Cortical responses to tactile stimuli in preterm infants

The conventional assessment of preterm somatosensory functions using averaged cortical responses to electrical stimulation ignores the characteristic components of preterm somatosensory evoked responses (SERs). Our study aimed to systematically evaluate the occurrence and development of SERs after tactile stimulus in preterm infants. We analysed SERs performed during 45 electroencephalograms (EEGs) from 29 infants at the mean post‐menstrual age of 30.7 weeks. Altogether 2,087 SERs were identified visually at single‐trial level from unfiltered signals capturing also their slowest components. We observed salient SERs with a high‐amplitude slow component at a high success rate after hand (95%) and foot (83%) stimuli. There was a clear developmental change in both the slow wave and the higher‐frequency components of the SERs. Infants with intraventricular haemorrhage (IVH; eleven infants) had initially normal SERs, but those with bilateral IVH later showed a developmental decrease in the ipsilateral SER occurrence after 30 weeks of post‐menstrual age. Our study shows that tactile stimulus applied at bedside elicits salient SERs with a large slow component and an overriding fast oscillation, which are specific to the preterm period. Prior experimental research indicates that such SERs allow studying both subplate and cortical functions. Our present findings further suggest that they might offer a window to the emergence of neurodevelopmental sequelae after major structural brain lesions and, hence, an additional tool for both research and clinical neurophysiological evaluation of infants before term age.     

Functional imaging of brain responses to pain. A review and meta-analysis (2000).

Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated.     

Structural brain imaging in schizophrenia: a selective review.

Structural neuroimaging studies have provided some of the most consistent evidence for brain abnormalities in schizophrenia. Since the initial computed tomography study by Johnstone and co-workers, which reported lateral ventricular enlargement in schizophrenia, advances in brain imaging technology have enabled further and more refined characterization of abnormal brain structure in schizophrenia in vivo. This selective review discusses the major issues and findings in structural neuroimaging studies of schizophrenia. Among these are evidence for generalized and regional brain volume abnormalities, the specificity of anatomic findings to schizophrenia and to men versus women with schizophrenia, the contribution of genetic influences, and the timing of neuroanatomic pathology in schizophrenia. The second section reviews new approaches for examining brain structure in schizophrenia and their applications to studies on the pathophysiology of schizophrenia.     

The relationship of structural brain imaging parameters to antipsychotic treatment response: a review.

Over the last decade, a number of studies have attempted to relate brain morphology to treatment response to neuroleptics. This approach has scientific potential to define subtypes of schizophrenia as well as potential clinical utility. In the present report, a review of 33 studies, including a meta-analysis, is provided. Although the overall test of the effect was not significant, the analysis revealed marked heterogeneity in the results of the various studies. The following factors were significant predictors of effect size: age, illness duration and age of onset of the patient cohort, the percentage of patients with marked structural abnormality included in the study overall, the duration of treatment and the degree of symptom improvement in the study overall. The following factors were unrelated to study effect size: date of study, gender, and the presence of a washout period. In future studies, attention to the parameters utilized in the meta-analysis should help to clarify the strength and generality of the relationship between brain morphology and treatment response.     

Modulation of brain and behavioural responses to cognitive visual stimuli with varying signal-to-noise ratios.

OBJECTIVE: To study behavioral and brain responses to variations in signal-to-noise ratio (SNR) of cognitive visual stimuli. METHODS: We presented meaningful words visually, embedded in varying amounts of dynamic noise, and utilized magnetoencephalography (MEG) to measure responses to the words. A multidipole model of the evoked fields was constructed to quantify the strengths and latencies of the neuronal sources at each noise level. The recognition rates of the words were measured in separate behavioral sessions. RESULTS: MEG revealed sequential activation of occipital and occipito-temporal areas (latencies 130-250 and 170-350 ms, respectively) followed by activity in superior temporal cortex (230-640 ms). The strengths and latencies of all identified sources followed functions similar to the SNR of the stimulus. The peak amplitudes and shortest latencies of all sources coincided with the maximum SNR of the stimulus. The occipito-temporal and temporal sources as well as the word recognition rate accurately followed the SNR of the stimulus whereas the early occipital source exhibited a more peaked dependence on the SNR. CONCLUSIONS: Evoked responses expectedly peaked at the maximum SNR of the stimulus. Interestingly, early visual responses showed sharper peaks than longer-latency sources as a function of the noise level. This can be understood as the higher-level processes analyzing the stimuli more holistically and thus being less sensitive to the salience of simple visual features. The similar noise-dependence of the longer-latency sources and the recognition rate provides new evidence for the relevance of these activations in the recognition of written words. SIGNIFICANCE: This study contributes to the understanding of brain activity evoked by degraded stimuli with cognitive content.     

