Kristy A. Nielson

fMRI of Healthy Older Adults During Stroop Interference

The Stroop interference effect, caused by difficulty inhibiting overlearned word reading, is often more pronounced in older adults. This has been proposed to be due to declines in inhibitory control and frontal lobe functions with aging. Initial neuroimaging studies of inhibitory control show that older adults have enhanced activation in multiple frontal areas, particularly in inferior frontal gyrus, indicative of recruitment to aid with performance of the task. The current study compared 13 younger and 13 older adults, all healthy and well educated, who completed a Stroop test during functional magnetic resonance imaging. Younger adults were more accurate across conditions, and both groups were slower and less accurate during the interference condition. The groups exhibited comparable activation regions, but older adults exhibited greater activation in numerous frontal areas, including the left inferior frontal gyrus. The results support the recruitment construct and suggest, along with previous research, that the inferior frontal gyrus is important for successful inhibition.

Intact Physiological Response to Arousal with Impaired Emotional Recognition in Alexithymia

Background: The purpose of the present study was to clarify the relationship between the recognition of emotion and physiological response to emotion (i.e. arousal) in alexithymia. Methods: This study investigated differences in physiological arousal state, as measured by continuous heart rate, electrodermal activity (EDA) and self-reported emotional intensity before and after exposure to an emotionally arousing or neutral videotape among 41 high- or low-alexithymic young adult participants. Results: Across subjects, emotionally negative stimuli produced increased physiological arousal. However, high-alexithymic participants exposed to the arousing videotape did not report increased subjective emotional intensity, as did low-alexithymic participants. In addition, the baseline EDA of high-alexithymic participants was significantly higher than that of the low-alexithymic participants. Conclusions: Results support the prediction that alexithymia leads to a decoupling between subjective and physiological arousal when exposed to emotionally negative stimuli. This decoupling may increase alexithymic individuals’ risks for stress-related illness.

Beta-adrenergic receptor antagonist antihypertensive medications impair arousal-induced modulation of working memory in elderly humans.

It is well-established that administration of moderate doses of the adrenal catecholamines epinephrine or norepinephrine shortly after training results in the enhancement of later retention performance in laboratory animals. These substances, released endogenously as a result of arousal, are thought to modulate memory processes by stimulating peripheral receptors that send neural messages to the brain, thus altering the memory storage process. The applicability of this hypothesis to the modulation of memory processes in humans was tested in this experiment by using elderly subjects who were chronically taking beta-receptor antagonist medications to control hypertension. A moderate level of muscle-tension-induced arousal was produced by having subjects squeeze a hand dynamometer during the initial storage and recall of highlighted words in short 200-word paragraphs. Twenty young normal individuals, 22 normotensive elderly subjects, 21 elderly subjects taking either calcium-channel blockers or angiotensin-converting enzyme inhibitors to control hypertension, and 21 elderly subjects taking beta-blocker antihypertensive medications served as subjects. The young subjects, normal elderly subjects, and those taking non-beta-blocker medications all showed enhanced long-term recognition performance as a result of the arousal manipulation. However, those subjects chronically taking beta-receptor-antagonist medications showed no enhancement of memory.

Frontal recruitment during response inhibition in older adults replicated with fMRI

Recent research has explored age-related differences in multiple areas of cognitive functioning using fMRI, PET, and SPECT. However, because these studies used different tasks, subjects, and methods, little is known about whether the results of these studies are generalizable or repeatable. The present study replicated a previous study [Psychol. Aging 17 (2002) 56] using the same Go/No-go task with a subset of 11 of the original older adult subjects, and using the same fMRI scanner and imaging methods. A direct comparison was made between these participants at Time 1 and Time 2 for both behavioral and functional data. These participants were also compared to a new young adult group of 11 participants. Although the current young adult group did not perform as well as the original young adult group, the original finding of enhanced left prefrontal activation in older adults relative to younger adults was replicated. Furthermore, when comparing Time 1 to Time 2, older adults exhibited comparable areas of activation, but significantly greater magnitude of activation at Time 1 in a few clusters. The findings indicate that older adults exhibit more bilateral brain activity during this task than young adults, which appears compensatory and is repeatable over time. The magnitude of regional activation, however, may vary with extraneuronal factors such as signal-to-noise ratio or task experience. This study adds to existing research suggesting that bilateral frontal activation is a predominant finding in the aging literature, and not specific to certain tasks in age group comparisons.

