Effect of memantine on CBF and CMRO2 in patients with early Parkinson's disease

Objectives –  Parkinson's disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N -methyl- d -aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (rCBF) and oxygen metabolism in the basal ganglia of patients with early-stage PD.
Methods –  Quantitative positron emission tomography (PET) recordings were obtained with [¹⁵O]water and [¹⁵O]oxygen in 10 patients, scanned first in a baseline condition, and again 6 weeks after treatment with a daily dose of 20 mg memantine. Dynamic PET data were analyzed using volume of interest and voxel-based approaches.
Results –  The treatment evoked rCBF decreases in basal ganglia, and in several frontal cortical areas. The regional cerebral metabolic rate of oxygen (rCMRO₂) did not decrease in any of the a priori defined regions, and consequently the oxygen extraction fraction was increased in these regions. Two peaks of significantly decreased rCMRO₂ were detected near the frontal poles in both hemispheres, using a posteriori voxel-based analysis.
Conclusions –  Although we did not find the predicted decrease in basal ganglia oxygen consumption, our data suggest that treatment with memantine actively modulates neuronal activity and/or hemodynamic response in basal ganglia of PD patients. This finding may be relevant to the putative neuroprotective properties of NMDAR antagonists.     

A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals

Ten nondepressed patients with obsessive-compulsive disorder (OCD) who were characterized by predominant checking rituals were compared with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral blood flow levels (rCBF) were measured with positron emission tomography (H₂¹⁵O) across four conditions: rest, auditory stimulation with idiosyncratic normal or abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest. Order of neutral and obsessive stimulation was randomized. Higher subjective responses to obsessive than to neutral stimulation were found in both groups; subjective response was higher in OCD patients when obsessive stimulation was presented first. A four-way analysis of variance (group × stimulation order × hemisphere × condition [neutral or obsessive stimulation]) was performed on stimulation minus rest normalized rCBF values. Control subjects had significantly higher rCBF in the thalamus and putamen. A trend toward higher rCBF in OCD patients was found in the superior temporal regions. When neutral stimulation was presented first, rCBF was significantly higher in the caudate region of control subjects. Obsessive stimulation was associated with higher rCBF than neutral stimulation in orbitofrontal regions in both groups of subjects. Under obsessive stimulation, superior temporal and orbitofrontal activities were correlated in OCD patients but not in control subjects. Our study suggests specific abnormalities of information processing in the basal ganglia and temporal structures of compulsive checkers.     

Effect of Seizures on Cerebral Blood Flow Measured with 15–H2O and Positron Emission Tomography

Summary: To study quantitative alterations in regional cerebral blood flow (rCBF) accompanying seizures, and to assess the utility of ictal activation PET scanning as a noninvasive clinical tool for localization of epileptogenic foci, we used pentylenetetrazole (F'TZ) to induce seizures during ¹⁵O-water positron emission tomography (PET) CBF measurement in 15 patients with uncontrolled complex partial seizures (CPS) who had been referred for surgical evaluation. Continuous EEG monitoring was performed during the PET scans. After baseline scans were obtained, each patient was injected with 150–300 mg PTZ. Two patients had generalized tonic-clonic seizures (GTCs). CBF increases were asymmetrical. Two patients (in 1 the seizure occurred spontaneously, without PTZ injection) who had CPS had bitemporal 70–80% increases in CBF. Thalamic CBF increased during both CPS and GTCS. Five patients had an increase in focal EEG in-terictal abnormality, accompanied by focal flow decreases in 3. PTZ injection not accompanied by clinical seizures did not increase CBF. Partial seizures may be associated with bilateral increases in CBF, and subcortical gray regions are involved in ictal activation.     

The effect of apomorphine and buspirone on regional cerebral blood flow during the performance of a cognitive task-measuring neuromodulatory effects of psychotropic drugs in man

Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory – verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin_1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.     

Temporal Lobe CO2 Vasoreactivity in Patients with Complex Partial Seizures

Abstract: The topography of CO, vasoreactivity during hyperventilation in 8 patients with complex partial seizure (CPS) was visualized using the regional cerebral blood flow (rCBF) as measured by H₂¹⁵O-PET (positron emission tomography) and compared with that of 10 normal volunteers. In the normal volunteers, the vascular response to CO₂ (VrCO₂=ΔCBF%/APaCO₂) in the temporal lobe was 2.46±10.56 (%/mmHg). In the patients with CPS, VrCO₂ in the temporal lobe of the affected side was 2.08±0.40 (%/mmHg), while VrCO₂ on the contralateral side was 2.30 ± 0.46 (%/mmHg). There was a significant difference in VrCO₂ between the affected side of the temporal lobes and the temporal lobes of the normal volunteers. Furthermore, there was a tendency for VrCO₂ to be lower in the affected than in the contralateral side of the temporal lobe in patients with CPS. As CO₂ is the main regulator of CBF, this impaired vasoreactivity may reflect the brain dysfunction in the seizure focus and adjacent areas.     

