Biomedical subjects

Nathaniel M Alpert

Publications and source records attributed to Nathaniel M Alpert.

At least 19 recordsLinked to original sources

PubMed2006

Decreased striatal D1 binding as measured using PET and [11C]SCH 23,390 in patients with major depression with anger attacks.

This study assessed striatal dopamine 1 (D1) receptor binding in patients with major depressive disorder and anger attacks (MDD+A) and healthy volunteers. We used positron emission tomography with [(11)C]SCH 23,390 to compare 10 patients with MDD+A to 10 healthy volunteers. [(11)C]SCH 23,390 binding in bilateral striata was significantly lower in the MDD+A group when compared to healthy volunteers. These results implicate striatal D1 receptor dysfunction in MDD+A and further suggest an association between dopaminergic transmission and anger or aggression.

Adult↗

PubMed2006

A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder.

OBJECT: Deep brain stimulation (DBS) of the ventral [anterior internal] capsule/ventral striatum (VC/VS) is under investigation as an alternative to anterior capsulotomy for severe obsessive-compulsive disorder (OCD). In neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial. METHODS: Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal-basal ganglia-thalamic circuit. Data were analyzed using statistical parametric mapping. In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus. CONCLUSIONS: Acute DBS at the VC/VS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VC/VS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient's subsequent clinical response to chronic DBS.

Adult↗

PubMed2005

Optimization of dynamic measurement of receptor kinetics by wavelet denoising.

The most important technical limitation affecting dynamic measurements with PET is low signal-to-noise ratio (SNR). Several reports have suggested that wavelet processing of receptor kinetic data in the human brain can improve the SNR of parametric images of binding potential (BP). However, it is difficult to fully assess these reports because objective standards have not been developed to measure the tradeoff between accuracy (e.g. degradation of resolution) and precision. This paper employs a realistic simulation method that includes all major elements affecting image formation. The simulation was used to derive an ensemble of dynamic PET ligand (11C-raclopride) experiments that was subjected to wavelet processing. A method for optimizing wavelet denoising is presented and used to analyze the simulated experiments. Using optimized wavelet denoising, SNR of the four-dimensional PET data increased by about a factor of two and SNR of three-dimensional BP maps increased by about a factor of 1.5. Analysis of the difference between the processed and unprocessed means for the 4D concentration data showed that more than 80% of voxels in the ensemble mean of the wavelet processed data deviated by less than 3%. These results show that a 1.5x increase in SNR can be achieved with little degradation of resolution. This corresponds to injecting about twice the radioactivity, a maneuver that is not possible in human studies without saturating the PET camera and/or exposing the subject to more than permitted radioactivity.

Algorithms↗

PubMed2005

Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage.

Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode (13)C- NMR spectroscopy to elucidate profound differences between hearts from diabetic rats (DR, streptozotocin treatment) and normal rats (NR). The incorporation of [2,4,6,8,10,12,14,16-(13)C(8)]palmitate into the TAG pool was monitored in isolated hearts perfused with physiological (0.5 mM palmitate, 5 mM glucose) and elevated substrate levels (1.2 mM palmitate, 11 mM glucose) characteristic of the diabetic condition. Surprisingly, although the normal hearts were enriched at a near-linear profile for >or=2 h before exponential characterization, exponential enrichment of TAG in diabetic hearts reached steady state after only 45 min. Consequently, TAG turnover rate was determined by fitting an exponential model to enrichment data rather than conventional two-point linear analysis. In the high-substrate group, both turnover rate (DR 820+/- 330, NR 190 +/-150 nmol.min(-1).g(-1) dry wt; P< 0.001) and [TAG] content (DR 78 +/-10, NR 32+/- 4 micromol/g dry wt; P< 0.001) were greater in the diabetic group. At lower substrate concentrations, turnover was greater in diabetics (DR 530+/-300, NR 160+/- 30; P<0.05). However, this could not be explained by simple mass action, because [TAG] content was similar between groups [DR 34+/- 7, NR 39+/- 9 micromol/g dry wt; not significant (NS)]. Consistent with exponential enrichment data, (13)C fractional enrichment of TAG was lower in diabetics (low- substrate groups: DR 4+/-1%, NR 10+/- 4%, P<0.05; high-substrate groups: DR 8+/- 3%, NR 14+/- 9%, NS), thereby supporting earlier speculation that TAG is compartmentalized in the diabetic heart.

