Changes in effective connectivity of human superior parietal lobule under multisensory and unisensory stimulation

Previous event-related potential (ERP) studies have identified the superior parietal lobule (SPL) as actively multisensory. This study compares effective, or contextually active, connections to this region under unisensory and multisensory conditions. Effective connectivity, the influence of one brain region over another, during unisensory visual, unisensory auditory and multisensory audiovisual stimulation was investigated. ERPs were recorded from subdural electrodes placed over the parietal lobe of three patients while they conducted a rapid reaction-time task. A generative model of interacting neuronal ensembles for ERPs was inverted in a scheme allowing investigation of the connections from and to the SPL, a multisensory processing area. Important features of the ensemble model include inhibitory and excitatory feedback connections to pyramidal cells and extrinsic input to the stellate cell pool, with extrinsic forward and backward connections delineated by laminar connection differences between ensembles. The framework embeds the SPL in a plausible connection of distinct neuronal ensembles mirroring the integrated brain regions involved in the response task. Bayesian model comparison was used to test competing feed-forward and feed-backward models of how the electrophysiological data were generated. Comparisons were performed between multisensory and unisensory data. Findings from three patients show differences in summed unisensory and multisensory ERPs that can be accounted for by a mediation of both forward and backward connections to the SPL. In particular, a negative gain in all forward and backward connections to the SPL from other regions was observed during the period of multisensory integration, while a positive gain was observed for forward projections that arise from the SPL.     

Auditory-somatosensory multisensory interactions in humans: Dissociating detection and spatial discrimination

Simple reaction times (RTs) to auditory-somatosensory (AS) multisensory stimuli are facilitated over their unisensory counterparts both when stimuli are delivered to the same location and when separated. In two experiments we addressed the possibility that top-down and/or task-related influences can dynamically impact the spatial representations mediating these effects and the extent to which multisensory facilitation will be observed. Participants performed a simple detection task in response to auditory, somatosensory, or simultaneous AS stimuli that in turn were either spatially aligned or misaligned by lateralizing the stimuli. Additionally, we also informed the participants that they would be retrogradely queried (one-third of trials) regarding the side where a given stimulus in a given sensory modality was presented. In this way, we sought to have participants attending to all possible spatial locations and sensory modalities, while nonetheless having them perform a simple detection task. Experiment 1 provided no cues prior to stimulus delivery. Experiment 2 included spatially uninformative cues (50% of trials). In both experiments, multisensory conditions significantly facilitated detection RTs with no evidence for differences according to spatial alignment (though general benefits of cuing were observed in Experiment 2). Facilitated detection occurs even when attending to spatial information. Performance with probes, quantified using sensitivity (d′), was impaired following multisensory trials in general and significantly more so following misaligned multisensory trials. This indicates that spatial information is not available, despite being task-relevant. The collective results support a model wherein early AS interactions may result in a loss of spatial acuity for unisensory information.     

Hippocampal involvement in retrieval of odor vs. object memories

The aim of this study was to investigate the role of the human hippocampus in episodic retrieval of odors, in comparison with episodic retrieval of visual objects. Subjects encoded a set of unique odors and objects, and retrieval was tested the next day during functional magnetic resonance imaging (fMRI). Subjects were shown the names of old (studied) and new (unstudied) odors and objects, and asked to indicate which of these stimuli had been presented the previous day. The results showed that brain activation was weaker and more restricted during retrieval of odors than during retrieval of objects, which possibly reflects a general visual dominance effect. Yet, retrieval of odors and objects yielded overlapping clusters of activation the bilateral hippocampi, and the left‐sided activation was specifically increased during successful retrieval (hits > correct rejections) in both modalities. Moreover, retrieval of odors uniquely activated olfactory cortical regions, likely to reflect cortical reinstatement of sensory details. Our fMRI study is the first to make a direct comparison between olfactory and visual episodic memory, and the results provide clear evidence for modality‐independent functions of the hippocampus. © 2012 Wiley Periodicals, Inc.     

