Biomedical subjects

Anna Barnes

Publications and source records attributed to Anna Barnes.

12 recordsLinked to original sources

PubMed2006

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

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PubMed2006

Hemodynamic impairment as a stimulus for functional brain reorganization.

We used functional magnetic resonance imaging to investigate whether hemispheral hemodynamic impairment can play an independent role in the functional reorganization of motor-related activity in the brain. Fourteen patients with large vessel occlusion but no infarct performed a simple motor task with the hand contralateral to the occluded vessel. Statistical parametric maps of regional activity were generated to compare the distribution of motor-related activity among patients with that of control subjects. Patients were classified into normal or abnormal cerebral hemodynamics on the basis of intracerebral vasomotor reactivity using transcranial Doppler and carbon dioxide inhalation. Controls and patients with normal vasomotor reactivity showed typical motor activity in contralateral motor areas. When the 9 patients with abnormal vasomotor reactivity were compared with the 14 control subjects in a single analysis, unique motor activation was identified in ipsilateral motor regions in the nonhypoperfused hemisphere. In a confirmatory analysis, blood oxygen level-dependent (BOLD) signal intensity was averaged in prespecified motor regions of interest. A significant group by hemisphere interaction was identified, driven by higher ipsilateral and lower contralateral hemisphere BOLD signal in patients with abnormal vasomotor reactivity compared with controls (F=12.40, P=0.002). The average ipsilateral motor region signal intensity was also significantly higher in the subgroup of patients with abnormal vasoreactivity and no TIA compared with controls (P=0.04). Our results suggest that hemodynamic impairment in one hemisphere, even in the absence of any focal lesion or any symptoms can be associated with a functional reorganization to the opposite hemisphere.

Adult↗

PubMed2005

FDG PET in the differential diagnosis of parkinsonian disorders.

The differential diagnosis of parkinsonian disorders can be challenging, especially early in the disease course. PET imaging with [(18)F]-fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of regional glucose metabolism in patient cohorts with idiopathic Parkinson's disease (PD), as well as variant forms of parkinsonism such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBGD). In this study, we assessed the utility of FDG PET in the differential diagnosis of individual patients with clinical parkinsonism. 135 parkinsonian patients were referred for FDG PET to determine whether their diagnosis could be made accurately based upon their scans. Imaging-based diagnosis was obtained by visual assessment of the individual scans and also by computer-assisted interpretation. The results were compared with 2-year follow-up clinical assessments made by independent movement disorders specialists who were blinded to the original PET findings. We found that blinded computer assessment agreed with clinical diagnosis in 92.4% of all subjects (97.7% early PD, 91.6% late PD, 96% MSA, 85% PSP, 90.1% CBGD, 86.5% healthy control subjects). Concordance of visual inspection with clinical diagnosis was achieved in 85.4% of the patients scanned (88.4% early PD, 97.2% late PD, 76% MSA, 60% PSP, 90.9% CBGD, 90.9% healthy control subjects). This study demonstrates that FDG PET performed at the time of initial referral for parkinsonism accurately predicted the clinical diagnosis of individual patients made at subsequent follow-up. Computer-assisted methodologies may be particularly helpful in situations where experienced readers of FDG PET images are not readily available.

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PubMed2004

Thalamic stimulation for parkinsonian tremor: correlation between regional cerebral blood flow and physiological tremor characteristics.

We used (15)O-labeled water (H(2)(15)O) positron emission tomography (PET) to study eight Parkinson's disease (PD) patients with unilateral ventral intermediate (Vim) thalamic nucleus deep brain stimulation (DBS) for severe tremor. Triaxial accelerometry (TRIAX) was used during imaging to obtain on-line measures of tremor characteristics. Regional cerebral blood flow (rCBF) scans together with TRIAX recordings were collected in three stimulation conditions (OFF, MID, and ON, corresponding, respectively, to 0%, 50%, and 100% reductions in mean accelerometry signal). Statistical Parametric Mapping (SPM99) revealed significant rCBF reductions during stimulation in the ipsilateral sensorimotor cortex (SMC) and the contralateral cerebellum, as well as concurrent increases in the ipsilateral ventral thalamus (P < 0.05, corrected). Covariate analysis of rCBF with physiological tremor characteristics revealed that tremor acceleration correlated positively with changes in the SMC and supplementary motor cortex ipsilaterally (P < 0.05, uncorrected), and negatively with changes in the ipsilateral cuneus (P < 0.05, corrected). After removing tremor acceleration effects, changes in tremor frequency correlated negatively with changes in the contralateral dentate nucleus and pons (P < 0.05, uncorrected). Our results suggest that Vim DBS for PD tremor modulates the activity of cerebello-thalamo-cortical pathways. Specific tremor characteristics relate to activity in different nodes of this system.

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PubMed2004

Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism.

