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D D Spencer

Publications and source records attributed to D D Spencer.

At least 37 records · Page 2Linked to original sources

Investigation of the human hippocampal formation using a randomized event-related paradigm and Z-shimmed functional MRI.

Functional neuroimaging of the hippocampal formation has presented a challenge to neuroscientists because of the small size of the hippocampus proper and its location at the basal level of the brain. Choosing the appropriate control condition for subtraction-based studies has also proved difficult. Event-related experimental designs are a powerful tool in behavioral and electrophysiological studies. Recently, such experimental designs have been applied to functional MR imaging studies but these studies used large intertrial intervals in order to separate the slow blood flow response from temporally adjacent events, severely limiting the number of events that can be presented in a single run. This leads to poor statistical power and restrictions on the design of the experimental paradigm. We present data obtained using a rapidly presented, randomized event-related paradigm, combined with a novel fMRI imaging method designed to improve imaging in basal brain regions. The results demonstrate bilateral activation in the hippocampal formation in identification of novel complex scenes distinct from a learned basis set of complex scenes. Differential activation is obtained in the counter task of identifying a learned target complex scene against a background of novel scenes. The results are also compared with the more conventional block design complex scene paradigms previously reported by others. The block design provides strong posterior activation, likely related more to visual scene processing, whereas the event-related design provides more anterior hippocampal activation with the encoding of novel scenes.

Adult↗

Reproducibility of serial peri-ictal single-photon emission tomography difference images in epilepsy patients undergoing surgical resection.

Peri-ictal single-photon emission tomography (SPET) difference images co-registered to magnetic resonance imaging (MRI) visualize regional cerebral blood flow (rCBF) changes and help localize the epileptogenic area in medically refractory epilepsy. Few reports have examined the reproducibility of SPET difference image results. Epilepsy patients having two peri-ictal and at least one interictal SPET scan who later underwent surgical resection were studied. Localization accuracy of peri-ictal SPET difference images results, interictal electroencephalography (EEG), and ictal EEG from the first (seizure 1) and second (seizure 2) seizure, as well as MRI and positron emission tomography (PET) findings, were compared using surgical resection site as the standard. Thirteen patients underwent surgical resection (11 temporal lobe and 2 extratemporal). SPET results from seizure 1 were localized to the surgical site in 12/13 (92%) patients, while SPET results from seizure 2 were localized in 13/13 (100%) patients. All other modalities were less accurate than the SPET results interictal EEG--seizure 1 6/13 (46%); ictal EEG--seizure 1 5/13 (38%); interictal intracranial EEG--seizure 2 4/9 (44%); ictal intracranial EEG--seizure 2 results 8/9 (89%); MRI 6/13 (46%); PET 9/13 (69%)[. SPET results were reproducible in 12/13 (92%) patients. SPET difference images calculated from two independent peri-ictal scans appear to be reproducible and accurately localize the epileptogenic area. While SPET difference images visualize many areas of rCBF change, the quantification of these results along with consideration of injection time improves the diagnostic interpretation of the results.

Adult↗

Differential neurite growth on astrocyte substrates: interspecies facilitation in green fluorescent protein-transfected rat and human neurons.

In the present study, we used co-culture of astrocytes from one species with neurons from a different species to examine neuritic outgrowth. We include a focus on human cells. Three types of neuron were used, including rat hippocampal dentate granule cells, rat hypothalamic neurons and human cortical neurons. To visualize neuronal processes, neurons were either immunostained with GABA antiserum or transfected with the jellyfish green fluorescent protein gene. The entire axonal and dendritic fields of single neurons could be quantitatively analysed based on their strong green fluorescent protein label. Astrocytes were obtained from rat hippocampus or hypothalamus, chicken cortex, normal human cortex, human cortex lesion, and from the sclerotic human hippocampus after surgery for intractable temporal lobe epilepsy. In the absence of astrocytes, isolated neurons died within three to four days. In contrast, neurons from both rat and human brains survived and extended dendrites and axons on rat, chicken and human astrocytes or in their conditioned medium. Astrocytes from interspecies cultures were not only capable of enhancing the survival of neuron co-cultures, but neuronal neurite extension in some cases was even greater on heterospecific astrocytes than on homospecific astrocytes. To support the hypothesis that synaptogenesis of rat hippocampal neurons was accelerated by a substrate of human astrocytes, we used a functional assay based on time-lapse confocal laser or digital imaging of calcium responses to transmitter release; synaptic responses were found earlier when rat neurons were grown on rat or human astrocytes than in the absence of these astrocytes. These data indicate that rodent glial cells enhance human neurite extension, and that rat neurite outgrowth can be used as a type of bioassay for the neurite promoting capacity of different derivations of human glia.