The role of expectation in multisensory body representation – neural evidence

Sensory events contribute to body ownership, the feeling that the body belongs to me. However, the encoding of sensory events is not only reactive, but also proactive in that our brain generates prediction about forthcoming stimuli. In previous studies, we have shown that prediction of sensory events is a sufficient condition to induce the sense of body ownership. In this study, we investigated the underlying neural mechanisms. Participants were seated with their right arm resting upon a table just below another smaller table. Hence, the real hand was hidden from the participant's view and a life‐sized rubber model of a right hand was placed on the small table in front of them. Participants observed a wooden plank while approaching – without touching – the rubber hand. We measured the phenomenology of the illusion by means of questionnaire. Neural activity was recorded by means of near‐infrared spectroscopy (fNIRS). Results showed higher activation of multisensory parietal cortices in the rubber hand illusion induced by touch expectation. Furthermore, such activity was correlated with the subjective feeling of owning the rubber hand. Our results enrich current models of body ownership suggesting that our multisensory brain regions generate prediction on what could be my body and what could not. This finding might have interesting implications in all those cases in which body representation is altered, anorexia, bulimia nervosa and obesity, among others.     

Precise discrimination of object position in the human pulvinar

Very little is known about the human pulvinar; suggestions for its function include relaying input from cortical areas, allocating visual attention, supporting feature binding, and other integrative processes. The diversity of hypotheses about pulvinar function highlights our lack of understanding of its basic role. A conspicuously missing piece of information is whether the human pulvinar encodes visual information topographically. The answer to this question is crucial, as it dramatically constrains the sorts of computational and cognitive processes that the pulvinar might carry out. Here we used fMRI to test for position-sensitive encoding in the human pulvinar. Subjects passively viewed flickering Gabor stimuli, and as the spatial separation between Gabors increased, the correlation between patterns of activity across voxels within the right pulvinar decreased significantly. The results demonstrate the existence of precise topographic coding in the human pulvinar lateralized to the right hemisphere, and provide a means of functionally localizing this topographic region.     

Early memories, object relations, and current relationship functioning

This study examined the relationship between dependency themes in 140 inpatients' early childhood memories (EM) and social interactions involving dependent behavior. Hierarchical regression analyses revealed that the type of dependent EM predicted overt behavior above and beyond demographic and diagnostic categories. Patients expressing clinging dependent themes in their narratives had greater involvement in social activities in the therapeutic community program and with nurses, whereas patients expressing counterdependent themes engaged in more hostile interactions with nursing staff members, were more self-destructive, and had more emergency department admissions over the course of inpatient treatment. Results are considered in light of the clinical utility of EMs.     

A role for the inferior colliculus in multisensory speech integration

Multisensory integration can occur at relatively low levels within the central nervous system. Recent evidence suggests that multisensory audio-visual integration for speech may have a subcortical component, as acoustic processing in the human brainstem is influenced by lipreading during speech perception. Here, stimuli depicting the McGurk illusion (a demonstration of auditory-visual integration using speech stimuli) were presented to a 12-year-old child (FX) with a circumscribed unilateral lesion of the right inferior colliculus. When McGurk-type stimuli were presented in the contralesional hemifield, illusory perception reflecting bimodal integration was significantly reduced compared with the ipsilesional hemifield and a group of age-matched controls. These data suggest a functional role for the inferior colliculus in the audio-visual integration of speech stimuli.     

Reactivation during encoding supports the later discrimination of similar episodic memories

Episodic memory is characterized by remembering events as unique combinations of features. Even when some features of events overlap, we are later often able to discriminate among them. Here we ask whether hippocampally mediated reactivation of an earlier event when a similar one occurs supports subsequent memory that two similar but not identical events occurred (mnemonic discrimination). In two experiments, participants viewed objects (Experiment 1) or scenes (Experiment 2) during functional MRI (fMRI). After scanning, participants had to remember whether repeated items had been identical or similar. In Experiment 2, representational similarity between the 1st and 2nd presentation predicted participants' ability to remember that the presentations were different, suggesting that the first item was reactivated while viewing the second. A similar but weaker result was found in Experiment 1 that did not survive correction for multiple comparisons. Furthermore, both experiments yielded evidence that the hippocampus was involved in reactivation; hippocampal pattern similarity (and, in Experiment 2, hippocampal activity during the 2nd presentation) correlated with pattern similarity in several regions of visual cortex. These results provide the first fMRI evidence that hippocampally mediated reactivation contributes to the later memory that two similar, but different events occurred. © 2016 Wiley Periodicals, Inc.     