In this study, we tested the hypotheses that (1) the acquisition of sequential information is related to the integrity of dopaminergic input to the caudate nucleus; and (2) the integrity of dopaminergic input to the caudate nucleus correlates significantly with brain activation during sequence acquisition. Twelve early stage Parkinson's disease (PD) patients and six age-matched healthy volunteers were scanned using a dual tracer PET imaging design. All subjects were scanned with [(18)F]fluoropropyl-betaCIT (FPCIT) to measure striatal dopamine transporter (DAT) binding and with [(15)O]water to assess activation during a sequence learning task where movements were made to a repeating sequence of eight targets. Caudate and putamen DAT binding in the PD cohort was reduced by 15% and 43%, respectively. In PD, caudate DAT binding correlated with target acquisition (R = 0.57, P < 0.05), while putamen DAT binding did not correlate with performance. In volunteers, caudate DAT binding correlated with learning-related activation (P < 0.05, corrected for multiple comparisons) in the left dorsolateral and ventral prefrontal cortices, the anterior cingulate and premotor regions, and the right cerebellum. A significant correlation with caudate DAT binding was additionally detected in the right anteromedial thalamus, extending into the rostral midbrain. By contrast, in the PD cohort, most of these regional relationships were lost: Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic tone. Our findings suggest that sequence learning is normally associated with tight coupling between dopaminergic input to the caudate and thalamo-cortical functional activity. Despite minimal reductions in nigro-caudate input, PD patients demonstrate a loss of this coupling early in the disease.

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PubMed2004

Serotonin modulation of cerebral glucose metabolism in normal aging.

Age-related alterations in serotonin function may increase the vulnerability to psychiatric and neurodegenerative disorders in late life. The neuroendocrine and cerebral metabolic response to the acute administration of the selective serotonin reuptake inhibitor, citalopram (40mg, IV), was measured in 17 normal control subjects using positron emission tomography (PET) to evaluate changes in serotonin function with normal aging. The citalopram-induced change in cerebral metabolism was positively correlated with age in the right precuneus, right paracentral lobule, and left middle temporal gyrus and negatively correlated with age in the left anterior cingulate gyrus, right inferior and middle frontal gyri, right insula, and right inferior parietal lobule. The positive correlations in mainly posterior brain regions indicate that normal aging is associated with an increase in metabolism after citalopram administration, whereas the negative correlations in mainly anterior brain regions indicate that normal aging is associated with a greater decrease in metabolism. These results suggest different compensatory processes in anterior compared to posterior brain regions secondary to the age-related loss of serotonin innervation.

Adult↗

PubMed2004

Perfusion SPECT in cochlear implantation and promontory stimulation.

BACKGROUND: Recent studies of profoundly deaf patients with cochlear implants have demonstrated that these patients are able to process sound in the auditory cortex in a similar way to normal subjects. However, there are large variations in outcome. Various clinical criteria are used for subject selection and the decision as to which ear is to be implanted involves electrical stimulation of the promontory which is used to confirm the persistence of auditory neurones and fibres that can be utilized by the cochlear implant. In this study we have used SPECT with Tc-HMPAO to investigate activation of the auditory cortex in cochlear implantees post-surgery. In addition we also investigated whether electrical stimulation of the promontory does produce change in blood flow in the auditory cortex in pre-surgery candidates, which would indicate viable auditory networks that can be utilized by a cochlear implant device. METHODS AND RESULTS: Image analysis was performed with SPM99. Results of a simple subtraction paradigm indicated bilateral activation of auditory cortex and Wernicke's area in the post-implant group during auditory stimulus (speech) and bilateral activation of the ventral lateral posterior thalamus and bilateral auditory association cortex BA21/22/42, in the pre-implant group during electrical stimulus but no activation of the primary auditory cortex. A conjunction analysis used to investigate the common areas of activation across both groups during the stimulus condition showed that there was a common bilateral activation of the primary auditory cortex in both groups (BA22/41/42). In addition, analysis of a subset of the seven post-implant subjects who did not comprehend the speech in our study showed an activation (Pu<0.05, where Pu is the peak voxel threshold, uncorrected for multiple comparisons) in the left auditory cortex that extended into area BA22 synonymous with Wernicke's area. This supports the theory that this region has a sensory role.

Adult↗

PubMed2003

Differential cortical and subcortical activations in learning rotations and gains for reaching: a PET study.