2-Amino-5-phosphonovalerate↗

Effects of cell volume fraction changes on apparent diffusion in human cells.

Diffusion-weighted imaging was used to study the relationship between apparent diffusion coefficient (ADC) and cell volume fraction in cell suspensions and packed arrays. Cell volume fraction was varied by changing extracellular fluid osmolarity (for human glial cells) and by changing cell density (for human glial and red blood cells). In packed arrays of glial cells, ADC increased 10% when cells shrank and decreased 13% when cells swelled. ADC decreased 34% as cell density increased from 0 to 72%. In erythrocyte suspensions, ADC decreased 90% as the cell density increased from 0 to 89%. These results agree with theoretical predictions.

Adult↗

Contribution of the anteromedial temporal lobes to the evaluation of facial emotion.

Amygdala damage can result in impairments in evaluating facial expressions largely specific to fear. In contrast, right-hemisphere cortical lesions result in a more global deficit in facial emotion evaluation. This study addressed these 2 contrasting findings by investigating amygdala and adjacent cortical contributions to the evaluation of facial emotion in 12 patients with right and 11 patients with left unilateral anteromedial temporal lobectomy (RTL and LTL, respectively) and 23 normal controls. RTL but not LTL patients revealed impaired intensity ratings that included but were not exclusive to fear, with the most severe deficits confined to expressions related to affective states of withdrawal-avoidance. This suggests that affective hemispheric specializations in cortical function may extend to subcortical limbic regions. In addition, the right amygdala and adjacent cortex may be part of a neural circuit representing facial expressions of withdrawal.

Adult↗

Intracranial EEG seizure-onset patterns in neocortical epilepsy.

PURPOSE: We investigated neocortical seizure-onset patterns recorded by intracranial EEG with regard to anatomic location, pathologic substrate, and prognostic value for surgical outcome. METHODS: Seizure onset was analyzed in 53 neocortical resective epilepsy surgery patients. Anatomic location was divided into temporal and extratemporal. Pathologic substrate was classified as developmental, mature, and negative or non-specific gliosis. Onset frequency was categorized by visual analysis into tradition EEG frequency bands. Spatial extent was divided into focal (fewer than four contacts) and regional (more than five contacts). Waveform at seizure onset was divided into several types based on their morphology. Onset features were examined with respect to anatomic location, pathologic substrate, and surgical outcome. RESULTS: Seizure-onset frequency was significantly related to spatial distribution and to anatomic location. Extratemporal and regional onset were more commonly in the gamma range, and temporal and focal onset in the beta frequency range or slower. Waveform could be categorized into five different patterns, of which low voltage fast activity (LVFA) was the most common form (57%). LVFA and rhythmic alpha-theta spike activity were more common in developmental than in mature pathology, whereas rhythmic sinusoidal waves at onset were found in only mature substrates. Waveform pattern showed a possible correlation with surgical outcome (p = 0.097): LVFA and rhythmic sinusoidal waves onset patterns were associated with favorable outcome more often (40.4%) than the other three patterns (6.3%). Slow onset suggested poor outcome in the subgroup of developmental pathology (p = 0.062). CONCLUSIONS: Certain electrographic seizure-onset features are associated with specific substrates and outcomes, whereas others reflect the anatomic location and its connections independent of the pathology.

Adolescent↗

Cerebrospinal fluid cleft with cortical dimple: MR imaging marker for focal cortical dysgenesis.

