Age-dependent consequences of seizures: relationship to seizure frequency, brain damage, and circuitry reorganization

Seizures in the developing brain pose a challenge to the clinician. In addition to the acute effects of the seizure, there are questions regarding the impact of severe or recurrent seizures on the developing brain. Whether provoked seizures cause brain damage, synaptic reorganization, or epilepsy is of paramount importance to patients and physicians. Such questions are especially relevant in the decision to treat or not treat febrile seizures, a common occurrence in childhood. These clinical questions have been addressed using clinical and animal research. The largest prospective studies do not find a causal connection between febrile seizures and later temporal lobe epilepsy. The immature brain seems relatively resistant to the seizure-induced neuronal loss and new synapse formation seen in the mature brain. Laboratory investigations using a developmental rat model corresponding to human febrile seizures find that even though structural changes do not result from hyperthermic seizures, synaptic function may be chronically altered. The increased understanding of the cellular and synaptic mechanisms of seizure-induced damage may benefit patients and clinicians in the form of improved therapies to attenuate damage and changes induced by seizures and to prevent the development of epilepsy.     

Can small lesions induce language reorganization as large lesions do?

Shift of the cortical mechanisms of language from the usually dominant left to the non-dominant right hemisphere has been demonstrated in the presence of large brain lesions. Here, we report a similar phenomenon in a patient with a cavernoma over the anterolateral superior temporal gyrus associated with epilepsy. Language mapping was performed by two complementary procedures, magnetoencephalography, and electrocorticography. The maps, indicated right temporal lobe dominance for receptive language and left frontal lobe dominance for expressive language. These results indicate that a small lesion, associated with epilepsy, may produce selective shifting of receptive language mechanisms as large lesions have been known to produce.     

The link between brain learning, attention, and consciousness

The processes whereby our brains continue to learn about a changing world in a stable fashion throughout life are proposed to lead to conscious experiences. These processes include the learning of top-down expectations, the matching of these expectations against bottom-up data, the focusing of attention upon the expected clusters of information, and the development of resonant states between bottom-up and top-down processes as they reach an attentive consensus between what is expected and what is there in the outside world. It is suggested that all conscious states in the brain are resonant states and that these resonant states trigger learning of sensory and cognitive representations. The models which summarize these concepts are therefore called Adaptive Resonance Theory, or ART, models. Psychophysical and neurobiological data in support of ART are presented from early vision, visual object recognition, auditory streaming, variable-rate speech perception, somatosensory perception, and cognitive-emotional interactions, among others. It is noted that ART mechanisms seem to be operative at all levels of the visual system, and it is proposed how these mechanisms are realized by known laminar circuits of visual cortex. It is predicted that the same circuit realization of ART mechanisms will be found in the laminar circuits of all sensory and cognitive neocortex. Concepts and data are summarized concerning how some visual percepts may be visibly, or modally, perceived, whereas amodal percepts may be consciously recognized even though they are perceptually invisible. It is also suggested that sensory and cognitive processing in the What processing stream of the brain obey top-down matching and learning laws that are often complementary to those used for spatial and motor processing in the brain's Where processing stream. This enables our sensory and cognitive representations to maintain their stability as we learn more about the world, while allowing spatial and motor representations to forget learned maps and gains that are no longer appropriate as our bodies develop and grow from infanthood to adulthood. Procedural memories are proposed to be unconscious because the inhibitory matching process that supports these spatial and motor processes cannot lead to resonance.     

Rapid modulation of distributed brain activity by Transcranial Magnetic Stimulation of human motor cortex

This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.     

What Are the Brain Mechanisms on Which Psychological Processes Are Based?

ABSTRACT— That the human brain is the organ of the mind is not in dispute, but we know remarkably little about the brain mechanisms underlying the mind. What are the functional structures and computational processes of the human brain that subserve cognition, emotion, and behavior? Given the complexity of the human brain, progress in understanding the functional organization and structure of the human brain depends on sophisticated theoretical specifications of the psychological representations and processes that differentiate two or more comparison conditions. Psychological scientists, therefore, are well positioned to lead the search for brain mechanisms underlying psychological processes. Doing so constitutes an expansion of the purview of psychological science beyond a science of behavior, and beyond a science of the mind, to include a science of the brain. Such an expansion of the mission of psychological science has implications for the infrastructure and training needs of the discipline.     

