The neuroscience of memory: implications for the courtroom.

Although memory can be hazy at times, it is often assumed that memories of violent or otherwise stressful events are so well encoded that they are effectively indelible and that confidently retrieved memories are almost certainly accurate. However, findings from basic psychological research and neuroscience studies indicate that memory is a reconstructive process that is susceptible to distortion. In the courtroom, even minor memory distortions can have severe consequences that are partly driven by common misunderstandings about memory--for example, that memory is more veridical than it may actually be.

Intrinsic functional connectivity of the human medial temporal lobe suggests a distinction between adjacent MTL cortices and hippocampus.

Functional connectivity analyses can offer insights into mechanisms of the brain that might not be revealed by traditional fMRI. These analyses compare seed voxels' activity over time to the activity of other voxels over time and identify correlations between regions. This study is the first to perform functional connectivity analyses in the human medial temporal lobe (MTL) at high enough resolution to resolve the hippocampal subfields. We calculated the average correlation coefficients between the MTL cortices, which include the entorhinal (ERC), perirhinal (PRC), and parahippocampal cortex (PHC), and the hippocampal subfields dentate gyrus/CA3, CA1, and subiculum. We found that the hippocampal subfields had relatively high correlations with each other both within and across hemispheres, but did not have exceptionally strong correlations with the MTL cortices. The opposite was also seen where there was a relatively high correlation coefficient between the ERC and PRC, but both regions had low correlation coefficients with the hippocampal subfields. We also found greater functional connectivity within a hemisphere than across hemispheres. These effects were replicated across multiple datasets which differed in task demands, participants' age, and scanner sequence/slice acquisition. Notably, all datasets were better correlated to these patterns of intrinsic functional connectivity than to a model based on anatomical constraints. This is consistent with evidence that functional connectivity is not a direct mapping of anatomical connectivity. These patterns of functional connectivity imply a distinction between the MTL cortices and the hippocampus and speak to our understanding of the organization of the MTL.

Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity.

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input.

Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults.

There is widespread evidence that memory deteriorates with aging, however the exact mechanisms that underlie these changes are not well understood. Given the growing size of the aging population, there is an imperative to study age-related neurocognitive changes in order to better parse healthy from pathological aging. Using a behavioral paradigm that taxes pattern separation (the ability to differentiate novel yet similar information from previously learned information and thus avoid interference), we investigated age-related neural changes in the human hippocampus using high-resolution (1.5 mm isotropic) blood-oxygenation level-dependent fMRI. Recent evidence from animal studies suggests that hyperactivity in the CA3 region of the hippocampus may underlie behavioral deficits in pattern separation in aged rats. Here, we report evidence that is consistent with findings from the animal studies. We found a behavioral impairment in pattern separation in a sample of healthy older adults compared with young controls. We also found a related increase in CA3/dentate gyrus activity levels during an fMRI contrast that stresses pattern separation abilities. In a detailed analysis of behavior, we also found that the pattern of impairment was consistent with the predictions of the animal model, where larger changes in the input (greater dissimilarity) were required in order for elderly adults to successfully encode new information as distinct from previously learned information. These findings are also consistent with recent fMRI and behavioral reports in healthy aging, and further suggest that a specific functional deficit in the CA3/dentate network contributes to memory difficulties with aging.

A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment.

Changes in memory performance are one of the hallmark symptoms of mild cognitive impairment and are affected by healthy aging as well. Pattern separation, which refers to the process of orthogonalizing overlapping inputs into distinct memory representations, may be a sensitive marker of these memory changes. Here, we describe a paradigm, the Behavioral Pattern Separation Task-Object Version (BPS-O task), which reveals age-related changes in pattern separation performance. Specifically, we report an age-related decline in pattern separation in healthy adults, ranging from ages 20 to 89. When we classify those individuals aged 60 and older into two groups, Aged Unimpaired (AU) and Aged Impaired (AI) based on their delayed word recall performance, we observe impairments in pattern separation performance in the Impaired group, but no overall impairment in recognition performance. In contrast, those individuals diagnosed with mild cognitive impairment demonstrate worse performance than age-matched controls in both pattern separation and recognition memory performance. Therefore, the BPS-O task provides a sensitive measure for observing changes in memory performance across the lifespan and may be useful for the early detection of memory impairments that may provide an early signal of later development to mild cognitive impairment.