Animals↗

PubMed2005

High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease.

OBJECTIVES: We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans. BACKGROUND: Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known. METHODS: Fourteen patients with ischemic heart disease, age 62 +/- 12 years (mean +/- SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as "normal" versus "abnormal" on the basis of MBF response to adenosine 140 microg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis. RESULTS: Folate was associated with a reduction in mean arterial pressure (100 +/- 12 mm Hg vs. 96 +/- 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 +/- 0.59 ml/min/g vs. 2.16 +/- 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 +/- 0.59 vs. ml/min/g 1.41 +/- 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 +/- 0.61 ml/min/g vs. 2.12 +/- 0.69 ml/min/g, placebo vs. folate, p = NS). CONCLUSIONS: The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.

Adenosine↗

PubMed2005

Effects of sildenafil on myocardial blood flow in humans with ischemic heart disease.

BACKGROUND: We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease. METHODS: Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given approximately 2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow <1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow >1.65 ml/min per g were averaged and combined into a normal zone for that patient. RESULTS: At rest, rate pressure product (heart rate x systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76+/-0.48 placebo versus 0.64+/-0.20 sildenafil, both P=NS; mean+/-SD). Both rate pressure product and myocardial blood flow increased (P<0.01) with cold pressor stress (11+/-3 K and 1.14+/-0.59 placebo versus 10+/-3 K and 1.21+/-0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6+/-0.7) exceeded that with adenosine and placebo (2.0+/-1.3, P<0.04, paired sign test). CONCLUSION: Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that alpha-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease.

Adult↗

PubMed2005

Two types of image generation: evidence from PET.

Is there more than one method whereby people can generate visual mental images? Participants generated images after learning patterns in two ways. In one condition, they memorized descriptions of how segments are arranged to form patterns; in another, they memorized segments and mentally amalgamated them into patterns. In both conditions, identical stimuli cued them to form images while brain activation was monitored using PET. Comparison of the two imagery conditions revealed different activation between hemispheres when images were formed after patterns were learned by mentally combining segments versus when images were formed from stored verbal descriptions. Thus, images can be generated in at least two ways. However, this laterality difference was subtle; the majority of brain areas were activated in common across conditions. This overall similarity is counter to what would be expected if image generation is simply perceptual exploration in the absence of appropriate stimuli, as is posited by perceptual activity theory.

Adolescent↗

PubMed2004

Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD.

CONTEXT: Theoretical neuroanatomic models of posttraumatic stress disorder (PTSD) and the results of previous neuroimaging studies of PTSD highlight the potential importance of the amygdala and medial prefrontal regions in this disorder. However, the functional relationship between these brain regions in PTSD has not been directly examined. OBJECTIVE: To examine the relationship between the amygdala and medial prefrontal regions during symptom provocation in male combat veterans (MCVs) and female nurse veterans (FNVs) with PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 17 (7 men and 10 women) Vietnam veterans with PTSD (PTSD group) and 19 (9 men and 10 women) Vietnam veterans without PTSD (control group). MAIN OUTCOME MEASURES: We used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the recollection of personal traumatic and neutral events. Psychophysiologic and emotional self-report data also were obtained to confirm the intended effects of script-driven imagery. RESULTS: The PTSD group exhibited rCBF decreases in medial frontal gyrus in the traumatic vs neutral comparison. When this comparison was conducted separately by subgroup, MCVs and FNVs with PTSD exhibited these medial frontal gyrus decreases. Only MCVs exhibited rCBF increases in the left amygdala. However, for both subgroups with PTSD, rCBF changes in medial frontal gyrus were inversely correlated with rCBF changes in the left amygdala and the right amygdala/periamygdaloid cortex. Furthermore, in the traumatic condition, for both subgroups with PTSD, symptom severity was positively related to rCBF in the right amygdala and negatively related to rCBF in medial frontal gyrus. CONCLUSIONS: These results suggest a reciprocal relationship between medial prefrontal cortex and amygdala function in PTSD and opposing associations between activity in these regions and symptom severity consistent with current functional neuroanatomic models of this disorder.

