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Manuel F. Casanova - One of the best experts on this subject based on the ideXlab platform.
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Transcranial magnetic stimulation (TMS) therapy for autism: an international consensus conference held in conjunction with the international meeting for autism research on May 13th and 14th, 2014
Frontiers in human neuroscience, 2015Co-Authors: Lindsay M. Oberman, Manuel F. Casanova, Peter G. Enticott, Alexander Rotenberg, Alvaro Pascual-leone, James T. MccrackenAbstract:The Centers for Disease Control and Prevention currently estimate the prevalence of Autism Spectrum Disorder (ASD) in the U.S. at 1:68 children (Baio, 2014). Despite decades of research across multiple levels of analysis, we currently lack a reliable biomarker that may facilitate diagnosis, illuminate pathophysiology, or guide treatment. The development of novel treatment strategies for ASD will require efforts for better clinical characterization, identification of more homogeneous subgroups for studies, and improved understanding of underlying pathophysiology. There is growing support for early intensive interventions in this population (Reichow, 2012). Pharmacological treatments have been shown to be effective in treating some of the common secondary and comorbid features of ASD (Hampson et al., 2012), but there is currently no pharmacotherapy conclusively shown to improve the core symptoms (Oberman, 2012). Recently a number of investigators have begun to explore the use of transcranial magnetic stimulation (TMS) as a tool to characterize ASD pathophysiology, and to test its therapeutic potential. TMS is a safe and well-tolerated method for non-invasive focal Cortical stimulation where small intracranial electrical currents are generated by a rapidly fluctuating extracranial magnetic field. In an effort to share recent progress in the use of TMS in ASD, promote collaboration across laboratories, and establish consensus on parameters that may be useful for the study of pathophysiology and the potential treatment of ASD, leading experts in the field gathered in Atlanta, GA on May 13th and 14th 2014 for the “Transcranial Magnetic Stimulation (TMS) Therapy for Autism Consensus Conference” organized and supported by the Clearly Present Foundation with additional support from Neuronetics, Inc. and Autism Speaks. Alvaro Pascual-Leone began the conference by discussing the basic mechanisms and safety of TMS in clinical populations. TMS can be applied in single pulses to investigate corticospinal excitability, pairs of pulses to study intraCortical inhibition and facilitation, and repeated trains of TMS (rTMS) to both to study and therapeutically modulate excitability and plasticity in a number of neurological and psychiatric conditions (Kobayashi and Pascual-Leone, 2003). The effects of rTMS can be expected to differ considerably by virtue of varying parameters of stimulation and knowledge of underlying symptom pathophysiology. TMS is considered quite safe if applied within current safety guidelines; however, it does pose some risk for adverse side-effects (Rossi et al., 2009). Though relatively few patients with ASD have participated in TMS protocols, the frequency and quality of side-effects shown thus far approximates that seen in the general population (Oberman et al., 2013). As with any other condition, factors including medications and medical history need to be assessed when determining risk for an individual. There are currently no identified ASD-specific risk factors for TMS-induced adverse effects. Even though ASD can be associated with an increased risk for seizures, in TMS studies to date, there is no evidence of increased epileptogenic risk in ASD when safety guidelines and recommendations are followed. Manuel Casanova then provided a targeted review of the literature on the pathophysiology of ASD. Postmortem studies have shown evidence of abnormalities of neuronal migration in the brains of individuals with ASD (Bailey et al., 1998), which include displaced neurons manifesting as focal Cortical dysplasias in a majority of individuals with ASD (Casanova et al., 2013). Morphometric analysis of cells within the malformed cortex has suggested a reduced number of interneurons (Casanova et al., 2013). This is consistent with previous reports of abnormalities in ASD within the peripheral Cortical Minicolumn neuropil space, the compartment where most inhibitory cells are located (Casanova et al., 2002). Both EEG and vibrotactile studies corroborate a deficit of Cortical lateral inhibition (Keita et al., 2011; Puts et al., 2014). He proposed that this deficit could account for the seizures and sensory abnormalities often reported in ASD. Lindsay Oberman discussed the use of TMS as an investigative device to study Cortical excitability and plasticity in ASD. These studies show that a number of basic mechanisms and circuits are atypical while other measures appear to be normal (see Oberman et al., 2013). Specifically, motor thresholds and baseline motor-Cortical excitability measures appear to be normal. There is heterogeneity in the response to paired-pulse paradigms with impaired inhibition in some individuals, typical response in others, and paradoxical facilitation in another subgroup. Studies exploring corticospinal plasticity mechanisms, using two different rTMS protocols [theta burst stimulation (TBS) and paired associative stimulation (PAS)], have shown abnormalities. However, the direction of the abnormality is unclear with TBS studies showing enhanced response (Oberman et al., 2012) and PAS showing reduced response (Jung et al., 2013). There are a number of open questions related to the use of TMS as an investigative