Breakdown of category-specific word representations in a brain-constrained neurocomputational model of semantic dementia

The neurobiological nature of semantic knowledge, i.e., the encoding and storage of conceptual information in the human brain, remains a poorly understood and hotly debated subject. Clinical data on semantic deficits and neuroimaging evidence from healthy individuals have suggested multiple cortical regions to be involved in the processing of meaning. These include semantic hubs (most notably, anterior temporal lobe, ATL) that take part in semantic processing in general as well as sensorimotor areas that process specific aspects/categories according to their modality. Biologically inspired neurocomputational models can help elucidate the exact roles of these regions in the functioning of the semantic system and, importantly, in its breakdown in neurological deficits. We used a neuroanatomically constrained computational model of frontotemporal cortices implicated in word acquisition and processing, and adapted it to simulate and explain the effects of semantic dementia (SD) on word processing abilities. SD is a devastating, yet insufficiently understood progressive neurodegenerative disease, characterised by semantic knowledge deterioration that is hypothesised to be specifically related to neural damage in the ATL. The behaviour of our brain-based model is in full accordance with clinical data—namely, word comprehension performance decreases as SD lesions in ATL progress, whereas word repetition abilities remain less affected. Furthermore, our model makes predictions about lesion- and category-specific effects of SD: our simulation results indicate that word processing should be more impaired for object- than for action-related words, and that degradation of white matter should produce more severe consequences than the same proportion of grey matter decay. In sum, the present results provide a neuromechanistic explanatory account of cortical-level language impairments observed during the onset and progress of semantic dementia

Is that a belt or a snake? object attentional selection affects the early stages of visual sensory processing

<p>Abstract</p> <p>Background</p> <p>There is at present crescent empirical evidence deriving from different lines of ERPs research that, unlike previously observed, the earliest sensory visual response, known as C1 component or P/N80, generated within the striate cortex, might be modulated by selective attention to visual stimulus features. Up to now, evidence of this modulation has been related to space location, and simple features such as spatial frequency, luminance, and texture. Additionally, neurophysiological conditions, such as emotion, vigilance, the reflexive or voluntary nature of input attentional selection, and workload have also been related to C1 modulations, although at least the workload status has received controversial indications. No information is instead available, at present, for objects attentional selection.</p> <p>Methods</p> <p>In this study object- and space-based attention mechanisms were conjointly investigated by presenting complex, familiar shapes of artefacts and animals, intermixed with distracters, in different tasks requiring the selection of a relevant target-category within a relevant spatial location, while ignoring the other shape categories within this location, and, overall, all the categories at an irrelevant location. EEG was recorded from 30 scalp electrode sites in 21 right-handed participants.</p> <p>Results and Conclusions</p> <p>ERP findings showed that visual processing was modulated by both shape- and location-relevance <it>per se</it>, beginning separately at the latency of the early phase of a precocious negativity (60-80 ms) at mesial scalp sites consistent with the C1 component, and a positivity at more lateral sites. The data also showed that the attentional modulation progressed conjointly at the latency of the subsequent P1 (100-120 ms) and N1 (120-180 ms), as well as later-latency components. These findings support the views that (1) V1 may be precociously modulated by direct top-down influences, and participates to object, besides simple features, attentional selection; (2) object spatial and non-spatial features selection might begin with an early, parallel detection of a target object in the visual field, followed by the progressive focusing of spatial attention onto the location of an actual target for its identification, somehow in line with neural mechanisms reported in the literature as "object-based space selection", or with those proposed for visual search.</p

Early and Late Stage Mechanisms for Vocalization Processing in the Human Auditory System

The human auditory system is able to rapidly process incoming acoustic information, actively filtering, categorizing, or suppressing different elements of the incoming acoustic stream. Vocalizations produced by other humans (conspecifics) likely represent the most ethologically-relevant sounds encountered by hearing individuals. Subtle acoustic characteristics of these vocalizations aid in determining the identity, emotional state, health, intent, etc. of the producer. The ability to assess vocalizations is likely subserved by a specialized network of structures and functional connections that are optimized for this stimulus class. Early elements of this network would show sensitivity to the most basic acoustic features of these sounds; later elements may show categorically-selective response patterns that represent high-level semantic organization of different classes of vocalizations. A combination of functional magnetic resonance imaging and electrophysiological studies were performed to investigate and describe some of the earlier and later stage mechanisms of conspecific vocalization processing in human auditory cortices. Using fMRI, cortical representations of harmonic signal content were found along the middle superior temporal gyri between primary auditory cortices along Heschl\u27s gyri and the superior temporal sulci, higher-order auditory regions. Additionally, electrophysiological findings also demonstrated a parametric response profile to harmonic signal content. Utilizing a novel class of vocalizations, human-mimicked versions of animal vocalizations, we demonstrated the presence of a left-lateralized cortical vocalization processing hierarchy to conspecific vocalizations, contrary to previous findings describing similar bilateral networks. This hierarchy originated near primary auditory cortices and was further supported by auditory evoked potential data that suggests differential temporal processing dynamics of conspecific human vocalizations versus those produced by other species. Taken together, these results suggest that there are auditory cortical networks that are highly optimized for processing utterances produced by the human vocal tract. Understanding the function and structure of these networks will be critical for advancing the development of novel communicative therapies and the design of future assistive hearing devices

