Melanie Cohn

Memory enhancement induced by hypothalamic/fornix deep brain stimulation.

Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double‐blinded “on” versus “off” manner demonstrated that stimulation increased recollection but not familiarity‐based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions. Ann Neurol 2008;63:119–123

Does lateral parietal cortex support episodic memory? Evidence from focal lesion patients

Although neuroimaging and human lesion studies agree that the medial parietal region plays a critical role in episodic memory, many neuroimaging studies have also implicated lateral parietal cortex, leading some researchers to suggest that the lateral region plays a heretofore underappreciated role in episodic memory. Because there are very few extant lesion data on this matter, we examined memory in six cases of focal lateral parietal damage, using both clinical and experimental measures, in which we distinguished between recollection and familiarity. The patients did not have amnesia, but they did show evidence of disrupted recollection on an anterograde memory task. Although the exact mechanisms remain to be elucidated, lateral parietal damage appears to impair some aspects of episodic memory.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change.

Linking DMN connectivity to episodic memory capacity: What can we learn from patients with medial temporal lobe damage?

Computational models predict that focal damage to the Default Mode Network (DMN) causes widespread decreases and increases of functional DMN connectivity. How such alterations impact functioning in a specific cognitive domain such as episodic memory remains relatively unexplored. Here, we show in patients with unilateral medial temporal lobe epilepsy (mTLE) that focal structural damage leads indeed to specific patterns of DMN functional connectivity alterations, specifically decreased connectivity between both medial temporal lobes (MTLs) and the posterior part of the DMN and increased intrahemispheric anterior–posterior connectivity. Importantly, these patterns were associated with better and worse episodic memory capacity, respectively. These distinct patterns, shown here for the first time, suggest that a close dialogue between both MTLs and the posterior components of the DMN is required to fully express the extensive repertoire of episodic memory abilities.

Recollection versus strength as the primary determinant of hippocampal engagement at retrieval

We examined whether hippocampal activity in recognition relates to the strength of the memory or to recollective experience, a subject of considerable current debate. Participants studied word pairs and then made two successive recognition decisions on each item: first on the uncued target and then on the target presented with the studied cue word. We compared recollection and familiarity patterns of activation in fMRI for these decisions. Critically, our analyses attempted in two ways to equate perceived memory strength while varying the associative information available. First, activity for targets judged familiar before cueing was contrasted with activity for the same items in the second decision as a function of whether the targets converted to recollection or remained familiar when the context cues were provided. We found increased hippocampal activity following cueing only with recollective conversion. Second, we investigated whether hippocampal activity was modulated by the rated familiarity strength of cued items or whether it increased uniquely in recollection. Hippocampal activation was not modulated parametrically by familiarity strength and recollected items were associated with greater activity relative to highly familiar items. Together, our results support the notion that it is recollection of context, rather than memory strength, that underlies hippocampal engagement at retrieval.

Altered resting state brain dynamics in temporal lobe epilepsy can be observed in spectral power, functional connectivity and graph theory metrics.

Despite a wealth of EEG epilepsy data that accumulated for over half a century, our ability to understand brain dynamics associated with epilepsy remains limited. Using EEG data from 15 controls and 9 left temporal lobe epilepsy (LTLE) patients, in this study we characterize how the dynamics of the healthy brain differ from the “dynamically balanced” state of the brain of epilepsy patients treated with anti-epileptic drugs in the context of resting state. We show that such differences can be observed in band power, synchronization and network measures, as well as deviations from the small world network (SWN) architecture of the healthy brain. The θ (4–7 Hz) and high α (10–13 Hz) bands showed the biggest deviations from healthy controls across various measures. In particular, patients demonstrated significantly higher power and synchronization than controls in the θ band, but lower synchronization and power in the high α band. Furthermore, differences between controls and patients in graph theory metrics revealed deviations from a SWN architecture. In the θ band epilepsy patients showed deviations toward an orderly network, while in the high α band they deviated toward a random network. These findings show that, despite the focal nature of LTLE, the epileptic brain differs in its global network characteristics from the healthy brain. To our knowledge, this is the only study to encompass power, connectivity and graph theory metrics to investigate the reorganization of resting state functional networks in LTLE patients.