A delivery device for presentation of tactile stimuli during functional magnetic resonance imaging

We describe a novel stimulus delivery system designed to present tactile stimuli to a subject in the tunnel of a magnetic resonance imaging (MRI) system. Using energy from an air-driven piston to turn a wheel, the device advances a conveyor belt with a pre-determined sequence of stimuli that differ in their spatial features into the tunnel of the MRI. The positioning of one or several stimulus objects in a window near the subject's hand is controlled by a photoelectric device that detects periodic openings in the conveyor belt. Using this electric signal to position each presentation avoids cumulative positioning errors and provides a signal related to the progression of the experiment. We used a series of shapes that differed in their spatial features but the device could carry stimuli with a diversity of shapes and textures. This flexibility allows the experimenter to design a wide variety of psychophysical experiments in the haptic world and possibly to compare and contrast these stimuli with the cognitive treatment of similar stimuli delivered to the other senses. Appropriate experimental design allows separation of motor, sensory and memory storage phases of mental processes.     

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.     

Temporal and spatio-temporal attention to tactile stimuli in extinction patients

The temporal deployment of attention to tactile stimuli delivered to the same or to a symmetrical position of the body was assessed in 6 Right-Brain Damaged (RBD) patients with left tactile extinction and 6 healthy controls. Two different tasks called Temporal (T) and Spatio-Temporal (ST) extinction were used. In the T task single or double electro tactile stimuli were delivered to the same point to the left or, in separate blocks, to the right index finger. Double stimuli were separated by different Stimulus Onset Asynchronies (SOAs). In the ST task, stimuli could be single (left or right) or double (left and right). Double stimuli were delivered to the index finger of both hands simultaneously or sequentially. In both tasks subjects were asked to report the number of the stimuli they perceived. In the ST task, subjects were also requested to report the stimuli location. Results show that in both tasks RBD patients' detection of left sided stimuli was significantly lower than of right sided stimuli detection, mainly at shortest SOAs. Moreover, detection of left sided stimuli was higher when two stimuli were delivered in sequence and in symmetrical body areas and in different sides of the space than when stimuli were delivered in sequence in the same body area. Results suggest that the interaction between spatial and temporal variables enhances the ability of tactile extinction patients to detect left sided stimuli.     

Summation of rapid tactile stimuli in parietal lobe disease.

The perception threshold for trains of rapid tactile pulses, applied to the index finger, has been measured in patients with parietal lobe lesions and in patients with median nerve lesions. The former patients had increased perception thresholds for single tactile pulses on the abnormal side. With successively prolonged pulse trains, the threshold decreased exponentially to reach a stable level after 150-400 ms. In contrast, the median nerve patients had increased perception thresholds for tactile pulses irrespective of pulse train duration.     

The quest for an image of brain: a brief historical and technical review of brain imaging techniques.

Each of the brain imaging techniques in common clinical use (skull radiography, midline ultrasonography, isotope scan, pneumoencephalography, angiography and computerized tomography) depicts some structural or functional characteristic of the brain. Each produces a correspondingly restricted concept of the status of the brain. Computerized tomography, which defines the radiodensity of head tissues, has a fundamental advantage over the other techniques in that it defines with quite good resolution a characteristic of brain tissue itself (radiodensity), rather than visualizing some anatomic compartment other than brain parenchyma. It provides an explicit image of the brain quite analogous to gross sections of the brain seen at autopsy. Computerized tomography has already substantially reshaped the practice of neurology wherever it has become available and probably will come to play a role as pivotal in clinical neurology as does bone radiography in orthopedics.     

Human frequency-following responses to monaural and binaural stimuli.

Frequency-following responses, with latencies circa 6 msec, were recorded from five normal-hearing human subjects to brief 500 c/sec tone bursts presented monaurally. The frequency-following responses appear as peaks occurring at 2 msec intervals superimposed on a slow wave (pedestal-like) component. Comparisons were made between the frequency-following responses evoked by binaural and monaural stimuli. The results show that the binaural responses may be interpreted as the sum of two monaural responses. It is concluded, therefore, that there are two independent populations of neurons, each capable of generating a frequency-following response is not a microphonic-like response but rather that the individual waves in the frequency-following response are evoked by the collective activity of phase-locked single units. Finally, on the basis of the distinctness of the individual waves in the frequency-following response, it is concluded that the neural generators of the response must be spatially compact.     