Amygdala↗

PubMed2004

Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks.

CONTEXT: Although a variety of functional neuroimaging studies have used emotion induction paradigms to investigate the neural basis of anger in control subjects, no functional neuroimaging studies using anger induction have been conducted in patient populations. OBJECTIVE: To study the neural basis of anger in unmedicated patients with major depressive disorder with anger attacks (MDD + A), unmedicated patients with MDD without anger attacks (MDD - A), and controls. DESIGN: We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm. SETTING: Academic medical center. PARTICIPANTS: Thirty individuals, evenly divided among the 3 study groups. INTERVENTIONS: In separate conditions, participants were exposed to anger and neutral autobiographical scripts during the positron emission tomography study. Subjective self-report and psychophysiologic data were also collected. MAIN OUTCOME MEASURES: Voxelwise methods were used for analyses of regional cerebral blood flow changes for the anger vs neutral contrast within and between groups. RESULTS: Controls showed significantly (P<.001) greater regional cerebral blood flow increases in the left ventromedial prefrontal cortex during anger induction than patients with MDD + A, whereas these differences were not present in other between-group analyses. Also, in controls, an inverse relationship was demonstrated between regional cerebral blood flow changes during anger induction in the left ventromedial prefrontal cortex and left amygdala, whereas in patients with MDD + A there was a positive correlation between these brain regions during anger induction. There was no significant relationship between these brain regions during anger induction in patients with MDD - A. CONCLUSION: These results suggest a pathophysiology of MDD + A that is distinct from that of MDD - A and that may be responsible for the unique clinical presentation of patients with MDD + A.

Adult↗

PubMed2004

Hippocampal function in posttraumatic stress disorder.

Recent studies have reported memory deficits and reduced hippocampal volumes in posttraumatic stress disorder (PTSD). The goal of the current research was to use functional neuroimaging and a validated explicit memory paradigm to examine hippocampal function in PTSD. We used positron emission tomography (PET) and a word-stem completion task to study regional cerebral blood flow (rCBF) in the hippocampus in 16 firefighters: 8 with PTSD (PTSD group) and 8 without PTSD (Control group). During PET scanning, participants viewed three-letter word stems on a computer screen and completed each stem with a word they had previously encoded either deeply (High Recall condition) or shallowly (Low Recall condition). Relative to the Control group, the PTSD group exhibited significantly smaller rCBF increases in the left hippocampus in the High vs Low Recall comparison. However, this finding reflected relatively elevated rCBF in the Low Recall condition in the PTSD group. Collapsing across High and Low Recall conditions, (1) the PTSD group had higher rCBF in bilateral hippocampus and left amygdala than the Control group, and (2) within the PTSD group, symptom severity was positively associated with rCBF in hippocampus and parahippocampal gyrus. The groups did not significantly differ with regard to accuracy scores on the word-stem completion task. The PTSD group had significantly smaller right (and a trend for smaller left) hippocampal volumes than the Control group. The results suggest an abnormal rCBF response in the hippocampus during explicit recollection of nonemotional material in firefighters with PTSD, and that this abnormal response appears to be driven by relatively elevated hippocampal rCBF in the comparison condition.

Adult↗

PubMed2003

Priming of new associations: a PET study.

Cognitive properties of associative priming are different from those of the non-associative priming. We examined areas associated with associative priming to understand its cortical processing. After subjects had studied pairs of unrelated words, they were shown one of the studied words and a 3-letter word-stem that could be completed using either the word that was paired with the presented studied word (same context), or with a different word (different context). As compared to the fixation, both conditions elicited increased activations in the left prefrontal and decreased activation in the extrastriate cortex. Medial temporal lobe was activated only in the same-context condition. This finding helps to understand why associative priming is impaired in some amnesic patients.

Adult↗

PubMed2003

Striatal dopamine release during unrewarded motor task in human volunteers.

