Cary R. Savage

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.

Predictors of cognitive change in older persons : MacArthur studies of successful aging

This study used a linear structural relations modeling technique (LISREL) to examine longitudinal data for 1,192 persons from a community-based population. The goal was to test the ability of an a priori model to predict cognitive change over a 2.0- to 2.5-year period in older adults aged 70-79 at the initial evaluation. The model included 22 demographic, physical, and psychosocial variables as predictors of cognitive function and cognitive change. The study used an exploratory-confirmatory design, enabling cross-validation of the model developed in the exploratory set in the confirmatory sample. Structural equation modeling analyses identified 4 endogenous model variable (education, strenuous activity, peak pulmonary expiratory flow rate, and self-efficacy) as direct predictors of cognitive change over the study period.

Organizational strategies mediate nonverbal memory impairment in obsessive–compulsive disorder

BACKGROUNDnPrevious neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure.nnnMETHODSnWe examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function.nnnRESULTSnOCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set.nnnCONCLUSIONSnImmediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

Striatal recruitment during an implicit sequence learning task as measured by functional magnetic resonance imaging

Prior research has repeatedly implicated the striatum in implicit sequence learning; however, imaging findings have been inconclusive with respect to the sub‐territories and laterality involved. Using functional magnetic resonance imaging (fMRI), we studied brain activation profiles associated with performance of the serial reaction time task (SRT) in 10 normal right‐handed males. Behavioral results indicate that significant implicit learning occurred, uncontaminated by significant explicit knowledge. Concatenated fMRI data from the entire cohort revealed significant right‐lateralized activation in both the caudate and putamen. Analysis of fMRI data from individual subjects showed inter‐individual variability as to the precise territories involved, including right as well as left caudate and putamen. Interestingly, all seven subjects who manifested robust learning effects exhibited significant activation within the putamen. Moreover, among those seven subjects, the magnitude of signal intensity change within the putamen correlated significantly with the magnitude of reaction time advantage achieved. These findings demonstrate right‐sided striatal activation across subjects during implicit sequence learning, but also highlight interindividual variability with respect to the laterality and striatal subterritories involved. In particular, results from individual subjects suggest that, during the SRT, the reaction time advantage garnered via implicit sequence learning might be predominantly associated with activity within the putamen. Hum. Brain Mapping 5:124–132, 1997.

The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.

The Massachusetts General Hospital (MGH) Hairpulling Scale: 1. Development and Factor Analyses

We developed the MGH Hairpulling Scale to provide a brief, self-report instrument for assessing repetitive hairpulling. Seven individual items, rated for severity from 0 to 4, assess urges to pull, actual pulling, perceived control, and associated distress. We administered the scale to 119 consecutive patients with chronic hairpulling. Statistical analyses indicate that the seven items form a homogenous scale for the measurement of severity in this disorder.

The role of hippocampus and frontal cortex in age-related memory changes : a PET study

THE purpose of this study was to examine the neuroanatomical correlates of explicit retrieval of episodic memories in older and young adults. We used an experimental paradigm that allowed us to separate the effort involved in attempting to retrieve a recently studied word from the actual recollection of the item. Both older and younger adults showed hippocampal blood flow increases in association with recollection of a studied word. In contrast, younger but not older adults showed bilateral blood flow increases in anterior prefrontal cortex during retrieval attempts: older adults showed more posterior frontal lobe activations during attempted retrieval. We conclude that the hippocampus activations may reflect a commonality in the way that older and younger adults remember past events, whereas differences in frontal activation may reflect age-related changes in their retrieval strategies.

The neural network basis for abnormalities of attention and executive function in major depressive disorder: implications for application of the medical disease model to psychiatric disorders.

The deficits in attention and executive function characteristic of major depressive disorder (MDD) are reviewed. The networks underlying attention and executive function, the neuropsychological tests commonly used to evaluate these domains, and the neuroanatomy of MDD are also discussed. A neural network approach to the attentional and executive function deficits of MDD has ramifications for hypothesis-guided research, the cognitive model of depression, and application of the medical disease model to psychiatric disorders.

The relationship between semantic organization and memory in obsessive-compulsive disorder.

Background: A variety of evidence suggests that frontostriatal dysfunction is involved in obsessive-compulsive disorder (OCD). This evidence includes both neuroimaging findings and results from studies using neuropsychological assessments. Previous studies have documented nonverbal memory deficits in individuals with OCD, whereas verbal learning and memory were less affected. Methods: The present study examined both verbal and nonverbal memory in a sample of 17 untreated outpatients with OCD. We also evaluated the effects of encoding strategies which are believed to be mediated by frontostriatal system functioning. Results: OCD patients were significantly impaired in both verbal and nonverbal memory performance. This deficit was correlated with impairments in organizational and semantic clustering strategies at the time of encoding. Conclusions: Deficits in organizational strategies are consistent with frontostriatal dysfunction models in OCD.

Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging

A morphometric magnetic resonance imaging (MRI) study compared volumes of brain structures in 10 female subjects with trichotillomania (repetitive hair-pulling) versus 10 normal controls matched for sex, age, handedness, and education. Three-dimensional MRI scans were blindly normalized and segmented using well-characterized semiautomated intensity and differential contour algorithms by signal intensity-frequency histograms. Consistent with one a priori hypothesis, left putamen volume was found to be significantly smaller in trichotillomania subjects as compared with normal matched controls. This is the first report of a structural brain abnormality in trichotillomania. Results are discussed in terms of putative relationships between trichotillomania, Tourettes syndrome, and obsessive-compulsive disorder.