Processing and Analysis of Form, Colour and Binocular Disparity in the Human Brain: Functional Anatomy by Positron Emission Tomography

With the purpose of mapping those anatomical structures participating in the processing and analysis of form, colour and disparity information, we have measured, with positron emission tomography and [¹⁵O]butanol, regional cerebral blood flow (rCBF) as an indicator of regional cerebral metabolic activity in 13 right-handed male volunteers during visual discrimination of colour, form and disparity information. The brain images were anatomically standardized using a computerized brain atlas and statistically significant changes were localized by cluster analysis. The changes in rCBF between specific activation and reference states were measured and the volumes of changes were determined, as were the loci and volumes of areas commonly activated by two or three different tasks. Each of the tasks activated over a dozen distinct and separate fields in the cortex–in the occipital, parietal, temporal and frontal lobes as well as the cerebellum. A number of overlapping fields were commonly activated in two tasks (four in the form and colour tasks, five in the form and disparity tasks, and eleven in the colour and disparity tasks), and two field overlaps were present in all three tasks (in the right superior frontal and left lingual gyri). These findings indicate that, in a visual discrimination task, the processing and analysis of single visual submodalities take place in a number of cortical fields in the human brain. As the same visual submodality is processed and analysed by numerous fields and the same field may participate in the processing of different submodalities, a divergence-convergence pattern of information processing is present in the human brain. This observation supports a hypothesis based on earlier studies in primates, namely that information processing in the visual system requires the concerted activation of a relatively large number of fields of functional networks in the brain.     

Correlation between EEG and cognitive abilities: sex differences

EEG activity was recorded during rest in 9 male and 9 female volunteers, aged 23 and 27, from C3, C4, T3, T4, P3, P4, O1 and O2, referenced to the ipsilateral earlobe. In a separate session verbal, spatial and abstract reasoning subtests of the Differential Aptitude Test were administered. Samples of EEG activity of 20.48 s were analysed and the interhemispheric correlation was obtained. Interhemispheric correlation in the alpha band was significantly higher in women than in men at central, parietal and occipital derivations. Significant correlations were found between D.A.T. scores and interhemispheric correlation, positive for women with abstract and spatial aptitudes in the central cortex, and negative for men with spatial, abstract and verbal scores in most derivations recorded. The opposite sign of men and women's correlations suggests the existence of a different cerebral functional organization, women showing lower hemispheric differentiation than men.     

Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow

Women have better verbal memory, and higher rates of resting regional cerebral blood flow (rCBF). This study examined whether there are also sex differences in the relationship between verbal episodic memory and resting rCBF. Twenty eight healthy right-handed volunteers (14 male, 14 female) underwent a neuropsychological evaluation and a Positron Emission Tomography (PET) (15)O-water study. Immediate and delayed recall was measured on the logical memory subtest of the Wechsler Memory Scale - Revised (WMS-R), and on the California Verbal Learning Test (CVLT). Resting rCBF (ml/100 g/min) was calculated for four frontal, four temporal, and four limbic regions of interest (ROIs). Women had better immediate recall on both WMS-R and CVLT tasks. Sex differences in rCBF were found for temporal lobe regions. Women had greater bilateral blood flow in a mid-temporal brain region. There were also sex differences in rCBF correlations with performance. Women produced positive correlations with rCBF laterality in the temporal pole. Greater relative CBF in the left temporal pole was associated with better WMS-R immediate and delayed recall in women only. These results suggest that trait differences in temporal pole brain-behavior relationships may relate to sex differences in verbal episodic memory.     

Interictal Spikes Increase Cerebral Glucose Metabolism and Blood Flow: A PET Study

Summary: Purpose: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges.
Methods: To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer [¹⁵O]H₂O and with [¹⁸F]fluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively.
Results: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: -71, z: 39; t = 4.5; p <0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 μmol/100 g/min with eyes open and 44.1 μmol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone.
Conclusions: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism.     

