Human cortical processing of colour and pattern

The present study investigates human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that we specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. We did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. We found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions. (C) 2001 Wiley-Liss, Inc.

Computational models of cortical visual processing.

The visual responses of neurons in the cerebral cortex were first adequately characterized in the 1960s by D. H. Hubel and T. N. Wiesel [(1962) J. Physiol. (London) 160, 106-154; (1968) J. Physiol. (London) 195, 215-243] using qualitative analyses based on simple geometric visual targets. Over the past 30 years, it has become common to consider the properties of these neurons by attempting to make formal descriptions of these transformations they execute on the visual image. Most such models have their roots in linear-systems approaches pioneered in the retina by C. Enroth-Cugell and J. R. Robson [(1966) J. Physiol. (London) 187, 517-552], but it is clear that purely linear models of cortical neurons are inadequate. We present two related models: one designed to account for the responses of simple cells in primary visual cortex (V1) and one designed to account for the responses of pattern direction selective cells in MT (or V5), an extrastriate visual area thought to be involved in the analysis of visual motion. These models share a common structure that operates in the same way on different kinds of input, and instantiate the widely held view that computational strategies are similar throughout the cerebral cortex. Implementations of these models for Macintosh microcomputers are available and can be used to explore the models' properties.

Auditory localisation and recognition after left inferior collicular lesion: effects of work load on cortical activation patterns (fMRI study)

Evidence from neuropsychological and activation studies (Clarke et al., 2oo0, Maeder et al., 2000) suggests that sound recognitionand localisation are processed by two anatomically and functionally distinct cortical networks. We report here on a case of a patientthat had an interruption of auditory information and we show: i) the effects of this interruption on cortical auditory processing; ii)the effect of the workload on activation pattern.A 36 year old man suffered from a small left mesencephalic haemotrhage, due to cavernous angioma; the let% inferior colliculuswas resected in the surgical approach of the vascular malformation. In the acute stage, the patient complained of auditoryhallucinations and of auditory loss in right ear, while tonal audiometry was normal. At 12 months, auditory recognition, auditorylocalisation (assessed by lTD and IID cues) and auditory motion perception were normal (Clarke et al., 2000), while verbal dichoticlistening was deficient on the right side.Sound recognition and sound localisation activation patterns were investigated with fMRI, using a passive and an activeparadigm. In normal subjects, distinct cortical networks were involved in sound recognition and localisation, both in passive andactive paradigm (Maeder et al., 2OOOa, 2000b).Passive listening of environmental and spatial stimuli as compared to rest strongly activated right auditory cortex, but failed toactivate left primary auditory cortex. The specialised networks for sound recognition and localisation could not be visual&d onthe right and only minimally on the left convexity. A very different activation pattern was obtained in the active condition wherea motor response was required. Workload not only increased the activation of the right auditory cortex, but also allowed theactivation of the left primary auditory cortex. The specialised networks for sound recognition and localisation were almostcompletely present in both hemispheres.These results show that increasing the workload can i) help to recruit cortical region in the auditory deafferented hemisphere;and ii) lead to processing auditory information within specific cortical networks.References:Clarke et al. (2000). Neuropsychologia 38: 797-807.Mae.der et al. (2OOOa), Neuroimage 11: S52.Maeder et al. (2OOOb), Neuroimage 11: S33

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc.

In vivo neuropathology of cortical changes in elderly persons with schizophrenia.

BACKGROUND: Elderly schizophrenia patients frequently develop cognitive impairment of unclear etiology. Magnetic resonance imaging (MRI) studies revealed brain structural abnormalities, but the pattern of cortical gray matter (GM) volume and its relationship with cognitive and behavioral symptoms are unknown. METHODS: Magnetic resonance scans were taken from elderly schizophrenia patients (n = 20, age 67 +/- 6 SD, Mini-Mental State Examination [MMSE] 23 +/- 4), Alzheimer's disease (AD) patients (n = 20, age 73 +/- 9, MMSE 22 +/- 4), and healthy elders (n = 20, age 73 +/- 8, MMSE 29 +/- 1). Patients were assessed with a comprehensive neuropsychological and behavioral battery. Cortical pattern matching and a region-of-interest analysis, based on Brodmann areas (BAs), were used to map three-dimensional (3-D) profiles of differences in patterns of gray matter volume among groups. RESULTS: Schizophrenia patients had 10% and 11% lower total left and right GM volume than healthy elders (p < .001) and 7% and 5% more than AD patients (p = .06 and ns). Regions that had both significantly less gray matter than control subjects and gray matter volume as low as AD mapped to the cingulate gyrus and orbitofrontal cortex (BA 30, 23, 24, 32, 25, 11). The strongest correlate of gray matter volume in elderly schizophrenia patients, although nonsignificant, was the positive symptom subscale of the Positive and Negative Syndrome Scale, mapping to the right anterior cingulate area (r = .42, p = .06). CONCLUSIONS: The orbitofrontal/cingulate region had low gray matter volume in elderly schizophrenia patients. Neither cognitive impairment nor psychiatric symptoms were significantly associated with structural differences, even if positive symptoms tended to be associated with increased gray matter volume in this area.

Atypical coordination of cortical oscillations in response to speech in autism.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.

