Gail Musen

Implicit and explicit memory for visual patterns

The article reports an investigation of implicit and explicit memory for novel, visual patterns. Implicit memory was assessed by a speeded perception task, and explicit memory by a four-alternative, forced-choice recognition task. Tests were given either immediately after testing or 7 days later. The results suggest that a single exposure of a novel, nonverbal stimulus is sufficient to establish a representation in memory that is capable of supporting long-lived perceptual priming. In contrast, recognition memory showed significant loss over the same delay. Performance measures in the two tasks showed stochastic independence on the first trial after a single exposure to each pattern. Finally, a specific occurrence of a previously studied item could be retrieved from explicit memory but did not affect the accuracy of perception in the implicit memory test. The results extend the domain of experimental dissociations between explicit and implicit memory to include novel, nonverbal stimuli.

Resting-State Brain Functional Connectivity Is Altered in Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients. We compared T2DM patients (n = 10, age = 56 ± 2.2 years, fasting plasma glucose [FPG] = 8.4 ± 1.3 mmol/L, HbA1c = 7.5 ± 0.54%) with nondiabetic age-matched control subjects (n = 11, age = 54 ± 1.8 years, FPG = 4.8 ± 0.2 mmol/L) using resting-state functional magnetic resonance imaging to evaluate functional connectivity strength among DMN regions. We also evaluated hippocampal volume, cognition, and insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR). Control subjects showed stronger correlations versus T2DM patients in the DMN between the seed (posterior cingulate) and bilateral middle temporal gyrus (β = 0.67 vs. 0.43), the right inferior and left medial frontal gyri (β = 0.75 vs. 0.54), and the left thalamus (β = 0.59 vs. 0.37), respectively, with no group differences in cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated with functional connectivity in the right inferior frontal gyrus and precuneus. T2DM patients showed reduced functional connectivity in the DMN compared with control subjects, which was associated with insulin resistance in selected brain regions, but there were no group effects of brain structure or cognition.

Implicit learning of color-word associations using a Stroop paradigm.

Our experiments asked whether implicit learning occurs for novel nonverbal associations. We presented subjects with color names printed in incongruent colors; subjects were asked to name the color in which the word was printed. In Experiment 1, each of 7 color words were associated with the same incongruent color across 6 blocks of trials, and then the color-word associations were abruptly changed. Both control subjects and patients with amnesia reduced their color-naming times across the first 6 trial blocks, and naming times increased when the color-word associations were changed. In Experiment 2, similar results were obtained when neutral words were associated with colors. In Experiment 3, we found that naming times were not disrupted when an irrelevant dimension (typecase) was changed. Finally, in Experiment 4, we found that the effect persisted across a 5-min delay. These studies provide evidence that implicit learning occurs for nonverbal associations and is independent of the brain structures damaged in amnesia.

Impact of diabetes and its treatment on cognitive function among adolescents who participated in the Diabetes Control and Complications Trial.

OBJECTIVE—The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13–19 years at entry in the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS—This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, ∼18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition. RESULTS—There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis. CONCLUSIONS—Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes.

The effects of type 1 diabetes on cerebral white matter

Aim/hypothesisStudies investigating the structure, neurophysiology and functional outcomes of white matter among type 1 diabetes patients have given conflicting results. Our aim was to investigate the relationship between type 1 diabetes and white matter hyperintensities.MethodWe assessed white matter integrity (using magnetic resonance imaging), depressive symptoms and neuropsychological function in 114 type 1 diabetes patients and 58 age-matched non-diabetic controls.ResultsOnly Fazekas grade 1 and 2 white matter hyperintensities were found among 114 long-duration, relatively young diabetes patients; the severity of lesions did not differ substantially from 58 healthy controls. White matter hyperintensities were not associated with depressive history or with clinical characteristics of diabetes, including retinopathy, severe hypoglycaemia or glycaemia control.Conclusions/interpretationOur data do not support an association between diabetes characteristics and white matter hyperintensities among relatively young type 1 diabetes participants.

