- Email: [email protected]
Negative symptoms in patients with basal ganglia strokes
FRIDAY,, MAY 20
fect. The reasons for this lack of effect will be discussed.
238. POST-STROKE MAJOR DEPRESSION: PARKINSONISM AND THALAMOCORTICAL SYSTEMS RELATIONS E.C. Lauterbach, S.T. Price, A.N. Wilson, V.S. Knopik, J.G. Jackson, & C.M. Kavali
BIOL PSYCHIATRY 681 !994;35:615-747
that basal ganglia indirect pathway perturbation may produce reduced thalamocortieal stimulation of iimbic cortex, eventuating GA. Associations of GAD with parkinsonism and ADNOS with dystonia may suggest that functional disturbance of the nigra and ceruleus produce a GAD-forme frnste (ADNOS) while pathological disturbance of these structures produces a full expression of GAD. Perhaps anxiety worsens as central dopamine and norepinephrine levels fall.
240. POST-STROKE BIPOLAR DISORDERS: AGE AND THE THALAMUS
Mercer University School of Medicine, Macon, GA, 31207 We studied 45 subjects with MRl-identified lesions limited to the basal ganglia or cerebellum. 24.4% had post-stroke secondary (2°) DSM-llI-R depressive disorders: Major Depression (MD) 9 subjects; Depressive Disorder NOS (DDNOS) 2; Dysthymia 0. Subjects were never depressed prior to infarction. 2° MD was more common than ECA age-, sex-, and race-matched conlrol life prevalence: OR 3.50, 95% Ci - 0.88 ,.13.92, p,,0.03). Based upon previous work, we hypothesized 2° MD associations with Parkinsonism, thalamic lesions, and dystunia. 2° MD: We compared post-stroke 2o MD to similar controls who had depression before their stroke (n-9) using Mann-Whitney U and Fisher's Exact tests. There was more Parkinsonism (6 subjects, p-0.038) with higher PDRS scores (p-0.065) and illness stage (p-0.072), and more thalamic lesions (5 subjects, p-0.033), but no greater dystonia (5 subjects) although there was less dystonic geste (i subject, p-0.024) in 2° MD subjects. 2° MD subjects had a longer follow-up interval (42.9±22.2 vs. 21.9±!6.0 months, U-52.0, p-0.035) and more cerebellar signs on exam (6 subjects, !)-0.025). 2° MD did not differ from controls in regard to demographics, social factors, or depression rating scales (BDI and HRSD). These data suggest associations of late-developing post-stroke 2° MD with Parkinsonism and dystonic phenomena, implicating ventral striatal dopamine. Cerebellar signs and thalamic lesions suggest centromedian or pulvinar thalamocortical (glutamatergic) insufficiencies. Pallidal lesions in 7 of 9 are consistent with this, or may imply thalamo-orbitofrontal overdrive in post-stroke MD.
239. POST-STROKE GENERALIZED ANXIETY: PARKINSONISM, DYSTONIA, & THE GLOBUS PALLIDUS E.C. Lauterbach, A.N. Wilson, S.T. Price, V.S. Knopik, & J.G. Jackson
E.C. Lauterbach, A.N. Wilson, S.T. Price, V.S. Knopik, & J.G. Jackson Mercer University School of Medicine, Macon, GA, 3 ! 207 We studied 45 subjects with MRI identified isolated focal basal ganglia or cerebellar lesions. We found 3 subjects (6.7%) with post-stroke secondary (2o) DSM-Ill-R bipolar disorders: i with Bipolar Disorder (BD); 2 with Bipolar Disorder NOS (BDNOS). One BDNOS subject had Bipolar I! features. Subjects never had mood disorders prior to infarction. Based upon previous work, we hypothesized an association between bipolar disorders and (1) young age; (2) dystonia; (3) thalamic integrity; (4) cerebellar lesions. We compared 2o bipolar disorders to similar post-stroke controls lacking 2o psychiatric disorders using Mann-Whituey U and Fisher's Exact tests. Secondary bipolar disorders: all were younger (age 35.3+10. I yrs vs. 64.6+!4.1 yrs, MWU-i.00, p<.021), had cerebellar signs (3 subjects, p,¢.08), and lacked thalamic lesions (3 subjects, p<.08) in comparison to controls. Secondary BDNOS: both subjects (age 29.5+0.Tyrs) had post-stroke dystonia (p<.091). Secondary BD: this subject (age 47) lacked dystonia. Controls did not differ on other demographics, social factors, or depression scales in comparison with 2o bipolar disorders or 2oBDNOS. Younger individuals with cerebellar and basal ganglia signs may be at increased risk for post-stroke bipolar disorders. The mediodorsal thalamus may be more vulnerable earlier in life to aberrant input from basal ganglia and cerebellar lesions, leading to bipolar phenomena via thalamocortical relays. The potential relation to dystonia suggests that ventral putaminai pathways may be particularly relevant to atypical bipolar disorder.
