Mesial Temporal Cortex Research Articles

Measurement of 5-HT1A Receptor Density and in-vivo Binding Parameters of [18F]mefway in the Nonhuman Primate

The goal of this work was to characterize the in-vivo behavior of [(18)F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine(1A) (5-HT(1A)) receptor density (B(max)). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [(18)F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of B(max) and specific binding parameters k(off) and k(on) for estimation of apparent K(D). The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K(1), k(2), k(off), B(max), and K(Dapp) in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with B(max) values of 42±8 and 36±8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24±4, 19±4, and 13±2 pmol/mL, respectively. The K(Dapp) of mefway for the 5-HT(1A) receptor sites was 4.3±1.3 nmol/L. In conclusion, these results show that M-I [(18)F]mefway PET experiments can be used for the in-vivo measurement of 5-HT(1A) receptor density.

Interictal Type 1 Cannabinoid Receptor Binding is Increased in Female Migraine Patients

To compare binding of the type 1 cannabinoid receptor (CB1R) between migraine patients and healthy volunteers. It has been suggested that endocannabinoid deficiency may play a role in the pathophysiology of migraine. Nonetheless, biochemical studies substantiating this idea remain scarce and are faced with methodological shortcomings partly because of the difficulty to perform measurements of endocannabinoids within the central nervous system itself. An observational cross-sectional study was conducted in 20 female migraine patients and 18 healthy women matched for age and body mass index. Positron emission tomography acquisition was performed 90 minutes after intravenous injection of the radioligand [(18)F]MK-9470 to assess binding of [(18)F]MK-9470 to CB1R. Binding of CB1 R was globally increased in migraine patients vs healthy controls (average gray matter difference +16%; P = .009, 2-sample 2-sided Student's t-test). There were no correlations between CB1R binding and any predefined migraine characteristics. Increases in CB1R binding were most pronounced in the anterior cingulate, mesial temporal, prefrontal, and superior frontal cortices. The increased interictal CB1R binding, especially in brain regions that exert top-down influences to modulate pain, supports the idea that endocannibinoid deficiency is present in female patients suffering from episodic migraine.

Engagement of Temporal Lobe Regions Predicts Response to Educational Interventions in Adolescent Struggling Readers

Brain activation profiles obtained using magnetoencephalography were compared between middle-school students experiencing reading difficulties and non-reading-impaired students during performance of a continuous printed word recognition task. Struggling readers underwent small-group remedial instruction, and students who showed significant gains in word reading efficiency at a one-year follow-up assessment were classified as Adequate Responders whereas those not demonstrating such gains as Inadequate Responders. At baseline, compared to Inadequate Responders, the activation profiles of Adequate Responders featured increased activity in the left middle, superior temporal, and ventral occipitotemporal regions, as well as in the right mesial temporal cortex. The degree of activity in these regions was a significant predictor of improvement in word reading efficiency beyond the prediction afforded by baseline reading accuracy or fluency measures. The engagement of brain areas that typically serve as key components of the brain circuit for reading may be an important factor in predicting response to intervention in older students who experience reading difficulties.

An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate

[(18)F]Mefway is a serotonin 5-HT(1A) PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [(18)F]mefway permits (18)F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[(18)F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[(18)F]mefway and trans-[(18)F]mefway to evaluate the properties of cis-[(18)F]mefway for 5-HT(1A) PET imaging. The cis- and trans-[(18)F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [(18)F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BP(ND)) using the CB as a reference region. Averaged over the two subjects, BP(ND) values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[(18)F]mefway and cis-[(18)F]mefway, respectively. The cis-labeled [(18)F]mefway tracer has low specific binding throughout the 5-HT(1A) regions of the brain compared to trans-[(18)F]mefway, suggesting that the target-to-background binding of cis-[(18)F]mefway may limit its use for in vivo assessment of 5-HT(1A) binding.

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

The mechanisms involved in the transition to an epileptic seizure remain unclear. To examine them, we used tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability along with alkalinization or low Mg(2+). During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of subjects with epilepsy revealed that similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster and had larger amplitudes than interictal discharges and had a distinct initiation site. These events depended on glutamatergic mechanisms and were preceded by pyramidal cell firing, whereas interneuron firing preceded interictal events that depended on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggered seizures. Thus, the subiculum supports seizure generation, and the transition to seizure involves an emergent glutamatergic population activity.

Time course of electromagnetic activity associated with detection of rare events

The neural origins of the cortical response to rare sensory events remain poorly understood. Using simultaneous event-related potentials and magnetic resonance imaging, we investigated the anatomical profile of regional activity at various processing stages during performance of auditory and visual variants of an oddball paradigm. The earliest rarity-detection response was found in sensory-specific cortices, rapidly spreading to tertiary association areas, mesial temporal and frontal cortices by 150-200 ms. P3m-related activity was not found in sensory-specific cortices. On the basis of the anatomic distribution of P3m-related activity, this component is likely to reflect more generalized cognitive abilities hosted by association cortical regions.

In vivo kinetics of [F‐18]MEFWAY: A comparison with [C‐11]WAY100635 and [F‐18]MPPF in the nonhuman primate

[F-18]Mefway was developed to provide an F-18 labeled positron emission tomography (PET) neuroligand with high affinity for the serotonin 5-HT(1A) receptor to improve the in vivo assessment of the 5-HT(1A) system. The goal of this work was to compare the in vivo kinetics of [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 in the rhesus monkey. Each of four monkeys were given bolus injections of [F-18]mefway, [C-11]WAY100635, and [F-18]MPPF and scans were acquired with a microPET P4 scanner. Arterial blood was sampled to assay parent compound throughout the time course of the PET experiment. Time activity curves were extracted in the high 5-HT(1A) binding areas of the anterior cingulate cortex (ACG), mesial temporal cortex, raphe nuclei, and insula cortex. Time activity curves were also extracted in the cerebellum, which was used as a reference region. The in vivo kinetics of the radiotracers were compared based on the nondisplaceable distribution volume (V(ND) ) and binding potential (BP(ND) ). At 30 min, the fraction of radioactivity in the plasma due to parent compound was 19%, 28%, and 29% and cleared from the arterial plasma at rates of 0.0031, 0.0078, and 0.0069 (min⁻¹) ([F-18]mefway, [F-18]MPPF, [C-11]WAY100635). The BP(ND) in the brain regions were mesial temporal cortex: 7.4 ± 0.6, 3.1 ± 0.4, 7.0 ± 1.2, ACG: 7.2 ± 1.2, 2.1 ± 0.2, 7.9 ± 1.2; raphe nuclei: 3.7 ± 0.6, 1.3 ± 0.3, 3.3 ± 0.7; and insula cortex: 4.2 ± 0.6, 1.2 ± 0.1, 4.7 ± 1.0 for [F-18]mefway, [F-18]MPPF, and [C-11]WAY100635 respectively. In the rhesus monkey, [F-18]mefway has similar in vivo kinetics to [C-11]WAY100635 and yields greater than 2-fold higher BP(ND) than [F-18]MPPF. These properties make [F-18]mefway a promising radiotracer for 5-HT(1A) assay, providing higher counting statistics and a greater dynamic range in BP(ND).

Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [11C]DASB and [18F]altanserin-PET study

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [(18)F]altanserin and [(11)C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([(11)C]DASB). Overall [(18)F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [(11)C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [(11)C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT(2A) receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.

Surgical treatment of patients with drug‐resistant hypermotor seizures

To describe the clinical, electrophysiologic, neuroradiologic, and histologic findings in our patients with drug-resistant hypermotor seizures (HMSs) and to evaluate the outcome of their surgical treatment. Twenty-three patients were identified by criteria for drug-resistant HMS. Surgical treatment and presurgical evaluation modalities including semiology, magnetic resonance imaging (MRI), interictal/ictal scalp video-EEG (electroencephalography), and intracranial recording were analyzed retrospectively. The common seizure frequency of 60-300 per month was observed among 15 patients. Sixteen patients (69.6%) experienced auras such as fear and palpitation. Marked agitation was observed in 12 patients and mild agitation in 11 patients. Groaning/shouting and asymmetric posturing were common accompanying symptoms. Asymmetric posturing was observed more often in patients with mild agitation than in those with marked agitation (p = 0.027). MRI detected focal abnormalities in six patients. Intracranial recording was conducted in 16 patients. The origins of seizures were localized in mesial frontal cortex in four patients, dorsolateral frontal cortex in four patients, and mesial temporal cortex in two patients. The epileptogenic zones (EZs) were resected from the frontal lobe in 21 patients and from the temporal lobe in 2 patients. The follow-up ranged from 12-60 months. Seventeen patients (73.9%) had been seizure-free, 11 of whom had presented with marked agitation (11 of 12) and 6 with mild agitation (6 of 11) (p = 0.069). Histologic examinations demonstrated focal cortical dysplasia (FCD) in 18 patients. The HMSs can originate from both the mesial and dorsolateral frontal cortex, and occasionally from the temporal lobe. Patients with drug-resistant HMSs should be recommended for resective surgical treatment.

