Giuseppe Iaria

Retrosplenial and hippocampal brain regions in human navigation: complementary functional contributions to the formation and use of cognitive maps

The ability to orientate within familiar environments relies on the formation and use of a mental representation of the environment, namely a cognitive map. Neuropsychological and neuroimaging studies suggest that the retrosplenial and hippocampal brain regions are involved in topographical orientation. We combined functional magnetic resonance imaging with a virtual‐reality paradigm to investigate the functional interaction of the hippocampus and retrosplenial cortex during the formation and utilization of cognitive maps by human subjects. We found that the anterior hippocampus is involved during the formation of the cognitive map, while the posterior hippocampus is involved when using it. In conjunction with the hippocampus, the retrosplenial cortex was active during both the formation and the use of the cognitive map. In accordance with earlier studies in non‐human animals, these findings suggest that, while navigating within the environment, the retrosplenial cortex complements the hippocampal contribution to topographical orientation by updating the individuals location as the frame of reference changes.

Defining the face processing network: optimization of the functional localizer in fMRI.

Functional localizers that contrast brain signal when viewing faces versus objects are commonly used in functional magnetic resonance imaging studies of face processing. However, current protocols do not reliably show all regions of the core system for face processing in all subjects when conservative statistical thresholds are used, which is problematic in the study of single subjects. Furthermore, arbitrary variations in the applied thresholds are associated with inconsistent estimates of the size of face‐selective regions‐of‐interest (ROIs). We hypothesized that the use of more natural dynamic facial images in localizers might increase the likelihood of identifying face‐selective ROIs in individual subjects, and we also investigated the use of a method to derive the statistically optimal ROI cluster size independent of thresholds. We found that dynamic facial stimuli were more effective than static stimuli, identifying 98% (versus 72% for static) of ROIs in the core face processing system and 69% (versus 39% for static) of ROIs in the extended face processing system. We then determined for each core face processing ROI, the cluster size associated with maximum statistical face‐selectivity, which on average was approximately 50 mm3 for the fusiform face area, the occipital face area, and the posterior superior temporal sulcus. We suggest that the combination of (a) more robust face‐related activity induced by a dynamic face localizer and (b) a cluster‐size determination based on maximum face‐selectivity increases both the sensitivity and the specificity of the characterization of face‐related ROIs in individual subjects. Hum Brain Mapp 2009.

Disconnection in prosopagnosia and face processing

Face perception is a function with significant complexity, reflected in cognitive models that propose a hierarchy of parallel and serial processing stages. Current neuroimaging data also show that face perception involves a core processing network of cortical modules, which are likely specialized for different functions involved in face processing. The core face processing network is further linked to an extended face processing network which is not solely involved in the perception of faces, but rather contains modules mediating the processing of semantic, biographic and emotional information about people. The segregation of these processes within discrete anatomic regions creates the potential for disconnection between regions to generate neuropsychological deficits involving faces. In this review we consider the types of disconnection possible both within the core face processing system and between the core and extended systems, the pattern of deficits that would be considered as evidence of such disconnections, the potential anatomy of lesions that would create them, and whether any cases exist that meet these criteria.

The correlates of subjective perception of identity and expression in the face network: an fMRI adaptation study.

The recognition of facial identity and expression are distinct tasks, with current models hypothesizing anatomic segregation of processing within a face-processing network. Using fMRI adaptation and a region-of-interest approach, we assessed how the perception of identity and expression changes in morphed stimuli affected the signal within this network, by contrasting (a) changes that crossed categorical boundaries of identity or expression with those that did not, and (b) changes that subjects perceived as causing identity or expression to change, versus changes that they perceived as not affecting the category of identity or expression. The occipital face area (OFA) was sensitive to any structural change in a face, whether it was identity or expression, but its signal did not correlate with whether subjects perceived a change or not. Both the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS) showed release from adaptation when subjects perceived a change in either identity or expression, although in the pSTS this effect only occurred when subjects were explicitly attending to expression. The middle superior temporal sulcus (mSTS) showed release from adaptation for expression only, and the precuneus for identity only. The data support models where the OFA is involved in the early perception of facial structure. However, evidence for a functional overlap in the FFA and pSTS, with both identity and expression signals in both areas, argues against a complete independence of identity and expression processing in these regions of the core face-processing network.

Developmental topographical disorientation: Case one

Topographical disorientation is the inability to orient within the environment, usually acquired from lesions to different cerebral regions participating in the attentional, perceptual or memory functions involved during navigation. We present the first case of a patient with topographical disorientation in the absence of any structural lesion and with intact sensory and intellectual function. Experimental tests in both real and virtual environments revealed a selective impairment in forming a mental representation of the environment, namely a cognitive map. Consistent with the patients behavioural findings, a functional magnetic resonance imaging (fMRI) study showed lack of activation in the hippocampal complex and the retrosplenial cortex while forming a cognitive map of the environment. Although the lack of neural activity results in a negative finding that generally has low interpretative value, in this specific case our findings may provide useful information. First, in a group of healthy control subjects performing the same task, activity within the hippocampal complex and retrosplenial cortex were detected in each individual participant. Second, we found that within the same regions (showing lack of neural activity while forming a cognitive map of the environment) increased neural activity was detected while the patient was performing a different navigation task. This case is the first evidence reported in the literature showing that topographical disorientation may occur as a developmental defect causing a lifelong disorder affecting daily activities.