device in ASD including developmental effects, effects related to intellectual disability and functioning, and what underlying mechanisms are driving the observed heterogeneity in the population. Peter Enticott discussed the efficacy of rTMS as a therapeutic intervention in ASD. A number of studies using low-frequency rTMS in an effort to enhance Cortical inhibitory tone in dorsolateral prefrontal cortex have resulted in improvements in EEG indices of attention, information processing, and error monitoring as well as behavioral improvements in repetitive behaviors and irritability (Sokhadze et al., 2014). Low-frequency stimulation to left pars triangularis resulted in improved object naming in a single session study (Fecteau et al., 2011). High-frequency stimulation, designed to enhance excitability, has suggested improvements in self-reported social relating and social anxiety following medial prefrontal cortex stimulation (Enticott et al., 2014) and significant improvements in eye-hand coordination following premotor stimulation (Panerai et al., 2013). Although an emerging literature, these studies collectively provide support for the potential efficacy of rTMS in ASD (Oberman et al., 2013). However, the small study samples, lack of blind assessments, and limited use of control or comparison conditions limit the interpretation of these early investigations. James McCracken concluded the conference by discussing key factors to consider when designing clinical trials for ASD. These factors included identification of valid and reliable endpoints, incorporation of blind assessments, need for credible control conditions, establishment of effective stimulation parameters, need to relate changes in electrophysiologic endpoints to functional change, and identification of biomarkers that can be used to reduce the heterogeneity of the sample and stratify participants to treatment strategies that are best matched to their underlying pathophysiology. To this end, those present discussed the utility of developing functional imaging and TMS indices as potential standardized biomarkers and the need for larger, multisite trials to establish validity of these measures across development and levels of functioning and reliability of these measures across centers. At the conclusion of the conference, there was enthusiasm for the potential use of TMS in ASD. Further work is necessary to achieve consensus on the key factors discussed by Dr. McCracken, but the expertise and commitment is present in the research and clinical community to work toward the end goal of designing and implementing large-scale, double blind, multisite clinical trials of rTMS for ASD in the near future. Those present committed to collaborate across laboratories to establish mutually agreed upon protocols and to meet again within 1 year.
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Modular Signatures and Neural Avalanches in Epileptic Brain Networks
Recent Advances on the Modular Organization of the Cortex, 2015Co-Authors: Manuel F. Casanova, Ana Ciurea, Ioana Mîndruţă, Mihai Dragos Maliiă, Jean Ciurea, Andrei Barborică, Cristian Donos, Ioan OprisAbstract:Epileptic seizures are characterized by a rich dynamic spectrum consisting of excessive, abnormal and synchronized firing of neuron ensembles. Such abnormal firing has been quantitatively characterized via power laws in neural avalanches. The term “neural avalanche” has been used to illustrate the excessively amplified neural firing patterns that lead to epileptic seizures. The pattern of amplified firing in neural avalanches betrays a modular signature in the spread of activation across Cortical Minicolumns. According to this modular approach of epilepsy, the excessive amplification of neural firing in a Cortical Minicolumn results from a defect within the “inhibitory curtain” surrounding the pyramidal cells. The functional basis of this approach provides insights into potential clinical interventions.
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Prefrontal Cortical Minicolumn: from executive control to disrupted cognitive processing.
Brain : a journal of neurology, 2014Co-Authors: Ioan Opris, Manuel F. CasanovaAbstract:The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in Minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal Cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across Cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-Cortical interactions between interlaminar prefrontal Cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer's and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving Cortical Minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular Cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal Cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in Cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of Cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders.
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NeoCortical Modularity And The Cell Minicolumn
2012Co-Authors: Manuel F. CasanovaAbstract:Acknowledgement Introduction A Life that Transformed the Neurosciences Scientific Achievements An Apologia for a Paradigm Shift in the Neurosciences Reflections on the Structure of the Cortical Minicolumn The Cell Column in Comparative Anatomy Encephalisation, Minicolumns, and Hominid Evolution The Generation and Migration of Cortical Interneurons Minicolumnar Patterns in the Global Cortical Response to Sensory Stimulation Minicolumnar Morphometry: Computerised Image Analysis The Verticality Index: A Quantitative Approach to the Analysis of the Columnar Arrangement of Neurons in the Primate Neocortex Mountcastle Principle of Columnar Cortex as a Basis for the Theory of Higher Brain Function: Clinical Relevance Index.