Spatio–temporal dynamics of olfactory processing in the human brain: an event-related source imaging study

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H 2S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution.

Altered spontaneous neuronal activity of the default-mode network in mesial temporal lobe epilepsy

Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.

Massive Intracranial Hemorrhage Associated With Pleomorphic Xanthoastrocytoma -Case Report-

A 60-year-old woman with a history of intermittent headaches and frequent seizures for 30 years presented with a massive intracranial hematoma in the left medial temporal lobe with thick subarachnoid hemorrhage. She had been treated with anticonvulsant medication under a diagnosis of left mesial temporal sclerosis based on magnetic resonance imaging findings. Cerebral angiography on admission revealed occlusion of the P(2) segment of the left posterior cerebral artery (PCA) and extravasation of contrast medium during the procedure. The patient underwent left temporal lobectomy including the lesioned mesial temporal cortex, and the ruptured P(2) segment of the PCA was removed as well. The operative finding of the ruptured aneurysm was pseudoaneurysm. Histological examination of the resected PCA segment demonstrated a pleomorphic xanthoastrocytoma invading the outer wall of the PCA. Presumably the bleeding was caused by the rupture of a pseudoaneurysm secondary to leptomeningeal involvement of this typically benign tumor.

Nutrition and Alzheimer's disease.

Alzheimer's disease begins with cognitive deficiencies that gradually become worse with the extension of cerebral lesions. Other troubles arise such as loss of independence, orientation impairments, disordered eating behavior, and weight loss. This weight loss increases the risk of infections, skin ulcers, and falls and consequently decreases quality of life in Alzheimer's patients. Various hypotheses (increased energy expenditure, mesial temporal cortex atrophy) were suggested to explain weight loss. We set up a Health Promotion Program that aims to prevent weight loss in patients with Alzheimer's disease. This program uses various tools (nutrition calendar, Mini Nutritional Assessment, nutrition education sessions) described in this article.

Neural correlates of affective picture processing — A depth ERP study

Using functional neuroimaging techniques (PET and fMRI), various cortical, limbic, and paralimbic structures have been identified in the last decade as neural substrates of human emotion. In this study we used a novel approach (intracerebral recordings of event-related potentials) to add to our knowledge of specific brain regions involved in affective picture processing. Ten intractable epileptic patients undergoing pre-surgical depth electrode recording viewed pleasant, neutral, and unpleasant pictures and intracerebral event-related potentials (ERPs) were recorded. A total of 752 cortical and subcortical sites were investigated. Significant differences in ERPs to unpleasant as compared to neutral or pleasant pictures were frequently and consistently observed in recordings from various brain areas – the mesial temporal cortex (the amygdala, the hippocampus, the temporal pole), the lateral temporal cortex, the mesial prefrontal cortex (ACC and the medial frontal gyrus), and the lateral prefrontal cortex. Interestingly, the mean latencies of responses to emotional stimuli were somewhat shorter in the frontal lobe structures (with evidently earlier activation within lateral prefrontal areas when compared to mesial prefrontal cortex) and longer in the temporal lobe regions. These differences, however, were not significant. Additional clearly positive findings were observed in some rarely investigated regions – in the posterior parietal cortex, the precuneus, and the insula. An approximately equivalent number of positive findings was revealed in the left and right hemisphere structures. These results are in agreement with a multisystem model of human emotion, distributed far beyond the typical limbic system and substantially comprising lateral aspects of both frontal lobes as well.

Apnoea in relation to neonatal temporal lobe haemorrhage

Background Six term newborns presented with apnoea and temporal lobe haemorrhage. Aim In this observational study, we described involvement of the limbic system in apnoeic term newborns with temporal lobe injury. Methods Six term newborns presented to the neonatal care unit with apnoea within the first 2 days of life. Ultrasound (US) and MRI of the brain were obtained in the first week of life. Results Apnoea was related to temporal lobe haemorrhage in all. During apnoeic periods four had focal epileptic activity on EEG. All lesions were detected first with US. On MRI, haemorrhages were located in the parenchyma, the subdural and/or subarachnoid space. Three haemorrhages were surrounded by infarction in the temporal lobe. In three infants hippocampus and mesial temporal cortex were affected. In two basal temporal cortex only was involved. Vascular anomalies were excluded by MRA, serial MRI or serial US with Doppler imaging. Conclusion Term infants with seizure associated apnoea may present with haemorrhage and/or infarction to hippocampus, mesial and basal temporal cortex. This study supports the existence and possible disruption of descending influences from the temporal cortex and/or amygdala on brainstem breathing centres in the term newborn.

