Neuronal activity in the human lateral temporal lobe. II. Responses to the subjects own voice.

We have recorded neuronal responses in the lateral temporal lobe of man to overt speech during open brain surgery for epilepsy. Tests included overt naming of objects and reading words or short sentences shown on a projector screen, repetition of tape recorded words or sentences presented over a loudspeaker, and free conversation. Neuronal activity in the dominant and non-dominant temporal lobe were about equally affected by overt speech. As during listening to language (see Creutzfeldt et al. 1989), responses differed between recordings from sites in the superior and the middle or inferior temporal gyrus. In the superior temporal gyrus all neurons responded clearly and each in a characteristic manner. Activation could be related to phonemic aspects, to segmentation or to the length of spoken words or sentences. However, neurons were mostly differently affected by listening to words and language as compared to overt speaking. In neuronal populations recorded simultaneously with one or two microelectrodes, some neurons responded predominantly to one or the other type of speech. Excitatory responses during overt speaking were always auditory. In the middle temporal gyrus more neurons (about 2/3) responded to overt speaking than to listening alone. Activations elicited during overt speech were seen in about 1/3 of our sample, but they were more sluggish than those recorded in the superior gyrus. A prominent feature was suppression of on-going activity, which we found in about 1/3 of middle and in some superior temporal gyrus neurons. This suppression could preced vocalization by up to a few hundred ms, and could outlast it by up to 1 s. Evoked ECoG-potentials to words heard or spoken were different, and those to overt speech were more widespread

Neuronal activity in the human lateral temporal lobe. I. Responses to speech.

Single and multiple unit neuronal activity was recorded from the cortex of the lateral temporal lobe in conscious humans during open brain surgery for the treatment of epilepsy. Recordings were obtained from the right and left superior, middle and inferior temporal gyrus of 34 patients (41 recording sites). Recordings were restricted to regions to be resected during subsequent surgery. This excluded recordings from language areas proper. Neuronal responses to words and sentences presented over a loudspeaker and during free conversation were recorded. No significant differences between the right and left hemisphere were obvious. All neurons in the superior temporal gyrus responded to various aspects of spoken language with temporally well defined activation/inhibition patterns, but not or only little to non-linguistic noises or tones. Excitatory responses were typically short or prolonged (up to several hundred ms) bursts of discharges at rates above 20/sec, reaching peak rates of 50–100/s. Such responses could be specifically related to certain combinations of consonants suggesting a function in categorization, they could depend on word length, could differentiate between polysyllabic and compound words of the same length or could be unspecifically related to language as such. No formant specific responses were found, but the prolonged excitations across syllables suggest that consonant/vowel combinations may play a role for some activation patterns. Responses of some neurons (or neuronal populations) depended on the attention paid to the words and sentences, or the task connected with them (repeat words, speech addressed to the patient demanding something). Neurons in the middle and inferior temporal gyrus were only little affected by listening to single words or sentences, but some were unspecifically activated by words or while listening to sentences. Excitatory responses varied within a limited range of discharge rates usually below 5–10/s. Phonetic distortion of spoken language could reduce responses in superior temporal gyrus neurons, but also the slight changes in discharge rate of middle temporal neurons could be absent during distorted and uncomprehensible speech sounds. We conclude that superior temporal gyrus neuron responses reflect some general phonetic but not semantic aspects of spoken language. Middle and inferior temporal gyrus neurons do not signal phonetic aspects of language, but may be involved in understanding language under certain conditions

The interpretation of mu suppression as an index of mirror neuron activity: past, present and future

Mu suppression studies have been widely used to infer the activity of the human mirror neuron system (MNS) in a number of processes, ranging from action understanding, language, empathy and the development of autism spectrum disorders (ASDs). Although mu suppression is enjoying a resurgence of interest, it has a long history. This review aimed to revisit mu’s past, and examine its recent use to investigate MNS involvement in language, social processes and ASDs. Mu suppression studies have largely failed to produce robust evidence for the role of the MNS in these domains. Several key potential shortcomings with the use and interpretation of mu suppression, documented in the older literature and highlighted by more recent reports, are explored here

Self-organization and the selection of pinwheel density in visual cortical development

Self-organization of neural circuitry is an appealing framework for understanding cortical development, yet its applicability remains unconfirmed. Models for the self-organization of neural circuits have been proposed, but experimentally testable predictions of these models have been less clear. The visual cortex contains a large number of topological point defects, called pinwheels, which are detectable in experiments and therefore in principle well suited for testing predictions of self-organization empirically. Here, we analytically calculate the density of pinwheels predicted by a pattern formation model of visual cortical development. An important factor controlling the density of pinwheels in this model appears to be the presence of non-local long-range interactions, a property which distinguishes cortical circuits from many nonliving systems in which self-organization has been studied. We show that in the limit where the range of these interactions is infinite, the average pinwheel density converges to $\pi$. Moreover, an average pinwheel density close to this value is robustly selected even for intermediate interaction ranges, a regime arguably covering interaction-ranges in a wide range of different species. In conclusion, our paper provides the first direct theoretical demonstration and analysis of pinwheel density selection in models of cortical self-organization and suggests to quantitatively probe this type of prediction in future high-precision experiments.Comment: 22 pages, 3 figure

Designing Irreversible Inhibitors—Worth the Effort?

This is the peer-reviewed version of the following article: González-Bello, C. (2016). Designing Irreversible Inhibitors-Worth the Effort?. Chemmedchem, 11(1), 22-30, which has been published in final form at https://doi.org/10.1002/cmdc.201500469. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingDespite the unquestionable success of numerous irreversible drugs that are currently in clinical use, such as acetylsalicylic acid (Aspirin) and penicillin, the number of such approved drugs is much lower than that of noncovalent drugs. Over the years, the potential off‐target effects of these types of compounds have been the primary concern that has hampered their development. However, their remarkable advantages over noncovalent drugs and a better analysis of the risks have decreased the widespread skepticism surrounding them. The design of irreversible inhibitors is a challenge, particularly considering that in some cases their efficacy is due to complex and unexpected mechanisms of action. In this review the main advantages of irreversible inhibition are summarized, and the complexity of certain covalent modification mechanisms is highlighted with selected examplesSpanish Ministry of Economy and Competitiveness. Grant Number: SAF2013-42899-R Xunta de Galicia. Grant Number: GRC2013-041 European Regional Development Fund (ERDF)S