MAO-A and the EEG Recognition Memory Signal in Left Parietal Cortex

A key part of episodic memory, or memory for the events of our lives, is recognition memory. Recognition memory is the ability to remember previously encountered stimuli. Studies have linked recognition memory to the old/new effect, an EEG indicator of stimulus familiarity. Monoamine oxidase A (MAO-A) is an enzyme that catalyzes monoamines, leading to the depletion of norepinephrine, epinephrine, serotonin, and dopamine. MAO-A is more efficiently transcribed in individuals with a 4 repeating sequence variation (4R) of the MAO-A gene leading to less monoamine availability. As many of these monoamines have been linked to episodic memory, we hypothesized that individuals homozygous for the 4R MAO-A polymorphism would show differences in mean EEG signal amplitudes during recognition memory. EEG data was recorded as participants viewed both new words and words that had been previously presented. Our results show that mean peak amplitudes over the left parietal cortex 500-800 ms post-stimulus presentation for hits were greater than those for correct rejections, indicating the old/new effect. Critically, our results revealed an interaction between mean hit and correct rejection amplitude over the left parietal cortex and MAO-A group. Individuals homozygous for the 4R variation (the High MAO-A group) do not show an old/new effect due to increased correct rejection amplitudes. These results suggest that less monoamine availability leads to new stimuli being identified as old by the left parietal cortex

Modeling the effect of dendritic input location on MEG and EEG source dipoles

The cerebral sources of magneto- and electroencephalography (MEG, EEG) signals can be represented by current dipoles. We used computational modeling of realistically shaped passive-membrane dendritic trees of pyramidal cells from the human cerebral cortex to examine how the spatial distribution of the synaptic inputs affects the current dipole. The magnitude of the total dipole moment vector was found to be proportional to the vertical location of the synaptic input. The dipole moment had opposite directions for inputs above and below a reversal point located near the soma. Inclusion of shunting-type inhibition either suppressed or enhanced the current dipole, depending on whether the excitatory and inhibitory synapses were on the same or opposite side of the reversal point. Relating the properties of the macroscopic current dipoles to dendritic current distributions can help to provide means for interpreting MEG and EEG data in terms of synaptic connection patterns within cortical areas.National Center for Research Resources (U.S.) (P41RR14075)National Institutes of Health (U.S.) (Grants NS57500 and NS037462

Intra-Cranial Recordings of Brain Activity During Language Production

Recent findings in the neurophysiology of language production have provided a detailed description of the brain network underlying this behavior, as well as some indications about the timing of operations. Despite their invaluable utility, these data generally suffer from limitations either in terms of temporal resolution, or in terms of spatial localization. In addition, studying the neural basis of speech is complicated by the presence of articulation artifacts such as electro-myographic activity that interferes with the neural signal. These difficulties are virtually absent in a powerful albeit much less frequent methodology, namely the recording of intra-cranial brain activity (intra-cranial electroencephalography). Such recordings are only possible under very specific clinical circumstances requiring functional mapping before brain surgery, most notably in patients that suffer from pharmaco-resistant epilepsy. Here we review the research conducted with this methodology in the field of language production, with explicit consideration of its advantages and drawbacks. The available evidence is shown to be diverse, both in terms of the tasks and the cognitive processes tested and in terms of the brain localizations being studied. Still, the review provides valuable information for characterizing the dynamics of the neural events occurring in the language production network. Following modality specific activities (in auditory or visual cortices), there is a convergence of activity in superior temporal sulcus, which is a plausible neural correlate of phonological encoding processes. Later, between 500 and 800 ms, inferior frontal gyrus (around Broca’s area) is involved. Peri-rolandic areas are recruited in the two modalities relatively early (200–500 ms window), suggesting a very early involvement of (pre-) motor processes. We discuss how some of these findings may be at odds with conclusions drawn from available meta-analysis of language production studies

Activation of the Left Inferior Frontal Gyrus in the First 200 ms of Reading: Evidence from Magnetoencephalography (MEG)

BACKGROUND: It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question. METHODOLOGY/PRINCIPAL FINDINGS: MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100-250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at approximately 130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at approximately 115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at approximately 140 ms, at a location coincident with the fMRI-defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus. CONCLUSIONS/SIGNIFICANCE: These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code

On the Estimation of Population-Specific Synaptic Currents from Laminar Multielectrode Recordings

Multielectrode array recordings of extracellular electrical field potentials along the depth axis of the cerebral cortex are gaining popularity as an approach for investigating the activity of cortical neuronal circuits. The low-frequency band of extracellular potential, i.e., the local field potential (LFP), is assumed to reflect synaptic activity and can be used to extract the laminar current source density (CSD) profile. However, physiological interpretation of the CSD profile is uncertain because it does not disambiguate synaptic inputs from passive return currents and does not identify population-specific contributions to the signal. These limitations prevent interpretation of the CSD in terms of synaptic functional connectivity in the columnar microcircuit. Here we present a novel anatomically informed model for decomposing the LFP signal into population-specific contributions and for estimating the corresponding activated synaptic projections. This involves a linear forward model, which predicts the population-specific laminar LFP in response to synaptic inputs applied at different positions along each population and a linear inverse model, which reconstructs laminar profiles of synaptic inputs from laminar LFP data based on the forward model. Assuming spatially smooth synaptic inputs within individual populations, the model decomposes the columnar LFP into population-specific contributions and estimates the corresponding laminar profiles of synaptic input as a function of time. It should be noted that constant synaptic currents at all positions along a neuronal population cannot be reconstructed, as this does not result in a change in extracellular potential. However, constraining the solution using a priori knowledge of the spatial distribution of synaptic connectivity provides the further advantage of estimating the strength of active synaptic projections from the columnar LFP profile thus fully specifying synaptic inputs