Left and right superior parietal lobule in tactile object discrimination

Tactile object discrimination is one of the major manual skills of humans. While the exploring finger movements are not perceived explicitly, attention to the movement-evoked kinaesthetic information gates the tactile perception of object form. Using event-related functional magnetic resonance imaging in seven healthy subjects we found one area in the right superior parietal cortex, which was specifically activated by kinaesthetic attention during tactile object discrimination. Another area with similar location in the left hemisphere was related to the maintenance of tactile information for subsequent object discrimination. We conclude that kinaesthetic information is processed in the anterior portion of the superior parietal cortex (aSPL) with a right hemispheric predominance for discrimination and a left hemispheric predominance for information maintenance.     

The role of the orbitofrontal cortex in human discrimination learning

Several lines of evidence implicate the prefrontal cortex in learning but there is little evidence from studies of human lesion patients to demonstrate the critical role of this structure. To this end, we tested patients with lesions of the frontal lobe (n = 36) and healthy controls (n = 35) on two learning tasks: the weather prediction task (WPT), and an eight-pair concurrent visual discrimination task (‘Choose’). Performance of both tasks was previously shown to be disrupted in patients with Parkinson's disease; the Choose deficit was only present when patients were medicated. Patients with damage to the orbitofrontal cortex (OFC) were significantly impaired on Choose, compared to both healthy controls and non-OFC lesion patients. The OFC lesion patients showed a mild deficit on the first 50 trials of the WPT, compared to the control subjects but not non-OFC lesion patients. The selective deficit in the OFC patients on Choose performance could not be attributed to the larger lesion size in this group, and the deficit was not correlated with the volume of damage to adjacent prefrontal subregions (e.g. anterior cingulate cortex). These data support the notion that the OFC play a role in normal discrimination learning, and suggest qualitative similarities in learning performance of patients with OFC damage and medicated PD patients.     

Greater loss of object than spatial mnemonic discrimination in aged adults

Previous studies across species have established that the aging process adversely affects certain memory‐related brain regions earlier than others. Behavioral tasks targeted at the function of vulnerable regions can provide noninvasive methods for assessing the integrity of particular components of memory throughout the lifespan. The present study modified a previous task designed to separately but concurrently test detailed memory for object identity and spatial location. Memory for objects or items is thought to rely on perirhinal and lateral entorhinal cortices, among the first targets of Alzheimer's related neurodegeneration. In line with prior work, we split an aged adult sample into “impaired” and “unimpaired” groups on the basis of a standardized word‐learning task. The “impaired” group showed widespread difficulty with memory discrimination, whereas the “unimpaired” group showed difficulty with object, but not spatial memory discrimination. These findings support the hypothesized greater age‐related impacts on memory for objects or items in older adults, perhaps even with healthy aging. © 2015 Wiley Periodicals, Inc.     

Motivation-related neuronal activity in the object discrimination task in monkey septal nuclei

Septal nuclei are suggested to work as an interface between the hippocampal formation, involved in higher cognitive functions, and the hypothalamus, involved in motivational behaviors such as feeding, drinking, and intracranial self-stimulation. In the present study, to elucidate a role of the septal nuclei in motivational behaviors, single neuron activity was recorded from water- and food-deprived monkeys during discrimination of objects associated with juice, and during ingestion of juice. Of 349 neurons recorded from two monkeys, 67 responded in the ingestion phase of the object discrimination task. Of these 67 neurons, 31 were further tested with the noncontingent liquid (juice or water) test in which liquid was provided until the animals became satiated. These 31 septal neurons were classified into two groups: type I neurons (n = 10) responded to juice ingestion with inhibition, and type II neurons (n = 21) responded with excitation. The spontaneous firing rates of the type I neurons were higher in the deprived condition and decreased as the animal became satiated by intake of liquid. Nine type II neurons responded to the sight of a white object associated with juice as well as ingestion of juice. The response magnitudes of the type II neurons to both the sight of the white object and ingestion of juice also decreased by satiation. However, spontaneous firing rates of the type II neurons did not change. These activity changes of both type I and II neurons were well correlated with changes in motivational state of the monkey estimated by the behavioral test. The results suggest that the activity of type I neurons reflects thirst or hunger drive levels, and that responses of type II neurons are related to reward perception. These type I and II neurons were located mainly in the anterior part of the septal nuclei. Results of the present study suggest, along with previous lesion and anatomical studies, that the septal nuclei exert a powerful influence on the motivational/drive systems through the projection to the hypothalamus. Hippocampus 1997;7:536–548. © 1997 Wiley-Liss, Inc.     

