PubMed Health⌕ Search

Biomedical subjects

C R Savage

Publications and source records attributed to C R Savage.

At least 19 recordsLinked to original sources
PubMed2001

Missing the forest for the trees? Deficient memory for linguistic gist in obsessive-compulsive disorder.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) exhibit recall deficits on word learning tasks, mediated by their failure to detect semantic connections among the words. METHODS: In the present experiment, using methods devised by Bransford & Franks (1971), we tested whether this encoding problem impairs their extraction of gist from complex linguistic material. RESULTS: Consistent with our hypothesis, OCD patients extracted less gist from related sentences than did healthy participants. The groups did not differ in recognition memory for individual sentences or in criterion for affirming previously encountered sentences as 'old', as evinced by signal detection indices of memory sensitivity (d') and response bias (beta), or in recognition memory confidence. CONCLUSIONS: These data provide further evidence that OCD patients exhibit less reliance on organizational strategies than do healthy control participants. These data are consistent with neuropsychological research suggestive of prefrontal executive problems in OCD.

Adult↗
PubMed2001

Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: evidence from PET.

The prefrontal cortex has been implicated in strategic memory processes, including the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way they are applied in novel or ambiguous situations-failure to initiate effective strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed and unrelated. During the spontaneous condition, subjects heard 24 words that were related in four categories but presented in mixed order, and they were not informed of this structure beforehand. Any semantic reorganization was, therefore, initiated spontaneously by the subject. In the directed condition, subjects were given a different list of 24 related words and explicitly instructed to notice relationships and mentally group related words together to improve memory. The unrelated list consisted of 24 unrelated words. Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activations were found in left inferior prefrontal cortex (inferior frontal gyrus) and left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additional covariate analyses in the first spontaneous condition indicated that blood flow in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood flow in OFC during encoding predicted which subjects would spontaneously initiate effective strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by supporting the early mobilization of effective behavioural strategies in novel or ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization.

Acoustic Stimulation↗
PubMed2001

Is age at symptom onset associated with severity of memory impairment in adults with obsessive-compulsive disorder?

OBJECTIVE: Age at onset is a potentially important marker for neurobiological features of obsessive-compulsive disorder (OCD). This study examined the relationship between age at symptom onset and memory impairment in adults with OCD. METHOD: The authors used the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test to compare memory functioning of 37 adult OCD patients with self-reported childhood onset of symptoms (onset at less than 18 years of age) with that of 31 patients with adult-onset symptoms. RESULTS: No differences were found between the two groups on any of the verbal and nonverbal memory measures. CONCLUSIONS: Self-reported age at symptom onset is not associated with memory performance in adult patients with OCD according to tests previously found to be sensitive to frontal-striatal system dysfunction and impairment in OCD. Such dysfunction appears to be a consistent feature of OCD in adults, regardless of age at initial symptom onset.

Adolescent↗
PubMed2001

Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods.

In summary, contemporary pathophysiological models of OCD and related disorders implicate CSTC circuitry. In this chapter, we have reviewed relevant concepts related to implicit learning and more specifically, the use of an implicit sequence learning paradigm as a probe of striato-thalamic function. An initial PET investigation of patients with OCD confirmed a priori hypotheses of failure to recruit right striatum, despite the absence of a performance deficit (22). A modified version of the SRT was studied in conjunction with fMRI and yielded reliable right-lateralized striatal activation in a cohort of 10 male subjects, with clear spatial dissociation of caudate and putamen activation foci (119). Subsequent studies in our laboratory suggest that this paradigm also yields a reliable temporal window of thalamic deactivation, and hence a means for assessing thalamic gating in human subjects (120). Finally, as presented in this chapter, preliminary data from the fMRI-SRT in patients with OCD and TS as well as normal control subjects appear to replicate and extend the findings from our original PET-SRT study in OCD. Future investigations in our laboratory will seek to elaborate upon these preliminary results. In particular, we intend to study psychiatric comparison groups to establish the generalizability and/or specificity of these findings across disorders. Within OCD, we hope to explore the relationship between abnormal brain-activation patterns and symptom dimensions (34). Further, by studying subjects with remitted OCD who have been successfully treated, we hope to determine whether the observed brain-activation abnormalities represent state or trait markers. Finally, we have already begun to test a hypothesis of parallel processing deficiency in OCD by using a dual-task version of the SRT that makes simultaneous demands on implicit and explicit information processing systems (128). It is our hope that this program of research will yield new insights about OCD and related disorders, including TS. Most importantly, as other teams of investigators pursue complementary lines of inquiry, it is our wish that collective efforts in this field will lead to improved diagnosis and treatment, if not cure or prevention, for those who are afflicted with these illnesses.

Corpus Striatum↗
PubMed2000

Characteristics of memory dysfunction in body dysmorphic disorder.

Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive-compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing.

Adult↗
PubMed2000

Strategic processing and episodic memory impairment in obsessive compulsive disorder.

There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.

Adult↗
PubMed2000

Reliability and validity of a scoring system for measuring organizational approach in the Complex Figure Test.

