Dynamics of cortical activation in a hemianopic patient

Although residual vision in patients with cortical blindness is common, its brain mechanisms are poorly known. To study these mechanisms we measured neuromagnetic responses to visual stimuli in a patient with right posterior cerebral lesion and left visual field hemianopia. His vision had partially recovered with intensive training before our measurements. Compared with the processing in the healthy side, early occipital responses were attenuated for both passive viewing of checkerboard reversal patterns and a letter identification task. In both conditions there were prominent longer-latency responses at the right superior temporal cortex. We suggest that the activation in the superior temporal cortex can partially compensate for the failure to produce synchronized population responses at the early stages of visual cortical processing.     

Impairments of Gestalt perception in the intact hemifield of hemianopic patients are reflected in gamma-band EEG activity

Gamma-band responses (GBRs) are associated with Gestalt perception processes. In the present EEG study, we investigated the effects of perceptual grouping on the visual GBR in the perimetrically intact visual field of patients with homonymous hemianopia and compared them to healthy participants.All observers were presented either random arrays of Gabor elements or arrays with an embedded circular arrangement. For the hemianopic patients, the circle was presented in their intact hemifield only. For controls, the hemifield for the circle presentation was counterbalanced across subjects. The participants were instructed to detect the circle by pressing a corresponding button. A wavelet transform based on Morlet wavelets was employed for the calculation of oscillatory GBRs.The early evoked GBR exhibited a larger amplitude and shorter latency for the healthy group compared to hemianopic patients and was associated with behavioral measures. The late total GBR between 200 and 400 ms after stimulus onset was significantly increased for Gestalt-like patterns in healthy participants. This effect was not manifested in patients.The present findings indicate deficits in the early and late visual processing of Gestalt patterns even in the intact hemifield of hemianopic patients compared to healthy participants.     

Spatial representation in the normal visual field: a study of hemifield line bisection

We examined bisection of lines viewed in only one hemifield by normal subjects. Subjects first performed a traditional version of line bisection, by indicating the perceived midpoint of a line on paper with a penmark. Bisection was accurate when they were allowed to shift their gaze over the stimulus, but it was biased towards the central visual field (centripetally) when gaze was fixed so that the line was seen in only one hemifield. In a second experiment, lines with transectors at various locations were presented briefly on a screen and subjects had to indicate on which side of the perceived midpoint the transector was located. A centripetal bias was still found, indicating that it has a perceptual origin. The interaction between bias and effects of tangent line presentation suggested that subjects were performing an angle bisection rather than a line bisection. Also, there was bias in not only right and left hemifields but also upper and lower hemifields. In a third experiment, increasing the width of the stimulus bars peripherally did not eliminate this bias. Bias was size-invariant along the horizontal meridian. This spatial version of Weber's law was modeled by a magnification function using an exponential equation. The slope of this function is much shallower than those currently known for V1, V4 and V5. We conclude that a centripetal bias exists for hemifield line bisection and that this bias likely contributes to the contralateral bias of line bisection by hemianopic patients found in other studies.     

Transfer of cortical motor representation after a perinatal cerebral insult

In a 16-year-old boy with hemiplegia and severe, intractable epilepsy after a neonatal cerebral ischemic insult, cortical motor control was only equivocally assessed by functional magnetic resonance imaging. Therefore, high-precision navigated transcranial magnetic stimulation was performed, which demonstrated that cortical control of muscles on the paretic side was selectively affected. Leg muscle control was located in the contralateral hemisphere, as expected in healthy individuals, whereas forearm muscles were controlled from both hemispheres, and hand muscles were controlled only from the hemisphere ipsilateral to the paresis.     

