Ian E. Holliday

A specific and rapid neural signature for parental instinct.

Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of ones own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG) in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC), an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA). In mOFC the first significant peak (p<0.001) in differences in power between infant and adult faces was found at around 130 ms in the 10–15 Hz band. These early differences were not found in the FFA. In contrast, differences in power were found later, at around 165 ms, in a different band (20–25 Hz) in the right FFA, suggesting a feedback effect from mOFC. These findings provide evidence in humans of a potential brain basis for the “innate releasing mechanisms” described by Lorenz for affection and nurturing of young infants. This has potentially important clinical applications in relation to postnatal depression, and could provide opportunities for early identification of families at risk.

Visual word recognition: the first half second.

We used magnetoencephalography (MEG) to map the spatiotemporal evolution of cortical activity for visual word recognition. We show that for five-letter words, activity in the left hemisphere (LH) fusiform gyrus expands systematically in both the posterior-anterior and medial-lateral directions over the course of the first 500 ms after stimulus presentation. Contrary to what would be expected from cognitive models and hemodynamic studies, the component of this activity that spatially coincides with the visual word form area (VWFA) is not active until around 200 ms post-stimulus, and critically, this activity is preceded by and co-active with activity in parts of the inferior frontal gyrus (IFG, BA44/6). The spread of activity in the VWFA for words does not appear in isolation but is co-active in parallel with spread of activity in anterior middle temporal gyrus (aMTG, BA 21 and 38), posterior middle temporal gyrus (pMTG, BA37/39), and IFG.

Induced visual illusions and gamma oscillations in human primary visual cortex

Using magnetoencephalography, we studied the spatiotemporal properties of cortical responses in terms of event‐related synchronization and event‐related desynchronization to a range of stripe patterns in subjects with no neurological disorders. These stripes are known for their tendency to induce a range of abnormal sensations, such as illusions, nausea, dizziness, headache and attacks of pattern‐sensitive epilepsy. The optimal stimulus must have specific physical properties, and maximum abnormalities occur at specific spatial frequency and contrast. Despite individual differences in the severity of discomfort experienced, psychophysical studies have shown that most observers experience some degree of visual anomaly on viewing such patterns. In a separate experiment, subjects reported the incidence of illusions and discomfort to each pattern. We found maximal cortical power in the gamma range (30–60 Hz) confined to the region of the primary visual cortex in response to patterns of 2–4 cycles per degree, peaking at 3 cycles per degree. This coincides with the peak of mean illusions and discomfort, also maximal for patterns of 2–4 cycles per degree. We show that gamma band activity in V1 is a narrow band function of spatial frequency. We hypothesize that the intrinsic properties of gamma oscillations may underlie visual discomfort and play a role in the onset of seizures.

Localization and Functional Analysis of Human Cortical Area V5 Using Magneto-Encephalography

Using a multi-channel SQUID-based neuromagnetometer, we have determined the location, temporal dynamics and functional response properties of the human homologue of the primate cortical area V5 (MT). We provide evidence that area V5 in humans is located near the occipito-temporal border in a minor sulcus immediately below the superior temporal sulcus. This area is selective for low spatial frequencies ( ≤4.0 c/deg), responds to a wide range of temporal frequencies ( ≤ 35 Hz) and shows response saturation for stimulus contrasts greater than 10%. In addition, we find that this area is not responsive to purely chromatic patterns but is responsive to motion-contrast stimuli. Our results are consistent with the hypothesis that area V5 in humans represents a stage of processing within the magnocellular pathway. We discuss our results in relation to the widespread belief that area V5 in humans is specifically concerned with motion perception.

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 ∼130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at ∼115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at ∼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.

Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching

OBJECTIVE To introduce a new technique for co-registration of Magnetoencephalography (MEG) with magnetic resonance imaging (MRI). We compare the accuracy of a new bite-bar with fixed fiducials to a previous technique whereby fiducial coils were attached proximal to landmarks on the skull. METHODS A bite-bar with fixed fiducial coils is used to determine the position of the head in the MEG co-ordinate system. Co-registration is performed by a surface-matching technique. The advantage of fixing the coils is that the co-ordinate system is not based upon arbitrary and operator dependent fiducial points that are attached to landmarks (e.g. nasion and the preauricular points), but rather on those that are permanently fixed in relation to the skull. RESULTS As a consequence of minimizing coil movement during digitization, errors in localization of the coils are significantly reduced, as shown by a randomization test. Displacement of the bite-bar caused by removal and repositioning between MEG recordings is minimal ( approximately 0.5 mm), and dipole localization accuracy of a somatosensory mapping paradigm shows a repeatability of approximately 5 mm. The overall accuracy of the new procedure is greatly improved compared to the previous technique. CONCLUSIONS The test-retest reliability and accuracy of target localization with the new design is superior to techniques that incorporate anatomical-based fiducial points or coils placed on the circumference of the head.

