Visual restoration in cortical blindness: insights from natural and TMS-induced blindsight

Unilateral damage to visual cortex of the parietal or occipital lobe can cause the patient to be unaware of contralesional visual information due to either hemispatial neglect or hemianopia. It is now known that both neglect and hemianopia result from the disruption of a dynamic interaction between cortical visual pathways and more phylogenetically primitive visual pathways to the midbrain. We consider the therapeutic implications of these cortical-subcortical interactions in the rehabilitation of hemianopia. We start with the pheonmenon of "blindsight", in which patients with hemianopia can be shown, by implicit measures of visual detection or discrimination, to process visual information without conscious awareness. Some variants of blindsight have been postulated to recruit subcortical processes, while others may reflect compensatory optimisation of processing of spared visual cortex. Both mechanisms may offer opportunities for innovative strategies for rehabilitation of visual field defects. We relate the neural mechanisms that have been proposed to underlie blindsight to those that have been suggested to underlie the recovery of visual function after rehabilitation. It is suggested that the similarity and overlap of the neural processes supporting blindsight and recovery of visual function might provide insights for effective rehabilitation strategies for restoring visual functions.     

Intensity modulation of TMS-induced cortical excitation: primary motor cortex

The intensity dependence of the local and remote effects of transcranial magnetic stimulation (TMS) on human motor cortex was characterized using positron-emission tomography (PET) measurements of regional blood flow (BF) and concurrent electromyographic (EMG) measurements of the motor-evoked potential (MEP). Twelve normal volunteers were studied by applying 3 Hz TMS to the hand region of primary motor cortex (M1(hand)). Three stimulation intensities were used: 75%, 100%, and 125% of the motor threshold (MT). MEP amplitude increased nonlinearly with increasing stimulus intensity. The rate of rise in MEP amplitude was greater above MT than below. The hemodynamic response in M1(hand) was an increase in BF. Hemodynamic variables quantified for M1(hand) included value-normalized counts (VNC), intensity (z-score), and extent (mm(3)). All three hemodynamic response variables increased nonlinearly with stimulus intensity, closely mirroring the MEP intensity-response function. VNC was the hemodynamic response variable which showed the most significant effect of TMS intensity. VNC correlated strongly with MEP amplitude, both within and between subjects. Remote regions showed varying patterns of intensity response, which we interpret as reflecting varying levels of neuronal excitability and/or functional coupling in the conditions studied.     

Retinotopic modulation of space misrepresentation in unilateral neglect: evidence from quadrantanopia

A patient with right sided brain damage suffered contralesional neglect, inferior quadrantanopia (with 0 degrees sparing in the left eye and 13 degrees sparing in the right), and a visual field restriction (to 15 degrees ) in the upper contralesional quadrant of the left eye. In binocular vision, the patient showed underestimation of the horizontal size of contralesional line segments unless cued to localise their end points. When asked to reproduce, in monocular vision, 10 degrees and 20 degrees distances between two attentionally cued end points lying on the frontal vertical plane, the patient showed relative contralesional overextension and ipselesional underextension along the directions falling within the blind sectors of the neglected space. No asymmetry was present along the directions falling within the seeing sectors of the same space. These findings suggest precise retinotopic modulation of space misrepresentation in unilateral neglect.     

Inhibition of auditory cortical responses to ipsilateral stimuli during dichotic listening: evidence from magnetoencephalography

The present magnetoencephalography (MEG) study on auditory evoked magnetic fields (AEFs) was aimed at verifying whether during dichotic listening the contralateral auditory pathway inhibits the ipsilateral one, as suggested by behavioural and patient studies. Ten healthy subjects were given a randomized series of three complex tones (261, 293 and 391 Hz, 500 ms duration), which were delivered monotically and dichotically with different intensities [60, 70 or 80 dBA (audio decibels)]. MEG data were recorded from the right auditory cortex. Results showed that the M100 amplitude over the right auditory cortex increased progressively when tones of increasing intensity were provided at the ipsilateral (right) ear. This effect on M100 was abolished when a concurrent tone of constant intensity was delivered dichotically at the contralateral (left) ear, suggesting that the contralateral pathway inhibited the ipsilateral one. The ipsilateral inhibition was present only when the contralateral tone fundamental frequency was similar to the ipsilateral tone. It was proposed that the occlusion mechanism would be exerted in cortical auditory areas as the dichotic effects were observed at M100 but not M50 component. This is the first evidence showing a neurophysiological inhibition driven by the contralateral auditory pathway over the ipsilateral one during dichotic listening.     

