Lateral intraparietal area (LIP) neurons are thought to compute the decision of where to look. Specifically, their firing rate is thought to represent accumulated evidence for a decision by ramping up to a high level, the putative decision bound, before an eye movement to a given location. However, LIP neurons are also highly responsive to visual stimuli. Because all previous research put a visual stimulus (a saccadic target) in the response field (RF) location of a neuron during decision formation, it is unknown if LIP neurons can still show decision computation without this visual drive. We therefore recorded the spiking activity of LIP neurons in a conventional decision task where a monkey decides the direction of a noisy motion stimulus and indicates his decision with a saccade. On half the trials, the Choice Targets remained on for the whole trial, as is conventionally done. On the remaining trials, targets were flashed at the beginning of the trial and absent during motion-viewing. Furthermore, we recorded the activity of any neuron with an RF, instead of only neurons exhibiting persistent memory activity before an instructed saccade. This enabled us to also test the long-held assumption that only cells with persistent memory activity show decision signals. Our results show that 1) cells without persistent activity indeed show decision signals, 2) population response drops without RF stimulation (although individual neurons were affected in diverse ways), 3) distinct, repeating response “motifs” exist among cells, 4) a signal exists where neural response is lower for stronger motion strength stimuli, regardless of direction. These results prove that contrary to dogma, a neuron’s ability to show a long “memory” response is not related to an ability to accumulate evidence over time for a decision. Also, LIP firing rate cannot be interpreted as a pure decision variable because it simultaneously represents decision-irrelevant, visual stimuli. Finally, diverse, but repeating responses among cells suggest the existence of cell types in LIP. These results demonstrate that LIP acts as a bank of potentially useful signals, and raises the question of how they might be used for a decision. / text

The posterior parietal cortex (PPC) has been reliably implicated in visuospatial attention, such that the dorsal regions (dPPC) are associated with voluntary ‘top-down’ attention, whereas the ventral regions (vPPC) are associated with automatic ‘bottom-up’ attentional processes. The Attention-to-Memory model (AtoM: Ciaramelli, Grady, & Moscovitch, 2008) has suggested that it also plays a similar role in memory retrieval, suggesting that the PPC mediates a domain-general attentional process. Furthermore, domain-generality of attentional processes may account for differences in perception and memory function accompanying old age. This study examined domain-generality by determining the shared variance in performance of tasks thought to recruit top-down and bottom-up attentional processes mediated across both domains. Results clearly suggested generality across domains in top-down processing; and in bottom-up processing, depending on its operationalization. Ageing was characterized by an absence of shared variance across domains and slower reaction times during bottom-up attentional reorienting only in perception.

The posterior parietal cortex (PPC) has been reliably implicated in visuospatial attention, such that the dorsal regions (dPPC) are associated with voluntary ‘top-down’ attention, whereas the ventral regions (vPPC) are associated with automatic ‘bottom-up’ attentional processes. The Attention-to-Memory model (AtoM: Ciaramelli, Grady, & Moscovitch, 2008) has suggested that it also plays a similar role in memory retrieval, suggesting that the PPC mediates a domain-general attentional process. Furthermore, domain-generality of attentional processes may account for differences in perception and memory function accompanying old age. This study examined domain-generality by determining the shared variance in performance of tasks thought to recruit top-down and bottom-up attentional processes mediated across both domains. Results clearly suggested generality across domains in top-down processing; and in bottom-up processing, depending on its operationalization. Ageing was characterized by an absence of shared variance across domains and slower reaction times during bottom-up attentional reorienting only in perception.