Assessing interactions of linear and nonlinear neuronal sources using MEG beamformers : a proof of concept

OBJECTIVE This study aimed to explore methods of assessing interactions between neuronal sources using MEG beamformers. However, beamformer methodology is based on the assumption of no linear long-term source interdependencies [VanVeen BD, vanDrongelen W, Yuchtman M, Suzuki A. Localization of brain electrical activity via linearly constrained minimum variance spatial filtering. IEEE Trans Biomed Eng 1997;44:867-80; Robinson SE, Vrba J. Functional neuroimaging by synthetic aperture magnetometry (SAM). In: Recent advances in Biomagnetism. Sendai: Tohoku University Press; 1999. p. 302-5]. Although such long-term correlations are not efficient and should not be anticipated in a healthy brain [Friston KJ. The labile brain. I. Neuronal transients and nonlinear coupling. Philos Trans R Soc Lond B Biol Sci 2000;355:215-36], transient correlations seem to underlie functional cortical coordination [Singer W. Neuronal synchrony: a versatile code for the definition of relations? Neuron 1999;49-65; Rodriguez E, George N, Lachaux J, Martinerie J, Renault B, Varela F. Perceptions shadow: long-distance synchronization of human brain activity. Nature 1999;397:430-3; Bressler SL, Kelso J. Cortical coordination dynamics and cognition. Trends Cogn Sci 2001;5:26-36]. METHODS Two periodic sources were simulated and the effects of transient source correlation on the spatial and temporal performance of the MEG beamformer were examined. Subsequently, the interdependencies of the reconstructed sources were investigated using coherence and phase synchronization analysis based on Mutual Information. Finally, two interacting nonlinear systems served as neuronal sources and their phase interdependencies were studied under realistic measurement conditions. RESULTS Both the spatial and the temporal beamformer source reconstructions were accurate as long as the transient source correlation did not exceed 30-40 percent of the duration of beamformer analysis. In addition, the interdependencies of periodic sources were preserved by the beamformer and phase synchronization of interacting nonlinear sources could be detected. CONCLUSIONS MEG beamformer methods in conjunction with analysis of source interdependencies could provide accurate spatial and temporal descriptions of interactions between linear and nonlinear neuronal sources. SIGNIFICANCE The proposed methods can be used for the study of interactions between neuronal sources.

Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography (MEG)

The aim of this study was to use the technique of magnetoencephalography (MEG) to determine the effects of strabismic amblyopia on the processing of spatial information within the occipital cortex of humans. We recorded evoked magnetic responses to the onset of a chromatic (red/green) sinusoidal grating of periodicity 0.5-4.0 c deg-1 using a 19-channel SQUID-based neuromagnetometer. Evoked responses were recorded monocularly on six amblyopes and six normally-sighted controls, the stimuli being positioned near the fovea in the lower right visual field of each observer. For comparison, the spatial contrast sensitivity function (CSF) for the detection of chromatic gratings was measured for one amblyope and one control using a two alternate forced-choice psychophysical procedure. We chose red/green sinusoids as our stimuli because they evoke strong magnetic responses from the occipital cortex in adult humans (Fylan, Holliday, Singh, Anderson & Harding. (1997). Neuroimage, 6, 47-57). Magnetic field strength was plotted as a function of stimulus spatial frequency for each eye of each subject. Interocular differences were only evident within the amblyopic group: for stimuli of 1-2 c deg-1, the evoked responses had significantly longer latencies and reduced amplitudes through the amblyopic eye (P < 0.05). Importantly, the extent of the deficit was uncorrelated with either Snellen acuity or contrast sensitivity. Localization of the evoked responses was performed using a single equivalent current dipole model. Source localizations, for both normal and amblyopic subjects, were consistent with neural activity at the occipital pole near the V1/V2 border. We conclude that MEG is sensitive to the deficit in cortical processing associated with human amblyopia, and can be used to make quantitative neurophysiological measurements. The nature of the cortical deficit is discussed.

Attentional shifting and the role of the dorsal pathway in visual word recognition

A substantial amount of evidence has been collected to propose an exclusive role for the dorsal visual pathway in the control of guided visual search mechanisms, specifically in the preattentive direction of spatial selection [Vidyasagar, T. R. (1999). A neuronal model of attentional spotlight: Parietal guiding the temporal. Brain Research and Reviews, 30, 66-76; Vidyasagar, T. R. (2001). From attentional gating in macaque primary visual cortex to dyslexia in humans. Progress in Brain Research, 134, 297-312]. Moreover, it has been suggested recently that the dorsal visual pathway is specifically involved in the spatial selection and sequencing required for orthographic processing in visual word recognition. In this experiment we manipulate the demands for spatial processing in a word recognition, lexical decision task by presenting target words in a normal spatial configuration, or where the constituent letters of each word are spatially shifted relative to each other. Accurate word recognition in the Shifted-words condition should demand higher spatial encoding requirements, thereby making greater demands on the dorsal visual stream. Magnetoencephalographic (MEG) neuroimaging revealed a high frequency (35-40Hz) right posterior parietal activation consistent with dorsal stream involvement occurring between 100 and 300ms post-stimulus onset, and then again at 200-400ms. Moreover, this signal was stronger in the shifted word condition, compared to the normal word condition. This result provides neurophysiological evidence that the dorsal visual stream may play an important role in visual word recognition and reading. These results further provide a plausible link between early stage theories of reading, and the magnocellular-deficit theory of dyslexia, which characterises many types of reading difficulty.

Evaluation of MRI-MEG/EEG co-registration strategies using Monte Carlo simulation

We present a Monte Carlo analysis method for evaluating MRI-MEG/EEG co-registration techniques. The method estimates the error in co-registration as a function of position within the brain. Using this analysis technique, we demonstrate the limitations of conventional head-based fiducial point methods, and propose a new strategy utilising a dental bite-bar incorporating accurately machined fiducial markers. Results presented demonstrate the improved accuracy of MEG/EEG to MRI co-registration using the bite-bar.