PURPOSE: To determine whether the magnetic resonance (MR) imaging feature of a cerebrospinal fluid (CSF) cleft and cortical dimple can be used as a marker for cortical dysgenesis. MATERIALS AND METHODS: MR images in 875 patients with epilepsy were evaluated for the following features of focal cortical dysgenesis: cortical thickening, indistinct junction between gray and white matter, macrogyria, and abnormal sulcal pattern. Images with these features were reevaluated to determine the relationship between the CSF cleft-cortical dimple complex and focal cortical dysgenesis and its contribution to diagnosis. The cleft-dimple complex was defined as a prominent CSF space associated with a region of cortical volume loss adjacent to the dysgenesis. RESULTS: Seventy-one patients had cortical dysgenesis, including 27 with cellular proliferation abnormalities, 18 with migration abnormalities, 25 with cortical organization abnormalities, and one with miscellaneous anomalies. Histologic correlation was available in 20 patients. There was an associated cortical dimple in 29 (41%) patients. This association was strongest in patients with cortical organization abnormalities: It was present in 22 of the 25 (88%) patients. In 12 (48%) patients with abnormalities of cortical organization, the CSF cleft was easier to detect than other features of cortical dysgenesis or contributed directly to the MR imaging diagnosis. CONCLUSION: The cleft-dimple complex is a marker for subtle cases of focal cortical dysgenesis and may be due to maldevelopment. In patients with seizures, the presence of a cleft-dimple complex should alert the physician to scrutinize adjacent regions for developmental anomalies.

Adult↗

Temporal lobectomy in children: cognitive outcome.

OBJECT: The authors sought to determine the impact of early temporal lobectomy (in patients younger than age 17 years) on intellectual functioning. The efficacy of temporal lobectomy for treating seizures is well established and the procedure is becoming more acceptable as a treatment for children whose seizures are intractable. However, cognitive outcomes of temporal lobectomy in children and adolescents are largely unreported. The present study takes advantage of a unique multicenter collaboration to examine retrospectively intellectual functioning in a large sample of children who underwent temporal lobectomy. METHODS: Intellectual functioning was assessed before and after temporal lobectomy for treatment of medication-resistant seizures in 82 patients at eight centers of epilepsy surgery. All children underwent standard presurgical examinations, including electroencephalography-video monitoring, magnetic resonance (MR) imaging, and neuropsychological testing, at their respective centers. Forty-three children underwent left temporal lobectomy and 39 underwent right temporal lobectomy. For the entire sample, there were no significant declines in intelligence quotient (IQ) following surgery. Children who underwent left temporal lobectomy demonstrated no significant loss in verbal intellectual functioning and improved significantly in nonverbal intellectual functioning. Children who underwent right temporal lobectomy did not demonstrate significant changes in intellectual functioning. Although group scores showed no change in overall IQ values, an analysis of individual changes revealed that approximately 10% of the sample experienced a significant decline and 9% experienced significant improvement in verbal functioning. Significant improvement in nonverbal cognitive function was observed in 16% of the sample and only 2% of the sample showed significant declines. Risk factors for significant decline included older patient age at the time of surgery and the presence of a structural lesion other than mesial temporal sclerosis on MR imaging. CONCLUSIONS: The present study provides preliminary data for establishing the risk of cognitive morbidity posed by temporal lobectomy performed during childhood. With respect to global intellectual functioning, a slight improvement was significantly more likely to occur than a decline. However, there were several patients in whom significant declines did occur. It will be necessary to study further the factors associated with such declines. In addition, further study of more specific cognitive functions, particularly memory, is needed.

Adolescent↗

Choroid plexus changes after temporal lobectomy.

BACKGROUND AND PURPOSE: Postoperative contrast-enhanced MR imaging of the brain is routinely used when evaluating for residual or recurrent brain tumor. It is imperative to be aware of morphologic changes and imaging features that typically occur in response to surgical manipulation at the postoperative site to avoid misinterpretation of imaging findings. Our purpose was to determine normal postoperative changes and alterations in the choroid plexus among patients who had undergone temporal lobectomy in order to distinguish this appearance from pathologic changes that may be seen in the presence of infection or recurrent tumors. METHODS: We reviewed 159 MR scans from 95 patients with hippocampal sclerosis or gliosis who underwent temporal lobectomy for treatment of intractable epilepsy. Choroid plexus location and size were assessed on contrast-enhanced T1-weighted images. RESULTS: After temporal lobectomy, the choroid plexus enlarged and sagged into the resection site. Increase in the size of the choroid plexus occurred in 58% of cases overall. The degree of enhancement also increased after surgery, sometimes resulting in a nodular pattern of enhancement. The changes were most marked during the 1st week after temporal lobectomy, and showed an enlarged, markedly enhancing choroid plexus on 86% of the scans. CONCLUSION: Postoperative changes of the choroid plexus after temporal lobectomy include sagging into the resection site, an increased size, and an increased degree of enhancement. Normal postoperative morphologic characteristics may mimic neoplastic enhancement pattern. Familiarity with this appearance is important to avoid a pitfall in diagnosis of recurrent postoperative temporal lobe neoplasms.