Retinotopic mapping reveals extrastriate cortical basis of homonymous quadrantanopia

It has been conventionally assumed that cortically based quadrantic visual field deficits (homonymous quadrantanopias) are caused by lesions in striate cortex (V1), extending precisely to the horizontal meridian representation. A more recent model, supported by anatomic MRI evidence, consists of an exclusively extrastriate cortical basis (e.g. V2, V3, VP, V4v). Employing fMRI, we sought to distinguish between these models through retinotopic mapping of a patient with an upper right homonymous quadrantanopia. As expected, maps of the lower right quadrant and left hemifield were normal. The map corresponding to the impaired upper right quadrant was normal in V1 and V2, with little or no activity in VP and V4v. These results provide functional evidence that extrastriate cortical lesions can elicit homonymous quadrantanopias.     

The spatial representation of numerical and non-numerical sequences: evidence from neglect

Psychophysical and neuropsychological studies have revealed that humans represent numbers along a continuous, left-to-right oriented mental line. However, it has been recently claimed that this format of representation is not special to numbers because non-numerical sequences would be spatially coded in the same way. To test this hypothesis, the present study investigated the effects of left neglect upon the bisection of numerical and non-numerical intervals. Eight patients with left neglect performed a visual line bisection task and three mental bisection tasks with number, letter, and month intervals. The error pattern in the number bisection task, indexed by the modulating effect of interval length, mirrored that of the visual task and confirmed the left-to-right spatial orientation of the mental number line. In contrast, the bisection of non-numerical intervals showed a very different pattern. The results suggest that the spatial layout characterizing numerical representations constitutes a specific property of numbers rather than a general characteristic of ordered sequences.     

The representation of polysemy: MEG evidence

Most words in natural language are polysemous, that is, they can be used in more than one way. For example, paper can be used to refer to a substance made out of wood pulp or to a daily publication printed on that substance. Although virtually every sentence contains polysemy, there is little agreement as to how polysemy is represented in the mental lexicon. Do different uses of polysemous words involve access to a single representation or do our minds store distinct representations for each different sense? Here we investigated priming between senses with a combination of behavioral and magnetoencephalographic measures in order to test whether different senses of the same word involve identity or mere formal and semantic similarity. Our results show that polysemy effects are clearly distinct from similarity effects bilaterally. In the left hemisphere, sense-relatedness elicited shorter latencies of the M350 source, which has been hypothesized to index lexical activation. Concurrent activity in the right hemisphere, on the other hand, peaked later for sense-related than for unrelated target stimuli, suggesting competition between related senses. The obtained pattern of results supports models in which the representation of polysemy involves both representational identity and difference: Related senses connect to same abstract lexical representation, but are distinctly listed within that representation.     

The representation of homophones: more evidence from the remediation of anomia

This paper compares two theoretical positions regarding the mental representation of homophones: first, that homophones have one phonological word form but two grammatical representations (lemmas, e.g., Levelt et al., 1999; Dell, 1990), or second, that they have two separate phonological word forms (e.g., Caramazza et al., 2001). The adequacy of these two theoretical accounts for explaining the pattern of generalisation obtained in the treatment of homophone naming in aphasia is investigated. Two single cases are presented, where phonological treatment techniques are used to improve word retrieval. Treatment comprised picture naming of one member of a homophone pair using a phonological cueing hierarchy. A significant improvement in word retrieval was found for both the treated and the untreated homophones, while there was no improvement for phonologically and semantically related controls. It is argued that the data support a shared representation for homophones at the word form level. However, current theories cannot explain the pattern of generalisation found without the addition of a mechanism for repetition priming (e.g., suggested by Wheeldon and Monsell, 1992) and feedback between word form and lemmas to explain the results.     