A review of multivariate methods for multimodal fusion of brain imaging data

The development of various neuroimaging techniques is rapidly improving the measurements of brain function/structure. However, despite improvements in individual modalities, it is becoming increasingly clear that the most effective research approaches will utilize multi-modal fusion, which takes advantage of the fact that each modality provides a limited view of the brain. The goal of multi-modal fusion is to capitalize on the strength of each modality in a joint analysis, rather than a separate analysis of each. This is a more complicated endeavor that must be approached more carefully and efficient methods should be developed to draw generalized and valid conclusions from high dimensional data with a limited number of subjects. Numerous research efforts have been reported in the field based on various statistical approaches, e.g. independent component analysis (ICA), canonical correlation analysis (CCA) and partial least squares (PLS). In this review paper, we survey a number of multivariate methods appearing in previous multimodal fusion reports, mostly fMRI with other modality, which were performed with or without prior information. A table for comparing optimization assumptions, purpose of the analysis, the need of priors, dimension reduction strategies and input data types is provided, which may serve as a valuable reference that helps readers understand the trade-offs of the 7 methods comprehensively. Finally, we evaluate 3 representative methods via simulation and give some suggestions on how to select an appropriate method based on a given research.     

Adaptive anterior hippocampal responses to oddball stimuli.

An efficient memory system requires the ability to detect and preferentially encode novel stimuli. Human electrophysiological recordings demonstrate differential hippocampal responses to novel vs. familiar stimuli, as well as to oddball stimuli. Although functional imaging experiments of novelty detection have demonstrated hippocampal activation, oddball-evoked hippocampal activation has not been demonstrated. Here we use event-related functional magnetic resonance imaging (fMRI) to measure hippocampal responses to three types of oddball words: perceptual, semantic, and emotional. We demonstrate left anterior hippocampal sensitivity to all three oddball types, with adaptation of responses across multiple oddball presentations. This adaptive hippocampal oddball response was not modulated by depth of processing, suggesting a high degree of automaticity in the underlying process. However, an interaction with depth of encoding for semantic oddballs was evident in a more lateral left anterior hippocampal region. We conclude that the hippocampal response to oddballs demonstrates a second-order novelty effect, being sensitive to the "novelty of novelty" of oddball stimuli. The data provide support for a more general theory that a function of the anterior hippocampus is to register mismatches between expectation and experience.     

Perceiving the tree in the woods: segregating brain responses to stimuli constituting natural scenes

Conventional neuroscientific methods are inadequate for separating the brain responses related to the simultaneous processing of different parts of a natural scene. In the present human electroencephalogram (EEG) study, we overcame this limitation by tagging concurrently presented backgrounds and objects with different presentation frequencies. As a result, background and object elicited different steady-state visual evoked potentials (SSVEPs), which were separately quantified in the frequency domain. We analyzed the effects of semantic consistency and inconsistency between background and object on SSVEP amplitudes, topography, and tomography [variable resolution electromagnetic tomography (VARETA)]. The results revealed that SSVEPs related to background processing showed higher amplitudes in the consistent as opposed to the inconsistent condition, whereas object-related SSVEPs showed the reversed pattern of effects. Given the SSVEPs' sensitivity to visual attention, the results indicate that semantic inconsistency leads to greater attention focused on the object. If all image parts are semantically related, attention is rather directed to the background. The attentional advantage to inconsistent objects in a scene is likely the result of a mismatch between background-based expectations and semantic object information. A clear lateralization of the consistency effect in the anterior temporal lobes indicates functional hemispheric asymmetries in processing background- and object-related semantic information. In summary, the present study is the first to demonstrate the feasibility of SSVEPs to unravel the respective contributions of concurrent neuronal processes involved in the perception of background and object.     

Influence of response modality on awareness of contralesional tactile stimuli in right brain damaged patients

Thirty right brain-damaged (RBD) patients with left tactile extinction (19 of whom also showed neglect) were given a sequence of 240 tactile stimuli – 80 right, 80 left, 80 bilateral – across 4 different response conditions: (a) verbal report of stimulated side/s, (b) motor report of stimulated side/s, (c) verbal report of unstimulated side/s, (d) motor report of unstimulated side/s. Earlier experiments based on similar tasks but involving RBD patients with visual extinction and/or neglect have shown that visual awareness of contralesional stimuli can be influenced by manipulation of response conditions.