The purpose of this project was to compare the Attention to Memory (AtoM) and the Episodic Buffer (EB) Models. The AtoM model proposes that the ventral parietal cortex (VPC) and dorsal parietal cortex (DPC) are responsive to bottom-up and top- down attention to memory, respectively, (Cabeza, 2008; Cabeza et al., 2008; Ciaramelli et al., 2008). The EB model, on the other hand, proposes that the VPC is involved in the episodic buffer component of Baddeley's working memory model (Vilberg & Rugg, 2008). Using objective (source) and subjective (Remember/Know) retrieval tasks, specific patterns of PPC activity were posited based on the propositions of the AtoM model. These expectations included greater VPC activity for Remember and False Alarms compared to Correct Rejections and Subjective Know, greater DPC activity for Know and Objective Remember compared to Subjective Remember and correct rejections, and no difference in VPC activity for remembering both font and color compared to remembering only one contextual detail. During encoding participants saw words in one of two colors, red or yellow, and in one of two fonts, curvy or straight, and were required to indicate the color the word was presented in. Following each encoding scan participants performed either an Objective or Subjective retrieval task. During Objective retrieval task, participants performed a forced-choice source memory test choosing the word with the correct fontand color or the "new" option. During Subjective retrieval participants were presented with the word in a neutral font and white color and performed a Remember/Know test. On the Subjective retrieval task both VPC and DPC were active for recollection compared to familiar items and Correct Rejections. On the Objective retrieval task the DPC was active for all correct old responses. Neither the VPC nor the DPC were significantly active for False Alarms on both the Subjective and Objective tasks. Both VPC and DPC were more active for Subjective Remember compared to Objective Remember response. Neither PPC region was more active for remembering font and color compared to remembering only font or color. Memory load effects for retrieval of information from long-term memory were only seen in the hippocampus on the Subjective retrieval task. These patterns of activity support the role of the VPC in recollection, as seen on the Subjective task, and the role of the DPC in familiarity, as shown in both the Subjective and Objective tasks. The role of the VPC and DPC during recollection and familiarity processing supports both the AtoM and the EB model. The key predictor of the Episodic Buffer model, memory load effects, was not supported and provides the only evidence against one of the two proposed models. Future work should examine the role of the posterior parietal cortex in spontaneous episodic retrieval to assess the validity of the AtoM model. Advanced imaging analysis techniques should be used to determine functional connectivity between the PPC and frontal and temporal memory regions.

Locomotion requires visuospatial attention. However, the role and cortical control of visuospatial attention during locomotion remain unclear. Four experiments were conducted in this study to examine the role and cortical control of visuospatial attention during locomotion in healthy young adults. In the first experiment, we employed a visuospatial attention task at different phases of obstacle crossing during gait. The results suggested that toe-obstacle clearance was significantly reduced for the trailing limb when distraction interfered with visuospatial attention during the approaching phase of obstacle crossing. In the second experiment, subjects performed a visual Stroop task while approaching and crossing an obstacle during gait. The results for the second experiment indicated toe-obstacle clearance was significantly increased for the leading and trailing limbs. Taken together, it was found that different visual attention tasks lead to distinct modifications on obstacle crossing behaviors. In the third and fourth experiments, anodal transcranial direct current stimulation (tDCS) was applied over the right posterior parietal cortex (PPC) to examine the aftereffects on attention function and locomotor behavior. The results suggested that the orienting attention was significantly improved after anodal tDCS. In addition, the aftereffects of anodal tDCS potentially enhanced cognitive and motor performance while interacting with a challenging obstacle-crossing task in young healthy adults, suggesting that the right PPC contributes to attending visuospatial information during locomotion. This study demonstrated that visuospatial attention is critical for planning during locomotion and the right PPC contributes to this interplay of the neural processing of visuospatial attention during locomotion. This dissertation includes previously published and unpublished co-authored material.