The representation of lexical-syntactic information: evidence from syntactic and lexical retrieval impairments in aphasia

This study explored lexical-syntactic information - syntactic information that is stored in the lexicon - and its relation to syntactic and lexical impairments in aphasia. We focused on two types of lexical-syntactic information: predicate argument structure (PAS) of verbs (the number and types of arguments the verb selects) and grammatical gender of nouns. The participants were 17 Hebrew-speaking individuals with aphasia who had a syntactic deficit (agrammatism) or a lexical retrieval deficit (anomia) located at the semantic lexicon, the phonological output lexicon, or the phonological output buffer. After testing the participants' syntactic and lexical retrieval abilities and establishing the functional loci of their deficits, we assessed their PAS and grammatical gender knowledge. This assessment included sentence completion, sentence production, sentence repetition, and grammaticality judgment tasks. The participants' performance on these tests yielded several important dissociations. Three agrammatic participants had impaired syntax but unimpaired PAS knowledge. Three agrammatic participants had impaired syntax but unimpaired grammatical gender knowledge. This indicates that lexical-syntactic information is represented separately from syntax, and can be spared even when syntax at the sentence level, such as embedding and movement are impaired. All 5 individuals with phonological output buffer impairment and all 3 individuals with phonological output lexicon impairment had preserved lexical-syntactic knowledge. These selective impairments indicate that lexical-syntactic information is represented at a lexical stage prior to the phonological lexicon and the phonological buffer. Three participants with impaired PAS (aPASia) and impaired grammatical gender who showed intact lexical-semantic knowledge indicate that the lexical-syntactic information is represented separately from the semantic lexicon. This led us to conclude that lexical-syntactic information is stored in a separate syntactic lexicon. A double dissociation between PAS and grammatical gender impairments indicated that different types of lexical-syntactic information are represented separately in this syntactic lexicon.     

Anatomy of macaque fovea and spatial densities of neurons in foveal representation

Fine visual sampling in the macaque depends on the high density of cone outer and inner segments in the fovea. Cone pedicles, at the opposite, presynaptic end of the cone, are absent from the center of the fovea. Both ends of the cones, inner segments and pedicles, are closely packed within their respective monolayers, but the spatial density of foveal pedicles is lower because foveal pedicles are wider than inner segments. Because there is one pedicle for every inner segment, and because pedicles are wider than inner segments, increase in eccentricity finds increasing lateral displacement of the cone's pedicle from its inner segment. Further increase of eccentricity finds inner segment density falling below pedicle density, and so this lateral displacement declines. By 2-3 mm from the center, inner segments catch up with pedicles. Additional lateral displacements, of bipolar cells from pedicles and ganglion from bipolar cells, are largest for central-most elements and fall steeply with eccentricity. By taking into account all of these lateral displacements, the eccentricity of the cone inner segment(s) associated with a ganglion cell was determined, as was the area of inner segments represented by a unit area in the ganglion cell layer. Then raw ganglion cell densities were transformed to densities comparable to densities of inner segments and of cells in dorsal lateral geniculate nucleus. On average there appears to be close to 2 ganglion cells for each cone in the central fovea out to about 2.5 degrees. Thus, the density of foveal ganglion cells is sufficient to allow each red and each green cone to connect to 2 midget ganglion cells, and each blue cone to connect to 1 ganglion cell. Furthermore, there appears to be a single dorsal lateral geniculate cell for each ganglion cell.     