The Rey-Osterrieth Complex Figure Test (RCFT) is a widely-used measure of visuospatial construction and nonverbal memory. One of the critical aspects of this test is that organizing the figure into meaningful perceptual units during copy enhances its subsequent free recall from memory. This study examined the psychometric properties of a new system for quantifying the organizational approach to the RCFT figure and compared it to another compatible scoring system. We investigated interrater reliability of both systems and explored the influences of copy organization and copy accuracy on immediate recall. Seventy-one participants meeting DSM-IV criteria for obsessive-compulsive disorder and 55 healthy control participants completed the copy and immediate free recall condition of the RCFT. Interrater reliability was evaluated by Kappa coefficients and Pearson correlations. The effects of copy organization and copy accuracy on immediate recall were evaluated using multiple regression analyses. Results indicated that the organizational approach could be assessed with high reliability using both scoring systems. Organization during copy was a strong predictor for subsequent free recall from memory using both approaches. Multiple regression analysis indicated that all organizational elements were not equally predictive of memory performance. This new system represents a very simple and reliable approach to scoring organization on the RCFT, since it requires the identification of only 5 figure components. These characteristics should contribute to its clinical utility.

Adult↗
PubMed2000

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

Adolescent↗
PubMed2000

Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder.

BACKGROUND: Recent studies have suggested that obsessive-compulsive disorder (OCD) is a heterogeneous disorder with some forms related to tics and Tourette's disorder. The present study was undertaken to investigate the sensory phenomena in patients with OCD and/or Tourette's disorder to determine if these phenotypic features represent valid clinical indices for differentiating tic-related OCD from non-tic-related OCD. METHOD: We evaluated 20 adult outpatients with OCD, 20 with OCD plus Tourette's disorder, and 21 with Tourette's disorder, using a semistructured interview designed to assess several definitions of sensory phenomena reported in the literature. DSM-III-R criteria were used for the OCD and Tourette's disorder diagnoses. RESULTS: Sensory phenomena including bodily sensations, mental urges, and a sense of inner tension were significantly more frequent in the 2 Tourette's disorder groups when compared with the OCD alone group. Feelings of incompleteness and a need for things to be "just right" were reported more frequently in the OCD plus Tourette's disorder group compared with the other 2 groups. CONCLUSION: Sensory phenomena may be an important phenotypic measure for grouping patients along the OCD-Tourette's disorder spectrum. Sensory phenomena include bodily and mental sensations. Bodily sensations include focal or generalized body sensations (usually tactile, muscular-skeletal/visceral, or both) occurring either before or during the patient's performance of the repetitive behaviors. These sensations are more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone. Mental sensations include urge only, energy release (mental energy that builds up and needs to be discharged), incompleteness, and just-right perceptions. They are all more frequently found in patients with OCD plus Tourette's disorder than in patients with OCD alone.

Adult↗
PubMed1999

Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

BACKGROUND: Previous 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. METHODS: We 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. RESULTS: OCD 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. CONCLUSIONS: Immediate 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.

Adult↗
PubMed1999

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia.

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.

Adult↗
PubMed1998

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Basal Ganglia↗
PubMed1998

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.

Adult↗
PubMed1998

Tourette's disorder with and without obsessive-compulsive disorder in adults: are they different?

Clinical research has documented a bidirectional overlap between Tourette's disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic, phenomenological, comorbidity, and natural history perspectives. Patients with Tourette's disorder plus obsessive-compulsive disorder (TD + OCD), a putative subtype, share features of both. The purpose of this exploratory study was to evaluate correlates of patients with TD, OCD, and TD + OCD to determine whether TD + OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects with TD, OCD, or TD + OCD were evaluated with the Structured Clinical Interview for DSM-III-R supplemented with additional modules. The three groups differed in the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and substance use disorders (p < .04). These findings were accounted for by the elevated rates of the disorders in the TD + OCD group compared with the TD and OCD groups. These finding are most consistent with the hypothesis that TD + OCD is a more severe disorder than TD and OCD and may be more etiologically linked to TD than to OCD. These findings highlight the importance of assessment of the full spectrum of psychiatric comorbidity in patients with TD and OCD.

Adult↗
PubMed1998

Robot-aided functional imaging: application to a motor learning study.

The purpose of this study was to examine the neural activity underlying an implicit motor learning task. In particular, our goals were to determine whether initial phases of procedural learning of a motor task involve areas of the brain distinct from those involved in later phases of learning the task, and what changes in neural activity coincide with performance improvement. We describe a novel integration of robotic technology with functional brain imaging and its use in this study of implicit motor learning. A portable robotic device was used to generate forces that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that the subjects learned to manipulate. Positron emission tomography (PET) was used to measure indices of neural activity underlying learning of the motor task. Eight health, right-handed male subjects participated in the study. Results support the hypothesis that different stages of implicit learning (early and late implicit learning) occur in an orderly fashion, and that distinct neural structures may be involved in these different stages. In particular, neuroimaging results indicate that the cortico-striatal loop may play a significant role during early learning, and that the cortico-cerebellar loop may play a significant role during late learning.

Adult↗
PubMed1997

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.

Adult↗