241. NEGATIVE SYMPTOMS IN PATIENTS WITH BASAL GANGLIA STROKES I. Galynker, I. Levinson, C. Miner, & T. Feinberg
Mercer University School of Medicine, Macon, GA, 3 ! 207 Beth Israel Medical Center, New York, NY 10003 We studied 45 subje=ts with MRl-identified lesions limited to the basal ganglia or cerebellum. 8.9% had post-stroke secondary (2°) DSM-IlI-R generalized anxiety disorders (GA): 2 with Generalized Anxiety Disorder (GAD), 2 with Anxiety Disorder NOS (ADNOS). None suffered GA prior to infarction. We hypothesized GA would be associated with paUidal lesions, dystonia, and parkinsonism in comparison to similar post-stroke controls lacking 2° psychiatric disorders. 2" GA: all 4 subjects had pallidal lesions (p<.025), had lower mental status scores (47.5i6.8 vs. 49.7+16.5, Mann-Whitney U-6.00, p<.031), and were more often black (2, p<.077), but were not different on other demographic or social factors. 2° Major Depression was comorbid (4, p<.007; BDI 13.0±8.5, U,.29.5, p<.01; HRSD 8.0±!.4, U-36.0, p<.0025). 2° GAD: both subjects had parkinsonism (PDRS 18.5±7.8 vs. 6.2_+.5.0, 1.1-17.0, p<.029). None had dystonia. 2° ADNOS: both subjects had dystonia at rest (p<.091; duration !_+0vs. 2_+0years, U-0.00, p<.023). None had parkinsonism. These data suggest that post-stroke 2° GAs are associated with pallidal lesions and post-stroke Major Depression, parkinsonism, and dystonia. This suggests
Dysregulation of cortical-striatal-thalamic dopaminergic pathways is thought to be involved in the etiology of schizophrenia. If this hypothesis is correct, disruption of cortical-striatai-thalamic circuitry by way of a cerebro-vascular accident should lead to the emergence of some of the symptoms of schizophrenia. In this pilot study, Positive and Negative Symptoms Scale (PANSS) and Scale for Assessment of Negative Symptoms (SANS) were used to assess the prevalence of positive and negative symptoms in 9 patients with basal ganglia strokes. Eleven age-matched patients with parietal and cerebellar strokes were used as controls. The mean PANSS Negative Symptom Subscale score for patients with basal ganglia strokes (M :k 5D - 21.55 + 8.00) was significantly higher than that for the control group (7.45 + 2.50, t-test p<0.002). Similar results were obtained for SANS scores: subjects 40.77 + 31.24; controls 8.09 + 8.74; t-test p - 0.01. Neither group manifested clinically significant positive symptoms (PANSS Positive symptom subscale: subjects 7.7 + 1.09, controis 8.9 ± 3.08), or symptoms of depression (HAM-D: subjects 4.4 :!:3.9,
682
BIOLPSYCHIATRY 1994;35:615-747
controls 1.9 + 2.5). Group differences were not statistically significant for these measures. Also, within the groups there was no significant correlation between negative symptoms as measured by PANSS and SANS and positive symptoms or depression. The results of this study suggest the presence of deficit symptoms in subcortical strokes unrelated to possible poststroke depression, and support the etiologic role of the striatum in negative symptoms of schizophrenia.
