Sebastian Guderian

Reward-related fMRI activation of dopaminergic midbrain Is associated with enhanced hippocampus- dependent long-term memory formation

Long-term potentiation in the hippocampus can be enhanced and prolonged by dopaminergic inputs from midbrain structures such as the substantia nigra. This improved synaptic plasticity is hypothesized to be associated with better memory consolidation in the hippocampus. We used a condition that reliably elicits a dopaminergic response, reward anticipation, to study the relationship between activity of dopaminergic midbrain areas and hippocampal long-term memory in healthy adults. Pictures of object drawings that predicted monetary reward were associated with stronger fMRI activity in reward-related brain areas, including the substantia nigra, compared with non-reward-predicting pictures. Three weeks later, recollection and source memory were better for reward-predicting than for non-reward-predicting pictures. FMRI activity in the hippocampus and the midbrain was higher for reward-predicting pictures that were later recognized compared with later forgotten pictures. These data are consistent with the hypothesis that activation of dopaminergic midbrain regions enhances hippocampus-dependent memory formation, possibly by enhancing consolidation.

Medial temporal theta state before an event predicts episodic encoding success in humans

We report a human electrophysiological brain state that predicts successful memory for events before they occur. Using magnetoencephalographic recordings of brain activity during episodic memory encoding, we show that amplitudes of theta oscillations shortly preceding the onsets of words were higher for later-recalled than for later-forgotten words. Furthermore, single-trial analyses revealed that recall rate in all 24 participants tested increased as a function of increasing prestimulus theta amplitude. This positive correlation was independent of whether participants were preparing for semantic or phonemic stimulus processing, thus likely signifying a memory-related theta state rather than a preparatory task set. Source analysis located this theta state to the medial temporal lobe, a region known to be critical for encoding and recall. These findings provide insight into state-related aspects of memory formation in humans, and open a perspective for improving memory through theta-related brain states.

Quantitative MR analyses of the hippocampus: Unspecific metabolic changes in aging

The age-related structural changes of the human hippocampus are not entirely understood. The goal of the present investigation was to understand better the nature of age-related hippocampal changes by a comparative MR-analysis of four complementary aspects of hippocampal integrity: total volume, metabolite concentration, neuron to glial cell ratio and amount of extracellular diffusion space for water. To that end, we applied MR-based methods of manual and computerized (voxel-based morphometry) volumetry, diffusion-weighted imaging and 1H MR spectroscopy to characterize specific age-related hippocampal effects in a group of 22 healthy old adults in comparison with a group of 13 healthy younger adults. Age-related reductions of the hippocampal N-acetyl aspartate to creatine/choline ratio together with only marginal age-related reductions in hippocampal volumes and increases in diffusion parameters suggest that the process of aging affects mainly the metabolic status of the hippocampus with little equivalent age-related changes in hippocampal cell density. The metabolic changes are unspecific as they are not restricted to the hippocampus but equally occur in measures obtained from extrahippocampal temporal lobe regions.

Four types of novelty–familiarity responses in associative recognition memory of humans

Animal studies show that, like inferior temporal neurons, dorsolateral prefrontal and parietal neurons often respond more strongly to individual novel than to individual familiar stimuli. It is currently unclear whether the novelty preference of prefrontal and parietal neurons extends to associative memory. We used electromagnetic recordings (MEG/EEG) and functional magnetic resonance imaging in two groups of healthy young adults to identify neural populations outside the inferior temporal cortex that exhibit associative novelty (stronger responses for new than for old configurations of two familiar items), and to distinguish them from associative familiarity (stronger responses for old than for new configurations of two familiar items). Subjects were required to learn and were later tested for associations based on the spatial configurations of two stimuli (a face and a tool). At test, learned (old) and rearranged (new) spatial stimulus configurations had to be discriminated. This recognition memory test could only be solved through the associative relationship between individual items because all component items of the stimulus configurations were equally familiar. In both imaging modalities, right dorsolateral prefrontal cortex and right parietal cortex showed an associative novelty response, whereas the right superior temporal cortex showed an associative familiarity response. With EEG/MEG only, the right extrastriate cortex showed an early associative familiarity and a late associative novelty response, whereas the opposite pattern emerged in bilateral frontopolar cortex. Thus, through a multimodal approach, it was possible to identify four types of associative novelty/familiarity responses outside the inferior temporal cortex.

Relationship between Hippocampal Structure and Memory Function in Elderly Humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection.

Measures of hippocampal volumes, diffusion and 1H MRS metabolic abnormalities in temporal lobe epilepsy provide partially complementary information.

We assessed whether interictal measures of hippocampal volume, hippocampal diffusion and metabolic abnormalities yield correlated or complementary information about hippocampal pathology in patients with temporal lobe epilepsy (TLE). Volumes, apparent diffusion coefficients (ADC) and ratios of N‐acetyl‐aspartate (NAA) to Creatine/Phosphocreatine (Cr) and Choline (Cho) were measured from each hippocampus during one magnetic resonance imaging (MRI) session in patients with TLE. Structural MRI showed unilateral hippocampal sclerosis (HS) in 13 patients and was normal in the remaining nine patients. Pearsons correlation (two‐tailed) between ADC values and NAA/(Cr + Cho) ratios was significant (P = 0.04, r = −0.45) for the hippocampus ipsilateral to the epileptogenic zone as determined on the basis of interictal and ictal scalp EEG recordings. This finding was driven by a very high correlation between the two measures in the presence of HS (P < 0.001, r = −0.96). Furthermore, ipsilateral ADC values but not NAA/(Cr + Cho) ratios were correlated with disease duration (P = 0.001, r = 0.67). Hippocampal volumes did not correlate with either ADC values, NAA/(Cr + Cho) ratios or disease duration. These data suggest that hippocampal volumes, NAA/(Cr + Cho) ratios and ADC values capture partially complementary aspects of hippocampal pathology.

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function.

Two processes support visual recognition memory in rhesus monkeys.

A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans.