Sujith Vijayan

Rule Learning by Seven-Month-Old Infants

A fundamental task of language acquisition is to extract abstract algebraic rules. Three experiments show that 7-month-old infants attend longer to sentences with unfamiliar structures than to sentences with familiar structures. The design of the artificial language task used in these experiments ensured that this discrimination could not be performed by counting, by a system that is sensitive only to transitional probabilities, or by a popular class of simple neural network models. Instead, these results suggest that infants can represent, extract, and generalize abstract algebraic rules.

Vascular responses to syntactic processing: event-related fMRI study of relative clauses.

Event‐related functional magnetic resonance imaging was used to investigate the localization of syntactic processing in sentence comprehension. Matched pairs of sentences containing identical lexical items were compared. One member of the pair consisted of a syntactically simpler sentence, containing a subject relativized clause. The second member of the pair consisted of a syntactically more complex sentence, containing an object relativized clause. Ten subjects made plausibility judgments about the sentences, which were presented one word at a time on a computer screen. There was an increase in BOLD hemodynamic signal in response to the presentation of all sentences compared to fixation in both right and left occipital cortex, the left perisylvian cortex, and the left premotor and motor areas. BOLD signal increased in the left angular gyrus when subjects processed the complex portion of syntactically more complex sentences. This study shows that a hemodynamic response associated with processing the syntactically complex portions of a sentence can be localized to one part of the dominant perisylvian association cortex. Hum. Brain Mapping 15:26–38, 2001.

A neurophysiological-metabolic model for burst suppression.

Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia, hypothermia, and in pathological conditions such as coma and early infantile encephalopathy. We propose a unifying mechanism for burst suppression that accounts for all of these conditions. By constructing a biophysical computational model, we show how the prevailing features of burst suppression may arise through the interaction between neuronal dynamics and brain metabolism. In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression. Consequently, the model makes a number of specific predictions of experimental and clinical relevance.

Thalamocortical Mechanisms for the Anteriorization of Alpha Rhythms during Propofol-Induced Unconsciousness

As humans are induced into a state of general anesthesia via propofol, the normal alpha rhythm (8–13 Hz) in the occipital cortex disappears and a frontal alpha rhythm emerges. This spatial shift in alpha activity is called anteriorization. We present a thalamocortical model that suggests mechanisms underlying anteriorization. Our model captures the neural dynamics of anteriorization when we adjust it to reflect two key actions of propofol: its potentiation of GABA and its reduction of the hyperpolarization-activated current Ih. The reduction in Ih abolishes the occipital alpha by silencing a specialized subset of thalamocortical cells, thought to generate occipital alpha at depolarized membrane potentials (>−60 mV). The increase in GABA inhibition imposes an alpha timescale on both the cortical and thalamic portions of the frontal component that are reinforced by reciprocal thalamocortical feedback. Anteriorization can thus be understood as a differential effect of anesthetic drugs on thalamic nuclei with disparate spatial projections, i.e.: (1) they disrupt the normal, depolarized alpha in posterior-projecting thalamic nuclei while (2) they engage a new, hyperpolarized alpha in frontothalamic nuclei. Our model generalizes to other anesthetics that include GABA as a target, since the molecular targets of many such anesthetics alter the model dynamics in a manner similar to that of propofol.

Thalamic model of awake alpha oscillations and implications for stimulus processing

We describe a unique conductance-based model of awake thalamic alpha and some of its implications for function. The full model includes a model for a specialized class of high-threshold thalamocortical cells (HTC cells), which burst at the alpha frequency at depolarized membrane potentials (∼−56 mV). Our model generates alpha activity when the actions of either muscarinic acetylcholine receptor (mAChR) or metabotropic glutamate receptor 1 (mGluR1) agonists on thalamic reticular (RE), thalamocortical (TC), and HTC cells are mimicked. In our model of mGluR1-induced alpha, TC cells are equally likely to fire during any phase of alpha, consistent with in vitro experiments. By contrast, in our model of mAChR-induced alpha, TC cells tend to fire either at the peak or the trough of alpha, depending on conditions. Our modeling suggests that low levels of mGluR1 activation on a background of mAChR agonists may be able to initiate alpha activity that biases TC cells to fire at certain phases of alpha, offering a pathway for cortical control. If we introduce a strong stimulus by increasing the frequency of excitatory postsynaptic potentials (EPSPs) to TC cells, an increase in alpha power is needed to mimic the level of phasing of TC cells observed in vivo. This increased alpha power reduces the probability that TC cells spike near the trough of alpha. We suggest that mAChR-induced alpha may contribute to grouping TC activity into discrete perceptual units for processing, whereas mGluR1-induced alpha may serve the purpose of blocking unwanted stimuli from reaching the cortex.

