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D Silbersweig

Publications and source records attributed to D Silbersweig.

11 recordsLinked to original sources
PubMed1997

'Vascular depression' hypothesis.

We propose that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. The "vascular depression" hypothesis is supported by the comorbidity of depression, vascular disease, and vascular risk factors and the association of ischemic lesions to distinctive behavioral symptoms. Disruption of prefrontal systems or their modulating pathways by single lesions or by an accumulation of lesions exceeding a threshold are hypothesized to be central mechanisms in vascular depression. The vascular depression concept can generate studies of clinical and heuristic value. Drugs used for the prevention and treatment of cerebrovascular disease may be shown to reduce the risk for vascular depression or improve its outcomes. The choice of antidepressants in vascular depression may depend on their effect on neurologic recovery from ischemic lesions. Research can clarify the pathways to vascular depression by focusing on the site of the lesion, the resultant brain dysfunction, the presentation of depression and time of onset, and the contribution of nonbiological factors.

Aged↗
PubMed1997

Clinically defined vascular depression.

OBJECTIVE: The authors' goal was to examine the clinical presentation of a group of depressed elderly patients with clinically defined risk factors for vascular depression compared with a group of elderly depressed patients without such risk factors. METHOD: Cognitive deficits, disability, and depressive symptoms were examined in 33 consecutively recruited elderly patients defined as having vascular depression and 32 patients defined as having nonvascular depression according to their scores on the Cumulative Illness Rating Scale-Geriatrics. RESULTS: The patients with vascular depression had greater overall cognitive impairment and disability than those with nonvascular depression. Fluency and naming were more impaired in patients with vascular depression, and they had more retardation and less agitation as well as less guilt feelings and greater lack of insight. CONCLUSIONS: The symptoms of vascular depression are consistent with lesions that may damage striato-pallido-thalamo-cortical pathways and other areas. The concept of vascular depression can provide the impetus for investigations of prevention and treatment of cerebrovascular disease and for studies of the course of vascular depression and selection of antidepressants.

Age of Onset↗
PubMed1997

Brainstem evoked response abnormalities in late-life depression with vascular disease.

OBJECTIVE: The purpose of this study was to examine whether the brainstem evoked responses of geriatric depressed patients with vascular disease show greater changes in wave V latency after increased stimulation than do responses of geriatric depressed patients without vascular disease and elderly comparison subjects with and without vascular disease. METHOD: Geriatric patients with unipolar depression (N = 53) were recruited from a university psychiatric hospital. Elderly comparison subjects (N = 23) were recruited through advertisements. All subjects were assessed for depressive symptoms, cognitive performance, overall medical burden, vascular disease, and disability. Brainstem evoked response was elicited at stimulation rates of 11.4 and 80.0 clicks/sec. RESULTS: The interaction between depression and vascular disease had a significant effect on change in wave V latency. This effect was synergistic, more than an additive effect. Post hoc comparisons showed that the depressed patients with vascular disease had greater changes in wave V latency that did the depressed patients without vascular disease, comparison subjects with vascular disease, and comparison subjects without vascular disease. Linear discriminant function analysis showed that 82% of the subjects with abnormal changes in wave V latency (sensitivity: 75%, specificity: 81%) could be identified on the basis of ratings for depression and vascular disease. CONCLUSIONS: Demyelination afflicting the pons and mesencephalon may explain the greater change in wave V latency for the brainstem evoked response in depressed patients with vascular disease. Further studies combining brainstem evoked response with brain imaging may determine whether depression develops only after vascular disease leads to demyelination.

Aged↗
PubMed1996

Regional metabolic correlates of surgical outcome following unilateral pallidotomy for Parkinson's disease.

Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site.

Aged↗
PubMed1996

Functional neuroimaging of hallucinations in schizophrenia: toward an integration of bottom-up and top-down approaches.

Hallucinations in schizophrenia represent an important clinical problem, an interesting neuropsychological enigma, and a significant challenge for neuroscientific research. Functional neuroimaging techniques allow the in vivo, systems-level study of brain dysfunction underlying this debilitating symptom. Clinical and scientific vantage points that can inform the design and interpretation of functional neuroimaging studies of schizophrenic hallucinations are outlined. These include considerations of the phenomenology of hallucinations, the relationship of hallucinations to other symptoms of schizophrenia, and the neuropsychological functions that are thought to be disrupted in hallucinations. They also include the anatomical and chemical brain systems in which abnormalities are implicated in schizophrenia, the neurologic conditions in which hallucinations may occur, the neurochemical contexts that are associated with hallucinations, and the methodologic details of the functional neuroimaging techniques employed. Bottom-up and top-down functional neuroimaging strategies for the investigation of schizophrenic hallucinations with positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) are reviewed. Bottom-up approaches start with or measure the biology associated with hallucinations. Top-down approaches start from the specific neuropsychological dysfunctions thought to be associated with hallucinations. The distributed brain regions, systems and functions implicated in schizophrenic hallucination formation are then discussed in the context of an integration of bottom-up and top-down approaches. Focus is placed upon abnormalities in the functions of, and interactions among, auditory-linguistic association cortices, caudal and rostral limbic/paralimbic systems, prefrontal cortices, ventral striatum and (non-specific projection and associative) thalamic nuclei, as well as upon the glutamatergic, GABAergic and ventral tegmental dopaminergic modulation of these systems.