On the Implicit Learning of Novel Associations by Amnesic Patients and Normal Subjects

This study examined whether amnesic patients and normal subjects can acquire novel associations implicitly and whether such learning can occur rapidly in a single trial. In two experiments, subjects studied novel word pairs either once or multiple times and were then asked to read old, new, and recombined word pairs as quickly as possible. In this paradigm, the learning of novel associations would be indicated by slower reading times for recombined word pairs than for old word pairs. In a third experiment, a perceptual identification paradigm was used to assess implicit learning of new associations. One-trial learning of new associations was not observed in the first two experiments, but learning of new associations did occur after multiple learning trials. An advantage of old versus recombined word pairs was obtained after a single trial only in Experiment 3 (using perceptual identification) when the results were combined across subject groups.

Intact text-specific reading skill in amnesia

Amnesic patients were studied to determine whether the acquisition and retention of item-specific skills can be supported by nondeclarative (implicit) memory. In Experiment 1, subjects read 2 different passages 3 times in succession. Reading speed improved at a similar rate in both amnesic patients and normal subjects and was specific to the text that was read. In Experiment 2, amnesic patients and normal subjects read a passage 3 successive times and then reread the same passage after a 0-s, 10-min, 2-hr, or 1-day delay. In both groups, facilitation persisted for at least 10 min and disappeared within 2 hr. It is suggested that facilitated reading speed depends importantly on both semantic and perceptual information and that such information can be supported by nondeclarative memory.

Cerebral white matter integrity and resting-state functional connectivity in middle-aged patients with type 2 diabetes.

Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We examined whether middle-aged type 2 diabetic patients show reduced white matter integrity in fiber tracts important for cognition and whether this abnormality is related to preestablished altered resting-state functional connectivity in the default mode network (DMN). Diabetic and nondiabetic participants underwent diffusion tensor imaging, functional magnetic resonance imaging, and cognitive assessment. Multiple diffusion measures were calculated using streamline tractography, and correlations with DMN functional connectivity were determined. Diabetic patients showed lower fractional anisotropy (FA) (a measure of white matter integrity) in the cingulum bundle and uncinate fasciculus. Control subjects showed stronger functional connectivity than patients between the posterior cingulate and both left fusiform and medial frontal gyri. FA of the cingulum bundle was correlated with functional connectivity between the posterior cingulate and medial frontal gyrus for combined groups. Thus, middle-aged patients with type 2 diabetes show white matter abnormalities that correlate with disrupted functional connectivity in the DMN, suggesting that common mechanisms may underlie structural and functional connectivity. Detecting brain abnormalities in middle age enables implementation of therapies to slow progression of neuropathology.

Altered Prefrontal Glutamate–Glutamine–γ-Aminobutyric Acid Levels and Relation to Low Cognitive Performance and Depressive Symptoms in Type 1 Diabetes Mellitus

CONTEXT Neural substrates for low cognitive performance and depression, common long-term central nervous system-related changes in patients with type 1 diabetes mellitus, have not yet been studied. OBJECTIVE To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression. DESIGN Cross-sectional study. SETTING General clinical research center. PARTICIPANTS One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants. MAIN OUTCOME MEASURES With the use of proton magnetic resonance spectroscopy, prefrontal glutamate-glutamine-gamma-aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes. RESULTS Prefrontal Glx concentrations were 9.0% (0.742 mmol/L; P = .005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend = .002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P = .003, .01, and <.001, respectively) than in control subjects. Higher prefrontal Glx concentrations in patients were associated with lower performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression. CONCLUSIONS The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes.

Nonverbal priming in amnesia

In this experiment, we examined whether a group of well-characterized amnesic patients would exhibit normal priming for novel nonverbal materials after a single exposure. Both amnesic patients and normal control subjects studied line figures and were then given apriming test in which they were asked to reproduce both old (studied) and new (unstudied) figures after a brief exposure. The measure of priming was the number of old patterns drawn correctly relative to the number of new patterns drawn correctly. Both subject groups reproduced more old patterns than new patterns, and the effect was similar in the two groups. In contrast, amnesic patients were significantly impaired on a recognition memory test for the items that hadbeen presented. This study contributes to recent evidence that implicit memory can support the rapid acquisition of novel verbal and nonverbal information. Perceptual priming for auchmaterial is independent of the structures damaged in amnesia.