Epilepsy genes: the link between molecular dysfunction and pathophysiology

Our understanding of the genetic basis of epilepsy is progressing at a rapid pace. Gene mutations causing several of the inherited epilepsies have been mapped, and several more are likely to be added in coming years. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability. Mutations leading to epilepsy have been identified in genes encoding voltage- and ligand-gated ion channels (benign familial neonatal convulsions, autosomal dominant nocturnal frontal lobe epilepsy, generalized epilepsy with febrile seizures "plus"), neurotransmitter receptors (Angelman syndrome), the molecular cascade of cellular energy production (myoclonic epilepsy with ragged red fibers), and proteins without a known role in neuronal excitability (Unverricht-Lundborg disease). Gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.     

Evidence of Common Timing Processes in the Control of Manual,Orofacial, and Speech Movements

Recent investigations of timing in motor control have been interpreted as support for the concept of brain modularity. According to this concept, the brain is organized into functional modules that contain mechanisms responsible for general processes. Keele and colleagues (Keele & Hawkins, 1982; Keele & Ivry, 1987; Keele, Ivry, & Pokorny, 1987; Keele, Pokorny, Corcos, & Ivry, 1985) demonstrated that the within-subject variability in. cycle duration of repetitive movements is correlated across finger, forearm, and foot movements, providing evidence in support of a general timing module. The present study examines the notion of timing modularity of speech and nonspeech movements of the oral motor system as well as the manual motor system. Subjects produced repetitive movements with the finger, forearm, and jaw. In addition, a fourth task involved the repetition of a syllable. All tasks were to be produced with a 400-ms cycle duration; target duration was established with a pacing tone, which then was removed. For each task, the within-subject variability of the cycle duration was computed for the unpaced movements over 20 trials. Significant correlations were found between each pair of effectors and tasks. The present results provide evidence that common timing processes are involved not only in movements of the limbs, but also in speech and nonspeech movements of oral structures.     

Evidence of Common Timing Processes in the Control of Manual,Orofacial, and Speech Movements

Recent investigations of timing in motor control have been interpreted as support for the concept of brain modularity. According to this concept, the brain is organized into functional modules that contain mechanisms responsible for general processes. Keele and colleagues (Keele & Hawkins, 1982; Keele & Ivry, 1987; Keele, Ivry, & Pokorny, 1987; Keele, Pokorny, Corcos, & Ivry, 1985) demonstrated that the within-subject variability in cycle duration of repetitive movements is correlated across finger, forearm, and foot movements, providing evidence in support of a general timing module. The present study examines the notion of timing modularity of speech and nonspeech movements of the oral motor system as well as the manual motor system. Subjects produced repetitive movements with the finger, forearm, and jaw. In addition, a fourth task involved the repetition of a syllable. All tasks were to be produced with a 400-ms cycle duration; target duration was established with a pacing tone, which then was removed. For each task, the within-subject variability of the cycle duration was computed for the unpaced movements over 20 trials. Significant correlations were found between each pair of effectors and tasks. The present results provide evidence that common timing processes are involved not only in movements of the limbs, but also in speech and nonspeech movements of oral structures.     

Magnetic stimulation studies of visual cognition

The panoply of non-invasive techniques for brain imaging is responsible for much of the current excitement in cognitive neuroscience; sensory, perceptual and cognitive behaviour can now be correlated with cerebral blood flow as assessed by functional imaging, the electrical fields generated by populations of neurons or changes in magnetic fields created by electrical activity. Correlations between localized brain activity and behaviour, however, do not of themselves establish that any brain area is necessary for a particular task; necessity is the domain of the lesion technique. Transcranial magnetic stimulation (TMS) is a technique that can be used non-invasively to produce reversible functional disruption and has already been used to investigate visual detection, discrimination, attention and plasticity. The power of TMS as a `lesion' technique lies in the opportunity to combine reversible disruption with high degrees of spatial and temporal resolution. In this review we trace some of the major developments in the use of TMS as a technique for the investigation of visual cognition.     

Effects of early seizures on later behavior and epileptogenicity

Both clinical and laboratory studies demonstrate that seizures early in life can result in permanent behavioral abnormalities and enhance epileptogenicity. Understanding the critical periods of vulnerability of the developing nervous system to seizure-induced changes may provide insights into parallel or divergent processes in the development of autism. In experimental rodent models, the consequences of seizures are dependent on age, etiology, seizure duration, and frequency. Recurring seizures in immature rats result in long-term adverse effects on learning and memory. These behavioral changes are paralleled by changes in brain connectivity, changes in excitatory neurotransmitter receptor distribution, and decreased neurogenesis. These changes occur in the absence of cell loss. Although impaired cognitive function and brain changes have been well-documented following early-onset seizures, the mechanisms of seizure-induced dysfunction remain unclear.     