Since neglect and extinction can be double-dissociated both anatomically and behaviourally, the question arises of whether the underlying neuronal mechanisms are different. To answer this question the present work investigated the role of perceptual and premotor factors in generating tactile extinction in response to Double Simultaneous Stimulation (DSS). The hypothesis was that a directional response bias would result in an overall higher frequency of errors for verbal or motor responses indicating the ipsilesional side (right); a perceptual bias would instead result in errors distributed with similar frequency on the ipsilesional and the contralesional (left) side.

Results showed that, in RBD patients, contralesional extinction was not influenced by response conditions (verbal/motor; report of stimulated/unstimulated side) and presence/absence of neglect. This suggests that: (1) among RBD patients, directional response biases are unlikely to play a role in extinction of tactile stimuli on DSS; (2) the mechanisms underlying extinction are, at least to some extent, different from those underlying unilateral neglect.     

Functional magnetic resonance imaging of the brain: a quick review

Ability to non-invasively map the hemodynamic changes occurring focally in areas of brain involved in various motor, sensory and cognitive functions by functional magnetic resonance imaging (fMRI) has revolutionized research in neuroscience in the last two decades. This technique has already gained clinical use especially in pre-surgical evaluation of epilepsy and neurosurgical planning of resection of mass lesions adjacent to eloquent cortex. In this review we attempt to illustrate basic principles and techniques of fMRI, its applications, practical points to consider while performing and evaluating clinical fMRI and its limitations.     

Capturing the spatial percepts evoked by moving tactile stimuli: a novel approach

Forced-choice procedures are conventionally used to study the percepts evoked by stimuli that move across the skin and enable an unbiased estimation of subjects' sensory capacities. These procedures, however, require subjects to assign complicated percepts to one of a small number of experimenter-defined response categories, none of which may satisfactorily describe the perceptual experience. To address this limitation, we developed a psychophysical approach, which graphically captures spatial information about a moving stimulus in a holistic manner. Briefly summarized, the stimulus object controlled for location, velocity, direction and distance is moved across the skin of a blind-folded subject, after which the subject draws its path on a life-size, two-dimensional photograph of the body region stimulated. Using this approach, we demonstrated that the drawings contain perceptually relevant information, estimates of direction discrimination and subjective traverse length derived from the drawings closely parallel data obtained with forced-choice and magnitude estimation methods, respectively, and generate comparable psychophysical functions of stimulus velocity. In addition, information is represented in the complex shapes of the curves and in the locations at which they are drawn. Analyses of these latter features support the hypothesis that non-sensory factors (individual subject biases) also affect the drawings.     

Mislocalization of tactile stimuli applied to the trunk in spatial neglect

Introduction

In patients with spatial neglect, body perception and representation are impaired – especially the projection of the anterior body midline in anterior space (the subjective “straight ahead”). However, data on more lateral body parts and the posterior body surface are scarce. We explored deviations of the perception of different body points located to the left or right of the midline and on the anterior and posterior body surfaces, and their lesion correlates in right hemisphere stroke patients.

Methods

Nine patients with neglect (diagnosed with paper and pencil and behavioural tests) were compared with six non-neglect patients and 13 healthy controls. The subjects had to use a mannequin to designate the body location that had been stimulated by a blunt pencil tip. Four horizontally arranged series of locations were traced on the anterior and posterior body surfaces at shoulder and navel levels. Each horizontal series comprised five equidistant test points, from left to right and corresponded to eleven labelled points on the mannequin. Patient errors were confronted to their anatomic lesions (MRI).

Results

We found a significant (p ≤ .05) rightward deviation of the left-side points and midpoint and a significant leftward deviation of the right-most point in neglect patients. Non-neglect patients and control subjects designated all the test points accurately. The body side (anterior or posterior) and the line (shoulder or navel) did not influence performance. Controls showed a definite reduction in variability for the midline points, which disappeared in neglect patients who showed a severe global increase of this variability. Errors depended on lesions centred on the intraparietal sulcus.

Conclusions

These observations were compatible with a complex bias in body perception–representation extending to various lateral body points, with a left to right gradient. The right parietal cortex likely participates in processing such information.     

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.