Adolescent↗

Visualization of chemokine binding sites on human brain microvessels.

The chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) aid in directing leukocytes to specific locales within the brain and spinal cord during central nervous system inflammation. However, it remains unclear how these chemokines exert their actions across a vascular barrier, raising speculation that interaction with endothelial cells might be required. Therefore, experiments were performed to determine whether binding domains for these chemokines exist along the outer surface of brain microvessels, a feature that could potentially relay chemokine signals from brain to blood. Using a biotinylated chemokine binding assay with confocal microscopy and three-dimensional image reconstruction, spatially resolved binding sites for MCP-1 and MIP-alpha around human brain microvessels were revealed for the first time. Binding of labeled MCP-1 and MIP-1alpha could be inhibited by unlabeled homologous but not heterologous chemokine, and was independent of the presence of heparan sulfate, laminin, or collagen in the subendothelial matrix. This is the first evidence of specific and separate binding domains for MCP-1 and MIP-1alpha on the parenchymal surface of microvessels, and highlights the prospect that specific interactions of chemokines with microvascular elements influence the extent and course of central nervous system inflammation.

Binding, Competitive↗

Composite image formation in z-shimmed functional MR imaging.

A challenge in functional magnetic resonance imaging (fMRI) is to develop imaging methods that are highly sensitive to microscopic field inhomogeneities [the blood oxygenation level-dependent (BOLD) effect] and minimally sensitivity to macroscopic fields. z-Shimming compensates for the through-plane dephasing that arises in gradient-echo images due to magnetic field inhomogeneities. To date, an analysis of the formation of composite images from multiple z-shim acquisitions has not been presented. This work compares three strategies for forming composite images, one of which is introduced for the first time, against the nominal image acquisition. True-versus false-positive rates of activation detection are considered, in addition to the time efficiency of the methods. It is shown that z-shimming can provide uniform spatial sensitivity, resulting in increased activation detectability, in many cases outperforming the nominal imaging approach. Time efficiency is shown to be dependent on field uniformity. Theory, computer simulations, and results from fMRI studies are used to demonstrate the performance of these methods.

Arousal↗

Decrease in inhibition in dentate granule cells from patients with medial temporal lobe epilepsy.

Alterations in synaptic inhibition are associated with epileptiform activity in several acute animal models; however, it is not clear if there are changes in inhibition in chronically epileptic tissue. We have used intracellular recordings from granule cells of patients with temporal lobe epilepsy to determine whether synaptic inhibition is compromised. Two groups of patients with medial temporal lobe epilepsy were used, those with medial temporal lobe sclerosis (MTLE), and those with extrahippocampal masses (MaTLE) where the cell loss and synaptic reorganization that characterize MTLE are not seen. Although the level of tonic inhibition at the somata was not significantly different in the two patient groups, there was a reduction in the conductance of polysynaptic perforant path-evoked fast and slow inhibitory postsynaptic potentials (IPSPs) (53% and 66%, respectively). We found that there was a comparable decrease in the monosynaptic IPSP conductances examined in the presence of glutamatergic antagonists as that seen for the polysynaptically evoked IPSPs. These data suggest that the decrease in inhibition seen in normal artificial cerebrospinal fluid in MTLE granule cells cannot be solely explained by a decrease in excitatory input onto inhibitory interneurons and may reflect changes at the interneuron-granule cells synapse or in the number of specific inhibitory interneurons.

2-Amino-5-phosphonovalerate↗

MR imaging of implanted depth and subdural electrodes: is it safe?