Auditory priming of frequency and temporal information: effects of lateralised presentation

Asymmetric distribution of function between the cerebral hemispheres has been widely investigated in the auditory modality. The current approach borrows heavily from visual local-global research in an attempt to determine whether, as in vision, local-global auditory processing is lateralised. In vision, lateralised local-global processing likely relies on spatial frequency information. Drawing analogies between visual spatial frequency and auditory dimensions, two sets of auditory stimuli were developed. In the high-low stimulus set we manipulate frequency information, and in the fast-slow stimulus set we manipulate temporal information. The fast-slow stimuli additionally mimic visual hierarchical stimulus structure, in which the arrangement of local patterns determines the global pattern. Unlike previous auditory stimuli, the current stimulus sets contain the experimental flexibility of visual local-global hierarchical stimuli allowing independent manipulation of structural levels. Previous findings of frequency and temporal range priming were replicated. Additionally, by presenting stimuli monaurally, we found that priming of frequency ranges (but not temporal ranges) was found to vary by ear, supporting the contention that the hemispheres asymmetrically retain traces of prior frequency processing. These results contribute to the extensive literature revealing cerebral asymmetries for the processing of frequency information, and extend those results to the realm of priming.     

Focal Cerebral Magnetic Resonance Changes Associated with Partial Status Epilepticus

Summary: We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T₂ signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with "cryptogenic" temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T₂ Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T₂ intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.     

Cerebral bloodflow and oxygen metabolism in borderzone and territorial infarcts due to symptomatic carotid artery occlusion

It remains controversial whether borderzone infarcts are due to compromised cerebral perfusion and whether territorial infarcts are caused by artery-to-artery emboli in case of occlusion of the internal carotid artery. The present positron emission tomography study compares with normal controls, the average regional cerebral bloodflow (rCBF), regional oxygen extraction fraction (rOEF) and regional cerebral metabolic rate for oxygen (rCMRO₂) in the infarct area, the peri-infarct zone, the remaining homolateral hemisphere and in the contralateral hemisphere of 10 patients with borderzone and 17 patients with territorial infarcts, due to internal carotid artery occlusion by atherosclerosis and by cervical dissection. The steady-state technique with oxygen-15 was used. A nearly significant increase of rOEF with lowered rCBF and rCMRO₂ was observed in the peri-infarct zone of patients with territorial infarcts. In patients with borderzone infarcts rCMRO₂ was decreased in the peri-infarct zone, in the remaining homolateral hemisphere and in the contralateral hemisphere without changes in rCBF and rOEF. The present study finds no arguments that impaired cerebral perfusion is a more frequent cause of borderzone than of territorial infarcts.     

Relative Changes in Regional Cerebral Blood Flow During Spinal Cord Stimulation in Patients with Refractory Angina Pectoris

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H₂¹⁵O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at TI modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.     

Brain structure and function correlates of general and social cognition

AIMS: To examine how general (e.g., memory, attention) and social (emotional and interpersonal processes) cognition relate to measures of brain function and structure. METHODS: PCA was used to identify general and social cognitive factors from Brain Resource International Database in 1,316 subjects. The identified factors were correlated with each subject's corresponding brain structure (MRI) and function (EEG/ERP) data. RESULTS: Seven core cognitive factors were identified for general and three for social. General cognition was correlated with global grey matter, while social cognition was negatively correlated with grey matter in fronto-temporal-somatosensory regions. Executive function, information processing speed and verbal memory performance were correlated with delta-theta qEEG, while most general cognitive factors negatively correlated with beta qEEG. Faster information processing speed was correlated with alpha qEEG. Executive function and information processing speed was correlated with negative-going ERP amplitude and slower ERP latency at frontal sites, but at posterior sites negative correlations were found. DISCUSSION: In contrast to general cognition, social cognition is identified by different functional (automated) activity and more localized neural structures. Only general cognition, requiring more effortful, controlled processing is related to brain function measures, particularly in frontal cortices. INTEGRATIVE SIGNIFICANCE: Recording measures from multiple modalities including MRI, EEG/ERP, social and general cognition within the same subject provides a method of brain profiling for use in cognitive-neurotherapy and pharmacological studies.     

Correlations between cerebral blood flow variations and clinical parameters in temporal lobe epilepsy: an interictal study.