Previous studies suggest that horizontal reaching movements are planned vectorially with independent specification of direction and extent. The transformation from visual to hand-centered coordinates requires the learning of a task-specific reference frame and scaling factor. We studied learning of a novel reference frame by imposing a screen-cursor rotation and learning of a scaling factor by imposing a novel gain. Previous work demonstrates that rotation and gain learning have different time courses and patterns of generalization. Here we used PET to identify and compare brain areas activated during rotation and gain learning, with a baseline motor-execution task as the subtracted control. Previous work has shown that the time courses of rotation and gain adaptation have a short rapid phase followed by a longer slow phase. We therefore also sought to compare activations associated with the rapid and slower phases of adaptation. We isolated the rapid phase by alternating opposite values of the rotation or gain every 16 movements. The rapid phase of rotation adaptation activated the preSMA. More complete adaptation to the rotation activated right ventral premotor cortex, right posterior parietal cortex, and the left lateral cerebellum. The rapid phase of gain learning only activated subcortical structures: bilateral putamen and left cerebellum. More complete gain learning failed to show any significant activation. We conclude that the time course of rotation adaptation is paralleled by a frontoparietal shift in activated cortical regions. In contrast, early gain adaptation involves only subcortical structures, which we suggest reflects a more automatic process of contextual recalibration of a scaling factor.

Adaptation, Physiological↗

PubMed2003

Changes in regional cerebral blood flow with venlafaxine in the treatment of major depression.

OBJECTIVE: Neuroimaging studies reveal abnormalities of regional cerebral blood flow (rCBF) in major depression. In this study the authors prospectively investigated rCBF and clinical response to venlafaxine, a novel antidepressant. METHOD: A trial of venlafaxine was performed with seven patients referred with ICD-10 major depression. At entry and 6-week follow-up, the Beck Depression Inventory and Hamilton Depression Rating Scale were administered and rCBF was measured by means of single photon emission computed tomography with [(99m)Tc]hexamethylpropyleneamine oxime. Blood flow changes were explored with statistical parametric mapping. RESULTS: The subjects showed significant improvement after treatment. Statistical parametric mapping analysis revealed increased rCBF bilaterally in the thalamus and decreased rCBF in the left occipital lobe, right cerebellum, and temporal cortex bilaterally. CONCLUSIONS: These data confirm limbic cortical rCBF changes associated with effective antidepressant treatment.

Adult↗

PubMed2003

Evolving metabolic changes during the first postoperative year after subthalamotomy.

OBJECT: Short-term benefit from unilateral subthalamotomy for advanced Parkinson disease (PD) is associated with metabolic alterations in key targets of subthalamic nucleus (STN) and globus pallidus (GP) output. In this study positron emission tomography (PET) scanning was used to assess these changes and their relation to long-term benefits of subthalamotomy. METHODS: To determine whether the early postoperative changes persisted at longer-term follow up, the authors assessed six patients with advanced PD by using [18F]fluorodeoxyglucose-PET at 3 and 12 months postsurgery. The authors compared each of the postoperative images with baseline studies, and assessed interval changes between the short- and long-term follow-up scans. Clinical improvement at 3 and 12 months was associated with sustained metabolic decreases in the midbrain GP internus (GPi), thalamus, and pons of the lesioned side (p < 0.01). The activity of a PD-related multiregional brain network, which correlated with bradykinesia and rigidity, was reduced at both postoperative time points (p < 0.05). Comparisons of 3- and 12-month images revealed a relative metabolic increase in the GP externus (GPe) (p < 0.001), which was associated with worsening gait, postural stability, and tremor at long-term follow up. CONCLUSIONS: These findings indicate that subthalamotomy may have differential effects on each of the functional pathways that mediate parkinsonian symptomatology. Sustained relief of akinesia and rigidity is associated with suppression of a pathological network involving the GPi and its output. In contrast, the recurrence of tremor may relate to changes in the function of an STN-GPe oscillatory network.

Adult↗

PubMed2002

Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy, using 99mTc-HMPAO SPET brain images.

Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.

Adult↗

PubMedDate not supplied

Acute and chronic effects of citalopram on cerebral glucose metabolism in geriatric depression.

OBJECTIVE: In vivo studies of serotonin function have been limited by the lack of safe and selective pharmacologic agents and availability of suitable radiotracers. In the present study, the authors evaluated the cerebral metabolic effects of acute and continued administration of the selective serotonin reuptake inhibitor citalopram in patients with geriatric depression as a potential marker of serotonin dysfunction. METHODS: Six patients with geriatric depression and five comparison subjects underwent two resting positron emission tomography (PET) studies, performed after administration of a placebo infusion (Day 1) and a citalopram infusion (40 mg, Day 2). The patients were re-scanned after 8 weeks of treatment with the oral medication. RESULTS: The elderly comparison subjects demonstrated greater right-hemisphere cortical decreases than the patients. The depressed patients demonstrated greater left-hemisphere cortical decreases than comparison subjects. The depressed patients demonstrated greater increases in the right putamen and left occipital cortex. After 8 weeks of citalopram treatment, regional decreases and increases in metabolism were observed. CONCLUSION: These findings suggest regional deficits and also compensatory responses in the acute metabolic response to citalopram in the patients. These preliminary results suggest that the cerebral metabolic response to citalopram may be a useful marker of the pathophysiology of serotonin function in geriatric depression.

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