Pre-Surgical Language Mapping with Functional Magnetic Resonance Imaging

Patients with lesions in or near eloquent cortex typically undergo one of several invasive techniques to prevent loss of function following surgery. One of the most promising potential clinical applications of functional magnetic resonance imaging (fMRI) is to map these functions as part of the pre-surgical work-up to identify patients at-risk, guide the surgical entry, or tailor the surgical procedure to prevent deficits. While motor and sensory mapping are relatively straightforward, language mapping is far more complex. The language system is variable in location across individuals and in many cases may reorganize partially or completely to the contralateral hemisphere. In addition, multiple regions of the brain contribute to language functioning including essential regions that must not be removed in surgery, and contributory regions that may result in transient or insignificant impairments post-surgery. Despite these challenges, an increasing number of studies have supported the use of fMRI for pre-surgical language mapping in a variety of disorders. This article reviews the literature from three disorders for which patients benefit from preoperative language mapping: epilepsy, brain tumors, and arteriovenous malformations. Each disorder presents unique challenges to language mapping. Specific case studies are presented highlighting the both the potential benefits of preclinical fMRI for language mapping as well as the potential risks and pitfalls.     

语言功能偏侧化及其与利手、功能连接的关系

对大脑语言功能偏侧化的探索起始于早期对脑损伤病人的研究。现代脑影像学研究发现, 语言功能偏侧化涉及额叶、颞叶、扣带回、梭状回和辅助运动区等脑区。语言偏侧化与利手和静息态功能连接之间的关系表现为：右利手的语言优势位于左半球, 而左利手的则分布在左半球、右半球或两个半球; 语言功能偏侧化与利手系数、静息态半球内功能连接之间具有正相关关系, 与半球间功能连接呈负相关, 并且语言功能偏侧化与静息态功能连接之间的关系在左右利手个体之间存在差异。总之, 大脑语言功能偏侧化、利手和静息态功能连接三者之间存在相互影响, 基于脑连接和遗传机制的研究将有望揭示出其底层的神经生理机制。     

Neural synchrony in stochastic resonance, attention, and consciousness.

We describe briefly three of our lab's ongoing projects studying the role of neural synchrony in human perception and cognition. These projects arise from two main interests: the role of noise both in human perception and in neural synchrony, and neural synchrony as a basis for integration of functional modules in the brain. Our experimental work on these topics began with a study of the possibility that noise-influenced neural synchrony might be responsible for the fact that small amounts of noise added to weak signals can enhance their detectability (stochastic resonance). We are also studying the role of neural synchrony in attention and consciousness in several paradigms. On the basis of our own and related work by others, we conclude that (1) neural synchrony plays an important role in the integration of functional modules in the brain and (2) neural synchrony is profoundly affected and possibly regulated, in part, by the "noisiness" of the brain.     

A Simon effect induced by induced moton and location: evidence for a direct linkage of cognitive and motor maps

It has been argued that two distinct maps of visual space are formed: a cognitive map that is susceptible to illusions, and a motor map that represents the physical world veridically. In the present study, subjects responded to a nonspatial attribute of a visual target stimulus by pressing a left or right key, while an illusory horizontal displacement of the target was induced. A Simon-type effect was obtained to the induced target motion or position shift-that is, responses were faster when the illusory target motion or location corresponded to the response position. Further experiments indicated that the observed effects cannot be accounted for by attentional shifts. These results suggest that the content of the cognitive map does not only influence perceptual judgments but is also responsible for the automatic activation of response codes. In other words, perception and action seem to be fed by a common, cognitively penetrable, spatial representation.     

A Simon effect induced by induced motion and location: Evidence for a direct linkage of cognitive and motor maps

It has been argued that two distinct maps of visual space are formed: a cognitive map that is susceptible to illusions, and a motor map that represents the physical world veridically. In the present study, subjects responded to a nonspatial attribute of a visual target stimulus by pressing a left or right key, while an illusory horizontal displacement of the target was induced. A Simon-type effect was obtained to the induced target motion or position shift—that is, responses were faster when the illusory target motion or location corresponded to the response position. Further experiments indicated that the observed effects cannot be accounted for by attentional shifts. These results suggest that the content of the cognitive map does not only influence perceptual judgments but is also responsible for the automatic activation of response codes. In other words, perception and action seem to be fed by a common, cognitively penetrable, spatial representation.     

Imitation: is cognitive neuroscience solving the correspondence problem?

