Showing papers in "Cerebral Cortex in 1999"

Electrophysiological Studies of Human Face Perception. I: Potentials Generated in Occipitotemporal Cortex by Face and Non-face Stimuli

Abstract: This and the following two papers describe event-related potentials (ERPs) evoked by visual stimuli in 98 patients in whom electrodes were placed directly upon the cortical surface to monitor medically intractable seizures. Patients viewed pictures of faces, scrambled faces, letter-strings, number-strings, and animate and inanimate objects. This paper describes ERPs generated in striate and peristriate cortex, evoked by faces, and evoked by sinusoidal gratings, objects and letter-strings. Short-latency ERPs generated in striate and peristriate cortex were sensitive to elementary stimulus features such as luminance. Three types of face-specific ERPs were found: (i) a surface-negative potential with a peak latency of approximately 200 ms (N200) recorded from ventral occipitotemporal cortex, (ii) a lateral surface N200 recorded primarily from the middle temporal gyrus, and (iii) a late positive potential (P350) recorded from posterior ventral occipitotemporal, posterior lateral temporal and anterior ventral temporal cortex. Face-specific N200s were preceded by P150 and followed by P290 and N700 ERPs. N200 reflects initial face-specific processing, while P290, N700 and P350 reflect later face processing at or near N200 sites and in anterior ventral temporal cortex. Face-specific N200 amplitude was not significantly different in males and females, in the normal and abnormal hemisphere, or in the right and left hemisphere. However, cortical patches generating ventral face-specific N200s were larger in the right hemisphere. Other cortical patches in the same region of extrastriate cortex generated grating-sensitive N180s and object-specific or letter-string-specific N200s, suggesting that the human ventral object recognition system is segregated into functionally discrete regions.

Physiological characteristics of capacity constraints in working memory as revealed by functional MRI.

Abstract: A fundamental characteristic of working memory is that its capacity to handle information is limited. While there have been many brain mapping studies of working memory, the physiological basis of its capacity limitation has not been explained. We identified characteristics of working memory capacity using functional magnetic resonance imaging (fMRI) in healthy subjects. Working memory capacity was studied using a parametric ‘n-back’ working memory task involving increasing cognitive load and ultimately decreasing task performance. Loci within dorsolateral prefrontal cortex (DLPFC) evinced exclusively an ‘inverted-U’ shaped neurophysiological response from lowest to highest load, consistent with a capacity-constrained response. Regions outside of DLPFC, in contrast, were more heterogeneous in response and often showed early plateau or continuously increasing responses, which did not reflect capacity constraints. However, sporadic loci, including in the premotor cortex, thalamus and superior parietal lobule, also demonstrated putative capacity-constrained responses, perhaps arising as an upstream effect of DLPFC limitations or as part of a broader network-wide capacity limitation. These results demonstrate that regionally specific nodes within the working memory network are capacity-constrained in the physiological domain, providing a missing link in current explorations of the capacity characteristics of working memory.

When That Tune Runs Through Your Head: A PET Investigation of Auditory Imagery for Familiar Melodies

Abstract: The present study used positron emission tomography (PET) to examine the cerebral activity pattern associated with auditory imagery for familiar tunes. Subjects either imagined the continuation of nonverbal tunes cued by their first few notes, listened to a short sequence of notes as a control task, or listened and then reimagined that short sequence. Subtraction of the activation in the control task from that in the real-tune imagery task revealed primarily right-sided activation in frontal and superior temporal regions, plus supplementary motor area (SMA). Isolating retrieval of the real tunes by subtracting activation in the reimagine task from that in the real-tune imagery task revealed activation primarily in right frontal areas and right superior temporal gyrus. Subtraction of activation in the control condition from that in the reimagine condition, intended to capture imagery of unfamiliar sequences, revealed activation in SMA, plus some left frontal regions. We conclude that areas of right auditory association cortex, together with right and left frontal cortices, are implicated in imagery for familiar tunes, in accord with previous behavioral, lesion and PET data. Retrieval from musical semantic memory is mediated by structures in the right frontal lobe, in contrast to results from previous studies implicating left frontal areas for all semantic retrieval. The SMA seems to be involved specifically in image generation, implicating a motor code in this process.