Information processing in the human brain: magnetoencephalographic approach.

Rapid progress in effective methods to image brain functions has revolutionized neuroscience. It is now possible to study noninvasively in humans neural processes that were previously only accessible in experimental animals and in brain-injured patients. In this endeavor, positron emission tomography has been the leader, but the superconducting quantum interference device-based magnetoencephalography (MEG) is gaining a firm role, too. With the advent of instruments covering the whole scalp, MEG, typically with 5-mm spatial and 1-ms temporal resolution, allows neuroscientists to track cortical functions accurately in time and space. We present five representative examples of recent MEG studies in our laboratory that demonstrate the usefulness of whole-head magnetoencephalography in investigations of spatiotemporal dynamics of cortical signal processing.

The perception of touch and the ventral somatosensory pathway.

In humans, touching the skin is known to activate, among others, the contralateral primary somatosensory cortex on the postcentral gyrus together with the bilateral parietal operculum (i.e. the anatomical site of the secondary somatosensory cortex). But which brain regions beyond the postcentral gyrus specifically contribute to the perception of touch remains speculative. In this study we collected structural magnetic resonance imaging scans and neurological examination reports of patients with brain injuries or stroke in the left or right hemisphere, but not in the postcentral gyrus as the entry site of cortical somatosensory processing. Using voxel-based lesion-symptom mapping, we compared patients with impaired touch perception (i.e. hypoaesthesia) to patients without such touch impairments. Patients with hypoaesthesia as compared to control patients differed in one single brain cluster comprising the contralateral parietal operculum together with the anterior and posterior insular cortex, the putamen, as well as subcortical white matter connections reaching ventrally towards prefrontal structures. This finding confirms previous speculations on the 'ventral pathway of somatosensory perception' and causally links these brain structures to the perception of touch.

Auditory spatio-temporal brain dynamics and their consequences for multisensory interactions in humans.

Recent multisensory research has emphasized the occurrence of early, low-level interactions in humans. As such, it is proving increasingly necessary to also consider the kinds of information likely extracted from the unisensory signals that are available at the time and location of these interaction effects. This review addresses current evidence regarding how the spatio-temporal brain dynamics of auditory information processing likely curtails the information content of multisensory interactions observable in humans at a given latency and within a given brain region. First, we consider the time course of signal propagation as a limitation on when auditory information (of any kind) can impact the responsiveness of a given brain region. Next, we overview the dual pathway model for the treatment of auditory spatial and object information ranging from rudimentary to complex environmental stimuli. These dual pathways are considered an intrinsic feature of auditory information processing, which are not only partially distinct in their associated brain networks, but also (and perhaps more importantly) manifest only after several tens of milliseconds of cortical signal processing. This architecture of auditory functioning would thus pose a constraint on when and in which brain regions specific spatial and object information are available for multisensory interactions. We then separately consider evidence regarding mechanisms and dynamics of spatial and object processing with a particular emphasis on when discriminations along either dimension are likely performed by specific brain regions. We conclude by discussing open issues and directions for future research.

Fundamental deficits of auditory perception in Wernicke’s aphasia

Objective: This work investigates the nature of the comprehension impairment in Wernicke’s aphasia, by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. Wernicke’s aphasia, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. Methods: We examined analysis of basic acoustic stimuli in Wernicke’s aphasia participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in “moving ripple” stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. Results: Participants with Wernicke’s aphasia showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both frequency and dynamic modulation detection correlated significantly with auditory comprehension abilities in the Wernicke’s aphasia participants. Conclusion: These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectrotemporal nonverbal stimuli in Wernicke’s aphasia, which may have a causal contribution to the auditory language comprehension impairment Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.

The retina in Parkinson's disease

As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of ‘higher’ (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

Norepinephrine drives persistent activity in prefrontal cortex via synergistic α1 and α2 adrenoceptors

Optimal norepinephrine levels in the prefrontal cortex (PFC) increase delay-related firing and enhance working memory, whereas stress-related or pathologically high levels of norepinephrine are believed to inhibit working memory via α1 adrenoceptors. However, it has been shown that activation of Gq-coupled and phospholipase C-linked receptors can induce persistent firing, a cellular correlate of working memory, in cortical pyramidal neurons. Therefore, despite its importance in stress and cognition, the exact role of norepinephrine in modulating PFC activity remains elusive. Using electrophysiology and optogenetics, we report here that norepinephrine induces persistent firing in pyramidal neurons of the PFC independent of recurrent fast synaptic excitation. This persistent excitatory effect involves presynaptic α1 adrenoceptors facilitating glutamate release and subsequent activation of postsynaptic mGluR5 receptors, and is enhanced by postsynaptic α2 adrenoceptors inhibiting HCN channel activity. Activation of α2 adrenoceptors or inhibition of HCN channels also enhances cholinergic persistent responses in pyramidal neurons, providing a mechanism of crosstalk between noradrenergic and cholinergic inputs. The present study describes a novel cellular basis for the noradrenergic control of cortical information processing and supports a synergistic combination of intrinsic and network mechanisms for the expression of mnemonic properties in pyramidal neurons.

Mnemonic neuronal activity in somatosensory cortex.

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory.