Geoffrey L. Ahern

Neuroanatomical correlates of pleasant and unpleasant emotion.

Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system association with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmanns area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito-temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women.

Neural correlates of heart rate variability during emotion.

The vagal (high frequency [HF]) component of heart rate variability (HRV) predicts survival in post-myocardial infarction patients and is considered to reflect vagal antagonism of sympathetic influences. Previous studies of the neural correlates of vagal tone involved mental stress tasks that included cognitive and emotional elements. To differentiate the neural substrates of vagal tone due to emotion, we correlated HF-HRV with measures of regional cerebral blood flow (rCBF) derived from positron emission tomography (PET) and (15)O-water in 12 healthy women during different emotional states. Happiness, sadness, disgust and three neutral conditions were each induced by film clips and recall of personal experiences (12 conditions). Inter-beat intervals derived from electrocardiographic recordings during the 60-second scans were spectrally-analyzed, generating 12 separate measures of HF-HRV in each subject. The six emotion and six neutral conditions were grouped together and contrasted. We observed substantial overlap between emotion-specific rCBF and the correlation between emotion-specific rCBF and HF-HRV, particularly in the medial prefrontal cortex. Emotion-specific rCBF also correlated with HF-HRV in the caudate nucleus, periacqueductal gray and left mid-insula. We also observed that the elements of cognitive control inherent in this experiment (that involved focusing on the target mental state) had definable neural substrates that correlated with HF-HRV and to a large extent differed from the emotion-specific correlates of HF-HRV. No statistically significant asymmetries were observed. Our findings are consistent with the view that the medial visceromotor network is a final common pathway by which emotional and cognitive functions recruit autonomic support.

Longitudinal Modeling of Age-Related Memory Decline and the APOE ε4 Effect

BACKGROUND The APOE epsilon4 allele is associated with the risk of late-onset Alzheimers disease. The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown. METHODS Using local advertisements, we recruited cognitively normal subjects between the ages of 21 and 97 years, who were grouped according to their APOE epsilon4 status. We then followed the subjects with longitudinal neuropsychological testing. Anyone in whom mild cognitive impairment or dementia developed during follow-up was excluded. We compared the rates of decline in predetermined cognitive measures between carriers and noncarriers of the APOE epsilon4 allele, using a mixed model for longitudinal change with age. RESULTS We analyzed 815 subjects: 317 APOE epsilon4 carriers (79 who were homozygous for the APOE epsilon4 allele and 238 who were heterozygous) and 498 noncarriers. Carriers, as compared with noncarriers, were generally younger (mean age, 58.0 vs. 61.4 years; P<0.001) and were followed for a longer period (5.3 vs. 4.7 years, P=0.01), with an equivalent duration of formal education (15.4 years) and proportion of women (69%). Longitudinal decline in memory in carriers began before the age of 60 years and showed greater acceleration than in noncarriers (P=0.03), with a possible allele-dose effect (P=0.008). We observed similar although weaker effects on measures of visuospatial awareness and general mental status. CONCLUSIONS Age-related memory decline in APOE epsilon4 carriers diverges from that of noncarriers before the age of 60 years, despite ongoing normal clinical status.