Walking in the Corsi test: which type of memory do you need?

Sex differences are often reported in spatial abilities. However, some studies show conflicting results, which can be ascribed to the complexity of the variables involved in the visuo-spatial domain. Until a few years ago, it was widely accepted that men outperformed women on almost all spatial tasks. However, recently some studies [A. Postma, G. Jager, R.P.C. Kessels, H.P.F. Koppeschaar, J. van Honk, Sex differences for selective forms of spatial memory, Brain Cogn. 54 (2004) 24-34; D.H. McBurney, S.J.C. Gaulin, T. Devineni, C. Adams, Superior spatial memory of women: stronger evidence for the gathering hypothesis, Evol. Hum. Behav. 18 (1997) 165-174; Q. Rahman, G.D. Wilson, S. Abrahams, Sexual orientation related differences in spatial memory, J. Int. Neuropsychol. Soc. 9 (2003) 376-383] found sex differences for selective forms of spatial memory and described a female advantage in specific spatial abilities. In this paper, we studied sex differences by testing object locations and route memories with the Corsi Block-Tapping test (CBT), one of the non-verbal tasks most used in clinical settings, and its modified, large-scale version. Our results showed a performance advantage for males in both tests and a more homogeneous pattern of memory in females.

Sleep to find your way: The role of sleep in the consolidation of memory for navigation in humans

Although a large body of evidence indicates that sleep plays an important role in learning and memory processes, the actual existence of a sleep‐dependent spatial memory consolidation has been not firmly established. Here, by using a computerized 3D virtual navigation tool, we were able to show that topographical orientation in humans largely benefits from sleep after learning, while 10 h of wakefulness during the daytime do not exert similar beneficial effects. In particular, navigation performance enhancement needs sleep in the first post‐training night, and no further improvements were seen after a second night of sleep. On the other hand, sleep deprivation hinders any performance enhancement and exerts a proactive disruption of spatial memory consolidation, since recovery sleep do not revert its effects. Spatial memory performance does not benefit from the simple passage of time, and a period of wakefulness between learning and sleep does not seem to have the role of stabilizing memory traces. In conclusion, our results indicate that spatial performance improvement is observed only when learning is followed by a period of sleep, regardless of the retention interval length.

Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension

Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin‐inhibitor (CNI)‐related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on ≤1.5 gm/day of MMF. Mean follow‐up from the introduction of MMF is 31.5 months and mean length of follow‐up from the beginning of MMF monotherapy is 27.3 months. Renal function improved in 31/36 (89%) cases. Blood levels of cholesterol and triglycerides decreased in 13 of 17 (76%) and 15 of 17 (89%) patients, respectively. Arterial hypertension improved in 4 of 5 (80%) cases. A total of 8 patients showed a single episode of fluctuation of liver function tests during tapering off CNI. This feature was interpreted as an acute rejection (AR), based on the resolution of the clinical setting after escalation of MMF daily dose to 2 gm. A further patient developed a biopsy‐proven AR insensitive to MMF adjustment, requiring reinstitution of the CNI dose. No deaths or major toxicity requiring MMF discontinuation occurred. In conclusion, low dose MMF monotherapy is safe, effective, and well tolerated. Liver Transpl, 2007.

Navigational skills correlate with hippocampal fractional anisotropy in humans.

Individuals vary widely in their ability to orient within the environment. We used diffusion tensor imaging to investigate whether this ability, as measured by navigational performance in a virtual environment, correlates with the anatomic structural properties of the hippocampus, i.e., fractional anisotropy. We found that individuals with high fractional anisotropy in the right hippocampus are (a) faster in forming a cognitive map of the environment, and (b) more efficient in using this map for the purpose of orientation, than individuals with low fractional anisotropy. These results are consistent with the role of the hippocampus in navigation, and suggest that its microstructural properties may contribute to the intersubject variability observed in spatial orientation.

The role of sleep in the consolidation of route learning in humans: a behavioural study.

Considerable evidence support the role of sleep in learning and memory processes. In rodents, the relationships between sleep and memory consolidation have been extensively investigated by taking into account mainly spatial learning. On the contrary, in humans the relationship between sleep and spatial memory consolidation has so far been scarcely taken into account. Here, we investigated the importance of sleep in the consolidation of the spatial memory traces of a new route learned in a real-life unfamiliar environment. Fifty-one subjects followed a defined route in a neighbourhood they had never been to before. Then, they were tested in the laboratory in a sequence-recognition test requiring them to evaluate whether or not sequences of three views, taken along the route, represented a correct sequential order as seen while walking along the route. Participants were then assigned to one of three groups: the sleep group was retested after one nights sleep, the sleep-deprived group was retested after a night of sleep deprivation, and the day-control group was retested the same day after 8h of wakefulness. At retest, performance speed increased in all groups, whereas the accuracy in the sequence-recognition task was improved only in the sleep group: neither sleep deprivation nor the simple passage of time gave way to any performance improvement. These preliminary findings shed more light on the role of sleep in spatial memory consolidation by extending to humans the considerable evidence found in animals.