Le cortex pariétal postérieur (PPC) est une structure clé de l’intégration sensori-motrice qui forme, avec les structures frontales auxquelles il est connecté, des réseaux pariéto-frontaux aux fonctions spécifiques. Il est ainsi impliqué dans la planification et le contrôle des mouvements de préhension visuo-guidés mais aussi dans le contrôle de l’attention spatiale. L’atteinte fonctionnelle du membre supérieur et la négligence spatiale sont deux conséquences fréquentes et invalidantes après un accident vasculaire cérébral (AVC). Dans ces deux situations, il est démontré que la connectivité cérébrale des réseaux pariéto-frontaux est modifiée au sein de l’hémisphère lésé, mais aussi vers et au sein de l’hémisphère non-lésé. Par ailleurs, ces modifications semblent impliquées dans la genèse et/ou les mécanismes de récupération de la négligence spatiale et de la déficience motrice. Cependant, la spécificité des modifications de connectivité du PPC controlésionnel reste partiellement méconnue, en particulier si on considère les régions fonctionnelles spécialisées qui y ont été identifiées chez le sujet sain. Ces dernières incluent notamment les parties antérieure et postérieure du sillon intra-pariétal (respectivement aIPS et pIPS) et le cortex pariéto-occipital supérieur (SPOC). Les objectifs de ce travail étaient (1) d’étudier les modifications de la connectivité intra- et inter-hémisphérique de ces trois zones chez des patients post-AVC comparativement à un groupe de sujets contrôles sains, (2) de déterminer les liens de la connectivité avec la sévérité des déficiences motrices et visuo-spatiales, et enfin (3) de juger de l’effet de la modulation du PPC sur ces dernières.Dans un premier temps, nous avons mesuré, au repos, la connectivité des réseaux pariétofrontaux au sein de l’hémisphère controlésionnel en utilisant une technique de stimulation magnétique transcrânienne à impulsion double (ppTMS). La deuxième étude s’est intéressée aux aspects fonctionnels (IRM fonctionnelle de repos) et structurels (mesure de la fraction d’anisotropie sur des séquences de diffusion) de la connectivité intra- et inter-hémisphérique du PPC controlésionnel. Nous avons enfin analysé l’effet de la modulation inhibitrice du PPC controlésionnel (rTMS en mode thetaburst continu (cTBS)) sur les paramètres du mouvement de pointage avec le membre supérieur parétique.La première étude a mis en évidence une hyperexcitabilité des connexions pariéto-frontales chez les patients négligents lorsque la stimulation conditionnante concernait le SPOC, ce d’autant plus que la négligence péripersonnelle était sévère. La connectivité aIPS-M1 n’était pas différente entre sujets hémiparétique et contrôles, et le degré de déficience motrice n’était pas lié aux données de connectivité. Le travail d’imagerie a montré que la connectivité fonctionnelle et structurelle du PPC controlésionnel était altérée chez les patients, au sein de l’hémisphère controlésionnel mais aussi vers l’hémisphère lésé, de manière différente selon les sites du PPC. Les données de connectivité fonctionnelle montraient des liens avec la sévérité de la négligence spatiale mais peu avec celle de la déficience motrice. Enfin, l’inhibition du PPC controlésionnel par un protocole de cTBS pourrait améliorer l’excitabilité de M1 du coté lésé et certains paramètres spatiaux et temporels du mouvement de pointage. Les patients post-AVC présentaient donc des modifications étendues de connectivité cérébrale du PPC controlésionnel, à la fois intra- et inter-hémisphériques. Alors que des liens entre connectivité et négligence ont été mis en évidence, il n’existait que peu de relation avec la déficience motrice, probablement parce qu’elle est déterminée par un nombre important d’autres facteurs. Enfin, ce travail ouvre de nouvelles pistes d’évolution des stratégies de modulation par les techniques de stimulation cérébrale non-invasives en post-AVC. / The posterior parietal cortex (PPC) is a key structure for sensorimotor integration. It forms with the frontal areas to which it is connected the parieto-frontal networks that have specialized functions. It is involved in the planning and online control of visually-guided prehension but also in the control of spatial attention. Upper limb impairment and spatial neglect are two frequent and disabling consequences of stroke. In these two deficiencies, it has been shown that cerebral connectivity in the parieto-frontal networks is modified within the lesioned hemisphere, but also towards and within the non-lesioned hemisphere due to an imbalance in the interhemispheric influences between parietal areas. Furthermore, these modifications seem to be involved in the genesis and/or the recovery of spatial neglect and motor deficiency. However, the changes in connectivity remain partly unknown, especially if we consider the different PPC functional areas identified in healthy subjects in the PPC (anterior and posterior parts of the intraparietal sulcus (respectively aIPS and pIPS) and the superior parieto-occipital cortex (SPOC)). The aims of the present work were (1) to study the modifications of intra- and interhemispheric cerebral