Brain Rhythms Connect Impaired Inhibition to Altered Cognition in Schizophrenia

In recent years, schizophrenia research has focused on inhibitory interneuron dysfunction at the level of neurobiology and on cognitive impairments at the psychological level. Reviewing both experimental and computational findings, we show how the temporal structure of the activity of neuronal populations, exemplified by brain rhythms, can begin to bridge these levels of complexity. Oscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia.

Activity in the Barrel Cortex During Active Behavior and Sleep

The rate at which neurons fire has wide-reaching implications for the coding schemes used by neural systems. Despite the extensive use of the barrel cortex as a model system, relatively few studies have examined the rate of sensory activity in single neurons in freely moving animals. We examined the activity of barrel cortex neurons in behaving animals during sensory cue interaction, during non-stimulus-related activity, during various states of sleep, and during the administration of isoflurane. The activity of regular-spiking units (RSUs: predominantly excitatory neurons) and fast spiking units (FSUs: a subtype of inhibitory interneurons) was examined separately. We characterized activity by calculating neural firing rates, because several reports have emphasized the low firing rates in this system, reporting that both baseline activity and stimulus evoked activity is <1 Hz. We report that, during sensory cue interaction or non-stimulus-related activity, the majority of RSUs in rat barrel cortex fired at rates significantly >1 Hz, with 27.4% showing rates above 10 Hz during cue interaction. Even during slow wave sleep, which had the lowest mean and median firing rates of any nonanesthetized state observed, 80.0% of RSUs fired above 1 Hz. During all of the nonanesthetized states observed 100% of the FSUs fired well above 1 Hz. When rats were administered isoflurane and at a depth of anesthesia used in standard in vivo electrophysiological preparations, all of the RSUs fired below 1 Hz. We also found that >80% of RSUs either upmodulated or downmodulated their firing during cue interaction. These data suggest that low firing rates do not typify the output of the barrel cortex during awake activity and during sleep and indicate that sensory coding at both the individual and population levels may be nonsparse.

Frontal beta-theta network during REM sleep

We lack detailed knowledge about the spatio-temporal physiological signatures of REM sleep, especially in humans. By analyzing intracranial electrode data from humans, we demonstrate for the first time that there are prominent beta (15–35 Hz) and theta (4–8 Hz) oscillations in both the anterior cingulate cortex (ACC) and the DLPFC during REM sleep. We further show that these theta and beta activities in the ACC and the DLPFC, two relatively distant but reciprocally connected regions, are coherent. These findings suggest that, counter to current prevailing thought, the DLPFC is active during REM sleep and likely interacting with other areas. Since the DLPFC and the ACC are implicated in memory and emotional regulation, and the ACC has motor areas and is thought to be important for error detection, the dialogue between these two areas could play a role in the regulation of emotions and in procedural motor and emotional memory consolidation. DOI: http://dx.doi.org/10.7554/eLife.18894.001

Thalamic Mechanisms Underlying Alpha-Delta Sleep with Implications for Fibromyalgia

Alpha-delta sleep is the abnormal intrusion of alpha activity (8- to 13-Hz oscillations) into the delta activity (1- to 4-Hz oscillations) that defines slow-wave sleep. Alpha-delta sleep is especially prevalent in fibromyalgia patients, and there is evidence suggesting that the irregularities in the sleep of these patients may cause the muscle and tissue pain that characterizes the disorder. We constructed a biophysically realistic mathematical model of alpha-delta sleep. Imaging studies in fibromyalgia patients suggesting altered levels of activity in the thalamus motivated a thalamic model as the source of alpha activity. Since sodium oxybate helps to alleviate the symptoms of fibromyalgia and reduces the amount of alpha-delta sleep in fibromyalgia patients, we examined how changes in the molecular targets of sodium oxybate affected alpha-delta activity in our circuit. Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization-activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity. Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep. Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus; such drugs might have fewer side effects than drugs that act systemically.

The Roles of Sleep–Wake States and Brain Rhythms in Epileptic Seizure Onset

> Epilepsy is an illness of various shapes—and horrible. > > —Aretaeus of Cappadocia, ancient Greek physician ([Temkin, 1994][1]) Epilepsy is a collection of syndromes affecting more than 50 million people worldwide ([Annegers, 2001][2]). Seizures are classified as either generalized or focal