Imitation poses a unique problem: how does the imitator know what pattern of motor activation will make their action look like that of the model? Specialist theories suggest that this correspondence problem has a unique solution; there are functional and neurological mechanisms dedicated to controlling imitation. Generalist theories propose that the problem is solved by general mechanisms of associative learning and action control. Recent research in cognitive neuroscience, stimulated by the discovery of mirror neurons, supports generalist solutions. Imitation is based on the automatic activation of motor representations by movement observation. These externally triggered motor representations are then used to reproduce the observed behaviour. This imitative capacity depends on learned perceptual-motor links. Finally, mechanisms distinguishing self from other are implicated in the inhibition of imitative behaviour.     

Motor maps and synergies

Consider the process of raising and lowering the arm in the sagittal plane. Different parts of different muscles operate over different sectors of the angular range. How and why does the nervous system implement this differential muscle activation according to joint angle? We contend that such control depends on the adaptive formation of motor maps. These solve the problem of redundancy in the musculoskeletal system by connecting a relatively small number of cortical columns in the motor cortex to a large number of alpha motor neuron pools. We argue that motor maps are formed such that each functional muscle is activated in proportion to its moment arm about the movement. Because of this the required agonist and antagonist turning forces are generated with a minimum demand for metabolic energy. We know from biomechanical principles that, at any given posture, those muscle fibres that change length most in response to a small joint-angle change are those with the greatest moment arm. Likewise those that change least have the smallest. By establishing a model of the polynomial relationships between the lengths of functional muscles l and the corresponding changes in joint angles theta, the nervous system can generate signals partial differentiallj/ partial differentialthetai (where lj is the length of the jth functional muscle and thetai is the magnitude of the ith elemental movement). These signals create motor maps by modulating the gains of descending motor pathways. As a result, functional muscles are activated in proportion to their moment arms. This reduces the demand for metabolic energy to a minimum. Since moment arms change with joint angle, it also accounts for the experimental observations above. Such motor mapping effectively provides a minimum energy "wired-in" synergy. Established in utero, motor maps are the first stage of synergy formation and provide the basis for the development of subsequent task-dependent synergies.     

Massive redeployment,exaptation, and the functional integration of cognitive operations

The massive redeployment hypothesis (MRH) is a theory about the functional topography of the human brain, offering a middle course between strict localization on the one hand, and holism on the other. Central to MRH is the claim that cognitive evolution proceeded in a way analogous to component reuse in software engineering, whereby existing components—originally developed to serve some specific purpose—were used for new purposes and combined to support new capacities, without disrupting their participation in existing programs. If the evolution of cognition was indeed driven by such exaptation, then we should be able to make some specific empirical predictions regarding the resulting functional topography of the brain. This essay discusses three such predictions, and some of the evidence supporting them. Then, using this account as a background, the essay considers the implications of these findings for an account of the functional integration of cognitive operations. For instance, MRH suggests that in order to determine the functional role of a given brain area it is necessary to consider its participation across multiple task categories, and not just focus on one, as has been the typical practice in cognitive neuroscience. This change of methodology will motivate (even perhaps necessitate) the development of a new, domain-neutral vocabulary for characterizing the contribution of individual brain areas to larger functional complexes, and direct particular attention to the question of how these various area roles are integrated and coordinated to result in the observed cognitive effect. Finally, the details of the mix of cognitive functions a given area supports should tell us something interesting not just about the likely computational role of that area, but about the nature of and relations between the cognitive functions themselves. For instance, growing evidence of the role of “motor” areas like M1, SMA and PMC in language processing, and of “language” areas like Broca’s area in motor control, offers the possibility for significantly reconceptualizing the nature both of language and of motor control.     

A review of ideomotor approaches to perception,cognition, action,and language: advancing a cultural recycling hypothesis

The term “cultural recycling” derives from the neuronal recycling hypothesis, which suggests that representations of cultural inventions like written words, Arabic numbers, or tools can occupy brain areas dedicated to other functions. In the present selective review article, we propose a recycling hypothesis for the ideomotor mechanism. The ideomotor approach assumes that motor actions are controlled by the anticipation of the expected perceptual consequences that they aim to generate in the environment. Arguably, such action–perception mechanisms contribute to motor behaviour for human and non-human animals since millions of years. However, recent empirical studies suggest that the ideomotor mechanism can also contribute to word processing, number representation, and arithmetic. For instance, it has been shown that the anticipatory simulation of abstract semantics, like the numerical quantitative value of three items can prime processing of the associated Arabic number “3”. Arabic numbers, words, or tools represent cultural inventions, so that, from a theoretical perspective, we suggest an ideomotor recycling hypothesis for the interaction with such artefacts. In this view, the ideomotor mechanism spreads its influence to other functions beyond motor control, and is recycled to flexibly adapt different human behaviours towards dealing with more abstract concepts.