This study evaluates the safety of imaging chronic epilepsy patients with intracranial depth and subdural electrodes by magnetic resonance (MR). To identify an epileptogenic focus, the precise location of the electrode contacts is necessary, and MR can provide this information. However, many neurosurgeons and neuroradiologists are hesitant to scan patients by MR with these implanted, metallic electrodes for fear of electrode displacement, current induction or heating secondary to the strong magnetic field. In the present study, the subdural electrodes were made of stainless steel with either stainless steel or platinum contacts. The depth electrodes were made of either platinum or a nickel-chromium alloy (nichrome). We reviewed 98 cases in which patients with implanted depth electrodes, subdural electrodes, or both underwent MR scanning. A total of 143 depth electrodes, 688 subdural strips, and 38 subdural grids were implanted in the 98 procedures. MR scanning was performed on a 1.5-T unit and consisted of T1, T2, and/or spoiled gradient echo pulse sequences. There were no documented complications related to the MR scans. Based on this study and a review of the literature, we feel that MR imaging can safely localize intracranial electrodes.

Dura Mater↗

Differential neuronal and glial relations with parameters of ictal discharge in mesial temporal lobe epilepsy.

PURPOSE: EEG recordings of spontaneous seizures should provide clues to epilepsy pathogenesis and pathology. We examined onset, propagation, and termination characteristics of spontaneous seizures recorded by intracranial EEG in temporal lobe (TL) epilepsy in relation to neuronal, glial, and synaptic changes in the same tissue. METHODS: All of our patients with intracranial EEG recordings of spontaneous TL seizure onset, subsequent TL resection, and quantitative pathologic analysis of resected tissue were included. Seizure parameters were mean time to initial propagation, mean total electrical duration, uniformity of seizure-onset distribution and location, and percentage of seizures with spiking onset per patient. Tissue was analyzed for glial and neuronal density in hippocampal fields and presence of sprouting. Outcome was classified as seizure free or not. RESULTS: All seizures with onset in resected TL in 62 patients were analyzed. The percentage of each patient's seizures with spike onsets was significantly correlated with glial density in CA3 (p < 0.01). Initial propagation time was significantly and inversely correlated with neuronal density in CA4 (p < 0.02). Electrical seizure duration was significantly correlated with glial density in CA2 and CA3 (p < 0.02). Neuronal and glial density were significantly (and inversely) related to one another only in CAI (p < 0.001). Outcome was most significantly related to uniform hippocampal seizure onset. Presence or absence of sprouting was not significantly related to outcome or any EEG measure. CONCLUSIONS: These results suggest both glia and neurons exert independent influences on the expression of ictal discharges in seizures of medial TL onset. Glial density influenced interictal-ictal transition, whereas neuronal density influenced seizure propagation. These findings may have implications for pathogenesis.

Cell Count↗

Prediction of surgical outcome by interictal epileptiform abnormalities during intracranial EEG monitoring in patients with extrahippocampal seizures.

PURPOSE: Ictal intracranial EEG recordings obtained during continuous preoperative monitoring are often used to localize the region of seizure onset for purposes of surgical resection in patients with extrahippocampal seizures. Whether interictal epileptiform abnormalities during long-term monitoring can predict surgical outcome in this group is not established. METHODS: Intracranial EEGs of patients who underwent extrahippocampal resective epilepsy surgery were reviewed for interictal epileptiform abnormalities before medication discontinuation or first seizure occurrence. Interictal abnormalities were categorized as within or beyond the confines of surgical resection. We correlated these findings with the region of seizure onset, the pathologic substrate, and surgical outcome (by using Engel criteria) at 1-year minimum follow-up. RESULTS: Of 13 patients with interictal epileptiform abnormalities, six patients had interictal epileptiform discharges extending beyond the confines of surgical resection. These patients all had poor surgical outcome even if the region of electrographic seizure onset was resected. Seven patients had focal interictal epileptiform discharges, the entire extent of which were resected. All had good outcomes. All patients with structural lesions had focal interictal epileptiform abnormalities and good surgical outcomes. The spatial extent of interictal epileptiform discharges varied among patients with nonstructural lesions. However, those whose regions of interictal epileptiform abnormality were included in surgical resection also had good surgical outcome. CONCLUSIONS: The presence of interictal epileptiform discharges extending beyond the area of resection correlates with poor surgical outcome in patients with extrahippocampal epilepsy. In contrast, patients with focal interictal epileptiform discharges included in surgical resection have good surgical outcomes.