242. SPECIFICITYOF ANXIETY SYMPTOMS IN THE POST-STROKEPERIOD C.S. Castillo & R.G. Robinson University of Iowa College of Medicine We examitled the specificity of both vegetative and psychological anxiety symptoms in a group of 309 stroke patients followed over 2 years. Stroke patients were divided into anxious and nonanxious groups and followedup at 3, 6,12 and 24 months post.stroke. They were evaluated with the Present State Exam (PSE), Hamilton Depression Scale (HDS), Social Ties Checklist (STC), Social Functioning Exam (SFE), Johns Hopkins Functional Inventory (JHFI) and Mini-Mental Status Exam (MMSE). Groups were compared on the frequency and specificity of anxiety symptoms. The diagnostic power of DSM Ill-R Generalized Anxiety Disorder was compared to modified DSM IlI-R criteria using only anxiety specific symptoms to determine sensitivity and specificity of the current diagnostic criteria. No significant differences between groups were found on demographics (i.e. age, sex, socioeconomic status, marital status, previous psychiatric history or family psychiatric history), psychiatric varia. bles (i.e. PSE, HDS, STC, SFE), physical recovery variables (JHFI) or cognitive status (MMSE). The median number of vegetative and psychological symptoms in patients with anxiety were 5 (Q3-QI-4). This was 5 times the frequency of nonanxious patients (IS0.01). Vegetative symptoms such as restlessness, or automatic anxiety, and psychological symptoms such as nervous tension or anxious foreboding were specific to the anxious group throughout follow up. Symptoms such as poor concentra. tion and insomnia were only specific to anxiety at intake and 12 month visit (1~'0.01). When diagnostic criteria were modified to include only anxiety specific symptoms DSM IlI-R criteria had 100% sensitivity and 96% specificity at intake, 100% sensitivity and 90% specificity at 3 months, 100% sensitivity and 93% specificity at 6 months, 100% sensitivity and 75% specificity at 12 months and 95% sensitivity and 100% specificity at 24 months. This is the first study that shows that there is a core of anxiety symptoms that are specific to GAD patients throughout the post-stroke follow.up period and also the first one to suggest that DSM IlI-R criteria for GAD may be applicable to the post-stroke population.
243. MODULATION OF NEURONAL ACTIVITY BY A SEROTONERGIC AGONIST: A PET STUDY IN HUMANS. G. Brown, S. Kapur, J. Meyer, A.A. Wilson, & S. Houle The PET Center, The Clarke Institute, University of Toronto, 250 College Street, Toronto, M5T IRg, Canada The purpose of this study was to delineate the brain regions modulated by a serotonergic challenge. ! ! healthy male subjects, age range 21-35 years, were studied in a double-blind placebo-controlled counterbalanced design. Each subject received either 60 mg of dl-fenfluramine or placebo on two separate occasions 5-7 days apart. 3.5h later the subjects received 5mCi of tSF-FDG iv. To standardize activity during the tSF-FDG uptake
FRIDAY,, MAY20
phase (45 minutes), subjects undertook a continuous performance task in a quiet dark room on both occasions. After uptake, the subjects were scanned for 30 rain in a brain PET camera. The subjective-state was recorded periodically using a structured self administered questionnaire and prolactin levels were drawn at regular intervals. Subjects reported an increase in feelings of activation (F 3,33 - 4.56, p - 0.009) and euphoria (F 3,33 - 3.41, p - 0.03) on fenfluramine. Performance on the contim/ous performance task was not different on the two occasions (p = 0.36). Pmlactin levels showed the expected increase (F 5,55 - 2.83, p-0.02). Comparison of the PET images (using Statistical Parametric Mapping technique which corrects for differences in global activity and then conducts a paired-t comparison of the relative glucose metabolism at each pixel in the brain) revealed an increase, bilaterally, in the frontal cortex, Brodmann's areas 47, 46, 45 & 10, with fenfluramine (p<0.001). The magnitude of the effect was greater on the right side. A relative decrease in metabolism was noted in the occipital-temporal region bilaterally in Brodmann's areas 18, 19 & 37 in the fenfluramine condition (p¢9.001). While serotonergic innervation of the cortex is diffuse, the functional effects as revealed in our study suggest the existence of a discrete functional network of brain regions, specifically modulated by the serotonergic system.