The Functional Neuroanatomy of Target Detection: An fMRI Study of Visual and Auditory Oddball Tasks

Abstract: The neuronal response patterns that are required for an adequate behavioural reaction to subjectively relevant changes in the environment are commonly studied by means of oddball paradigms, in which occasional 'target' stimuli have to be detected in a train of frequent 'non-target' stimuli. The detection of such task-relevant stimuli is accompanied by a parietocentral positive component of the event-related potential, the P300. We performed EEG recordings of visual and auditory event-related potentials and functional magnetic resonance imaging (fMRI) when healthy subjects performed an oddball task. Significant increases in fMRI signal for target versus non-target conditions were observed in the supramarginal gyrus, frontal operculum and insular cortex bilaterally, and in further circumscribed parietal and frontal regions. These effects were consistent over various stimulation and response modalities and can be regarded as specific for target detection in both the auditory and the visual modality. These results therefore contribute to the understanding of the target detection network in human cerebral cortex and impose constraints on attempts at localizing the neuronal P300 generator. This is of importance both from a neurobiological perspective and because of the widespread application of the physiological correlates of target detection in clinical P300 studies.

Electrophysiological Studies of Human Face Perception. II: Response Properties of Face-specific Potentials Generated in Occipitotemporal Cortex

Abstract: In the previous paper the locations and basic response properties of N200 and other face-specific event-related potentials (ERPs) were described In this paper responsiveness of N200 and related ERPs to the perceptual features of faces and other images was assessed N200 amplitude did not vary substantially, whether evoked by colored or grayscale faces; normal, blurred or line-drawing faces; or by faces of different sizes Human hands evoked small N200s at face-specific sites, but evoked hand-specific ERPs at other sites Cat and dog faces evoked N200s that were 73% as large as to human faces Hemifield stimulation demonstrated that the right hemisphere is better at processing information about upright faces and transferring it to the left hemisphere, whereas the left hemisphere is better at processing information about inverted faces and transferring it to the right hemisphere N200 amplitude was largest to full faces and decreased progressively to eyes, face contours, lips and noses viewed in isolation A region just lateral to face-specific N200 sites was more responsive to internal face parts than to faces, and some sites in ventral occipitotemporal cortex were face-partspecific Faces with eyes averted or closed evoked larger N200s than those evoked by faces with eyes forward N200 amplitude and latency were affected by the joint effects of eye and head position in the right but not in the left hemisphere Full and three-quarter views of faces evoked larger N200s than did profile views The results are discussed in relation to behavioral studies in humans and single-cell recordings in monkeys

Electrophysiological Studies of Human Face Perception. III: Effects of Top-down Processing on Face-specific Potentials

Abstract: This is the last in a series of papers dealing with intracranial event-related potential (ERP) correlates of face perception. Here we describe the results of manipulations that may exert top-down influences on face recognition and face-specific ERPs, and the effects of cortical stimulation at face-specific sites. Ventral face-specific N200 was not evoked by affective stimuli; showed little or no habituation; was not affected by the familiarity or unfamiliarity of faces; showed no semantic priming; and was not affected by face-name learning or identification. P290 and N700 were affected by semantic priming and by face-name learning and identification. The early fraction of N700 and face-specific P350 exhibited significant habituation. About half of the AP350 sites exhibited semantic priming, whereas the VP350 and LP350 sites did not. Cortical stimulation evoked a transient inability to name familiar faces or evoked face-related hallucinations at two-thirds of face-specific N200 sites. These results are discussed in relation to human behavioral studies and monkey single-cell recordings. Discussion of results of all three papers concludes that: face-specific N200 reflects the operation of a module specialized for the perception of human faces; ventral and lateral occipitotemporal cortex are composed of a complex mosaic of functionally discrete patches of cortex of variable number, size and location; in ventral cortex there is a posterior-to-anterior trend in the location of patches in the order letter-strings, form, hands, objects, faces and face parts; P290 and N700 at face-specific N200 sites, and face-specific P350, are subject to top-down influences.

The Connectional Organization of the Cortico-thalamic System of the Cat

Abstract: Data on connections between the areas of the cerebral cortex and nuclei of the thalamus are too complicated to analyse with naked intuition. Indeed, the complexity of connection data is one of the major challenges facing neuroanatomy. Recently, systematic methods have been developed and applied to the analysis of the connectivity in the cerebral cortex. These approaches have shed light on the gross organization of the cortical network, have made it possible to test systematically theories of cortical organization, and have guided new electrophysiological studies. This paper extends the approach to investigate the organization of the entire corticothalamic network. An extensive collation of connection tracing studies revealed ~1500 extrinsic connections between the cortical areas and thalamic nuclei of the cat cerebral hemisphere. Around 850 connections linked 53 cortical areas with each other, and around 650 connections linked the cortical areas with 42 thalamic nuclei. Non-metric multidimensional scaling, optimal set analysis and non-parametric cluster analysis were used to study global connectivity and the ‘place’ of individual structures within the overall scheme. Thalamic nuclei and cortical areas were in intimate connectional association. Connectivity defined four major thalamocortical systems. These included three broadly hierarchical sensory or sensory/motor systems (visual and auditory systems and a single system containing both somatosensory and motor structures). The highest stations of these sensory/motor systems were associated with a fourth processing system composed of prefrontal, cingulate, insular and parahippocampal cortex and associated thalamic nuclei (the ‘fronto-limbic system’). The association between fronto-limbic and somato-motor systems was particularly close.

From Perception to Action: Temporal Integrative Functions of Prefrontal and Parietal Neurons

Abstract: The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception-action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception-action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal-parietal network in the integration of perception with action across time. Language: en

Nouns and Verbs in the Intact Brain: Evidence from Event-related Potentials and High-frequency Cortical Responses

Abstract: Lesion evidence indicates that words from different lexical categories, such as nouns and verbs, may have different cortical counterparts. In this study, processing of nouns and verbs was investigated in the intact brain using (i) behavioral measures, (ii) stimulus-triggered event-related potentials and (iii) high-frequency electrocortical responses in the gamma band. Nouns and verbs carefully matched for various variables, including word frequency, length, arousal and valence, were presented in a lexical decision task while electrocortical responses were recorded. In addition, information about cognitive processing of these stimuli was obtained using questionnaires and reaction times. As soon as ~200 ms after stimulus onset, event-related potentials disclosed electrocortical differences between nouns and verbs over widespread cortical areas. In a later time window, 500‐800 ms after stimulus onset, there was a significant difference between high-frequency responses in the 30 Hz range. Difference maps obtained from both event-related potentials and high-frequency responses revealed strong betweencategory differences of signals recorded above motor and visual cortices. Behavioral data suggest that these different physiological responses are related to semantic associations (motor or visual) elicited by these word groups. Our results are consistent with a neurobiological model of language representation postulating cell assemblies with distinct cortical topographies as biological counterparts of words. Assemblies representing nouns referring to visually perceived objects may include neurons in visual cortices, and assemblies representing action verbs may include additional neurons in motor, premotor and prefrontal cortices. Event-related potentials and high-frequency responses are proposed to indicate two different functional states of cell assemblies: initial full activation (‘ignition’) and continuous reverberatory activity.

Differential Origins of Neocortical Projection and Local Circuit Neurons: Role of Dlx Genes in Neocortical Interneuronogenesis

Abstract: Herein we review the evidence that neocortical projection neurons and interneurons are derived from distinct regions within the telencephalon. While neocortical projection neurons are derived from the ventricular zone of the neocortex, neocortical interneurons appear to be derived from the germinal zone of the basal ganglia. These interneurons follow a tangential migratory pathway from the ganglionic eminences to the cortex. Interneurons of the olfactory bulb follow a distinct tangential migration from the basal ganglia. The Dlx homeobox genes, which are essential for basal ganglia differentiation, are also required for the development of neocortical and olfactory bulb interneurons. Furthermore, evidence is presented that retroviral-mediated expression of DLX2 in neocortical cells can induce GABAergic interneuron differentiation.

Synchronization Between Temporal and Parietal Cortex During Multimodal Object Processing in Man

Abstract: A series of recordings in cat visual cortex suggest that synchronous activity in neuronal cell ensembles serves to bind the different perceptual qualities belonging to one object. We provide evidence that similar mechanisms seem also to be observable in human subjects for the representation of supramodal entities. Electroencephalogram (EEG) was recorded from 19 scalp electrodes (10/20 system) in 19 human subjects and EEG amplitude and coherence were determined during presentation of objects such as house, tree, ball. Objects were presented in three different ways: in a pictorial presentation, as spoken words and as written words. In order to find correlates of modality-independent processing, we searched for patterns of activation common to all three modalities of presentation. The common pattern turned out to be an increase of coherence between temporal and parietal electrodes in the 13-18 Hz beta1 frequency range. This is evidence that population activity of temporal cortex and parietal cortex shows enhanced coherence during presentation of semantic entities. Coherent activity in this low-frequency range might play a role for binding of multimodal ensembles.