Tonotopic cortical representation of periodic complex sounds

Most of the sounds that are biologically relevant are complex periodic sounds, i.e., they are made up of harmonics, whose frequencies are integer multiples of a fundamental frequency (Fo). The Fo of a complex sound can be varied by modifying its periodicity frequency; these variations are perceived as the pitch of the voice or as the note of a musical instrument. The center frequency (CF) of peaks occurring in the audio spectrum also carries information, which is essential, for instance, in vowel recognition. The aim of the present study was to establish whether the generators underlying the 100 m are tonotopically organized based on the Fo or CF of complex sounds. Auditory evoked neuromagnetic fields were recorded with a whole-head magnetoencephalography (MEG) system while 14 subjects listened to 9 different sounds (3 Fo x 3 CF) presented in random order. Equivalent current dipole (ECD) sources for the 100 m component show an orderly progression along the y-axis for both hemispheres, with higher CFs represented more medially. In the right hemisphere, sources for higher CFs were more posterior, while in the left hemisphere they were more inferior. ECD orientation also varied as a function of the sound CF. These results show that the spectral content CF of the complex sounds employed here predominates, at the latency of the 100 m component, over a concurrent mapping of their periodic frequency Fo. The effect was observed both on dipole placement and dipole orientation.     

Somatosensory cortical representation of the body size

The knowledge of the size of our own body parts is essential for accurately moving in space and efficiently interact with objects. A distorted perceptual representation of the body size often represents a core diagnostic criterion for some psychopathological conditions. The metric representation of the body was shown to depend on somatosensory afferences: local deafferentation indeed causes a perceptual distortion of the size of the anesthetized body part. A specular effect can be induced by altering the cortical map of body parts in the primary somatosensory cortex. Indeed, the present study demonstrates, in healthy adult participants, that repetitive Transcranial Magnetic Stimulation to the somatosensory cortical map of the hand in both hemispheres causes a perceptual distortion (i.e., an overestimation) of the size of the participants' own hand (Experiments 1–3), which does not involve other body parts (i.e., the foot, Experiment 2). Instead, the stimulation of the inferior parietal lobule of both hemispheres does not affect the perception of the own body size (Experiment 4). These results highlight the role of the primary somatosensory cortex in the building up and updating of the metric of body parts: somatosensory cortical activity not only shapes our somatosensation, it also affects how we perceive the dimension of our body.     

A short latency cortical component of the foveal VEP is revealed by hemifield stimulation.

Transient evoked potentials were recorded simultaneously over 5 electrodes placed in a horizontal row across the occiput. A range of spatial frequencies were presented as either full-field or hemifield stimuli. Subjects were 11 normal observers and 5 patients with lesions causing a homonymous hemianopic field defect. The shortest latency peak response was at approximately 70 msec, a negative potential (N70). For all spatial frequencies, full-field stimuli evoked a lower amplitude N70 at the midline than the sum of N70 amplitudes to two hemifield stimuli, suggesting partial cancellation. The latency and amplitude of N70 increased as spatial frequency increased. N70 and P100 differed in respect to their response to spatial frequency and field size, further suggesting that they may not be subsets of a unitary response. For hemifield stimulation, N70 had an ipsilateral maximum and attenuated or completely reversed in polarity across the midline. Consistent with the data of normals using hemifield stimuli, in 5 patients a full-field stimulus elicited an N70 lateralized contralaterally to the homonymous hemianopia, i.e., the ipsilateral N70 was absent. The absolute amplitude difference between the left and right electrodes was significant for hemifield stimulation in normals and full-field stimulation in the patients, but not for full-field stimulation in normals. Our results imply that the evaluation of N70 hemispheric distribution is useful for the evaluation of paramacular visual field defects.     

Reorganization of cortical hand representation in congenital hemiplegia

When damaged perinatally, as in congenital hemiplegia (CH), the corticospinal tract usually undergoes an extensive reorganization, such as the stabilization of normally transient projections to the ipsilateral spinal cord. Whether the reorganization of the corticospinal projections occurring in CH patients is also accompanied by a topographical rearrangement of the hand representations in the primary motor cortex (M1) remains unclear. To address this issue, we mapped, for both hands, the representation of the first dorsal interosseous muscle (1DI) in 12 CH patients by using transcranial magnetic stimulation co-registered onto individual three-dimensional magnetic resonance imaging; these maps were compared with those gathered in age-matched controls ( n  =   11). In the damaged hemisphere of CH patients, the representation of the paretic 1DI was either found in the hand knob of M1 ( n  =   5), shifted caudally ( n  =   5), or missing ( n  =   2). In the intact hemisphere of six CH patients, an additional, ipsilateral, representation of the paretic 1DI was found in the hand knob, where it overlapped exactly the representation of the non-paretic 1DI. In the other six CH patients, the ipsilateral representation of the paretic 1DI was either shifted caudally ( n  =   2) or was lacking ( n  =   4). Surprisingly, in these two subgroups of patients, the representation of the contralateral non-paretic 1DI was found in a more medio-dorsal position than in controls. The present study demonstrates that, besides the well-known reorganization of the corticospinal projections, early brain injuries may also lead to a topographical rearrangement of the representations of both the paretic and non-paretic hands in M1.     

