Michael R. Trimble

Bio: Michael R. Trimble is an academic researcher from UCL Institute of Neurology. The author has contributed to research in topics: Epilepsy & Tourette syndrome. The author has an hindex of 73, co-authored 289 publications receiving 19726 citations. Previous affiliations of Michael R. Trimble include University College London & Queen's University.

The precuneus: a review of its functional anatomy and behavioural correlates.

Abstract: Functional neuroimaging studies have started unravelling unexpected functional attributes for the posteromedial portion of the parietal lobe, the precuneus. This cortical area has traditionally received little attention, mainly because of its hidden location and the virtual absence of focal lesion studies. However, recent functional imaging findings in healthy subjects suggest a central role for the precuneus in a wide spectrum of highly integrated tasks, including visuo-spatial imagery, episodic memory retrieval and self-processing operations, namely first-person perspective taking and an experience of agency. Furthermore, precuneus and surrounding posteromedial areas are amongst the brain structures displaying the highest resting metabolic rates (hot spots) and are characterized by transient decreases in the tonic activity during engagement in non-self-referential goal-directed actions (default mode of brain function). Therefore, it has recently been proposed that precuneus is involved in the interwoven network of the neural correlates of self-consciousness, engaged in self-related mental representations during rest. This hypothesis is consistent with the selective hypometabolism in the posteromedial cortex reported in a wide range of altered conscious states, such as sleep, drug-induced anaesthesia and vegetative states. This review summarizes the current knowledge about the macroscopic and microscopic anatomy of precuneus, together with its wide-spread connectivity with both cortical and subcortical structures, as shown by connectional and neurophysiological findings in non-human primates, and links these notions with the multifaceted spectrum of its behavioural correlates. By means of a critical analysis of precuneus activation patterns in response to different mental tasks, this paper provides a useful conceptual framework for matching the functional imaging findings with the specific role(s) played by this structure in the higher-order cognitive functions in which it has been implicated. Specifically, activation patterns appear to converge with anatomical and connectivity data in providing preliminary evidence for a functional subdivision within the precuneus into an anterior region, involved in self-centred mental imagery strategies, and a posterior region, subserving successful episodic memory retrieval.

The subgenual anterior cingulate cortex in mood disorders.

Abstract: The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.

The psychiatric comorbidity of epilepsy

Abstract: Several studies have assessed the prevalence of psychiatric disorders in epilepsy. They are characterized by considerable heterogeneity, because of differences in the population setting and type of study. A non-systematic review of the literature allows us to draw some useful, although not definite, conclusions. Six per cent of people with epilepsy in the general population appear to suffer from a psychiatric disorder, while this rises to 10-20% in populations with temporal lobe and/or refractory epilepsy. Mood disorders are the most common culprit (24-74%), particularly depression (30%), followed by anxiety disorders (10-25%), psychoses (2-7%) and personality disorders (1-2%). This comorbidity appears to be related to endogenous and exogenous (including iatrogenic) factors and to the severity and chronicity of epilepsy. Conditions such as schizophrenia-like psychosis of epilepsy and interictal dysphoric disorder are represented only in epilepsy. Adequate recognition and treatment of psychiatric conditions in epilepsy is essential for patient management because of their considerable burden in morbidity and quality of life.

Complex brain networks: graph theoretical analysis of structural and functional systems

Abstract: Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.

The Brain's Default Network Anatomy, Function, and Relevance to Disease

Abstract: Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many