Quantitative In Vivo Measurement of Gyrification in the Human Brain: Changes Associated with Aging

Abstract: Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.

Quantifying Variability in the Planum Temporale: A Probability Map

Abstract: The acquisition of definitive evidence for systematic hemispheric asymmetries in the size of the planum temporale (PT) has been restricted by difficulties in identifying, standardizing and measuring the region of interest. In this paper an operational definition for identifying the problematic posterior border of the PT on magnetic resonance imaging (MRI) scans is proposed. An interactive voxel-painting program was used to identify and label the PT simultaneously in horizontal, sagittal and coronal planes in MRI scans, transformed into the standardized Talairach-Tournoux stereo-taxic space, from 50 normal right-handed volunteers. Both grey matter volume and cortical surface area of the PT were measured, while controlling for individual variation in overall brain shape and volume. The labeled tissue was averaged together to produce a probability map in standardized space of the region of interest. The PT region is highly variable, with no single voxel being labeled with a probability of >65%. In this study there were no significant hemispheric differences in volume or area of the PT. An asymmetry in area and volume was introduced by using an alternative method - the 'knife-cut' method - for identifying the posterior border. Implications for functional neuroimaging of the PT are discussed.

Separate Processing Dynamics for Texture Elements, Boundaries and Surfaces in Primary Visual Cortex of the Macaque Monkey

Abstract: A visual scene is rapidly segmented into the regions that are occupied by different objects and background. Segmentation may be initiated from the detection of boundaries, followed by the filling-in of the surfaces between these boundaries to render them visible. Alternatively, segmentation may be based on grouping of surface elements that are similar, so that boundaries are (implicitly) identified as the borders between elements that are grouped into objects. Here, we present recordings from awake monkey primary visual cortex that show that in late (>80 ms) components of the neural responses a correlate of boundary formation is expressed, followed by a filling-in (also called colouring) between the edges. These data favour a model of segmentation where boundary formation initiates surface filling-in.

Dissociation of Normal Feature Analysis and Deficient Processing of Letter-strings in Dyslexic Adults

Abstract: Neuroimaging studies have revealed that the functional organization of reading differs between developmentally dyslexic and nonimpaired individuals However, it is not clear how early in the reading process the differences between fluent and dyslexic readers start to emerge We studied cortical activity of ten dyslexic adults using magnetoencephalography (MEG), as they silently read words or viewed symbol-strings which were clearly visible or degraded with Gaussian noise This method has previously been used to dissociate between analysis of local features and pre-lexical word processing in fluent adult readers Signals peaking around 100 ms after stimulus onset and originating in the postero-medial extrastriate cortex were associated with increasing local luminance contrast in the noise patches These early visual responses were similar in dyslexic and non-impaired readers In contrast, the letter-string-specific responses peaking around 150 ms predominantly in the left inferior occipito-temporal cortex in fluent readers were undetectable in dyslexic readers Thus, while the early visual processing seems intact in dyslexic adults, the pattern of cortical activation starts to differ from that of fluent readers at the point where letter-stringspecific signals first emerge during reading

The Role of Cell Death in Regulating the Size and Shape of the Mammalian Forebrain

Abstract: The size of the cerebral cortex is determined by the rate of production of neurons and glial cells in the proliferative ventricular and subventricular zones. Recent studies from targeted mutations of different death-effector gene families indicate that programmed cell death (PCD) plays an important role in cell production and early morphogenesis of the mammalian forebrain before the formation of neuronal connections. For example, disruption of the c/Jun N-kinase signaling pathway by double-targeted mutation of both Jnk1 and Jnk2 results in increased PCD in the forebrain leading to precocious degeneration of cerebral precursors. In contrast, disturbance of the caspase cascade by targeted disruption of either casp-9 or casp-3 leads to decreased PCD causing expansion and exencephaly of the forebrain as well as supernumerary neurons in the cerebral cortex. The supernumerary neurons in these knockout mice align radially and form an expanded cortical plate which begins to form cerebral convolutions. Thus, the precise coordination of different apoptotic signaling pathways during early stages of neurogenesis is crucial for regulation of the proper cortical size and shape.