connectivity of these 3 PPC areas in post-stroke patients vs healthy controls, (2) determine the relationship between connectivity data and the severity of motor and visuo-spatial deficiencies, and (3) study the effect of a modulation of the PPC on these deficiencies.We first assessed the connectivity of parieto-frontal networks within the contralesional hemisphere using a paired-pulse transcranial magnetic stimulation protocol (ppTMS). In a second study, we addressed the functional (resting state fMRI) and structural (fractional anisotropy on diffusion weighted imagery) intra- and interhemispheric connectivity of the contralesional PPC. We finally study the effect of an inhibitory modulation of the contralesional PPC (continuous theta-burst stimulation (cTBS)) on reaching parameters with the paretic upper limb in stroke patients.In the first study, we demonstrated an hyperexcitability of parieto-frontal connections in neglect patients when the conditioning stimulus was applied over the SPOC, especially when peripersonal neglect was severe. Connectivity between the aIPS and M1 was not different between patients and healthy controls and the severity of motor deficiency was not associated with connectivity. The neuroimaging study revealed that functional and structural connectivity from the contralesional PPC was altered in stroke patients, within the contralesional hemisphere but also to the lesioned hemisphere, in different ways depending on the PPC site considered. Functional connectivity showed some relationships with neglect severity but almost not with motor deficiency. Finally, the inhibition of the contralesional PPC lead by a cTBS protocol may increase lesioned M1 excitability and some spatiotemporal parameters of pointing movements.In conclusion, post-stroke patients showed wide modifications of cerebral connectivity of the contralesional PPC, both within the contralesional and toward the lesioned hemisphere. Whereas we identified links between connectivity and neglect severity, relationships were poorer with motor deficiency, certainly since this last is determined by several other factors. Finally, this work puts light on new perspectives of modulation protocols using non-invasive brain stimulation in stroke patients.

Path integration is a navigational process that humans and animals use to track changes in their position and orientation. Animal and computational studies suggest that a spatially-tuned navigation system supports path integration, yet this system is not well understood in humans. Here, the prediction was tested that path integration mechanisms and goal-directed navigation in humans would recruit the same key brain regions within the parietal cortex and medial temporal lobes as predicted by animal and computational models. The three experiments described in this dissertation used behavioral and functional magnetic resonance imaging methods in 131 adults (18-35 years) to examine behavioral and brain correlates of navigation. In a landmark-free environment, path integration mechanisms are utilized to update position and orientation to a goal. Experiment 1 examined neural correlates of these mechanisms in the human brain. The results demonstrated that successful first and third person perspective navigation recruited the anterior hippocampus. The posterior hippocampus was found to track distance and temporal proximity to a goal location. The retrosplenial and posterior parietal cortices were additionally recruited for successful goal-directed navigation. In a landmark-rich environment, humans utilize route-based strategies to triangulate between their position, landmarks, and navigational goal. Experiment 2 contrasted path integration and landmark-based strategies by adding a solitary landmark to a sparse environment. The results demonstrated that successful navigation with and without an orienting landmark recruited the anterior hippocampus. Activity in the bilateral posterior hippocampus was modulated by larger triangulation between current position, landmark, and goal location during first person perspective navigation. The caudate nucleus was additionally recruited for landmark-based navigation. Experiment 3 used functional connectivity methods coupled with two fMRI tasks to determine whether areas responsive to optic flow, specifically V3A, V6, and the human motion complex (hMT+), are functionally connected to brain regions recruited during first person perspective navigation. The results demonstrated a functional relationship between optic flow areas and navigationally responsive regions, including the hippocampus, retrosplenial, posterior parietal, and medial prefrontal cortices. These studies demonstrate that goal-directed navigation is reliant upon a navigational system supported by hippocampal position computations and orientation calculations from the retrosplenial and posterior parietal cortices.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12817号 / 論医博第2079号 / 新制||医||1004(附属図書館) / 31304 / 京都大学大学院医学研究科脳統御医科学系専攻 / (主査)教授 河野 憲二, 教授 金子 武嗣, 教授 大森 治紀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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