244. LOCALIZATION OF THE FUNCTIONAL EFFECTS OF APOMORPHINE---A PET STUDY IN HUMANS. S. Kapur, J. Meyer, S. Houle, & G. Brown The PET Center, The Clarke Institute, University of Toronto, 250 College Street, Toronto, M5T IR8, Canada The purpose of this experiment was to elucidate the functional anatomy of the dopaminergic system in humans, by combining the administration of apomorphine, a dopamin¢ DI and D2 t~'eptor agonist, with PET. Eight right-handed male subjects, aged 20-34 years, free of medical or psychiatric illness, each had four PET scans with tsO water, in a single session. Two scans prior to (I 5 and 3 minutes before) and two scans after (25 and 37 minutes after) receiving 10 ttg/kg apomorphine subcutaneously. A self-administered multiple-item multiple-choice scale assessing arousal, anxiety and physical symptoms was used to monitor the behavioral effects of apomorphine. The subjects reported a significant decrease in arousal and an increase in physical side-effects (nausea and thirst) after receiving apomorphine. The regional cerebral blood flow PET images were corn.pared (within-subject repeated-measures design) on a pixel by pixel basis, using the Statistical Parametric Mapping technique. Apomorphine induced a significant (p<0.0001) increase in regional activity, bilaterally, in the anterior cingulate, medial frontal gyms, insular cortex, motor cortex and the dorsolateral prefrontal cortex. Significant decreases (p<0.0001) were observed in bilateral precuneus and retrosplenial regions. The effect was evident at both the time-intervals following apomorphine infusion. The activated regions closely mirror the known mcsocortical dopaminersic projections in humans. Comparison of these results with the known dopamine-receptor distribution suggests that these effects may be mediated via the DI and D4 receptor subtypes. It appears that the anterior cingulate, the insular cortex, the motor cortex, the dorsolateral prefrontal cortex and the retmsplenial-posterior cingulate region form a functional network of brain regions modulated by the dopaminergic neurotnmsmitter system. These cortical regions play an important role in higher executive functions, selection for action and motor activity. These f'mding provide a framework for understanding the role of dopamine in modulating of these functions and its role in the pathophysiology of schizophrenia and other psychomotor disorders.
fect. The reasons for this lack of effect will be discussed.
238. POST-STROKE MAJOR DEPRESSION: PARKINSONISM AND THALAMOCORTICAL SYSTEMS RELATIONS E.C. Lauterbach, S.T. Price, A.N. Wilson, V.S. Knopik, J.G. Jackson, & C.M. Kavali
BIOL PSYCHIATRY 681 !994;35:615-747
that basal ganglia indirect pathway perturbation may produce reduced thalamocortieal stimulation of iimbic cortex, eventuating GA. Associations of GAD with parkinsonism and ADNOS with dystonia may suggest that functional disturbance of the nigra and ceruleus produce a GAD-forme frnste (ADNOS) while pathological disturbance of these structures produces a full expression of GAD. Perhaps anxiety worsens as central dopamine and norepinephrine levels fall.
240. POST-STROKE BIPOLAR DISORDERS: AGE AND THE THALAMUS
Mercer University School of Medicine, Macon, GA, 31207 We studied 45 subjects with MRl-identified lesions limited to the basal ganglia or cerebellum. 24.4% had post-stroke secondary (2°) DSM-llI-R depressive disorders: Major Depression (MD) 9 subjects; Depressive Disorder NOS (DDNOS) 2; Dysthymia 0. Subjects were never depressed prior to infarction. 2° MD was more common than ECA age-, sex-, and race-matched conlrol life prevalence: OR 3.50, 95% Ci - 0.88 ,.13.92, p,,0.03). Based upon previous work, we hypothesized 2° MD associations with Parkinsonism, thalamic lesions, and dystunia. 2° MD: We compared post-stroke 2o MD to similar controls who had depression before their stroke (n-9) using Mann-Whitney U and Fisher's Exact tests. There was more Parkinsonism (6 subjects, p-0.038) with higher PDRS scores (p-0.065) and illness stage (p-0.072), and more thalamic lesions (5 subjects, p-0.033), but no greater dystonia (5 subjects) although there was less dystonic geste (i subject, p-0.024) in 2° MD subjects. 2° MD subjects had a longer follow-up interval (42.9±22.2 vs. 21.9±!6.0 months, U-52.0, p-0.035) and more cerebellar signs on exam (6 subjects, !)-0.025). 2° MD did not differ from controls in regard to demographics, social factors, or depression rating scales (BDI and HRSD). These data suggest associations of late-developing post-stroke 2° MD with Parkinsonism and dystonic phenomena, implicating ventral striatal dopamine. Cerebellar signs and thalamic lesions suggest centromedian or pulvinar thalamocortical (glutamatergic) insufficiencies. Pallidal lesions in 7 of 9 are consistent with this, or may imply thalamo-orbitofrontal overdrive in post-stroke MD.