Specialization of Left Auditory Cortex for Speech Perception in Man Depends on Temporal Coding

Abstract: Speech perception requires cortical mechanisms capable of analysing and encoding successive spectral (frequency) changes in the acoustic signal. To study temporal speech processing in the human auditory cortex, we recorded intracerebral evoked potentials to syllables in right and left human auditory cortices including Heschl's gyrus (HG), planum temporale (PT) and the posterior part of superior temporal gyrus (area 22). Natural voiced /ba/, /da/, /ga/) and voiceless (/pa/, /ta/, /ka/) syllables, spoken by a native French speaker, were used to study the processing of a specific temporally based acoustico-phonetic feature, the voice onset time (VOT). This acoustic feature is present in nearly all languages, and it is the VOT that provides the basis for the perceptual distinction between voiced and voiceless consonants. The present results show a lateralized processing of acoustic elements of syllables. First, processing of voiced and voiceless syllables is distinct in the left, but not in the right HG and PT. Second, only the evoked potentials in the left HG, and to a lesser extent in PT, reflect a sequential processing of the different components of the syllables. Third, we show that this acoustic temporal processing is not limited to speech sounds but applies also to non-verbal sounds mimicking the temporal structure of the syllable. Fourth, there was no difference between responses to voiced and voiceless syllables in either left or right areas 22. Our data suggest that a single mechanism in the auditory cortex, involved in general (not only speech-specific) temporal processing, may underlie the further processing of verbal (and non-verbal) stimuli. This coding, bilaterally localized in auditory cortex in animals, takes place specifically in the left HG in man. A defect of this mechanism could account for hearing discrimination impairments associated with language disorders.

Corticospinal Excitability Modulation to Hand Muscles During Movement Imagery

Abstract: Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were recorded from right abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles, sharing the same peripheral innervation but engaged in two different motor demands. In seven healthy and trained subjects, the latencies, amplitudes and variability of MEPs were investigated under the following, randomly intermingled, conditions: full muscular and mental relaxation; mental simulation of selective index finger or little finger abduction; mental non-motor activity (arithmetical calculation); and real motor task (little and index finger abduction). The whole procedure was performed by continuous audiovisual monitoring of electromyographic 'silence' in the tested muscles. The maximal facilitatory effects (= latency shortening and amplitude increase) on MEPs were induced by the real motor task. An amplitude potentiation of MEPs in both tested muscles was present during non-motor mental activity, in comparison to basal values. A further amplitude potentiation, without latency shifts, was confined to the muscle acting as 'prime mover' for the mentally simulated movement, according to the motor program dispatched but not executed by the subject. Similar results were also found in the F-wave, showing that mental simulation affects spinal motoneuronal excitability as well, although -- due to the lack of MEP and F-wave latency shift -- the main effect takes place at cortical level. The study shows that movement imagery can focus specific facilitation on the prime-mover muscle for the mentally simulated movement. This is mainly evident on FDI muscle, which controls fingers (i.e. the index) with highly corticalized motor representation.

Genetic Control of Cortical Regionalization and Connectivity

Abstract: Herein, the genetic control of regionalization and connectivity of the neocortex are reviewed. Evidence is accumulating which suggests that intrinsic mechanisms have a central role in controlling cortical regional specification and differentiation. Expression patterns of several genes (Id-2, Tbr-1, cadherin-6, cadherin-8, neuropilin-2, Wnt-7b, Eph-A7 and RZR-beta) are described; the expressions of these genes have regional boundaries which demarcate distinct functional areas of the cerebral cortex in neonatal mice.