Conscious access to the unisensory components of a cross-modal illusion

It is often claimed that binding information across sensory modalities leads to coherent, unitary mental representations. The dramatic illusions experienced as a result of intersensory conflict, such as the McGurk effect, are often attributed to a propensity of the perceptual system to impose multisensory coherence onto events originating from a common source. In contrast with this ssumption of unity, we report an unexpected ability to resolve the timing between sound and sight regarding multisensory events that induce an illusory reversal of the elements specified in each modality. This finding reveals that the brain can gain access, simultaneously, to unisensory component information as well as to the result of the integrated multisensory percept, suggesting some degree of penetrability in the processes leading to cross-modality binding.     

An involvement of acetylcholine in object discrimination learning and memory in the marmoset

Five marmosets (Callithrix jacchus) were tested, using a Wisconsin General Test Apparatus, on a series of junk object visual discrimination tasks, including new learning, 24-hr reversal and 24-hr retention. The effects of administering the cholinergic receptor blocking agent, scopolamine either just before or immediately after the new learning task, or just before the 24-hr reversal and retention tasks, were assessed. Results suggest that scopolamine impairs new learning and impairs the encoding of new information in long term memory. Some evidence of a mild retrieval deficit under scopolamine was also seen, while state-dependent effects were not apparent.     

The role of color in object recognition: Evidence from visual agnosia

Background: The diagnosis of the behavioural variant of frontotemporal dementia (bvFTD) can be challenging. At present there is a paucity of prospective work addressing the specificity of current diagnostic criteria for bvFTD with respect to long-term outcome (i.e., false positives versus true positives).

Methods: Here we report two individuals who met current clinical criteria for bvFTD and who underwent detailed long-term clinical and neuropsychological follow-up. In addition, both had serial volumetric MRI and functional metabolic (FDG-PET) imaging separated by 5 years.

Results: One case had a slow clinical decline as well as both progressive atrophy and hypometabolism in a frontotemporal distribution, consistent with a neurodegenerative FTD syndrome. However, the second developed neither atrophy nor hypometabolism and remained clinically stable, a decade from symptom onset.

Conclusion: We propose that these cases illustrate that while there may be a slow evolution in bvFTD, it is possible that some cases who meet current criteria may not have a neurodegenerative syndrome. If correct, this hypothesis has important implications for the current diagnostic criteria. A potential hierarchy for diagnostic certainty in bvFTD is suggested.     

DREADD-inactivation of dorsal CA1 pyramidal neurons in mice impairs retrieval of object and spatial memories

The hippocampus, a medial temporal lobe brain region, is critical for the consolidation of information from short-term memory into long-term episodic memory and for spatial memory that enables navigation. Hippocampal damage in humans has been linked to amnesia and memory loss, characteristic of Alzheimer's disease and other dementias. Numerous studies indicate that the rodent hippocampus contributes significantly to long-term memory for spatial and nonspatial information. For example, muscimol-induced depression of CA1 neuronal activity in the dorsal hippocampus impairs the encoding, consolidation, and retrieval of nonspatial object memory in mice. Here, a chemogenetic designer receptor exclusively activated by designer drugs (DREADDs) approach was used to test the selective involvement of CA1 pyramidal neurons in memory retrieval for objects and for spatial location in a cohort of male C57BL/6J mice. Activation of the inhibitory (hM4Di) DREADDs receptor expressed in CA1 neurons significantly impaired the retrieval of object memory in the spontaneous object recognition task and of spatial memory in the Morris water maze. Silencing of CA1 neuronal activity in hM4Di-expressing mice was confirmed by comparing Fos expression in vehicle- and clozapine-N-oxide-treated mice after exploration of a novel environment. Histological analyses revealed that expression of the hM4Di receptor was limited to CA1 neurons of the dorsal hippocampus. These results suggest that a common subset of CA1 neurons (i.e., those expressing hM4Di receptors) in mouse hippocampus contributed to the retrieval of long-term memory for nonspatial and spatial information. Our findings support the view that the contribution of the rodent hippocampus is like that of the primate hippocampus, specifically essential for global memory. Our results further validate mice as a suitable model system to study the neurobiological mechanisms of human episodic memory, but also in developing treatments and understanding the underlying causes of diseases affecting long-term memory, such as Alzheimer's disease.     

