Danielle M. Williams

Novel fearful faces activate the amygdala in healthy young and elderly adults

Activation of the amygdala to emotionally valenced stimuli, and particularly to fearful faces, has been widely demonstrated in healthy young adults. However, recent studies assessing amygdala responses to fearful emotional faces in the normal elderly have not shown similar results. The reason for this is uncertain, but it may relate to life-span developmental changes in processing emotional stimuli or structural alterations in the amygdala with aging. In order to examine whether the amygdala could be activated in the elderly, we developed a paradigm designed to engage the amygdala on several levels. Based on recent imaging work indicating that novelty and stimulus change activates the amygdala, we assessed amygdala responses in young and elderly adults to novel fearful faces (versus familiar neutral ones). We demonstrate a robust activation in both groups, indicating that the amygdala remains responsive in aging. This activation did not differ between the two groups when we examined regions of interest in the amygdala based on functional or structural criteria. However, there were significantly greater activations in the inferior temporal cortex in the young versus elderly subjects.

Neuroanatomical correlates of personality in the elderly.

Extraversion and neuroticism are two important and frequently studied dimensions of human personality. They describe individual differences in emotional responding that are quite stable across the adult lifespan. Neuroimaging research has begun to provide evidence that neuroticism and extraversion have specific neuroanatomical correlates within the cerebral cortex and amygdala of young adults. However, these brain areas undergo alterations in size with aging, which may influence the nature of these personality factor-brain structure associations in the elderly. One study in the elderly demonstrated associations between perisylvian cortex structure and measures of self transcendence [Kaasinen, V., Maguire, R.P., Kurki, T., Bruck, A., Rinne, J.O., 2005. Mapping brain structure and personality in late adulthood. NeuroImage 24, 315-322], but the neuroanatomical correlates of extraversion and neuroticism, or other measures of the Five Factor Model of personality have not been explored. The purpose of the present study was to investigate the structural correlates of neuroticism and extraversion in healthy elderly subjects (n=29) using neuroanatomic measures of the cerebral cortex and amygdala. We observed that the thickness of specific lateral prefrontal cortex (PFC) regions, but not amygdala volume, correlates with measures of extraversion and neuroticism. The results suggest differences in the regional neuroanatomic correlates of specific personality traits with aging. We speculate that this relates to the influences of age-related structural changes in the PFC.

A Functional Magnetic Resonance Imaging Study of Amygdala Responses to Human Faces in Aging and Mild Alzheimer’s Disease

BACKGROUND Neuropsychiatric symptoms are very common even in mild stages of Alzheimers disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. METHODS Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. RESULTS Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. CONCLUSIONS The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD.

Neural Correlates of Novelty and Face-Age Effects in Young and Elderly Adults

The human amygdala preferentially responds to objects of potential value, such as hedonically valenced and novel stimuli. Many studies have documented age-related differences in amygdala responses to valenced stimuli, but relatively little is known about age-related changes in the amygdalas response to novelty. This study examines whether there are differences in amygdala novelty responses in two different age groups. Healthy young and elderly adults viewed both young and elderly faces that were seen many times (familiar faces) or only once (novel faces) in the context of an fMRI study. We observed that amygdala responses to novel (versus familiar) faces were preserved with aging, suggesting that novelty processing in the amygdala remains stable across the lifespan. In addition, participants demonstrated larger amygdala responses to target faces of the same age group than to age out-group target faces (i.e., an age in-group effect). Differences in anatomic localization and behavioral results suggest that novelty and age in-group effects were differentially processed in the amygdala.

Increased Responsiveness to Novelty is Associated with Successful Cognitive Aging

The animal literature suggests that exposure to more complex, novel environments promotes neurogenesis and cognitive performance in older animals. Studies in humans indicate that participation in intellectually stimulating activities may serve as a buffer against mental decline and help to sustain cognitive abilities. Here, we show that across old adults, increased responsiveness to novel events (as measured by viewing duration and the size of the P3 event-related potential) is strongly linked to better performance on neuropsychological tests, especially those involving attention/executive functions. Cognitively high performing old adults generate a larger P3 response to visual stimuli than cognitively average performing adults. These results suggest that cognitively high performing adults successfully manage the task by appropriating more resources and that the increased size of their P3 component represents a beneficial compensatory mechanism rather than less efficient processing.

Age-related differences in novelty and target processing among cognitively high performing adults

Previous research on age-related changes in ERP components in response to novel and target stimuli has not carefully controlled for differences in level of cognitive status between age groups, which may have contributed to the common findings of increased P3 latency, decreased P3 amplitude, and altered P3 scalp distribution. Here, cognitively high-performing (top third based on published norms) old, middle-aged, and young adults matched for IQ, education, and gender participated in a novelty oddball paradigm. There were no age-associated differences in P3 latency. Older adults had a larger, more anteriorly distributed P3 amplitude to all stimulus types, even repetitive standards, suggesting they may rely on increased resources and effortful frontal activity to successfully process any kind of visual stimulus. However, after controlling for this non-specific age-related processing difference, the amplitude and scalp distribution of the P3 component to novel and target stimuli were comparable across age groups, indicating that for cognitively high functioning elders there may be no age-related differences specific to the processing of novel and target events as indexed by the P3 component.

Brain correlates of negative and positive visuospatial priming in adults

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.

Age-related differences in attention to novelty among cognitively high performing adults

Age-related differences in attention to novel events were studied in well-matched, cognitively high performing old, middle-aged and young subjects. Event-related potentials were recorded during a visual novelty oddball task in which subjects controlled viewing durations that served as a behavioral measure of attentional allocation. All age groups had a larger P3 amplitude and longer viewing duration to novel than to standard stimuli, with no age-related differences in the magnitude of these effects, indicating old individuals were as engaged by the processing of novelty as younger adults. Old subjects had a larger, more anteriorly distributed P3 component to novels and standards. The increased P3 amplitude differs from prior reports of a diminished P3 response with processes, including aging, that have a potentially deleterious impact on the brain. We hypothesise that cognitively high performing old individuals successfully manage the task by relying on additional neural resources and perhaps more effortful frontal activity than their younger counterparts.

D-cycloserine inhibits amygdala responses during repeated presentations of faces.

INTRODUCTION Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined. METHODS The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0+/-8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks. RESULTS Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected. CONCLUSION This finding may have relevance for testing treatments of anxiety and depression.

Age-sensitivity of the P3 in cognitively high-performing adults: Unsettled issues

We read with interest the thoughtful commentary by Fjelland Walhovd [9] on the study we reported in Neurobiologyof Aging on “Age-Related Differences in Novelty and Tar-get Processing among Cognitively High Performing Adults”[6]. In contrast to much of the literature, we did not findan age-related decline in P3 amplitude to novel stimuli.Rather,ouroldadultshadalarger,moreanteriorlydistributedP3 amplitude. We suggested that they may rely on moreresourcesandeffortfulfrontalactivitytosuccessfullymanagethedemandsofthetask.Moreover,ourinvestigationfoundnoage-associated differences in P3 latency. Our effort to under-stand why our results differed from much of the P3 literatureon aging led us to hypothesize that it may be due to our selec-tionofcognitivelyhighfunctioningadultswhowerematchedforperformance(relativetoage-matchedpeers)onneuropsy-chological tests, estimated IQ, education and gender.The authors’ criticism that we “ignor[ed] a vast litera-ture on P3 and aging” is not valid. We acknowledged thatour results differ from the dozens of papers in the literaturethat have reported on age-related changes in P3 (of whichover 20 were cited in our paper). Although these studies havetended to be very careful in regard to their electrophysiolog-ical methods and analyses, many have provided extremelylimited data on the subjects who participated. Subjects oftenhavebeendescribedsimplyintermsofbeingvolunteers(e.g.,[17]), of not having a history of psychiatric or neurologic dis-orders (e.g., [11,12,20] or of not falling below a cut off levelon a brief cognitive screen like the Mini Mental State Exam-ination (e.g., [13]). Regardless of the outcome of the currentdiscussion, we would strongly advocate that researchers pro-vide detailed accounts of the subjects in different age groups