Cognitive rehabilitation of memory for mild cognitive impairment: a methodological review and model for future research.

Several recent reviews have suggested that cognitive rehabilitation may hold promise in the treatment of memory deficits experienced by patients with mild cognitive impairment. In contrast to the previous reviews that mainly focused on outcome, the current review examines key methodological challenges that are critical for designing and interpreting research studies and translating results into clinical practice. Using methodological details from 36 studies, we first examine diagnostic variability and how the use of cutoffs may bias samples toward more severely impaired patients. Second, the strengths and limitations of several common rehabilitative techniques are discussed. Half of the reviewed studies used a multi-technique approach that precludes the causal attribution between any specific technique and subsequent improvement. Third, there is a clear need to examine the dose-response relationship since this information was strikingly absent from most studies. Fourth, outcome measures varied widely and frequently depended on neuropsychological tests with little theoretical justification or ecological relevance. Fifth, we discuss how the variability in each of these other four areas complicates efforts to examine training generalization. Overall, future studies should place greater emphasis on ecologically relevant treatment approaches and outcome measures and we propose a hierarchical model that may aid in this pursuit.

Neuropsychological outcome following thalamic stroke in adolescence: an identical twin comparison.

Objective: Medial thalamic stroke in adults commonly results in severe learning and memory impairments and executive dysfunction, particularly during the acute phase. However, there is limited research on the cognitive recovery from thalamic stroke in physically healthy adolescents. This study aimed to fill this gap in the literature by utilizing a monozygotic twin control to investigate the neuropsychological outcomes of bilateral thalamic stroke in adolescence. Method: We evaluated an otherwise healthy 17-year-old male with a history of premature birth, developmental delay, and learning disability 2 and 7 months after he sustained a bilateral medial/anterior thalamic stroke of unknown etiology. His identical twin brother served as a case control. Results: The patient presented with improvements in many cognitive skills between assessments, most notably processing speed. Despite some mild improvement, however, he presented with significant deficits in fine motor speed/coordination, spatial perception, and rapid naming. Additionally, he exhibited persistent, severe deficits in verbal learning and memory. Relative sparing of executive functions (i.e., planning and set-shifting) and attention on standardized measures in this case may be explained by good underlying health, limited extra-thalamic damage, and/or recovery of function. The effects of thalamic injury resulted in minimal adaptive dysfunction or deterrence from academic or athletic success for the presented case. Conclusions: These results suggest risk for deficits in encoding of new verbal information following bilateral thalamic stroke in adolescence, as well as risk for persistent cognitive deficits despite initial improvements. This is consistent with descriptions of anterograde memory impairments in adults with similar lesions.

Working memory contributes to the encoding of object location associations: Support for a 3-part model of object location memory.

A recent model by Postma and colleagues posits that the encoding of object location associations (OLAs) requires the coordination of several cognitive processes mediated by ventral (object perception) and dorsal (spatial perception) visual pathways as well as the hippocampus (feature binding) [1]. Within this model, frontoparietal network recruitment is believed to contribute to both the spatial processing and working memory task demands. The current study used functional magnetic resonance imaging (fMRI) to test each step of this model in 15 participants who encoded OLAs and performed standard n-back tasks. As expected, object processing resulted in activation of the ventral visual stream. Object in location processing resulted in activation of both the ventral and dorsal visual streams as well as a lateral frontoparietal network. This condition was also the only one to result in medial temporal lobe activation, supporting its role in associative learning. A conjunction analysis revealed areas of shared activation between the working memory and object in location phase within the lateral frontoparietal network, anterior insula, and basal ganglia; consistent with prior working memory literature. Overall, findings support Postma and colleague's model and provide clear evidence for the role of working memory during OLA encoding.

A two-part preliminary investigation of encoding-related activation changes after moderate to severe traumatic brain injury: hyperactivation, repetition suppression, and the role of the prefrontal cortex.