Tactile Attention Tasks Enhance Activation in Somatosensory Regions of Parietal Cortex: A Positron Emission Tomography Study

Abstract: We used positron emission tomography to study cortical regions mediating tactile attention. Cues selectively directed subjects to attend to the roughness or duration of contact with embossed gratings that rubbed against a single fingertip with controlled speed and force. The task required discriminating between paired gratings that differed in tactile features of roughness and/or length. For different blocks of trials, cues directed attention to one tactile feature or indicated a divided attention strategy to a change in either feature. All attention conditions unambiguously activated several somatosensory foci in the parietal cortex, including somatotopically appropriate portions of the primary somatosensory cortex in the postcentral gyrus (S1) and the secondary somatosensory region (S2) within parietal opercular regions. There was no evidence for separate processing foci for selective and divided attention strategies, or for selectively attending to roughness versus stimulus duration. We observed a greater magnitude blood flow change in S2 versus S1 during attention tasks, which suggests that S2 might actually influence S1 activity. Despite these differences, modulation of S1 and S2 supports concepts of early selection in tactile attention. There were also examples of non-sensory foci in frontal cortex, anterior cingulate gyrus and bilateral superior parietal regions at the fundus of the postcentral sulcus. Posterior parietal regions observed in this study did not overlap foci seen in studies of visual attention. Thus, the posterior parietal region may be subdivided into modality-specific subregions, each of which processes information needed to attend to a specific modality. These non-sensory areas may constitute a network that provides a source of modulating influences on the earlier stage, sensory areas.

Patterns of Age-related Shrinkage in Cerebellum and Brainstem Observed In Vivo Using Three-dimensional MRI Volumetry

Abstract: This study investigates the time course and regional differences in age-related volume loss in cerebellum and brainstem. Three-dimensional (3D) magnetic resonance imaging (MRI) volumetry was used to measure the volumes of 11 regions in the cerebellum and three regions in the brainstem in 48 healthy volunteers (age 19.8-73.1 years). Landmark-adjusted lattices were used to divide the cerebellum into three radial (lobules I-V = lingula/lobulus/culmen, lobules VI-VII = declive/folium/tuber, lobules VIII-X = pyramis/uvula/nodulus) and three transverse subdivisions (vermis, medial, lateral hemisphere). The radial sectors extended laterally throughout the vermis and the medial hemisphere. The brainstem was divided into midbrain, metencephalon (pons and tegmentum pontis) and medulla. Total cerebellar volume marginally declined with age using a linear regression model. An exponential model better described the age dependency of total cerebellar volume. The curve predicted that the volume remained stable until age 50 years and declined thereafter. Volume loss in the cerebellar vermis was striking. Shrinkage in the medial hemisphere was markedly less and only the inferior sector showed a trendwise negative association with age. The lateral hemisphere was not affected by age. No age effects were found for total brainstem volume, metencephalon and medulla. Only the mid-brain showed a trend for age-related shrinkage. The mediolateral gradient of decreasing age effects is similar to the histological pattern of alcoholic cerebellar atrophy (although our subjects were non-alcoholics according to DSM-IIIR criteria and laboratory data) suggesting that a common factor is involved in both processes. In search for a cause of the regional vulnerability, vascular, functional, structural and molecular/genetic factors may be considered.

An fMRI Version of the Farnsworth–Munsell 100-Hue Test Reveals Multiple Color-selective Areas in Human Ventral Occipitotemporal Cortex

Abstract: Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth‐Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth‐Munsell test may be useful in the study of achromatopsia.

On the Neural Correlates of Visual Perception

Abstract: Neurological findings suggest that the human striate cortex (V1) is an indispensable component of a neural substratum subserving static achromatic form perception in its own right and not simply as a central distributor of retinally derived information to extrastriate visual areas. This view is further supported by physiological evidence in primates that the finest-grained conjoined representation of spatial detail and retinotopic localization that underlies phenomenal visual experience for local brightness discriminations is selectively represented at cortical levels by the activity of certain neurons in V1. However, at first glance, support for these ideas would appear to be undermined by incontrovertible neurological evidence (visual hemineglect and the simultanagnosias) and recent psychophysical results on 'crowding' that confirm that activation of neurons in V1 may, at times, be insufficient to generate a percept. Moreover, a recent proposal suggests that neural correlates of visual awareness must project directly to those in executive space, thus automatically excluding V1 from a related perceptual space because V1 lacks such direct projections. Both sets of concerns are, however, resolved within the context of adaptive resonance theories. Recursive loops, linking the dorsal lateral geniculate nucleus (LGN) through successive cortical visual areas to the temporal lobe by means of a series of ascending and descending pathways, provide a neuronal substratum at each level within a modular framework for mutually consistent descriptions of sensory data. At steady state, such networks obviate the necessity that neural correlates of visual experience project directly to those in executive space because a neural phenomenal perceptual space subserving form vision is continuously updated by information from an object recognition space equivalent to that destined to reach executive space. Within this framework, activity in V1 may engender percepts that accompany figure-ground segregations only when dynamic incongruities are resolved both within and between ascending and descending streams. Synchronous neuronal activity on a short timescale within and across cortical areas, proposed and sometimes observed as perceptual correlates, may also serve as a marker that a steady state has been achieved, which, in turn, may be a requirement for the longer time constants that accompany the emergence and stability of perceptual states compared to the faster dynamics of adapting networks and the still faster dynamics of individual action potentials. Finally, the same consensus of neuronal activity across ascending and descending pathways linking multiple cortical areas that in anatomic sequence subserve phenomenal visual experiences and object recognition may underlie the normal unity of conscious experience.