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

A functional neuroimaging study of appetite loss in Alzheimer’s disease

Alzheimer's Disease (AD) is frequently associated with changes in appetite. This study investigated the relationship between regional cerebral perfusion and appetite loss in AD. 64 patients with possible or probable AD were characterized as being with (n=22) or without (n=44) appetite loss based on the Neuropsychiatric Inventory (NPI) Appetite subscale. 99mTc-ECD SPECT scans were coregistered to a standardized template in Talairach space generating mean ratios of uptake referenced to the cerebellum. Regions of interest (ROIs) included anterior cingulate cortex (ACC), middle mesial temporal cortex (MTC-m), inferior mesial temporal cortex (MTC-i), insula (INS), orbitofrontal cortex (OFC) and thalamus-hypothalamus (THAL). Backward stepwise logistic regression analysis of these ROIs showed hypoperfusion in the L-ACC (p=0.015) and L-OFC (p=0.015), relative sparing of perfusion in the R-ACC (p=0.010), R-OFC (p=0.010) and L-MTC-m (p=0.006), and greater anxiety (p=0.005) independently predicted loss of appetite (chi(2)=22.24, p=0.001, Nagelkerke R(2)=0.41). Hypoperfusion in the left anterior cingulate and left orbitofrontal cortices, and relative sparing of perfusion in the right anterior cingulate, right orbitofrontal and left middle mesial temporal cortices emerged as predictors of appetite loss in this sample of patients. These findings are consistent with impairments in the extrinsic motivational pathways of eating and impaired reward value of food as components of appetite loss in AD.

Reduced serotonin transporter binding in mesial temporal cortex in Alzheimer's disease: A [ 11C]DASB PET study

Reduced serotonin transporter binding in mesial temporal cortex in Alzheimer's disease: A [ 11C]DASB PET study

The neural correlates of sign versus word production

The production of sign language involves two large articulators (the hands) moving through space and contacting the body. In contrast, speech production requires small movements of the tongue and vocal tract with no observable spatial contrasts. Nonetheless, both language types exhibit a sublexical layer of structure with similar properties (e.g., segments, syllables, feature hierarchies). To investigate which neural areas are involved in modality-independent language production and which are tied specifically to the input–output mechanisms of signed and spoken language, we reanalyzed PET data collected from 29 deaf signers and 64 hearing speakers who participated in a series of separate studies. Participants were asked to overtly name concrete objects from distinct semantic categories in either American Sign Language (ASL) or in English. The baseline task required participants to judge the orientation of unknown faces (overtly responding ‘yes’/‘no’ for upright/inverted). A random effects analysis revealed that left mesial temporal cortex and the left inferior frontal gyrus were equally involved in both speech and sign production, suggesting a modality-independent role for these regions in lexical access. Within the left parietal lobe, two regions were more active for sign than for speech: the supramarginal gyrus (peak coordinates: −60, −35, +27) and the superior parietal lobule (peak coordinates: −26, −51, +54). Activation in these regions may be linked to modality-specific output parameters of sign language. Specifically, activation within left SMG may reflect aspects of phonological processing in ASL (e.g., selection of hand configuration and place of articulation features), whereas activation within SPL may reflect proprioceptive monitoring of motoric output.

O3-06-08: Pattern of amyloid plaque deposition with Pittsburgh compound-B (PIB) in mild cognitive impairment

quantified by distribution volume ratio (DVR). Results: Neocortical A deposition was present in 100% of AD subjects, 89% of DLB subjects, 43% of MCI subjects, 18% of elderly controls and no FTD subjects. PIB distribution was similar in AD and DLB, being greatest in medial frontal, precuneus, parietal and lateral temporal cortex, and caudate nuclei. Occipital, sensori-motor and mesial temporal cortex were less affected. Neocortical DVR measured 2.0 0.3 in AD, 1.6 0.3 in DLB, 1.5 0.4 in MCI, 1.2 0.2 in control and 1.1 0.1 in FTD subjects (p 0.01 for all differences). Five of the NC had cortical binding predominantly in frontal cortex with one progressing to MCI at 12-month follow-up. DVR correlated with MMSE and memory impairment across all subjects (r 0.7, p 0.0001) but not within groups (in AD group p 0.16), and with a shorter interval from onset of cognitive impairment to diagnosis in DLB (r 0.9, p 0.002). Conclusions: PIB PET will permit earlier diagnosis of AD and improve differential diagnosis of dementia. Longitudinal follow-up is required to determine the significance of the PIB binding in the normal elderly controls and MCI subjects. Our findings suggest that PIB PET will detect AD before demonstrable cognitive decline and therefore be a useful tool for early intervention trials.