Adolescent↗

Functional magnetic resonance imaging identifies abnormal visual cortical function in patients with occipital lobe epilepsy.

PURPOSE: To determine whether functional magnetic resonance imaging (fMRI) can reliably identify lateralized cortical dysfunction in patients with suspected occipital lobe epilepsy. METHODS: We compared visual cortical function of 10 patients with intractable occipital lobe epilepsy with nine control subjects' fMRI. Visual stimulation by using an alternating checkerboard pattern results in transient increases in the intensity of the proton magnetic resonance signal of water in the occipital lobes during echo-planar imaging. We used these stimulus-dependent changes in signal intensity to construct functional activation maps, which we registered onto anatomic images. RESULTS: After full-field stimulation, none of the patients with occipital lobe epilepsy had normal activation patterns, whereas eight of the nine control subjects had normal patterns (p = 0.001). Abnormalities consisted of either a markedly asymmetric activation pattern in six of 10 patients (p = 0.04), or a complete absence of activation in four of 10 patients (p = 0.05). The abnormal side of activation was concordant with the side of seizure onset in all six patients with asymmetric activation maps. Half-field stimulation produced less reliable results. Although more patients had abnormal activation maps than did controls with half-field stimulation (p = 0.04), the abnormal side was discordant with the side of seizure onset in three of the five patients who had markedly asymmetric activation patterns. CONCLUSIONS: These results suggest that fMRI with full-field stimulation is a reliable, noninvasive method for identifying areas of abnormal visual cortical function ipsilateral to the epileptogenic region in patients with occipital lobe epilepsy.

Adolescent↗

NPY inhibits glutamatergic excitation in the epileptic human dentate gyrus.

Neuropeptide Y (NPY) has been shown to depress hyperexcitable activity that has been acutely induced in the normal rat brain. To test the hypothesis that NPY can also reduce excitability in the chronically epileptic human brain, we recorded intracellularly from dentate granule cells in hippocampal slices from patients with hippocampal seizure onset. NPY had a potent and long-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4) evoked a mild and transient decrease. NPY-containing axons were found throughout the hippocampus, and in many epileptic patients were reorganized, particularly in the dentate molecular layer. NPY may therefore play a beneficial role in reducing granule cell excitability in chronically epileptic human tissue, and subsequently limit seizure severity.

2-Amino-5-phosphonovalerate↗

Lack of correlation between neuronal hyperexcitability and electrocorticographic responsiveness in epileptogenic human neocortex.

OBJECT: The purpose of this study was to determine whether intrinsic neuronal properties and synaptic responses differed between interictally active and inactive tissue removed in neocortical resections from patients undergoing surgical treatment for epilepsy. METHODS: Whole-cell patch recordings were performed in layer 2 or 3 and layer 5 pyramidal cells in neocortical slices obtained from tissue surgically removed from patients for the treatment of medically intractable seizures. Synaptic responses to stimulation at the layer 6-white matter border were used to classify cells as nonbursting if they responded with only a single action potential for all above-threshold stimuli (80%). These responses were usually followed by biphasic inhibitory postsynaptic potentials (IPSPs). Cells were classified as bursting if they fired at least three action potentials in response to synaptic stimulation (20%). These cells typically showed no IPSPs and responded in either an all-or-nothing or graded fashion. Approximately twice as many cells at layer 2 or 3 (29%) than cells at layer 5 (14%) fired synaptic bursts. Synaptic bursting was not associated with an alteration in a cell's response properties to gamma-aminobutyric acid. It was notable that, in tissue samples determined by electrocorticography (ECoG) to be either interictally active or not active, the proportion of cells that burst was exactly the same in both groups (24%). We found no cells with intrinsic burst firing. CONCLUSIONS: We conclude that synaptic bursting was characteristic of a small proportion of cells from epileptic tissue; however, this did not correlate with interictal spikes on ECoG.

Electric Conductivity↗