Right hemisphere has the last laugh: neural dynamics of joke appreciation

Understanding a joke relies on semantic, mnemonic, inferential, and emotional contributions from multiple brain areas. Anatomically constrained magnetoencephalography (aMEG) combining high-density whole-head MEG with anatomical magnetic resonance imaging allowed us to estimate where the humor-specific brain activations occur and to understand their temporal sequence. Punch lines provided either funny, not funny (semantically congruent), or nonsensical (incongruent) replies to joke questions. Healthy subjects rated them as being funny or not funny. As expected, incongruous endings evoke the largest N400m in left-dominant temporo-prefrontal areas, due to integration difficulty. In contrast, funny punch lines evoke the smallest N400m during this initial lexical–semantic stage, consistent with their primed “surface congruity” with the setup question. In line with its sensitivity to ambiguity, the anteromedial prefrontal cortex may contribute to the subsequent “second take” processing, which, for jokes, presumably reflects detection of a clever “twist” contained in the funny punch lines. Joke-selective activity simultaneously emerges in the right prefrontal cortex, which may lead an extended bilateral temporo-frontal network in establishing the distant unexpected creative coherence between the punch line and the setup. This progression from an initially promising but misleading integration from left frontotemporal associations, to medial prefrontal ambiguity evaluation and right prefrontal reprocessing, may reflect the essential tension and resolution underlying humor

Extracting Spatiotemporal Word and Semantic Representations from Multiscale Neurophysiological Recordings in Humans

With the recent advent of neuroimaging techniques, the majority of the research studying the neural basis of language processing has focused on the localization of various lexical and semantic functions. Unfortunately, the limited time resolution of functional neuroimaging prevents a detailed analysis of the dynamics involved in word recognition, and the hemodynamic basis of these techniques prevents the study of the underlying neurophysiology. Compounding this problem, current techniques for the analysis of high-dimensional neural data are mainly sensitive to large effects in a small area, preventing a thorough study of the distributed processing involved for representing semantic knowledge. This thesis demonstrates the use of multivariate machine-learning techniques for the study of the neural representation of semantic and speech information in electro/magneto-physiological recordings with high temporal resolution. Support vector machines (SVMs) allow for the decoding of semantic category and word-specific information from non-invasive electroencephalography (EEG) and magnetoenecephalography (MEG) and demonstrate the consistent, but spatially and temporally distributed nature of such information. Moreover, the anteroventral temporal lobe (avTL) may be important for coordinating these distributed representations, as supported by the presence of supramodal category-specific information in intracranial recordings from the avTL as early as 150ms after auditory or visual word presentation. Finally, to study the inputs to this lexico-semantic system, recordings from a high density microelectrode array in anterior superior temporal gyrus (aSTG) are obtained, and the recorded spiking activity demonstrates the presence of single neurons that respond specifically to speech sounds. The successful decoding of word identity from this firing rate information suggests that the aSTG may be involved in the population coding of acousto-phonetic speech information that is likely on the pathway for mapping speech-sounds to meaning in the avTL. The feasibility of extracting semantic and phonological information from multichannel neural recordings using machine learning techniques provides a powerful method for studying language using large datasets and has potential implications for the development of fast and intuitive communication prostheses.Engineering and Applied Science

What influences the accessibility of conceptual knowledge? Evidence from Experimental Psychology, Neuropsychology and Brain Stimulation

Previous studies have shown that accessibility of conceptual information declines when sets of semantically-related items are presented repeatedly, although the underlying basis of this effect is debated – it is unclear if comprehension can decline without massed repetition of individual items, or if this effect is restricted to lexical retrieval in picture naming. Furthermore, declining comprehension has been characterised as arising from both ‘too much activation’ (i.e., on-going strong activation of competitors) and ‘too much inhibition’ (i.e., a failure to overcome inhibition which may facilitate the earlier retrieval of semantically-related targets). The thesis explored the impact of experimental manipulations (speed of presentation; strength of association between category and target item; modality of presentation; type of semantic decision required), on the magnitude of declining comprehension in healthy young adults. Comprehension declined even without individual item repetition, especially for strongly-associated targets (which may have accrued more competition or inhibition). The effect was found irrespective of presentation modality and more strongly at fast presentation speeds (when there was less time to overcome competition/inhibition). Next, the thesis examined the impact of ageing and semantic aphasia on changes in comprehension within the continuous categorisation paradigm. In these populations, controlled retrieval of conceptual information is thought to be weakened (relative to younger adults and healthy controls without aphasia). This should exaggerate declines in comprehension that reflect difficulty overcoming competition, but reduce the effect if it arises from the inhibition of competitors on earlier trials. The results were in line with the second hypothesis, since older adults and patients with semantic aphasia maintained their performance throughout the categories, unlike younger adults. Lastly, the thesis examined how this effect is modulated by transcranial electrical stimulation delivered to a key brain region implicated in semantic control – left inferior frontal gyrus (LIFG). Stimulation of LIFG attenuated the effect of declining comprehension, perhaps because initial retrieval was facilitated (potentially reducing the inhibition of related information), and/or because subsequent target selection was strengthened. Together, these results provide a more comprehensive account of what drives declining performance in continuous categorisation in healthy young adults who have the capacity to strongly engage semantic control