Regional cerebral blood flow (rCBF) measurements were determined by the intravenous Xenon 133 technique in 80 patients suffering from temporal lobe epilepsy. All the patients had a normal CT scan. Three subgroups were differentiated, according to EEG and all-night polygraphic recordings: temporal lobe epilepsy with left (N = 25) or right (N = 25) EEG epileptic abnormalities and temporal lobe epilepsy with EEG abnormalities in both temporal regions with asynchronous occurrence (n = 30). In comparison with a control group (n = 20), there was (1) a marked reduction of blood flow in the temporal region corresponding to the site of the epileptic focus and (2) a reduction in blood flow in distant brain areas and the contralateral hemisphere. The rCBF decrease was highly correlated (p less than 0.001) with the disease severity (taking into account the complex partial seizure frequency and the number of secondary generalised seizures). Differences were found in the rCBF decrease between left and right temporal lobe epilepsy.     

Auditory priming of frequency and temporal information: Effects of lateralised presentation

Asymmetric distribution of function between the cerebral hemispheres has been widely investigated in the auditory modality. The current approach borrows heavily from visual local–global research in an attempt to determine whether, as in vision, local–global auditory processing is lateralised. In vision, lateralised local–global processing likely relies on spatial frequency information. Drawing analogies between visual spatial frequency and auditory dimensions, two sets of auditory stimuli were developed. In the high–low stimulus set we manipulate frequency information, and in the fast–slow stimulus set we manipulate temporal information. The fast–slow stimuli additionally mimic visual hierarchical stimulus structure, in which the arrangement of local patterns determines the global pattern. Unlike previous auditory stimuli, the current stimulus sets contain the experimental flexibility of visual local–global hierarchical stimuli allowing independent manipulation of structural levels. Previous findings of frequency and temporal range priming were replicated. Additionally, by presenting stimuli monaurally, we found that priming of frequency ranges (but not temporal ranges) was found to vary by ear, supporting the contention that the hemispheres asymmetrically retain traces of prior frequency processing. These results contribute to the extensive literature revealing cerebral asymmetries for the processing of frequency information, and extend those results to the realm of priming.     

Regional cerebral blood flow in various types of brain tumor

Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the ¹³³Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending ¹³³Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor.
It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain tissue function can be revealed even in the case of fairly small size tumors.     

On the neurobiology of creativity. Differences in frontal activity between high and low creative subjects

The aim was to investigate the relationship between creativity and hemispheric asymmetry, as measured by regional cerebral blood flow (rCBF). Two groups, each consisting of 12 healthy male subjects, who got either very high or low scores on a creativity test, were pre-selected for the rCBF investigation. rCBF was measured during rest and three verbal tasks: automatic speech (Auto), word fluency (FAS) and uses of objects (Brick). State and trait anxiety inventories were answered after the rCBF measurements. Intelligence tests were also administered. It was predicted that highly creative subjects would show a bilateral frontal activation on the divergent thinking task (Brick), while low creative subjects were expected to have a unilateral increase. Calculations were made of differences in blood flow levels between the FAS and the Brick measurements in the anterior prefrontal, frontotemporal and superior frontal regions. In accordance with our prediction, repeated measure-ANOVAs showed that the creativity groups differed significantly in all three regions. The highly creative group had increases, or unchanged activity, while the low creative group had mainly decreases. The highly creative group had higher trait anxiety than the low creative group. On the intelligence tests the low creative group was superior both on logical-inductive ability and on perceptual speed, while the groups were equal on verbal and spatial tests. The results are discussed in terms of complementary functions of the hemispheres.     

High Signal Intensity on T2- Weighted MRI Correlates with Hypoperfusion in Temporal Lobe Epilepsy

Single-photon emission computed tomography (SPECT) and [99mTc]HMPAO were used to assess the functional significance of nonspecific magnetic resonance imaging (MRI) abnormalities observed in patients with temporal lobe epilepsy and no focal lesion on CT scan. We studied 18 patients whose MRI was normal or showed high signal intensity on T2-weighted images (T2WIs) at the site of the EEG focus in 11 and 7 cases, respectively. EEG was monitored during regional cerebral blood flow (rCBF) study. Lateralized hypoperfusion was present in 7 of 17 interictal (41%) and in one postictal cases; it was located in the temporal lobe on the side of the EEG focus in all, and was significantly more frequent in patients with high signal intensity on T2WI (86%) than in patients with a normal MRI (18%). The degree of temporal perfusion asymmetry measured in each individual was higher in patients whose MRI was abnormal.