Brain Mapping↗
PubMed1995

The functional anatomy of recovery from auditory agnosia. A PET study of sound categorization in a neurological patient and normal controls.

H2(15)O-PET was used to investigate the functional anatomy of recovery in a patient (J.B.) with bilateral perisylvian strokes and auditory agnosia, who partially regained the ability to recognize environmental sounds, but remained clinically word-deaf. The patient and a group of six normal volunteers were scanned in the following three conditions: (i) passive listening to environmental sounds; (ii) categorization of environmental sounds; (iii) at rest. In normal subjects, passive listening as compared with rest was associated with significant activations in the auditory cortices and posterior thalami, and in the inferior parietal lobe and anterior insula/frontal opercular region on the right. In J.B., activations were observed in the spared auditory cortex and inferior parietal lobe of the right hemisphere and in regions adjacent to the perisylvian lesion in the left hemisphere (anterior insula/frontal opercular region, middle temporal gyrus and inferior parietal lobe). The recovered function, as measured by categorization of sounds compared with passive listening, in J.B. was associated with bilateral activation of a distributed network comprising (pre)frontal, middle temporal and inferior parietal cortices, as well as the right cerebellum and the right caudate nucleus. In addition, there was a left-sided activation of the anterior cingulate gyrus. In normal subjects, the same categorization task led to activation of a network comprising (pre)frontal, middle temporal and inferior parietal cortices in the left hemisphere only. These results suggest that bilateral activation (with recruitment of areas homologous to those known to be responsible for normal function), the engagement of peri-infarct regions, and the involvement of a more widespread neocortical network, are mechanisms of functional reorganization after injury that may enable recovery from, or compensation for, cognitive deficits.

Agnosia↗
PubMed1995

Functional anatomy of the mental representation of upper extremity movements in healthy subjects.

1. Differences in the distribution of relative regional cerebral blood flow during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe, an area was found that was mainly activated by execution presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of "motor behavior' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Relation between cerebral activity and force in the motor areas of the human brain.

1. Positron emission tomography (PET) studies were performed in six normal right-handed male volunteers (age 30 +/- 3) to investigate the relationship between cerebral activation as measured by relative regional cerebral blood flow (rCBF) and force peak exerted during right index finger flexion. The purpose was to determine in which central motor structures activity is directly correlated with force for repeatedly executed movements. 2. Twelve PET rCBF measurements were performed in each volunteer with the use of H2(15)O as a perfusion tracer. Volunteers pressed a Morse-key repetitively with their right index finger for 2 min while lying in a supine position in the PET camera. The device was fitted with strain gauges to measure the force peaks exerted upon it. Scans were collected twice each at five different levels of exerted force peak and in a resting state. Individual and group results were co-registered with anatomic magnetic resonance images (MRI). 3. Group analysis revealed four major regions with a high correlation between rCBF and different degrees of repetitively exerted force peaks. One was located in the arm area of the left lateral surface [primary somatosensory and motor cortex (SI, MI)]. The second area was situated on the left mesial surface of the brain, posterior to the anterior commissure (AC) and encompassing the first gyrus dorsal to the cingulate sulcus. This area is thought to be homologous to the posterior part of the supplementary motor area (SMA) in the monkey. The third area was the dorsal bank of the posterior cingulate sulcus. The fourth area showing a significant correlation between rCBF and force peaks was in the cerebellar vermis. 4. Individual PET data were co-registered with each individual's MRI in order to identify precisely the locations of structures demonstrating a positive correlation between rCBF and force peak. Activated areas on the mesial surface consisted of the same two distinct regions seen in the group data. In three subjects the focus on the lateral surface of the cortex appeared to extend into the caudal premotor area; in two it extended into the rostral part of the superior parietal area. In no subject did blood flow in the anterior cingulate areas and anterior SMA show a correlation with the force exerted. Cerebellar correlations were present in the vermis in all subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.

BACKGROUND: This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD: Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS: In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION: These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

Adult↗
PubMed1990

Carnitine treatment for stroke in rats.

Changes in the concentrations of carnitine, long-chain acylcoenzyme A, and long-chain acylcarnitine in ischemic myocardium parallel those in ischemic brain. Since carnitine treatment reverses these changes and improves function in ischemic hearts, we examined whether carnitine given to rats before focal cerebral ischemia (produced by tandem right common carotid artery and middle cerebral artery occlusion) alters infarct volume in four separate experiments. Mannitol was used to control for the osmotic effect of carnitine on brain edema in one experiment. While carnitine was found to significantly decrease infarct volume compared with saline in one experiment (p less than 0.05, Student's t test), this result could not be replicated in the subsequent three experiments. Because the positive treatment effect was not reproducible despite similar experimental conditions, the result of the first experiment was attributed to a type I error. Mannitol also showed no significant effect on infarct volume. This study emphasizes the need for concurrent controls with each group of treated animals and the need for replicating the results of a single experiment when testing for drug efficacy in animal models of focal cerebral ischemia.

Animals↗