Traumatic brain injury (TBI) survivors typically exhibit significant learning and memory deficits and also frequently demonstrate hyperactivation during functional magnetic resonance imaging (fMRI) tasks involving working memory encoding and maintenance. However, it remains unclear whether the hyperactivation observed during such working memory tasks is also present during long-term memory encoding. The preliminary experiments presented here were designed to examine this question. In Experiment 1, 7 healthy controls (HC) and 7 patients with moderate to severe TBI encoded ecologically relevant object location associations (OLA) while undergoing fMRI and then completed a memory test outside of the fMRI environment. fMRI data analysis included only the correctly encoded trials and revealed hyperactivation in the TBI relative to HC group in regions critical for OLA encoding, including bilateral dorsal and ventral visual processing areas, bilateral frontoparietal working memory network regions, and the left medial temporal lobe. There was also an incidental finding that this hyperactivation persisted after multiple exposures to the same stimulus, which may indicate an attenuated repetition suppression effect that could ultimately contribute to cognitive fatigue and inefficient memory encoding after TBI. Experiment 2 directly assessed repetition suppression in some of the same HC and TBI participants. During early encoding trials, the TBI group showed large areas of hyperactivation in the right prefrontal cortex and bilateral posterior parietal cortices relative to the HC. Following additional exposure to these stimuli, the TBI group showed repetition suppression in visual and spatial processing regions, but continued to show hyperactivation in the right dorsolateral prefrontal cortex. Findings from these preliminary studies may reflect that increased reliance on cognitive control mechanisms following TBI extends to memory encoding.

RBANS memory indices are related to medial temporal lobe volumetrics in healthy older adults and those with mild cognitive impairment.

The current study (i) determined whether NeuroQuant(®) volumetrics are reflective of differences in medial temporal lobe (MTL) volumes between healthy older adults and those with mild cognitive impairment (MCI) and (ii) examined the relationship between RBANS indices and MTL volumes. Forty-three healthy older adults and 57 MCI patients completed the RBANS and underwent structural MRI. Hippocampal and inferior lateral ventricle (ILV) volumes were obtained using NeuroQuant(®). Results revealed significantly smaller hippocampal and larger ILV volumes in MCI patients. MTL volumes were significantly related to the RBANS Immediate and Delayed Memory and Language indices but not the Attention or Visuoconstruction indices; findings that demonstrate anatomical specificity. Following discriminant function analysis, we calculated a cutpoint that may prove clinically useful for integrating MTL volumes into the diagnosis of MCI. These findings demonstrate the potential clinical utility of NeuroQuant(®) and are the first to document the relationship between RBANS indices and MTL volumes.

Impaired retention is responsible for temporal order memory deficits in mild cognitive impairment.

Temporal order memory, or remembering the order of events, is critical for everyday functioning and is difficult for patients with mild cognitive impairment (MCI). It is currently unclear whether these patients have difficulty acquiring and/or retaining such information and whether deficits in these patients are in excess of "normal" age-related declines. Therefore, the current study examined age and disease-related changes in temporal order memory as well as whether memory load played a role in such changes. Young controls (n=25), older controls (n=34), and MCI patients (n=32) completed an experimental task that required the reconstruction of sequences that were 3, 4, or 5 items in length both immediately after presentation (i.e., immediate recall) and again after a 10-min delay (i.e., delayed recall). During the immediate recall phase, there was an effect of age largely due to reduced performance at the two longest span lengths. Older controls and MCI patients only differed during the five span (controls>MCI). During the delayed recall, however, there were significant effects of both age and MCI regardless of span length. In MCI patients, immediate recall was significantly correlated with measures of executive functioning, whereas delayed recall performance was only related to other memory tests. These findings suggest that MCI patients experience initial temporal order memory deficits at the point when information begins to exceed working memory capacity and become dependent on medial temporal lobe functioning. Longer-term deficits are due to an inability to retain information, consistent with the characteristic medial temporal lobe dysfunction in MCI.

Regulating the expectation of reward via cognitive strategies.

Previous emotion regulation research has been successful in altering aversive emotional reactions. It is unclear, however, whether such strategies can also efficiently regulate expectations of reward arising from conditioned stimuli, which can at times be maladaptive (for example, drug cravings). Using a monetary reward-conditioning procedure with cognitive strategies, we observed attenuation in both the physiological (skin conductance) and neural correlates (striatum) of reward expectation as participants engaged in emotion regulation.