The Functional Neuroanatomy of Novelty Processing: Integrating ERP and fMRI Results

Abstract: Recent research indicates that non-tonal novel events, deviating from an ongoing auditory environment, elicit a positive event-related potential (ERP), the novel P3. Although a variety of studies examined the neural network engaged in novelty detection, there is no complete picture of the underlying brain mechanisms. This experiment investigated these neural mechanisms by combining ERP and functional magnetic resonance imaging (fMRI). Hemodynamic and electrophysiological responses were measured in the same subjects using the same experimental design. The ERP analysis revealed a novel P3, while the fMRI responses showed bilateral foci in the middle part of the superior temporal gyrus. When subjects attended to the novel stimuli only identifiable novel sounds evoked a N4-like negativity. Subjects showing a strong N4-effect had additional fMRI activation in right prefrontal cortex (rPFC) as compared to subjects with a weak N4-effect. This pattern of results suggests that novelty processing not only includes the registration of deviancy but may also lead to a fast access and retrieval of related semantic concepts. The fMRI activation pattern suggests that the superior temporal gyrus is involved in novelty detection, whereas accessing and retrieving semantic concepts related to novel sounds additionally engages the rPFC.

Face-selective Neurons During Passive Viewing and Working Memory Performance of Rhesus Monkeys: Evidence for Intrinsic Specialization of Neuronal Coding

Abstract: The functional organization of prefrontal cortex (PFC) is a central issue in cognitive neuroscience. Previous physiological investigations have often failed to reveal specialization within the PFC. However, these studies have generally not been designed to examine this issue. Methodological issues such as statistical criteria for specificity, the number of neurons sampled, the extent of cortex sampled, and the number, location and nature of the stimuli used are among the variables that need to be considered in evaluating the results of studies on functional localization. In the present study, we have examined neurons in macaque monkeys trained to fixate while viewing visual stimuli, including faces, or to use them as memoranda on a working memory task. Visual responses of over 1500 neurons were recorded throughout a wide expanse of the PFC (areas 12, 9, 46, 8 and 45). Neurons were considered selective for faces if the best response to a face was over twice as strong as that to any of a wide variety of non-face stimuli. Full electrode track reconstructions in three monkeys revealed in each that neurons which met this criterion were concentrated almost exclusively in three distinct subregions within the projection region of the temporal lobe visual areas. We further show that for all neurons, the most visually selective neurons (for faces, objects or color patterns) were also the most concentrated in the temporal lobe recipient PFC. Similar face selectivity, regional specialization, and delay or delay-like activity were observed in monkeys whether trained on memory tasks or not, which suggests that these are naturally occurring properties of prefrontal neurons. These results confirm neuronal and regional specialization for information processing in PFC and elucidate how heretofore unexamined experimental variables have a strong influence on the detection of regional specialization.