Is alexithymia the emotional equivalent of blindsight

A fundamental tenet of psychosomatic medicine is that interference with the experience and expression of emotions can have an adverse affect on health (Taylor 1987). Early in this century it was observed that the onset and course of certain physical diseases were adversely affected by the repression of certain conflictual ideas and their accompanying affects (Alexander 1950). A later alternative view was that a deficit or developmental arrest in the capacity for symbolic mental representation of emotion was the core problem in patients with psychosomatic disorders, typified by a diminished ability to identify and describe feelings (Ruesch 1948). This latter view has evolved into the concept of alexithymia, a term coined by Sifneos in 1972 meaning “absence of words for emotion” (Sifneos 1972). Sifneos and Nemiah posited that the deficit in the capacity for symbolization of emotion (in verbal behavior, fantasy, and dreams) resulted in a variety of manifestations, including abnormal physiology resulting in disease, a propensity for impulsive behavior, discomfort with and avoidance of social relationships, and an impaired capacity for self-care and self-regulation (Nemiah and Sifneos 1970). Subsequent research has revealed that alexithymia is associated with a variety of other psychiatric disorders, including posttraumatic stress disorder (PTSD), substance abuse and dependence, somatization, eating disorders, and panic disorder (Taylor et al 1991; Jimerson et al 1994; Parker et al 1993). It is not known whether the manifestations of alexithymia are similar or different in these various clinical contexts. Recent research has also demonstrated that alexithymia is associated with deficits in the recognition of both verbal and nonverbal emotional stimuli (Lane et al, in press). To obtain a current consensus about the essential features of alexithymia, Haviland and Reise (1996) recently generated a prototypical description of alexithymic individuals derived from 13 experts using the Q-sort method. The results of this survey are presented in Table 1. Alexithymic individuals manifest bland or flattened affect, tend to be somatically preoccupied, express themselves through action and nonverbal behavior, are interpersonally distant, become disorganized under stress, lack imagination and insight, and tend to be socially conforming. Early descriptions of alexithymic individuals included diminished facial expressions, which have been confirmed in recent empirical work (McDonald and Prkachin 1990), but also noted occasional brief, intense, dramatic outbursts of emotion such as tearfulness that end as abruptly as they From the Department of Psychiatry (RDL, GLA, GES, AWK) and Department of Neurology (GLA, GES, AWK), University of Arizona College of Medicine, and Department of Psychology, University of Arizona (RDL, GLA, GES, AWK), Tucson, Arizona. Address reprint request to Richard D. Lane, MD, Department of Psychiatry, Arizona Health Sciences Center, 1501 N. Campbell Avenue, Tucson, AZ 85724. Received January 18, 1996.

Differential lateralization for positive and negative emotion in the human brain: EEG spectral analysis.

The present experiment utilized EEG spectral analysis to investigate lateralization for emotional processes in the human brain. In frontal zones, a differential lateralization for positive and negative emotion was observed, with relative left-hemispheric activation (as measured by decreases in alpha abundance) for positive emotions and relative right-hemispheric activation for negative emotions. In parietal zones, a differential lateralization for verbal and spatial processes was observed, with relative left-hemispheric activation for verbal questions and relative right-hemispheric activation for spatial questions. Examination of EEG bands other than alpha (i.e. delta, theta, beta, and total power) suggested that emotional and cognitive processes are further distinguished by different EEG spectral patterns.

Differential lateralization for positive versus negative emotion.

Abstract Lateral eye movements were recorded in response to 60 reflective questions designed to manipulate (1) verbal/spatial requirements and (2) affective tone. Positive emotion questions evoked movements suggestive of relative left hemisphere involvement, while negative emotion questions evoked movements suggestive of relative right hemisphere involvement. Verbal/spatial effects emerged only in a subgroup of subjects showing bidirectional eye movement responses under these conditions. Lateralization effects for approach vs avoidance responding (and their accompanying emotional states) may be more fundamental than the higher cognitive verbal/ spatial dichotomy.

Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test.

Summary:  Purpose: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re‐investigate this topic with a larger N than has heretofore been used.

Peripheral clearance of amyloid β peptide by complement C3-dependent adherence to erythrocytes

Brain deposits of amyloid beta peptide (Abeta) have been a diagnostic hallmark of Alzheimers disease (AD) for nearly a century. Recent studies have demonstrated that Abeta is also present in peripheral blood. Here, we present evidence that circulating Abeta42 is subject to complement C3b-dependent adherence to complement receptor 1 (CR1) on erythrocytes, a classical set of mechanisms by which pathogens and proteins recognized as foreign are cleared from the bloodstream. Levels of Abeta42 targeted by this pathway differ significantly in AD compared to mild cognitive impairment and nondemented elderly controls.

Paraneoplastic temporal lobe epilepsy with testicular neoplasm and atypical amnesia

We report a patient who, at age 38, presented with temporal lobe seizures and an atypical memory disorder 3 years before the discovery of a testicular tumor. Detailed neuropsychological testing revealed a relatively isolated amnestic syndrome. The amnesia was atypical as the patient could retain information for hour-long periods, only to lose it later. Serologic studies revealed the presence of a circulating autoantibody that demonstrated an unusual affinity for the nucleolus of cerebral cortical neurons. Western blot analysis of cortical neurons revealed that this antibody reacted with proteins different from other previously identified paraneoplastic neurologic antigens (Hu, Yo, Ri). We believe this to be a case of paraneoplastic limbic encephalitis secondary to the testicular tumor. This patient presents unique characteristics with respect to the mode of presentation, features of the amnesia, and the presence of a circulating antibody with an unusual reactivity pattern.

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimers disease, Parkinsons disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimers Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinsons Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinsons Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.