Enlargement of cortical vibrissa representation in the surround of an ischemic cortical lesion

It has been shown that cortical lesions are associated with an increase of excitability in surrounding brain regions, and with a downregulation of GABA(A) receptors. In the present study we investigated whether this increased excitability affects the cortical map of inputs represented in areas surrounding the lesioned brain area. Focal lesions with a diameter of 2-2.5 mm were induced photochemically in the hindlimb area at the border of the primary somatosensory cortex of the rat. One week after lesioning, the cortical representation of the B3 vibrissa was studied using 14C-deoxyglucose (DG) autoradiography. In all animals mechanical stimulation of the B3 vibrissa produced a column-shaped DG-labeling in the somatosensory cortex, corresponding to the B3-barrel with a maximum of the glucose uptake in layer IV. In control animals without cortical lesions (n=6), stimulation increased the glucose uptake rate by 50.8+/-10.5% in layer IV. In lesioned animals (n=6) maximum DG-uptake in layer IV (54.8+/-8.6%) did not differ significantly from that in controls. However, as compared to control animals, lesioned animals showed also increased glucose uptake within the activated column in layers II/II (51.+/-11.1%, lesioned animals; 31.8+/-11.2%, controls; P<0.05, lesioned vs. control) and V (47.5+/-5.8%, lesioned animals, 28.8+/-10.5%, controls; P<0.05, lesioned vs. control). The diameter of the metabolically activated B3-barrel area of layer IV was expanded from 461.8+/-77.6 microm in control animals to 785.5+/-103.6 microm; P<0.01) in lesioned animals. Lesioned animals also showed expansion of the activated area in layers II/III (890.4+/-134.8 microm, lesioned animals; 430.6+/-95.1 microm, controls; P<0.01) and layer V (1117.5+/-163.6 microm, lesioned animals; 648.7+/-114.1 microm, controls; P<0.01). The depth profile of the activation columns showed a maximum in layer IV in control animals, which was expanded towards layers II/III and layer V in lesioned animals. It is concluded that cortical lesions alter the representational area of neighboring afferent inputs through disinhibition or 'unmasking' of pre-existing silent or ineffectual intracortical synapses. The present observations raise the possibility that the brain supports recovery from lesions by decreasing GABAergic inhibition, thereby facilitating a remapping of the cortical representation in neighboring brain areas.     

Estimation of active cortical current source regions using a vector representation scanning approach.

The objective of this article is to present a framework for cortical current source reconstruction that extracts a center and magnitude of electrical brain activity from EEG signals. High-resolution EEG recordings, a subject-specific MRI-based electromagnetic boundary element method (BEM) model, and a channel reduction technique are used. This new geometric measure combines the magnitude and spatial location of electrical brain activity of each of the identified subsets of channels into a three-dimensional resultant vector. The combination of the two approaches constitutes a source reconstruction scanning technique that provides a real-time estimation of cortical centers that can be tracked over time. Simulations demonstrate that the ability of this method to find the best-fit cortical location is more robust both in terms of accuracy and precision than traditional approaches for single-source conditions. Experimental validation demonstrates its ability to localize and separate cortical activity in plausible sites for two different motor tasks. Finally, this method provides a statistical measure to compare electrical brain activity associated with different motor tasks.     

Mapping the cortical representation of the lumbar paravertebral muscles.