Unseen stimuli modulate conscious visual experience: evidence from inter-hemispheric summation

Emotional facial expression can be discriminated despite extensive lesions of striate cortex. Here we report differential performance with recognition of facial stimuli in the intact visual field depending on simultaneous presentation of congruent or incongruent stimuli in the blind field. Three experiments were based on inter-hemispheric summation. Redundant stimulation in the blind field led to shorter latencies for stimulus detection in the intact field. Recognition of the expression of a half-face expression in the intact field was faster when the other half of the face presented to the blind field had a congruent expression. Finally, responses to the expression of whole faces to the intact field were delayed for incongruent facial expressions presented in the blind field. These results indicate that the neuro-anatomical pathways (extra-striate cortical and sub-cortical) sustaining inter-hemispheric summation can operate in the absence of striate cortex.     

Dissociation of lexical syntax and semantics: evidence from focal cortical degeneration

The question of whether information relevant to meaning (semantics) and structure (syntax) relies on a common language processor or on separate subsystems has proved difficult to address definitively because of the confounds involved in comparing the two types of information. At the sentence level syntactic and semantic judgments make different cognitive demands, while at the single word level, the most commonly used syntactic distinction (between nouns and verbs) is confounded with a fundamental semantic difference (between objects and actions). The present study employs a different syntactic contrast (between count nouns and mass nouns), which is crossed with a semantic difference (between naturally occurring and man-made substances) applying to words within a circumscribed semantic field (foodstuffs). We show, first, that grammaticality judgments of a patient with semantic dementia are indistinguishable from those of a group of age-matched controls, and are similar regardless of the status of his semantic knowledge about the item. In a second experiment we use the triadic task in a group of age-matched controls to show that similarity judgments are influenced not only by meaning (natural vs. manmade), but also implicitly by syntactic information (count vs. mass). Using the same task in a patient with semantic dementia we show that the semantic influences on the syntactic dimension are unlikely to account for this pattern in normals. These data are discussed in relation to modular vs. nonmodular models of language processing, and in particular to the semantic-syntactic distinction.     

Dissociation of action and object naming: evidence from cortical stimulation mapping

This cortical stimulation mapping study investigates the neural representation of action and object naming. Data from 13 neurosurgical subjects undergoing awake cortical mapping is presented. Our findings indicate clear evidence of differential disruption of noun and verb naming in the context of this naming task. At the individual level, evidence was found for punctuate regions of perisylvian cortex subserving noun and verb function. Across subjects, however, the location of these sites varied. This finding may help explain discrepancies between lesion and functional imaging studies of noun and verb naming. In addition, an alternative coding of these data served to highlight the grammatical class vulnerability of the target response. The use of this coding scheme implicates a role for the supramarginal gyrus in verb-naming behavior. These data are discussed with respect to a functional-anatomical pathway underlying verb naming.     

Non-linear input-output properties of the cortical networks mediating TMS-induced short-interval intracortical inhibition in humans

The effects of transcranial magnetic stimulation (TMS) on post-discharge histograms of single motor units in the first dorsal interosseous have been tested to estimate the input-output properties of cortical network-mediating short-interval intracortical inhibition (SICI) to pyramidal cells of the human primary motor cortex. SICI was studied using the paired pulse paradigm (2-ms interval): test TMS intensity was varied to evoke peaks of different size in post-discharge histograms, reflecting the corticospinal excitatory post-synaptic potential in the relevant spinal motoneuron, and conditioning TMS intensity was constant (0.6 × the resting motor threshold). Navigated brain stimulation was used to monitor the coil position. A linear relationship was observed between test peak size and test TMS intensity, reflecting linear summation of excitatory inputs induced by TMS. SICI was estimated using the difference between conditioned (produced by the paired pulses) and test peaks (produced by the isolated test pulse). Although the conditioning intensity (activating cortical inhibitory interneurons mediating SICI) was kept constant throughout the experiments, the level of SICI changed with the test peak size, in a non-linear fashion, suggesting that low-threshold cortical neurons (excitatory interneurons/pyramidal cells) are less sensitive to SICI than those of higher threshold. These findings provide the first experimental evidence, under physiological conditions, for non-linear input/output properties of a complex cortical network. Consequently, changes in the recruitment gain of cortical inhibitory interneurons can greatly modify the excitability of pyramidal cells and their response to afferent inputs.     