239. POST-STROKE GENERALIZED ANXIETY: PARKINSONISM, DYSTONIA, & THE GLOBUS PALLIDUS E.C. Lauterbach, A.N. Wilson, S.T. Price, V.S. Knopik, & J.G. Jackson
E.C. Lauterbach, A.N. Wilson, S.T. Price, V.S. Knopik, & J.G. Jackson Mercer University School of Medicine, Macon, GA, 3 ! 207 We studied 45 subjects with MRI identified isolated focal basal ganglia or cerebellar lesions. We found 3 subjects (6.7%) with post-stroke secondary (2o) DSM-Ill-R bipolar disorders: i with Bipolar Disorder (BD); 2 with Bipolar Disorder NOS (BDNOS). One BDNOS subject had Bipolar I! features. Subjects never had mood disorders prior to infarction. Based upon previous work, we hypothesized an association between bipolar disorders and (1) young age; (2) dystonia; (3) thalamic integrity; (4) cerebellar lesions. We compared 2o bipolar disorders to similar post-stroke controls lacking 2o psychiatric disorders using Mann-Whituey U and Fisher's Exact tests. Secondary bipolar disorders: all were younger (age 35.3+10. I yrs vs. 64.6+!4.1 yrs, MWU-i.00, p<.021), had cerebellar signs (3 subjects, p,¢.08), and lacked thalamic lesions (3 subjects, p<.08) in comparison to controls. Secondary BDNOS: both subjects (age 29.5+0.Tyrs) had post-stroke dystonia (p<.091). Secondary BD: this subject (age 47) lacked dystonia. Controls did not differ on other demographics, social factors, or depression scales in comparison with 2o bipolar disorders or 2oBDNOS. Younger individuals with cerebellar and basal ganglia signs may be at increased risk for post-stroke bipolar disorders. The mediodorsal thalamus may be more vulnerable earlier in life to aberrant input from basal ganglia and cerebellar lesions, leading to bipolar phenomena via thalamocortical relays. The potential relation to dystonia suggests that ventral putaminai pathways may be particularly relevant to atypical bipolar disorder.
241. NEGATIVE SYMPTOMS IN PATIENTS WITH BASAL GANGLIA STROKES I. Galynker, I. Levinson, C. Miner, & T. Feinberg
Mercer University School of Medicine, Macon, GA, 3 ! 207 Beth Israel Medical Center, New York, NY 10003 We studied 45 subje=ts with MRl-identified lesions limited to the basal ganglia or cerebellum. 8.9% had post-stroke secondary (2°) DSM-IlI-R generalized anxiety disorders (GA): 2 with Generalized Anxiety Disorder (GAD), 2 with Anxiety Disorder NOS (ADNOS). None suffered GA prior to infarction. We hypothesized GA would be associated with paUidal lesions, dystonia, and parkinsonism in comparison to similar post-stroke controls lacking 2° psychiatric disorders. 2" GA: all 4 subjects had pallidal lesions (p<.025), had lower mental status scores (47.5i6.8 vs. 49.7+16.5, Mann-Whitney U-6.00, p<.031), and were more often black (2, p<.077), but were not different on other demographic or social factors. 2° Major Depression was comorbid (4, p<.007; BDI 13.0±8.5, U,.29.5, p<.01; HRSD 8.0±!.4, U-36.0, p<.0025). 2° GAD: both subjects had parkinsonism (PDRS 18.5±7.8 vs. 6.2_+.5.0, 1.1-17.0, p<.029). None had dystonia. 2° ADNOS: both subjects had dystonia at rest (p<.091; duration !_+0vs. 2_+0years, U-0.00, p<.023). None had parkinsonism. These data suggest that post-stroke 2° GAs are associated with pallidal lesions and post-stroke Major Depression, parkinsonism, and dystonia. This suggests