Refractoriness within the semantic system: investigations on the access and the content of semantic memory

The starting purpose of this project was to investigate some issues related to the mechanisms underlying the efficient access to concepts within the semantic memory systems. These issues were mainly related to the role of refractoriness in explaining the comprehension deficits underlying semantic access. The insights derived from this first approach were then used to formulate and test hypotheses about the organization of the contents of the semantic system itself. The first part of the thesis presents an investigation of the semantic abilities of an unselected case-series of patients affected by tumours to either the left or right temporal lobes in order to detect possible semantic access difficulties. Semantic access deficits are typically attributed to the semantic system becoming temporarily refractory to repeated activation. Previous investigations on the topic were mainly based on single case reports, mainly on stroke patients. The rare examples of group studies suggested moreover the possibility that the syndrome might not be functionally unitary. The tasks used in the study were two word-to-picture matching tasks aimed to control for the typical variables held to be able to distinguish semantic access from degradation syndromes (consistency of access, semantic relatedness, word frequency, presentation rate and serial position). In the group of tumour patients tested access deficits were consistently found in patients with high grade tumours in the left posterior superior temporal lobe. However, the patients were overall only weakly affected by the typical temporal factors (presentation rate and serial position) characterizing an access syndrome as refractory. The pattern of deficit, together with the localization data, suggested that the deficit described is qualitatively different from typical semantic access syndromes and possibly caused by the disconnection of posterior temporal lexical input areas from the semantic system. In the second study we tried to answer the question whether semantic access deficits are caused by the co-occurrence of two causes (refractoriness and a lexicalsemantic disconnection) or whether the presence of refractoriness in itself is sufficient to induce all the behavioural effects described in access syndromes. A second aim of the study was moreover to investigate the precise locus of refractory behaviour, since refractory effects have also been reported in naming tasks in which the possibility exists that the interference might be located at a post-semantic lexical stage of processing. To address these issues a series of three behavioural experiments on healthy subjects was conducted. The tasks used were speeded versions of the same word-to picture matching tasks used in the previous study. A speeded paradigm was adopted in order to induce a mild refractory state also in healthy participants. The results showed that it was possible to induce, in the group of subjects tested, a performance similar to that of refractory semantic access patients. Since no post-semantic stage of processing is assumed to be necessary to perform these tasks it was argued that refractoriness arises due to interference occurring between representations within the semantic system itself. In the second part of the project, the finding that refractoriness arises due to interference involving semantic representations themselves, was used to investigate issues related to the organization of the content within the semantic memory. In particular, a second series of behavioural experiments was performed to investigate whether the way an object is manipulated is indeed a feature that defines manipulable objects at a semantic level. The tasks used were speeded word-to-picture matching tasks similar to those previously described. A significantly greater interference was found in the recognition of objects sharing similar manipulation than in the recognition of objects sharing only visual similarity. Moreover the repeated presentation of objects with similar manipulation created a \u2018negative\u2019 serial position effect (with error increasing over presentations), while the repeated presentation of objects sharing only visual similarity created an opposite \u2018positive\u2019 serial position effect (learning). The role of manipulability in the semantic representation of manipulable objects was further investigated in the last study of this work. In a second unselected group of brain tumour patients the ability to name living things and artifacts was investigated. Artifacts were manipulable objects, varying in the degree of their manipulability. Results from both behavioural and Voxel-based Lesion Symptom Mapping (VLSM) analyses showed that the only patients showing a selective deficit in naming artifacts (particularly highly manipulable objects) were patients with lesions in the posterior middle and superior portions of the left temporal lobe, an area lying within the basin of those regions involved in processing object-directed actions and previously linked to the processing of manipulable objects in a wide range of studies. The results of these last two studies support \u2018property-based networks\u2019 accounts of semantic knowledge rather than \u2018undifferentiated network\u2019 accounts. Overall this series of studies represents an attempt to better understand the mechanisms that underlie the access to semantic representations and, indirectly, the structure of representations stored within semantic networks. The insights obtained about the mechanisms of access to stored semantic representations were used as a tool to investigate the structures of the same semantic representations. A combination of different approaches was used (from behavioural speeded interference paradigms on healthy subjects, to neuropsychological case series investigations, as well as Voxel-based Lesion Symptom Mapping technique), to \u2018cross-validate\u2019 the results obtained at any level of analysis