The effects of accessory stimuli on information processing: evidence from electrophysiology and a diffusion model analysis

People typically respond faster to a stimulus when it is accompanied by a task-irrelevant accessory stimulus presented in another perceptual modality. However, the mechanisms responsible for this accessory-stimulus effect are still poorly understood. We examined the effects of auditory accessory stimulation on the processing of visual stimuli using scalp electrophysiology (Experiment 1) and a diffusion model analysis (Experiment 2). In accordance with previous studies, lateralized readiness potentials indicated that accessory stimuli do not speed motor execution. Surface Laplacians over the motor cortex, however, revealed a bihemispheric increase in motor activation-an effect predicted by nonspecific arousal models. The diffusion model analysis suggested that accessory stimuli do not affect parameters of the decision process, but expedite only the nondecision component of information processing. Consequently, we conclude that accessory stimuli facilitate stimulus encoding. The visual P1 and N1 amplitudes on accessory-stimulus trials were modulated in a way that is consistent with multisensory energy integration, a possible mechanism for this facilitation.     

Watching where you look: modulation of visual processing of foveal stimuli by spatial attention

Two experiments investigated the effect of sustained selective spatial attention upon the perceptual analysis of stimuli within the center of gaze. Spatial attention has typically been studied in relation to peripheral stimuli, and its relevance to the processing of central stimuli has remained relatively ignored. Here, behavioral measures in normal human volunteer participants showed that focused spatial attention can also influence responses to central stimuli, over and beyond the advantage conferred by their foveation. Event-related potentials (ERPs) showed that the action of attention upon foveal stimuli included the modulation of perceptual processing in extrastriate visual areas. Surprisingly, the visual modulation revealed an intriguing and consistent pattern of hemispheric asymmetry, in both experiments. These findings show that in addition to the established right hemisphere dominance of the brain areas that direct attention, the consequences of directed attention may also be asymmetrical.     

Neural correlates of foveal splitting in reading: evidence from an ERP study of Chinese character recognition

Recent research on foveal structure and reading suggests that the two halves of a centrally fixated word seem to be initially projected to, and processed in, different hemispheres. In the current study, we utilize two contrasting structures in Chinese orthography, “SP” (the semantic radical on the left and the phonetic radical on the right) and “PS” characters (the opposite structure), to examine foveal splitting effects in event-related potential (ERP) recordings. We showed that when participants silently named centrally presented characters, there was a significant interaction between character type and hemisphere in N1 amplitude: SP characters elicited larger N1 compared with PS characters in the left hemisphere, whereas the right hemisphere had the opposite pattern. This effect is consistent with the split fovea claim, suggesting that the two halves of a character may be initially projected to and processed in different hemispheres. There was no such interaction observed in an earlier component P1. Also, there was an interaction between character type and sex of the reader in N350 amplitude. This result is consistent with Hsiao and Shillcock's [Hsiao, J. H., & Shillcock, R. (2005b). Foveal splitting causes differential processing of Chinese orthography in the male and female brain. Cognitive Brain Research, 25, 531-536] behavioural study, which showed a similar interaction in naming response time. They argued that this effect was due to a more left-lateralized network for phonological processing in the male brain compared with the female brain. The results hence showed that foveal splitting effects in visual word recognition were observed in N1 the earliest, and could extend far enough to interact with the sex of the reader as revealed in N350.     

Reflex and cortical responses to dental stimuli

Tooth pulp stimulation may evoke reflex responses in the orbicularis oculi, temporal, masseter and retronuchal muscles, which may to a varying degree contaminate the cortical evoked responses. The use of repetitive stimulation reduces the amplitude of the cortical responses but avoids the onset of the majority of the muscle reflexes. The appearance of a silent period in the temporal muscle is hard to avoid and it alters the signal recorded from S1 for the first 60–70 msec. In the center-posterior leads, more protected from the EMG signal of the temporal muscle, a first negative deflection is recorded at 43 msec in 60% of subjects.This work was supported by Consiglio Nazionale delle Ricerche, Rome, under grants 79 01841 04 and 81 01830 04