Dysregulation of cortical-striatal-thalamic dopaminergic pathways is thought to be involved in the etiology of schizophrenia. If this hypothesis is correct, disruption of cortical-striatai-thalamic circuitry by way of a cerebro-vascular accident should lead to the emergence of some of the symptoms of schizophrenia. In this pilot study, Positive and Negative Symptoms Scale (PANSS) and Scale for Assessment of Negative Symptoms (SANS) were used to assess the prevalence of positive and negative symptoms in 9 patients with basal ganglia strokes. Eleven age-matched patients with parietal and cerebellar strokes were used as controls. The mean PANSS Negative Symptom Subscale score for patients with basal ganglia strokes (M :k 5D - 21.55 + 8.00) was significantly higher than that for the control group (7.45 + 2.50, t-test p<0.002). Similar results were obtained for SANS scores: subjects 40.77 + 31.24; controls 8.09 + 8.74; t-test p - 0.01. Neither group manifested clinically significant positive symptoms (PANSS Positive symptom subscale: subjects 7.7 + 1.09, controis 8.9 ± 3.08), or symptoms of depression (HAM-D: subjects 4.4 :!:3.9,
682
BIOLPSYCHIATRY 1994;35:615-747
controls 1.9 + 2.5). Group differences were not statistically significant for these measures. Also, within the groups there was no significant correlation between negative symptoms as measured by PANSS and SANS and positive symptoms or depression. The results of this study suggest the presence of deficit symptoms in subcortical strokes unrelated to possible poststroke depression, and support the etiologic role of the striatum in negative symptoms of schizophrenia.
242. SPECIFICITYOF ANXIETY SYMPTOMS IN THE POST-STROKEPERIOD C.S. Castillo & R.G. Robinson University of Iowa College of Medicine We examitled the specificity of both vegetative and psychological anxiety symptoms in a group of 309 stroke patients followed over 2 years. Stroke patients were divided into anxious and nonanxious groups and followedup at 3, 6,12 and 24 months post.stroke. They were evaluated with the Present State Exam (PSE), Hamilton Depression Scale (HDS), Social Ties Checklist (STC), Social Functioning Exam (SFE), Johns Hopkins Functional Inventory (JHFI) and Mini-Mental Status Exam (MMSE). Groups were compared on the frequency and specificity of anxiety symptoms. The diagnostic power of DSM Ill-R Generalized Anxiety Disorder was compared to modified DSM IlI-R criteria using only anxiety specific symptoms to determine sensitivity and specificity of the current diagnostic criteria. No significant differences between groups were found on demographics (i.e. age, sex, socioeconomic status, marital status, previous psychiatric history or family psychiatric history), psychiatric varia. bles (i.e. PSE, HDS, STC, SFE), physical recovery variables (JHFI) or cognitive status (MMSE). The median number of vegetative and psychological symptoms in patients with anxiety were 5 (Q3-QI-4). This was 5 times the frequency of nonanxious patients (IS0.01). Vegetative symptoms such as restlessness, or automatic anxiety, and psychological symptoms such as nervous tension or anxious foreboding were specific to the anxious group throughout follow up. Symptoms such as poor concentra. tion and insomnia were only specific to anxiety at intake and 12 month visit (1~'0.01). When diagnostic criteria were modified to include only anxiety specific symptoms DSM IlI-R criteria had 100% sensitivity and 96% specificity at intake, 100% sensitivity and 90% specificity at 3 months, 100% sensitivity and 93% specificity at 6 months, 100% sensitivity and 75% specificity at 12 months and 95% sensitivity and 100% specificity at 24 months. This is the first study that shows that there is a core of anxiety symptoms that are specific to GAD patients throughout the post-stroke follow.up period and also the first one to suggest that DSM IlI-R criteria for GAD may be applicable to the post-stroke population.