OBJECTIVE: The aim of this study was to map the cortical representation of the lumbar spine paravertebral (LP) muscles in healthy subjects. METHODS: Transcranial magnetic stimulation (TMS) was employed to map the cortical representations of the LP muscles at two sites. Stimuli were applied to points on a grid representing scalp positions. The amplitude of motor evoked potentials (n=6) was averaged for each position. RESULTS: The optimal site for evoking responses in the contralateral LP muscles was situated 1cm anterior and 4 cm lateral to the vertex. Ipsilateral responses were evoked from sites lateral to the optimal site for evoking contralateral responses. Contralateral responses were also obtained from areas anterior to the optimal site. CONCLUSIONS: Maps of these muscles can be produced. The results suggest discrete contra- and ipsilateral cortical projections. Anterior sites at which excitation can be evoked may indicate projections arising in the SMA are involved. SIGNIFICANCE: This study provides normative data regarding the cortical representation of the paravertebral muscles and provides a technique for evaluating cortical motor plasticity in patients presenting with spinal pathologies.     

Automatic cortical representation of auditory pitch changes in Rett syndrome

Background

Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral communication abilities. It becomes extremely difficult for clinicians and caretakers to accurately assess the level of preserved auditory functioning in these children, an issue of obvious clinical import. Non-invasive electrophysiological techniques allow for the interrogation of auditory cortical processing without the need for overt behavioral responses. In particular, the mismatch negativity (MMN) component of the auditory evoked potential (AEP) provides an excellent and robust dependent measure of change detection and auditory sensory memory. Here, we asked whether females with Rett syndrome would produce the MMN to occasional changes in pitch in a regularly occurring stream of auditory tones.

Methods

Fourteen girls with genetically confirmed Rett syndrome and 22 age-matched neurotypical controls participated (ages 3.9–21.1 years). High-density electrophysiological recordings from 64 scalp electrodes were made while participants passively listened to a regularly occurring stream of 503-Hz auditory tone pips that was occasionally (15 % of presentations) interrupted by a higher-pitched deviant tone of 996 Hz. The MMN was derived by subtracting the AEP to these deviants from the AEP produced to the standard.

Results

Despite clearly anomalous morphology and latency of the AEP to simple pure-tone inputs in Rett syndrome, the MMN response was evident in both neurotypicals and Rett patients. However, we found that the pitch-evoked MMN was both delayed and protracted in duration in Rett, pointing to slowing of auditory responsiveness.

Conclusions

The presence of the MMN in Rett patients suggests preserved abilities to process pitch changes in auditory sensory memory. This work represents a beginning step in an effort to comprehensively map the extent of auditory cortical functioning in Rett syndrome. These easily obtained objective brain measures of auditory processing have promise as biomarkers against which future therapeutic efforts can be assayed.

     

Structural anatomy of pure and hemianopic alexia

Background

The two most common types of acquired reading disorder resulting from damage to the territory of the dominant posterior cerebral artery are hemianopic and pure alexia. Patients with pronounced hemianopic alexia have a right homonymous hemianopia that encroaches into central or parafoveal vision; they read individual words well, but generate inefficient reading saccades when reading along a line of text. Patients with pure alexia also often have a hemianopia but are more disabled, making frequent errors on individual words; they have sustained damage to a brain region that supports efficient word identification.

Objective

To investigate the differences in lesion site between hemianopic alexia and pure alexia groups, as rehabilitative techniques differ between the two conditions.

Methods

High‐resolution magnetic resonance images were obtained from seven patients with hemianopic alexia and from six patients with pure alexia caused by a left occipital stroke. The boundary of each lesion was defined and lesion volumes were then transformed into a standard stereotactic space so that regional comparisons could be made.

Results

The two patient groups did not differ in terms of damage to the medial left occipital lobe, but those with pure alexia had additional lateral damage to the posterior fusiform gyrus and adjacent tissue.

