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Biomedical subjects

C R Savage

Publications and source records attributed to C R Savage.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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, Tourette's syndrome, and obsessive-compulsive disorder.

Adult↗

Neuroimaging and neuropsychology of the striatum. Bridging basic science and clinical practice.

Neuroimaging and neuropsychology are complementary disciplines that provide powerful means for assessing the structure and function of corticostriatal systems. Findings from four model basal ganglia disorders--OCD, TS, HD, and PD--are reviewed. This survey is intended as a vehicle for illustrating the breadth of current clinical and research applications, as well as the potential for future advances. The perspectives brought by neuroimaging and neuropsychology serve as a natural bridge from the basic neuroscience to the clinical practice articles in this issue.

Cognition Disorders↗

Neuropsychology of subcortical dementias.

Subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychological impairment. This article describes the neurobiological and cognitive features of three prototypical subcortical dementias, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy, concentrating of traits shared by disorders. Clinical features are also discussed, especially those which differentiate subcortical dementias from cortical dementias, such as Alzheimer's disease. The cortical-subcortical nomenclature has been criticized over the years, but it continues to provide an effective means of classifying dementia profiles in clinically and theoretically useful ways.

Cerebral Cortex↗

Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning.

Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder (OCD) to that of matched control subjects while they performed an implicit learning task. Although patients and control subjects evidenced comparable learning, imaging data from control subjects indicated bilateral inferior striatal activation, whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation. The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder. Furthermore, when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems, they instead appear to access brain regions normally associated with explicit (conscious) information processing.

Adult↗

Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de la Tourette's syndrome.

BACKGROUND: Obsessive-compulsive disorder (OCD) is heterogeneous, with some forms related to Gilles de la Tourette's syndrome (GTS). This is a phenomenological study designed to investigate the nature of these possible OCD subtypes and the relationship between OCD and GTS. METHOD: We evaluated 20 adult outpatients with OCD, 21 with GTS, and 20 with OCD plus GTS using a semi-structured interview designed to assess cognitive, sensory and autonomic phenomena preceding repetitive behaviours. RESULTS: More cognitions and autonomic anxiety and fewer sensory phenomena were reported in OCD than in GTS. Like the GTS group, the OCD plus GTS group reported more sensory phenomena and fewer cognitions than the OCD group. CONCLUSIONS: The presence or absence of cognitions, sensory phenomena, and autonomic anxiety distinguishes repetitive behaviours in patients with OCD from those with OCD plus GTS, and GTS. These subjective experiences may be useful in subtyping OCD and may represent valid predictors of prognosis and treatment response.

Adolescent↗

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.

Adult↗

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.

Adult↗

Conscious recollection and the human hippocampal formation: evidence from positron emission tomography.

We used positron emission tomography (PET) to examine the role of the hippocampal formation in implicit and explicit memory. Human volunteers studied a list of familiar words, and then they either provided the first word that came to mind in response to three-letter cues (implicit memory) or tried to recall studied words in response to the same cues (explicit memory). There was no evidence of hippocampal activation in association with implicit memory. However, priming effects on the implicit memory test were associated with decreased activity in extrastriate visual cortex. On the explicit memory test, subjects recalled many target words in one condition and recalled few words in a second condition, despite trying to remember them. Comparisons between the two conditions showed that blood-flow increases in the hippocampal formation are specifically associated with the conscious recollection of studied words, whereas blood-flow increases in frontal regions are associated with efforts to retrieve target words. Our results help to clarify some puzzles concerning the role of the hippocampal formation in human memory.

Adult↗

A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery.

BACKGROUND: Previous studies have used symptom provocation and positron emission tomography to delineate the brain systems that mediate various anxiety states. Using an analogous approach, the goal of this study was to measure regional cerebral blood flow changes associated with posttraumatic stress disorder (PTSD) symptoms. METHODS: Eight patients with PTSD, screened as physiologically responsive to a script-driven imagery symptom provocation paradigm, were exposed sequentially to audiotaped traumatic and neutral scripts in conjunction with positron emission tomography. Heart rate and subjective measures of emotional state were obtained for each condition. Statistical mapping techniques were used to determine locations of significant brain activation. RESULTS: Increases in normalized blood flow were found for the traumatic as compared with control conditions in right-sided limbic, paralimbic, and visual areas; decreases were found in left inferior frontal and middle temporal cortex. CONCLUSIONS: The results suggest that emotions associated with the PTSD symptomatic state are mediated by the limbic and paralimbic systems within the right hemisphere. Activation of visual cortex may correspond to the visual component of PTSD reexperiencing phenomena.

Adult↗

Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.

BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.

Adult↗

Cerebral structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric magnetic resonance imaging study.

BACKGROUND: A previous pilot study of only posterior brain regions found lower white-matter volume in patients with obsessive-compulsive disorder than in normal control subjects. We used new cohorts of patients and matched normal control subjects to study whole-brain volume differences between these groups with magnetic resonance imaging-based morphometry. METHODS: Ten female patients with obsessive-compulsive disorder and 10 female control subjects, matched for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized and segmented by means of well-characterized semiautomated intensity contour mapping and differential intensity contour algorithms. Brain structures investigated included the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus pallidus, hippocampus amygdala, third and fourth ventricles, corpus callosum, operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions, including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum, with adjacent white matter were also measured. Volumes found different between groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth Complex Figure Test measures. RESULTS: Confirming results of our earlier pilot study and expanding the findings to the whole brain, patients with obsessive-compulsive disorder had significantly less total white matter but, in addition, significantly greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder and nonverbal immediate memory correlated with opercular volume. CONCLUSIONS: Replication of volumetric white-matter differences suggests a widely distributed structural brain abnormality in obsessive-compulsive disorder. Whereas determining the etiogenesis may require research at a microscopic level, understanding its functional significance can be further explored via functional neuroimaging and neuropsychological studies.

Adult↗

Recall and recognition memory in obsessive-compulsive disorder.

This study examined recall and recognition memory in 20 nonmedicated patients with obsessive-compulsive disorder (OCD) and 20 matched control subjects. As hypothesized, OCD subjects showed abnormalities affecting delayed recall of nonverbal information but showed normal recognition. These results are interpreted as providing preliminary evidence of a nonverbal memory retrieval deficit consistent with proposed corticostriatal system dysfunction in OCD.

Adult↗

A positron emission tomographic study of simple phobic symptom provocation.

BACKGROUND: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms. METHODS: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation. RESULTS: Statistical parametric maps demonstrated significant increases in normalized regional blood flow for the symptomatic state compared with the control state in the anterior cingulate cortex, the insular cortex, the anterior temporal cortex, the somatosensory cortex, the posterior medial orbitofrontal cortex, and the thalamus. CONCLUSIONS: The results suggest that anxiety associated with the simple phobic symptomatic state is mediated by paralimbic structures. Moreover, activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.

Adult↗