Contribution of Working Memory to Transient Activation in Human Inferior Prefrontal Cortex during Performance of the Wisconsin Card Sorting Test

Abstract: The Wisconsin Card Sorting Test (WCST) is the standard task paradigm to detect human frontal lobe dysfunction. In this test, subjects sort card stimuli with respect to one of three possible dimensions (color, form and number). These dimensions are changed intermittently, whereupon subjects are required to identify by trial and error a new correct dimension and flexibly shift cognitive set. We decomposed the cognitive requirements at the time of the dimensional changes of the WCST, using functional magnetic resonance imaging (fMRI). By explicitly informing subjects of a new correct dimension, the working memory load for the trial-and-error identification of the new dimension was removed. Event-related fMRI still revealed transient activation time-locked to the dimensional changes in areas in the posterior part of the inferior frontal sulci. However, the activation was significantly smaller than in the original WCST in which subjects had to use working memory to identify the new dimension by trial and error. Furthermore, these areas were found to spatially overlap the areas activated by a working memory task. These results suggest that working memory and set-shifting act cooperatively in the same areas of prefrontal cortex to adapt us to changing environments.

Signal-, Set- and Movement-related Activity in the Human Brain: An Event-related fMRI Study

Abstract: Electrophysiological studies on monkeys have been able to distinguish sensory and motor signals close in time by pseudorandomly delaying the cue that instructs the movement from the stimulus that triggers the movement. We have used a similar experimental design in functional magnetic resonance imaging (fMRI), scanning subjects while they performed a visuomotor conditional task with instructed delays. One of four shapes was presented briefly. Two shapes instructed the subjects to flex the index finger; the other two shapes coded the flexion of the middle finger. The subjects were told to perform the movement after a tone. We have exploited a novel use of event-related fMRI. By systematically varying the interval between the visual and acoustic stimuli, it has been possible to estimate the significance of the evoked haemodynamic response (EHR) to each of the stimuli, despite their temporal proximity in relation to the time constant of the EHR. Furthermore, by varying the phase between events and image acquisition, we have been able to achieve high temporal resolution while scanning the whole brain. We dissociated sensory and motor components of the sensorimotor transformations elicited by the task, and assessed sustained activity during the instructed delays. In calcarine and occipitotemporal cortex, the responses were exclusively associated with the visual instruction cues. In temporal auditory cortex and in primary motor cortex, they were exclusively associated with the auditory trigger stimulus. In ventral prefrontal cortex there were movement-related responses preceded by preparatory activity and by signal-related activity. Finally, responses associated with the instruction cue and with sustained activity during the delay period were observed in the dorsal premotor cortex and in the dorsal posterior parietal cortex. Where the association between a visual cue and the appropriate movement is arbitrary, the underlying visuomotor transformations are not achieved exclusively through frontoparietal interactions. Rather, these processes seem to rely on the ventral visual stream, the ventral prefrontal cortex and the anterior part of the dorsal premotor cortex.

Sulcal Variability of Twins

Abstract: We investigated three-dimensional, depth-encoded line representations of neocortical sulci calculated from magnetic resonance image (MRI) datasets of 19 pairs of normal monozygotic twins. Monozygotic co-twins were significantly more alike than control pairs of unrelated twins matched from the same sample. Sulcal depth influenced sulcal similarity, with deeper sulci being more similar than superficial sulci. This was true both for the pairs of related co-twins and for the unrelated pairs, although the sulcal depth effect was stronger for the related twins. Our results indicate that the shape of deep (ontogenetically early) sulci of the human brain is more strongly predetermined than that of superficial sulci. The finding that sulcal similarity increased with sulcal depth especially within monozygotic twin pairs should stimulate further investigations of the relative importance of genetic versus shared environmental morphogenetic factors that must account for this result. In addition, we found that subjects with similar brain shape also have more similar sulcal patterns, suggesting that both features are the result of ontogenetically related processes. Sulcal comparisons across the entire sample suggested that the left posterior lateral hemispheric surface may be the least variable brain area. Methodologically, these results were obtained by the representation of sulci as three-dimensional polygonal lines (termed 'sulcal cuts') that are extracted automatically from MRI data sets using new image analysis techniques.

An anatomical landmark for the supplementary eye fields in human revealed with functional magnetic resonance imaging.

Abstract: Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus.

Spatial View Cells in the Primate Hippocampus: Allocentric View not Head Direction or Eye Position or Place

Abstract: Hippocampal function was analysed by making recordings from hippocampal neurons in monkeys actively walking in the laboratory. 'Spatial view' cells, which respond when the monkey looks at a part of the environment, were analysed. It is shown that these cells code for the allocentric position in space being viewed and not for eye position, head direction or the place where the monkey is located. This representation of space 'out there' would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.