Conclusions

Clinicians will be able to predict the type of reading disorder patients with left occipital lesions have from simple tests of reading speed and the distribution of damage to the left occipital lobe on brain imaging. This information will aid management decisions, including recommendations for reading rehabilitation.Although an acquired reading disorder (alexia) is usually part of a more generalised language disorder (aphasia), it can occur as an isolated deficit, usually as a consequence of damage to the brain within the distribution of the left posterior cerebral artery. The two common forms of isolated alexia are hemianopic alexia and pure alexia. The first is the result of a right homonymous hemianopia (RHH), which impairs text reading more than single‐word reading. This is because, in left‐to‐right readers, visual information to the right of fixation is needed to plan rightward reading saccades.^1,2,3 Scanning along a line of text is affected if the RHH encroaches to within 5° of fixation, in right foveal or parafoveal vision.⁴ However, the relationship between text‐reading speed and the number of degrees of sparing of central vision is not linear, and most symptomatic patients have defects encroaching to within 2–3° of fixation or less. By contrast, patients with pure alexia have a severe impairment of single‐word recognition. Although they often have an associated RHH, their syndrome is not a consequence of this deficit, and there have been a few patients with pure alexia without an accompanying field defect.¹ Rather, their impairment is the consequence of damage to a whole‐word recognition system that allows a skilled reader to recognise seven‐letter words as quickly as words of three letters. Patients with pure alexia have damage in the whole‐word recognition system, its connections to primary visual areas or, occasionally, its connections to “higher” language areas. Although these patients can still read, they rely on a more‐or‐less intact letter recognition system and a laborious reversed‐spelling procedure, covert or overt, to arrive at the word''s identity, so‐called “letter‐by‐letter reading”. Thus, the word “dog” is not recognised, but explicitly spelling out “d”, “o”, “g” permits essential reading.It is important to differentiate between the two conditions, as there is specific rehabilitation for hemianopic alexia.⁵ Although occasionally some success has been reported in retraining patients with pure alexia,⁶ most regard pure alexia as an irremediable condition. Pure alexia is more disabling, but many patients with hemianopic alexia find text reading so laborious that they give up recreational reading, and if reading speed is an important skill in their job, their continuing employment may be at risk.The aim of this study was to determine whether pure alexia and hemianopic alexia can be differentiated by the limits of their left occipital lesion on magnetic resonance images (MRIs). Although much has been written about the pathological anatomy of pure alexia,^7,8,9,10 this is the first study directly comparing lesion site and size between patients with pure alexia and hemianopic alexia. The outcome is practical, in terms of diagnosis and referral for appropriate rehabilitation. Further, it provides additional data that identify the region responsible for rapid whole‐word recognition, by excluding areas that may be damaged by posterior cerebral artery (PCA) territory stroke but do not contribute to the syndrome of pure alexia.     

Variability of residual vision in hemianopic subjects

Using stabilized visual field mapping techniques, seven hemianopic subjects were extensively investigated for residual visual abilities. Isolated islands of detection abilities were demonstrated by four of these subjects. Additional abilities demonstrated within these islands included saccadic and verbal localization, wavelength discrimination, form discrimination, and motion detection. These abilities were also accompanied by low-confidence ratings, and thus have the character of blindsight. It is noteworthy that different subjects demonstrated different abilities at different visual field locations, underscoring the between and within subject variability often observed with blindsight. Furthermore, magnetic resonance images obtained for each subject demonstrated variable sparing of occipital cortex. Such cortical sparing, in conjunction with the behavioral variability, supports the notion that some instances of blindsight are mediated by remnants of the primary visual pathway.     

Orderly cortical representation of vowel categories presented by multiple exemplars

This study aimed at determining how the human brain automatically processes phoneme categories irrespective of the large acoustic inter-speaker variability. Subjects were presented with 450 different speech stimuli, equally distributed across the [a], [i], and [u] vowel categories, and each uttered by a different male speaker. A 306-channel magnetoencephalogram (MEG) was used to record N1m, the magnetic counterpart of the N1 component of the auditory event-related potential (ERP). The N1m amplitude and source locations differed between vowel categories. We also found that the spectrum dissimilarities were reproduced in the cortical representations of the large set of the phonemes used in this study: vowels with similar spectral envelopes had closer cortical representations than those whose spectral differences were the largest. Our data further extend the notion of differential cortical representations in response to vowel categories, previously demonstrated by using only one or a few tokens representing each category.