SUMMARY: Striatal dopamine is associated with the processing of rewarded motor tasks. Its involvement in mediating unrewarded tasks is, however, unclear. We used a recently developed PET technique to dynamically measure the rate of displacement of a dopamine receptor ligand raclopride in healthy volunteers performing a finger opposition task. Rapid displacement of the ligand from the posterior putamen and the caudate immediately after the task initiation suggested striatal dopamine release during task performance. Since dopamine release was observed in the striatal areas that are implicated in unrewarded tasks by neuroimaging studies, the results demonstrate that the PET method can be used to extend the findings of conventional neuroimaging techniques, that do not provide information about signal transduction.

Adult↗

PubMed2003

Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia.

Hippocampus↗

PubMed2003

Implicit transfer of motor strategies in mental rotation.

Recent research indicates that motor areas are activated in some types of mental rotation. Many of these studies have required participants to perform egocentric transformations of body parts or whole bodies; however, motor activation also has been found with nonbody objects when participants explicitly relate the objects to their hands. The current study used positron emission tomography (PET) to examine whether such egocentric motor strategies can be transferred implicitly from one type of mental rotation to another. Two groups of participants were tested. In the Hand-Object group, participants performed imaginal rotations of pictures of hands; following this, they then made similar judgments of pictures of Shepard-Metzler objects. The Object-Object group performed the rotation task for two sets of Shepard-Metzler objects only. When the second condition in each group (which always required rotating Shepard-Metzler objects) was compared, motor areas (Area 6 and M1) were found to be activated only in the Hand-Object group. These findings suggest that motor strategies can be covertly transferred to imaginal transformations of nonbody objects.

Adolescent↗

PubMed2003

A novel method for noninvasive detection of neuromodulatory changes in specific neurotransmitter systems.

Over the last decade, it has become possible to study theories of cognition using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These methods yield statistical parametric maps of changes in cerebral blood flow (CBF) elicited by cognitive tasks. A limitation of these studies is that they provide no information about the underlying neurochemistry. However, it is possible to extend the concept of activation studies to include measurements targeting neurotransmitters and specific receptor populations. Cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level. The increased neurotransmitter level can be used to alter the kinetics of specifically bound radioligands. We describe a new approach to the design and analysis of neuromodulation experiments. This approach uses PET, a single-scan session design, and a linear extension of the simplified reference region model (LSSRM) that accounts for changes in ligand binding induced by cognitive tasks or drug challenge. In the LSSRM, an "activation" parameter is included that represents the presence or absence of change in apparent dissociation rate. Activation of the neurotransmitter is detected statistically when the activation parameter is shown to violate the null hypothesis. Simulation was used to explore the properties of the LSSRM with regard to model identifiability, effect of statistical noise, and confounding effects of CBF-related changes. Simulation predicted that it is possible to detect and map neuromodulatory changes in single-subject designs. A human study was conducted to confirm the predictions of simulation using (11)C-raclopride and a motor planning task. Parametric images of transport, binding potential, areas of significant dopamine release, and statistical parameters were computed. Examination of the kinetics of activation demonstrated that maximum dopamine release occurred immediately following task initiation and then decreased with a half-time of about 3 min. This method can be extended to explore neurotransmitter involvement in other behavioral and cognitive domains.

Adult↗

PubMed2003

Coregistration of head CT comparison studies: assessment of clinical utility.