The role of the dorsal funiculus of the primate in tactile discrimination

The critical role of the dorsal funiculus for tactile discriminations requiring active exploration of the stimulus object was tested in the monkey. Pairs of discriminanda (patterned disks) were constructed with geometric designs of such size and shape as to require active palpation for successful discrimination. For comparison, other discriminanda with tactile qualities which could be recognized by a more passive response topography were also examined. Section of the dorsal funiculus resulted in severe, long-lasting deficits in discrimination of the patterned disks, while discrimination of the tactile qualities not requiring active exploration was retained. No significant motor impairment was observed. Lesions in the spinothalamic or spinocervical systems had no effect on either type of cutaneous discrimination. The results support the view that the afferents from the monkey hand which travel in the dorsal funiculus are critically and possibly exclusively involved in the perception of tactile stimuli requiring a spatiotemporal transformation by the introduction of movement. It is further suggested that such movement need not be self-initiated.     

Joint engagement modulates object discrimination in toddlers: a pilot electrophysiological investigation

Joint engagement (JE) is a state in which two people attend to a common target. By supporting an infant’s attention to the target, JE promotes encoding of information. This process has not been studied in toddlers despite the fact that language and social interaction develop rapidly in this period. We asked whether JE modulates object discrimination in typically developing toddlers. In a pilot evaluation of a novel, naturalistic paradigm, toddlers (n = 11) were introduced to toys by an examiner with or without JE. Toddlers then viewed images of the toys while high-density electroencephalography (EEG) was recorded. Analysis focused on the differential neural response to objects presented in the two conditions. EEG components of interest included frontal positive component (Pb), negative component (Nc), and positive slow wave. Toddlers discriminated between conditions with a larger Pb peak amplitude to stimuli presented with JE and a larger Nc mean amplitude to the stimuli presented without JE, reflecting greater familiarity with the toys presented socially. Our findings suggest that JE supports object learning in toddlers, and supports the potential utility of this novel paradigm in both the assessment and the potential to detect impairment in social learning among toddlers.     

Disturbed functional brain interactions underlying deficient tactile object discrimination in Parkinson's disease

Somatosensory discrimination of cuboid objects was studied in a group of healthy volunteers and patients with Parkinson's disease using regional cerebral blood flow (rCBF) measurements obtained with positron emission tomography (PET) and 15O labeled water [H2 15O]. A 6-[18F]-fluoro-L-dopa (FDOPA) PET scan demonstrated that the patients may be grouped into those with normal and those with abnormally lowA FDOPA uptake in the caudate nucleus. The categorical group comparisons revealed that task-induced rCBF increases were deficient in bilateral motor and sensory cortical areas in the Parkinson patients. Moreover, deficient rCBF increases were evident in the mesial and right dorsolateral prefrontal cortex for patients in a more advanced disease state, who showed low FDOPA uptake in the caudate nucleus. A principal component analysis (PCA), performed on the rCBF data, identified three patterns (principal components, PCs) that differentiated patients from normals. The first PC represented a right-hemisphere dominant, bilateral group of brain areas known to be involved in tactile exploration. A second PC reflected a cortical-subcortical pattern of functional interactions, comprising cortical areas important for working memory processes. The third group-differentiating PC revealed a pattern of functional interactions involving bilateral temporo-parieto-occipital association cortices, which was consistent with a hypothesized supramodal network necessary for object discrimination. In an additional subgroup analysis, greater expression of the third PC pattern predicted greater caudate FDOPA uptake in patients. Our neuroimaging data revealed a disturbance of distinct patterns of brain functional interactions related to the sensorimotor deficit in Parkinson's disease and to deficits of cognitive information processing deficits in the more advanced stage of Parkinson's disease.