behaviors, and sleep-related violence. Parasomnias have a very bizarre nature, but are readily explainable, diagnosable, and treatable. They are hypothesized to be due to changes in brain organization across multiple states of being, and are particularly apt to occur during the incomplete transition or oscillation from one sleep state to another. Parasomnias are often explained on the basis that wakefulness and sleep are not mutually exclusive states, and abnormal intrusion of wakefulness into non-REM (NREM) sleep produces arousal disorders, and intrusion of wakefulness into REM sleep produces REM sleep parasomnias and REM sleep behavior disorder (RBD). Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), two closely related conditions that often result in disturbed sleep onset and sleep maintenance, are also reviewed in this article. Although the mechanisms that underlie idiopathic RLS or PLMD are not fully understood, there is currently substantial evidence that dopaminergic dysfunction is likely involved in both conditions. The discussion will conclude with the "other parasomnias" and sleep-related movement disorders of clinical interest to the neurologist.

Viral Vector–mediated Delivery of Estrogen Receptor-α to the Hippocampus Improves Spatial Learning in Estrogen Receptor-α Knockout Mice

Estrogen, which influences both classical genomic and rapid membrane-associated signaling cascades, has been implicated in the regulation of hippocampal function, including spatial learning. Gene mutation studies suggest that estrogen effects are mediated by estrogen receptor-α (ER-α); however, because gonadal steroids influence the organization of the hippocampus during development, it has been difficult to distinguish developmental effects from those specific to adults. In this study we show that lentiviral delivery of the gene encoding ER-α to the hippocampus of adult ER-α-knockout (ER-αKO) mice restores hippocampal responsiveness to estrogen and rescues spatial learning. We propose that constitutive estrogen receptor activity is important for maintaining hippocampus-dependent memory function in adults.

The role of motor-sensory feedback in the evolution of mind

AbstractSeemingly small changes in brain organization can have revolutionary consequences for function. An example is evolution's application of the primate action-planning mechanism to the management of communicative sequences. When feedback from utterances reaches the brain again through a mechanism that evolved to monitor action sequences, it makes another pass through the brain, amplifying the human power of thinking.

A new method of embryonic culture for assessing global changes in brain organization

While dissociated, reaggregated cells and organotypic slice cultures are useful models for understanding brain development, they only partially mimic the processes and organization that exist in vivo. Towards bridging the gap between in vitro and in vivo paradigms, a method for culturing intact brain tissue was developed using whole cerebral cortical hemispheres in which the anatomical and cellular organization of nervous system tissue is preserved. Single, free-floating telencephalic hemispheres were dissected from embryonic mice and placed into defined culture medium on an orbital shaker. Orbital shaking was necessary for optimal growth, and cortices grown under these conditions closely approximated in vivo parameters of cell division, differentiation, migration and cell death for up to 24 h. In addition to wild-type cultures, the method was compatible with genetically altered tissues. One particular advantage of this method is its ability to reveal global anatomical alterations in the embryonic brain following exposure to soluble growth factors. This method should thus be helpful for assessing a wide range of soluble molecules for their systemic effects on the embryonic brain.

Therapy-induced plasticity of cognitive functions in MS patients: Insights from fMRI

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system whose pathological mechanisms are still not completely understood. Physical as well as cognitive deterioration are consequences within the disease process that have an extensive impact on the patient’s quality of life. Therefore, understanding the functional background of spontaneous as well as induced remission is of high relevance. Studies on visualization of therapeutic effects of pharmacological or cognitive treatment by functional magnetic resonance imaging (fMRI) are still rare. From fMRI studies on focal brain lesions hypotheses on mechanisms of brain reorganization can be derived. This contribution will first give an overview of the existing studies using fMRI in MS, on cognitive decline, on cognitive treatment studies and its therapeutic effects on behavioural readouts in MS, and on therapy-induced brain plasticity and its possible visualization by fMRI. Results of a study on correlating the effects of cognitive training with changes in brain organization in patients with mild to severe cognitive impairment will be reported.

Stimulating plastic change

The plastic changes in brain organization that are thought to underlie learning can be studied in the relatively well-mapped areas of the primary sensory and motor cortices. There are now several demonstrations of sensory and motor representations changing over periods of minutes to months in response to peripheral injury or simply the learning of a behavioural task. Ziemann et al. have recently demonstrated that a transcranial magnetic stimulation technique involving a train of repeated pulses (rTMS) can be used to modulate neuroplasticity in human subjects[1]. They used a second TMS technique, involving just paired pulses, to examine intracortical facilitation and inhibition in the motor cortex. The application of rTMS to the motor cortex had no measurable effect but when it was combined with ischaemic nerve block of the hand, however, Ziemann et al. observed changes in intracortical facilitation and inhibition. Ischaemic nerve block applied alone for a similar period did not have such profound reorganizing effects. These results suggest a way of directly, but non-invasively, modulating human cortical plasticity.

Moving along to things left undone

This paper expands on three areas of clinical theory that are introduced and discussed in the lead paper and the others in this symposium. The first issue addressed is the concept of the real relationship as used in the moment of meeting model of psychotherapeutic change. Particular focus has been placed on the past, the present, and the hierarchy of goals in the treatment relationship. Second, the paper explores the concept of implicit relational knowledge with attention to the concepts of transference, countertransference, interpretation, and insight in the change process. Finally, the paper attends to the nature of the “now moment” in the moment of meeting model. Specifically explicated are ways this concept relates to changes in brain organization and also ways the moment of meeting model relates to other psychotherapy models, such as the relational schools and self-psychology. © 1998 Michigan Association for Infant Mental Health