Differentiable contributions of human amygdalar subregions in the computations underlying reward and avoidance learning.

To understand how the human amygdala contributes to associative learning, it is necessary to differentiate the contributions of its subregions. However, major limitations in the techniques used for the acquisition and analysis of functional magnetic resonance imaging (fMRI) data have hitherto precluded segregation of function with the amygdala in humans. Here, we used high-resolution fMRI in combination with a region-of-interest-based normalization method to differentiate functionally the contributions of distinct subregions within the human amygdala during two different types of instrumental conditioning: reward and avoidance learning. Through the application of a computational-model-based analysis, we found evidence for a dissociation between the contributions of the basolateral and centromedial complexes in the representation of specific computational signals during learning, with the basolateral complex contributing more to reward learning, and the centromedial complex more to avoidance learning. These results provide unique insights into the computations being implemented within fine-grained amygdala circuits in the human brain.

Appetitive and aversive taste conditioning in a computer game influences real-world decision making and subsequent activation in insular cortex.

A stimulus, by virtue of its pairing with a rewarding or an aversive outcome, can acquire motivating properties reflecting that outcome. However, there is uncertainty concerning the extent to which such properties might be carried across contexts. In the current study we sought to determine whether conditioning-dependent motivational properties can transfer from a computer game to the real world and, further, whether this conditioning might be expressed in terms of brain responses measured using functional magnetic resonance imaging (fMRI). We studied healthy participants conditioned with aversive and appetitive drinks in the context of a virtual cycling race. Three days after conditioning, participants returned for a fMRI session. We took this opportunity to observe the impact of incidental presentation of conditioned stimuli on a real-world decision (seat choice). We found a significant influence of conditioning on seat choice and, moreover, noted that individual susceptibility to this influence was reflected in differential insula cortex responses during subsequent scanning. The choice was also predicted by participants' personality scores and, as a statistical trend (p=0.07), by their sense of immersion in the game environment. Our data show that motivational properties of stimuli can transfer from the virtual to the real world. While much concern has been expressed over the impact of virtual experience on general levels of aggression and mood, our data point to another important consideration: the fact that a stimulus in the virtual environment can acquire motivational properties that persist and modify behavior in the real world.

Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task.

Mild cognitive impairment (MCI) patients report memory problems greater than those normally expected with ageing, but do not fulfil criteria for clinically probable Alzheimer's disease. Accumulating evidence demonstrates that impaired performance on the Paired Associates Learning (PAL) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) may be sensitive and specific for early and differential diagnosis of Alzheimer's disease. We adapted the basic CANTAB PAL task for functional magnetic resonance imaging (fMRI) in order to examine the functional brain deficits, at encoding and retrieval separately, in patients with MCI compared to healthy matched volunteers. As well as investigating the main effects of encoding and retrieval, we characterized neural responses in the two groups to increasing memory load. We focused on changes in BOLD response in the hippocampus and related structures, as an a priori region of interest based on what is known about the neuropathology of the early stages of Alzheimer's disease and previous information on the neural substrates of the PAL task. We also used structural MRI in the same patients to assess accompanying structural brain abnormalities associated with MCI. In terms of the BOLD response, the bilateral hippocampal activation in the MCI and control groups depended upon load, the MCI patients activating significantly more than controls at low loads and significantly less at higher loads. There were no other differences between MCI patients and controls in terms of the neural networks activated during either encoding or retrieval of the PAL task, including the prefrontal, cingulate and temporal cortex. The functional deficit in hippocampal activation in the MCI patients was accompanied by structural differences in the same location, suggesting that the decrease in hippocampal activation may be caused by a decrease in the amount of grey matter. This is one of the first studies to have used both encoding and retrieval phases of a memory paradigm for fMRI in MCI patients, and to have shown that the BOLD response in MCI patients can show both hyperactivation and hypoactivation in the same individuals as a function of memory load and encoding/retrieval. The findings suggest that performance on PAL might be a useful cognitive biomarker for early detection of Alzheimer's disease, especially when used in conjunction with neuroimaging.