RATIONALE AND OBJECTIVES: The authors evaluated the clinical utility of image coregistration in the interpretation of follow-up computed tomographic (CT) studies of the head. MATERIALS AND METHODS: Fourteen patients with 34 intracranial lesions underwent follow-up head CT. The images were coregistered automatically with proprietary software on a standard personal computer, and all patient demographic data were removed. A neuroradiologist read the coregistered images several days after first reading the nonregistered images. The reading was repeated some months later to assess intraobserver variability, and a second reader was recruited so that interobserver variability also could be assessed. The interpretations of nonregistered images served as controls for the interpretations of coregistered images. Readers were asked to assess changes in lesion size quantitatively and to record the time it took to evaluate each case. Differences in interpretation speed were evaluated with the t test. Univariate analysis was used to measure accuracy; interpretations were compared with those of a nonblinded senior neuroradiologist, which served as the diagnostic standard. Intra- and interindividual variability were assessed with the kappa statistic. RESULTS: The time needed to read the studies decreased by an average of 65.6% (P < .05), with statistically significant reductions for each reader. Coregistration also changed the interpretation results in 21.9% of cases. Coregistration increased the accuracy of reading, but not significantly. Intraobserver variability improved from 0.3554 to 0.7328 with coregistration, and interobserver variability improved from 0.2670 to 0.3309. CONCLUSION: Image coregistration is technically feasible and accurate. Coregistration of follow-up studies significantly reduces the time needed for comparison and interpretation. It does not detract from the accuracy of interpretation of follow-up studies and tends to decrease intra- and interobserver variability.

Brain Diseases↗

PubMed2003

Myocardial flow regulation in people with mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes/myoclonic epilepsy and ragged red fibers and other mitochondrial syndromes.

OBJECTIVE: This study tests the hypothesis that elevated levels of rest myocardial blood flow (MBF), indicative of inefficient aerobic metabolism, will be present in some patients with mitochondrial disorders but structurally normal hearts. BACKGROUND: Regulation of MBF is a complex process closely linked to myocardial energy production. Aerobic metabolism in turn depends on normal mitochondrial function and so investigation of patients with mitochondrial disorders may provide important information regarding heritable mechanisms involved in regulation of myocardial flow. METHODS: Rest and adenosine-stimulated MBF was measured by the positron emission tomography (PET) 13NH(3) technique in nine patients with mitochondrial disorders and compared with 15 age-matched control participants. RESULTS: Basal heart rate (beats/min) and rate pressure product (mm Hg/min) were elevated in patients (76+/-13 and 9302+/-1910, mean+/-SD, respectively) compared with control participants (63+/-9 and 7411+/-1531, P<0.01 and P<0.05, respectively). However, rest and adenosine-stimulated MBF (ml/min per g) did not differ significantly between groups (patients, 1.13+/-0.52 and 4.17+/-0.84, respectively; control participants, 0.85+/-0.30 and 3.56+/-0.63, respectively). Normalization of rest MBF to rate pressure product, however, demonstrated three patients whose values exceeded that of all control participants (chi2=5.71, P<0.05, Fisher's exact test). CONCLUSIONS: Elevated basal MBF, in some patients with mitochondrial disorders but structurally normal hearts, suggests the level of basal flow is responsive to efficiency of aerobic metabolism, which closely reflects mitochondrial function. Mitochondrial heteroplasmy with relative sparing of myocardial mitochondria may account for normal basal flow in others with these disorders.

Acidosis, Lactic↗

PubMed2003

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression.

OBJECT: Neurosurgical procedures are a viable intervention for severe, treatment-refractory major depression, although they have been associated with only modest rates of efficacy. The purpose of this study was to identify possible neuroimaging predictors of treatment response to anterior cingulotomy in patients with major depression. METHODS: Thirteen patients underwent stereotactic anterior cingulotomy for treatment-refractory major depression. Symptom severity was measured using the Beck Depression Inventory (BDI) both before and approximately 12 months after surgery. The authors performed [18F]fluorodeoxyglucose-positron emission tomography (PET) studies in all patients preoperatively. Statistical parametric mapping methods were used to test for loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in BDI scores. The mean (+/- standard deviation) change in the BDI score from the preoperative period (43.7 +/- 7.8) to the postoperative period (30.5 +/- 21.3) was 33.1 +/- 45.4%. Two loci--the left subgenual prefrontal cortex and left thalamus--were identified as sites at which preoperative metabolism was significantly correlated with subsequent improvement in depressive symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at these loci were associated with better postoperative results. CONCLUSIONS: Possible PET scanning predictors of treatment response were identified in patients with major depression who had undergone anterior cingulotomy. Further research will be necessary to determine the reproducibility of this finding. If confirmed, the availability of an index for noninvasively predicting a patient's response to cingulotomy for the treatment of major depression would be of great clinical value.

Adult↗