Neuropsychology in Temporal Lobe Epilepsy: Influences from Cognitive Neuroscience and Functional Neuroimaging

Neuropsychologists assist in diagnosis (i.e., localization of dysfunction) and in prediction (i.e., how cognition may change following surgery) in individuals being considered for temporal lobe surgery. The current practice includes behavioural testing as well as mapping function via stimulation, inactivation, and (more recently) functional imaging. These methods have been providing valuable information in surgical planning for 60 years. Here, we discuss current assessment strategies and highlight how they are evolving, particularly with respect to integrating recent advances in cognitive neuroscience.

Distinct hippocampal functional networks revealed by tractography-based parcellation

Recent research suggests the anterior and posterior hippocampus form part of two distinct functional neural networks. Here we investigate the structural underpinnings of this functional connectivity difference using diffusion-weighted imaging-based parcellation. Using this technique, we substantiated that the hippocampus can be parcellated into distinct anterior and posterior segments. These structurally defined segments did indeed show different patterns of resting state functional connectivity, in that the anterior segment showed greater connectivity with temporal and orbitofrontal cortex, whereas the posterior segment was more highly connected to medial and lateral parietal cortex. Furthermore, we showed that the posterior hippocampal connectivity to memory processing regions, including the dorsolateral prefrontal cortex, parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted interindividual relational memory performance. These findings provide important support for the integration of structural and functional connectivity in understanding the brain networks underlying episodic memory.

Neurocognitive and Seizure Outcomes of Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy

Objective. To report our institutional seizure and neuropsychological outcomes for a series of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH) between 2004 and 2011. Methods. A retrospective study of patients with mTLE was conducted. Seizure outcome was reported using time-to-event analysis. Cognitive outcome was reported using the change principal in component factor scores, one each, for intellectual abilities, visuospatial memory, and verbal memory. The Boston Naming Test was used for naming assessment. Language dominant and nondominant resections were compared separately. Students t-test was used to assess statistical significance. Results. Ninety-six patients (75 ATL, 21 SelAH) were included; fifty-four had complete neuropsychological follow-up. Median follow-up was 40.5 months. There was no statistically significant difference in seizure freedom or any of the neuropsychological outcomes, although there was a trend toward greater postoperative decline in naming in the dominant hemisphere group following ATL. Conclusion. Seizure and neuropsychological outcomes did not differ for the two surgical approaches which is similar to most prior studies. Given the theoretical possibility of SelAH sparing language function in patients with epilepsy secondary to mesial temporal sclerosis and the limited high-quality evidence creating equipoise, a multicenter randomized clinical trial is warranted.

Associative reinstatement: A novel approach to assessing associative memory in patients with unilateral temporal lobe excisions ☆

We investigated whether unilateral medial temporal lobe (MTL) damage disrupts associative reinstatement, which represents the gain in item memory when the studied associative information is reinstated at retrieval. We were interested to see whether associative reinstatement relies on the same relational binding operations that support other types of associative memory (associative identification and recollection) thought to be subserved by the MTL. In addition, we examined whether such damage affects the different types of associative memory to a greater extent than item memory and item familiarity, and whether a different pattern is seen in patients with language dominant relative to non-dominant temporal lobe resection when the studied material consists of verbal information. To do so, we used a word pair recognition paradigm composed of two tasks: (1) a pair recognition task that provides measures of associative reinstatement and item memory, and (2) an associative identification recognition task that provides a measure of associative identification memory. Estimates of item familiarity and recollection were derived from performance on both tasks using a variant of the process-dissociation procedure. Our results showed that associative reinstatement, like other types of associative memory measures, was impaired in patients with unilateral resection, irrespective of the side of damage. Item familiarity, however, was impaired solely following language dominant resection. The lack of a laterality effect in our relational measures was likely due to using an encoding task that promoted formation of both verbal and visual associations, whereas item-based familiarity could rely exclusively on verbal operations. We propose that associative reinstatement provides a sensitive measure of relational memory that is less dependent on strategic processing and therefore more appropriate for evaluating MTL function in patients.