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The Minicolumn hypothesis in neuroscience
Brain, 2002Co-Authors: Daniel P. Buxhoeveden, Manuel F. CasanovaAbstract:The Minicolumn is a continuing source of research and debate more than half a century after it was identified as a component of brain organization. The Minicolumn is a sophisticated local network that contains within it the elements for redundancy and plasticity. Although it is sometimes compared to subCortical nuclei, the design of the Minicolumn is a distinctive form of module that has evolved specifically in the neocortex. It unites the horizontal and vertical components of cortex within the same Cortical space. Minicolumns are often considered highly repetitive, even clone-like, units. However, they display considerable heterogeneity between areas and species, perhaps even within a given macrocolumn. Despite a growing recognition of the anatomical basis of the Cortical Minicolumn, as well as its physiological properties, the potential of the Minicolumn has not been exploited in fields such as comparative neuroanatomy, abnormalities of the brain and mind, and evolution.
David Laberge - One of the best experts on this subject based on the ideXlab platform.
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Cortical Minicolumn and corticothalamic circuit.
2013Co-Authors: Ray S. Kasevich, David LabergeAbstract:(A) Schematic diagram of a Minicolumn in monkey visual cortex (see Figure 19 in [46]). Shown are somas and apical dendrites of pyramidal neurons and somas of stellate neurons. (B) Schematic diagram showing the corticothalamic loop. A specific resonance profile in a Layer 5 apical dendrite is projected, via the thalamus, back to the first compartment of the same apical dendrite. The profile is also projected to apical dendrites of Layer 2/3 pyramidal neurons where it spreads to the basal dendrites and may influence the selection of inputs arriving from other Cortical Minicolumns. For clarity, the reticular nucleus, with its inhibitory projections to the thalamic principal neurons, is not shown. Adapted from [30], [31].
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2007 Special Issue: The apical dendrite theory of consciousness
Neural networks : the official journal of the International Neural Network Society, 2007Co-Authors: David Laberge, Ray S. KasevichAbstract:The neural basis of consciousness is theorized here to be the elevated activity of the apical dendrite within a thalamoCortical circuit. Both the anatomical and functional properties of these two brain structures are examined within the general context of the Cortical Minicolumn, which is regarded as the functional unit of the cerebral cortex. Two main circuits of the Minicolumn are described: the axis circuit, which sustains activity for extended durations and produces our sensory impressions, and the shell circuit, which performs input-output processing and produces identifications, categorizations, and ideas. The apical dendrite operates within the axis circuit to stabilize neural activity, which enables conscious impressions to be steady and to be sustained over long periods of time. In an attempt to understand how the conscious aspect of subjective impressions may be related to apical dendrite activity, we examine the characteristics of the electric and magnetic fields during the movement of charges along the apical dendrite. The physical correlate of consciousness is regarded here as the relatively intense electromagnetic field that is located along the inside and the outside close to the surface of the active apical dendrite.
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Apical dendrite activity in cognition and consciousness.
Consciousness and cognition, 2005Co-Authors: David LabergeAbstract:The ongoing steady nature of consciousness in everyday life implies that the underlying neural activity possesses a high level of stability. The prolonged cognitive events of sustained attention, imagery, and working memory also imply high stability of underlying neural activity. This paper proposes that stabilization of neural activity is produced by apical dendrite activity in pyramidal neurons within recurrent corticothalamic circuits, and proposes that the wave activities of apical dendrites that stabilize ongoing activity constitute the subjective impressions of an attended object and the entire sensory background. The Cortical Minicolumn, as the functional unit of the cortex, is separated into an axis consisting of layer 5 pyramidal neurons and a surrounding shell consisting of layer 2/3 pyramidal neurons. It is proposed that apical dendrites of the axis generate sensory impressions, and basal dendrites of the shell process the brief-lasting input-output identifications of objects that give rise to ideas.
Ioan Opris - One of the best experts on this subject based on the ideXlab platform.
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What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?
Frontiers in neuroanatomy, 2017Co-Authors: Ioan Opris, Stephano J. Chang, Brian R. NogaAbstract:The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal Cortical inter-laminar microcircuits. Inter-laminar Minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across Cortical layers during executive control. The integrative effect of dlPFC Minicolumns was shown by: i) increased correlated firing on correct vs. error trials; ii) decreased correlated firing when the number of non-matching images increased; and iii) similar spatial firing preference across Cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the Minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain’s prefrontal Cortical microcircuits.
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Modular Signatures and Neural Avalanches in Epileptic Brain Networks
Recent Advances on the Modular Organization of the Cortex, 2015Co-Authors: Manuel F. Casanova, Ana Ciurea, Ioana Mîndruţă, Mihai Dragos Maliiă, Jean Ciurea, Andrei Barborică, Cristian Donos, Ioan OprisAbstract:Epileptic seizures are characterized by a rich dynamic spectrum consisting of excessive, abnormal and synchronized firing of neuron ensembles. Such abnormal firing has been quantitatively characterized via power laws in neural avalanches. The term “neural avalanche” has been used to illustrate the excessively amplified neural firing patterns that lead to epileptic seizures. The pattern of amplified firing in neural avalanches betrays a modular signature in the spread of activation across Cortical Minicolumns. According to this modular approach of epilepsy, the excessive amplification of neural firing in a Cortical Minicolumn results from a defect within the “inhibitory curtain” surrounding the pyramidal cells. The functional basis of this approach provides insights into potential clinical interventions.
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Prefrontal Cortical Minicolumn: from executive control to disrupted cognitive processing.
Brain : a journal of neurology, 2014Co-Authors: Ioan Opris, Manuel F. CasanovaAbstract:The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in Minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal Cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across Cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-Cortical interactions between interlaminar prefrontal Cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer's and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving Cortical Minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular Cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal Cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in Cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of Cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders.
Margaret M. Esiri - One of the best experts on this subject based on the ideXlab platform.
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Microanatomical Correlates of Cognitive Ability and Decline: Normal Ageing, MCI, and Alzheimer’s Disease
Cerebral cortex (New York N.Y. : 1991), 2011Co-Authors: Steven A. Chance, Linda Clover, Helena Cousijn, Leila Currah, Rosemary Pettingill, Margaret M. EsiriAbstract:Few microanatomical measures have been reliably correlated with cognitive measures in aging and Alzheimer’s disease (AD), particularly in the early stages of degeneration, such as mild cognitive impairment (MCI). However, Cortical Minicolumn organization has been shown to correlate with cognitive ability in aging monkeys, and the present study extends this finding to humans. We have previously reported that Minicolumn spacing of cells in human association cortex is selectively reduced in normal aging (Minicolumn thinning). The present study found that such measures detected early disease changes in MCI as well as further Minicolumn thinning and disruption in AD. Plaques, tangles, and Minicolumns were quantified, postmortem, for 20 controls, 10 MCI, and 20 AD subjects. Minicolumn changes were correlated with premortem cognitive scores (mini-mental state examination and verbal fluency). Two regions were studied from each brain: association cortex in the planum temporale (BA22) and primary auditory cortex (BA41). The relationship between Minicolumns and cognitive function was strongest in association cortex, whereas in primary auditory cortex, it appeared to be an epiphenomenon of overall brain atrophy. Microanatomical changes reflecting selective regional vulnerability to AD pathology and differential involvement in the cognitive deficit of AD are therefore detectable in the early stage of MCI.
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Microanatomical correlates of cognitive ability and decline: normal ageing, MCI, and Alzheimer's disease.
'Oxford University Press (OUP)', 2011Co-Authors: Sa Chance, Clover L, Cousijn H, Currah L, Pettingill R, Margaret M. EsiriAbstract:Few microanatomical measures have been reliably correlated with cognitive measures in aging and Alzheimer's disease (AD), particularly in the early stages of degeneration, such as mild cognitive impairment (MCI). However, Cortical Minicolumn organization has been shown to correlate with cognitive ability in aging monkeys, and the present study extends this finding to humans. We have previously reported that Minicolumn spacing of cells in human association cortex is selectively reduced in normal aging (Minicolumn thinning). The present study found that such measures detected early disease changes in MCI as well as further Minicolumn thinning and disruption in AD. Plaques, tangles, and Minicolumns were quantified, postmortem, for 20 controls, 10 MCI, and 20 AD subjects. Minicolumn changes were correlated with premortem cognitive scores (mini-mental state examination and verbal fluency). Two regions were studied from each brain: association cortex in the planum temporale (BA22) and primary auditory cortex (BA41). The relationship between Minicolumns and cognitive function was strongest in association cortex, whereas in primary auditory cortex, it appeared to be an epiphenomenon of overall brain atrophy. Microanatomical changes reflecting selective regional vulnerability to AD pathology and differential involvement in the cognitive deficit of AD are therefore detectable in the early stage of MCI
Brian R. Noga - One of the best experts on this subject based on the ideXlab platform.
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What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?
Frontiers in neuroanatomy, 2017Co-Authors: Ioan Opris, Stephano J. Chang, Brian R. NogaAbstract:The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal Cortical inter-laminar microcircuits. Inter-laminar Minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across Cortical layers during executive control. The integrative effect of dlPFC Minicolumns was shown by: i) increased correlated firing on correct vs. error trials; ii) decreased correlated firing when the number of non-matching images increased; and iii) similar spatial firing preference across Cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the Minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain’s prefrontal Cortical microcircuits.