A task to manipulate attentional load, set-shifting, and inhibitory control: Convergent validity and test–retest reliability of the Parametric Go/No-Go Test

Traditional neuropsychological measures of executive functioning are difficult to employ in functional imaging and clinical trial contexts and have tremendous practice effects. They also have poor sensitivity and specificity, while test–retest reliability is often not assessed in computer-based tests. The present study evaluates some psychometric properties of a new Parametric Go/No-Go (PGNG) Task. The PGNG consists of three levels of difficulty assessing attention, set-shifting, and processing speed, with the two more difficult levels assessing inhibitory control. A total of 63 healthy control participants were recruited at two sites to evaluate the psychometric properties of the PGNG. The PGNG was found to have solid parametric characteristics and strong test–retest reliability. Modest convergent validity was also demonstrated with other executive-functioning tests. Learning effects were significantly less than those for the Trail Making Test. The present results provide solid initial support for the validity and reliability of the PGNG.

Semantic memory activation in amnestic mild cognitive impairment

Cognitively intact older individuals at risk for developing Alzheimers disease frequently show increased functional magnetic resonance imaging (fMRI) brain activation presumably associated with compensatory recruitment, whereas mild cognitive impairment (MCI) patients tend not to show increased activation presumably due to reduced neural reserve. Previous studies, however, have typically used episodic memory activation tasks, placing MCI participants at a performance disadvantage relative to healthy elders. In this event-related fMRI study, we employed a low effort, high accuracy semantic memory task to determine if increased activation of memory circuits is preserved in amnestic MCI when task performance is controlled. Fifty-seven participants, aged 65-85 years, comprised three groups (n = 19 each): amnestic MCI patients; cognitively intact older participants at risk for developing Alzheimers disease based on having at least one ApoE epsilon4 allele and a positive family history of Alzheimers disease (At Risk); and cognitively intact participants without Alzheimers disease risk factors (Control). fMRI was conducted on a 3T MR scanner while participants performed a famous name discrimination task. Participants also underwent neuropsychological testing outside the scanner; whole brain and hippocampal atrophy were assessed from anatomical MRI scans. The three groups did not differ on demographic variables or on fame discrimination performance (>87% correct for all groups). As expected, the amnestic MCI participants demonstrated reduced episodic memory performance. Spatial extent of activation (Fame--Unfamiliar subtraction) differentiated the three groups (Control = 0 ml, At Risk = 9.7 ml, MCI = 34.7 ml). The MCI and At Risk groups showed significantly greater per cent signal change than Control participants in 8 of 14 functionally defined regions, including the medial temporal lobe, temporoparietal junction, and posterior cingulate/precuneus. MCI participants also showed greater activation than Controls in two frontal regions. At Risk, but not MCI, participants showed increased activity in the left hippocampal complex; MCI participants, however, evidenced increased activity in this region when hippocampal atrophy was controlled. When performance is equated, MCI patients demonstrate functional compensation in brain regions subserving semantic memory systems that generally equals or exceeds that observed in cognitively intact individuals at risk for Alzheimers disease. This hyperactivation profile in MCI is even observed in the left hippocampal complex, but only when the extent of hippocampal atrophy is taken into consideration.

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

The Progression of β-amyloid Deposition in the Frontal Cortex of the Aged Canine

Abstract Brains from 41 aged canines (≥10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of β-amyloid (Aβ) in frontal cortex. We classified the Aβ patterns into four distinct types. Type I was characterized by small, faint deposits of Aβ in deep cortical layers. Type II consisted of diffuse deposits of Aβ mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the Aβ distribution pattern between the Old canines (10–15 years, n=22) and the Very Old canines (>15 years, n=19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (P

Positive and negative sources of emotional arousal enhance long-term word-list retention when induced as long as 30 min after learning.

The consolidation of newly formed memories occurs slowly, allowing memories to be altered by experience for some time after their formation. Various treatments, including arousal, can modulate memory consolidation when given soon after learning, but the degree of time-dependency of these treatments in humans has not been studied. Thus, 212 participants learned a word list, which was followed by either a positively or negatively valenced arousing video clip (i.e., comedy or surgery, respectively) after delays of 0, 10, 30 or 45 min. Arousal of either valence induced up to 30 min after learning, but not after 45 min, significantly enhanced one-week retrieval. The findings support (1) the time-dependency of memory modulation in humans and (2) other studies that suggest that it is the degree of arousal, rather than valence that modulates memory. Important implications for developing memory intervention strategies and for preserving and validating witness testimony are discussed.

Apolipoprotein‐E Genotyping of Diabetic Dementia Patients: Is Diabetes Rare in Alzheimer's Disease?

OBJECTIVES: To determine whether diabetes is rare in Alzheimer disease (AD) relative to other types of dementia and whether diabetics with dementia have a low frequency of the Apolipoprotein‐E E4 genotype.