243. MODULATION OF NEURONAL ACTIVITY BY A SEROTONERGIC AGONIST: A PET STUDY IN HUMANS. G. Brown, S. Kapur, J. Meyer, A.A. Wilson, & S. Houle The PET Center, The Clarke Institute, University of Toronto, 250 College Street, Toronto, M5T IRg, Canada The purpose of this study was to delineate the brain regions modulated by a serotonergic challenge. ! ! healthy male subjects, age range 21-35 years, were studied in a double-blind placebo-controlled counterbalanced design. Each subject received either 60 mg of dl-fenfluramine or placebo on two separate occasions 5-7 days apart. 3.5h later the subjects received 5mCi of tSF-FDG iv. To standardize activity during the tSF-FDG uptake
FRIDAY,, MAY20
phase (45 minutes), subjects undertook a continuous performance task in a quiet dark room on both occasions. After uptake, the subjects were scanned for 30 rain in a brain PET camera. The subjective-state was recorded periodically using a structured self administered questionnaire and prolactin levels were drawn at regular intervals. Subjects reported an increase in feelings of activation (F 3,33 - 4.56, p - 0.009) and euphoria (F 3,33 - 3.41, p - 0.03) on fenfluramine. Performance on the contim/ous performance task was not different on the two occasions (p = 0.36). Pmlactin levels showed the expected increase (F 5,55 - 2.83, p-0.02). Comparison of the PET images (using Statistical Parametric Mapping technique which corrects for differences in global activity and then conducts a paired-t comparison of the relative glucose metabolism at each pixel in the brain) revealed an increase, bilaterally, in the frontal cortex, Brodmann's areas 47, 46, 45 & 10, with fenfluramine (p<0.001). The magnitude of the effect was greater on the right side. A relative decrease in metabolism was noted in the occipital-temporal region bilaterally in Brodmann's areas 18, 19 & 37 in the fenfluramine condition (p¢9.001). While serotonergic innervation of the cortex is diffuse, the functional effects as revealed in our study suggest the existence of a discrete functional network of brain regions, specifically modulated by the serotonergic system.
244. LOCALIZATION OF THE FUNCTIONAL EFFECTS OF APOMORPHINE---A PET STUDY IN HUMANS. S. Kapur, J. Meyer, S. Houle, & G. Brown The PET Center, The Clarke Institute, University of Toronto, 250 College Street, Toronto, M5T IR8, Canada The purpose of this experiment was to elucidate the functional anatomy of the dopaminergic system in humans, by combining the administration of apomorphine, a dopamin¢ DI and D2 t~'eptor agonist, with PET. Eight right-handed male subjects, aged 20-34 years, free of medical or psychiatric illness, each had four PET scans with tsO water, in a single session. Two scans prior to (I 5 and 3 minutes before) and two scans after (25 and 37 minutes after) receiving 10 ttg/kg apomorphine subcutaneously. A self-administered multiple-item multiple-choice scale assessing arousal, anxiety and physical symptoms was used to monitor the behavioral effects of apomorphine. The subjects reported a significant decrease in arousal and an increase in physical side-effects (nausea and thirst) after receiving apomorphine. The regional cerebral blood flow PET images were corn.pared (within-subject repeated-measures design) on a pixel by pixel basis, using the Statistical Parametric Mapping technique. Apomorphine induced a significant (p<0.0001) increase in regional activity, bilaterally, in the anterior cingulate, medial frontal gyms, insular cortex, motor cortex and the dorsolateral prefrontal cortex. Significant decreases (p<0.0001) were observed in bilateral precuneus and retrosplenial regions. The effect was evident at both the time-intervals following apomorphine infusion. The activated regions closely mirror the known mcsocortical dopaminersic projections in humans. Comparison of these results with the known dopamine-receptor distribution suggests that these effects may be mediated via the DI and D4 receptor subtypes. It appears that the anterior cingulate, the insular cortex, the motor cortex, the dorsolateral prefrontal cortex and the retmsplenial-posterior cingulate region form a functional network of brain regions modulated by the dopaminergic neurotnmsmitter system. These cortical regions play an important role in higher executive functions, selection for action and motor activity. These f'mding provide a framework for understanding the role of dopamine in modulating of these functions and its role in the pathophysiology of schizophrenia and other psychomotor disorders.