Previous PET Research Articles

The Role of Pet Ownership and Attachment in Older Adults

AbstractAustralia is preparing for a population increase in persons aged over 65 years, which will likely result in increased mental health needs for this group. Sub-clinical levels of depression, anxiety and loneliness are common in older adults. Older adults are also more likely than any other age group to live alone. Research has suggested that older adults living on their own often report companion animals as providing important social support. Thirty-two community-dwelling older adults, between 60 and 75+ years of age, took part in this study examining attachment to pets in an older cohort. Previous or current pet ownership was a requirement for inclusion in the study in order to account for possible bias of nonpet owners on reporting pets as a positive influence on wellbeing. Results found support for the psychometric properties of a relatively new attachment scale designed for older adults. Results also indicated limited support for a relationship between pet attachment and quality of life in the study group. Implications for clinical work with older adults and areas for future research are discussed.

Functional Organization of Monkey Brain for Abstract Operation

When humans manipulate a control device under operational rules, with the goal of indirectly controlling a remote tool to achieve a desired outcome, they may rely on the power of internal representation to organize individual moves of the controller and tool into a set of sequences by mapping the motor space among hand, controller and tool. We recently used functional brain imaging (PET) to investigate activations in monkey brain associated with joystickcontrolled remote operation of a shovel to obtain food. Activated areas included the prefrontal cortex, posterior parietal cortex and cerebellum, regardless of the rules relating movements of the joystick to those of the shovel (Obayashi et al., 2004). If those areas are engaged in the mental manipulation of internal representation, then we should expect brain activity in the same regions during any similar remote operation, even with different controllers and/or operational rules. To address the above hypothesis in the current study, we used PET to measure regional cerebral blood flow (rCBF) of two monkeys during a task in which they were required to control a shovel remotely (to fetch a food pellet) by manipulating dual dials. Compared to unplanned movement of the dials, the active dual-dial operation was associated with robust activation of the prefrontal cortex, higher-order motor cortex, posterior parietal cortex and cerebellum, quite similar to that observed during remote operation with a joystick. The present study suggests that monkeys might be able to organize abstract sequential operations according to learned rules, and perhaps indeed to have insight into the nature of the causal relationships, implying the existence of a relatively sophisticated system of internal representation in the absence of language. The fact that the present results are consistent with our previous PET studies strengthens the view that the underlying mechanism for implicit manipulation of internal representations may involve a cerebro-cerebellar neural circuit including the frontal and parietal cortex.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

Occupancy of Striatal and Extrastriatal Dopamine D2 Receptors by Clozapine and Quetiapine

Clozapine and quetiapine have a low incidence of extrapyramidal side effects at clinically effective doses, which appears to be related to their significantly lower occupancy of striatal dopamine D2 receptors (DA D2r) compared to typical antipsychotic drugs (APDs). Animal studies have indicated that clozapine and quetiapine produce selective effects on cortical and limbic regions of the brain and in particular on dopaminergic neurotransmission in these regions. Previous PET and SPECT studies have reported conflicting results regarding whether clozapine produces preferential occupancy of cortical DA D2r. To examine whether clozapine and/or quetiapine produce preferential occupancy of DA D2r in cortex and limbic regions, we studied the occupancy of putamenal, ventral striatal, thalamic, amygdala, substantia nigra, and temporal cortical DA D2r using PET with [18F]fallypride in six schizophrenic subjects receiving clozapine monotherapy and in seven schizophrenic subjects receiving quetiapine monotherapy. Doses were chosen clinically to minimize psychopathology at tolerable levels of side effects such as drowsiness. All had minimal positive symptoms at the time of the study. Regional receptor occupancies were estimated using mean regional DA D2r levels calculated for 10 off-medication schizophrenic subjects. Both clozapine and quetiapine produced lower levels of putamenal DA D2r occupancy than those reported for typical APDs, 47.8 and 33.5%, respectively. Clozapine produced preferential occupancy of temporal cortical vs putamenal DA D2r, 59.8% (p=0.05, corrected for multiple comparisons), and significantly lower levels of occupancy in the substantia nigra, 18.4% (p=0.0015, corrected for multiple comparisons). Quetiapine also produced preferential occupancy of temporal cortical DA D2r, 46.9% (p=0.03, corrected for multiple comparisons), but did not spare occupancy of substantia nigra DA D2r. The therapeutic effects of clozapine and quetiapine appear to be achieved at less than the 65% threshold for occupancy seen with typical APDs, consistent with the involvement of non-DA D2r mechanisms in at least partially mediating the therapeutic effects of these drugs. Preferential occupancy of cortical DA D2r, sparing occupancy of substantia nigra receptors, and non-DA D2r-mediated actions may contribute to the antipsychotic actions of these and other atypical APDs.

Continuous ASL perfusion fMRI investigation of higher cognition: Quantification of tonic CBF changes during sustained attention and working memory tasks

Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6–12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7–11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow.

Prefrontal cortical response to verbal-spatial two-dimensional task measured by functional NIRS

Previous PET and functional MRI studies of working memory (WM) have suggested that prefrontal cortex (PFC) helps WM processes. However, there is controversy on the roles that different PFC regions play in information processes of different materials. Here, we reported a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by a two-dimensional (verbal versus spatial) n-back task. During the task being performed, concentration changes of oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in subjects' prefrontal cortex, which being correlated with cerebral activation, were examined by a 24-channel functional NIRS imager. The behavioral performances (accuracy and response time) were recorded simultaneously. Results revealed that as memory load increased, subjects showed poorer behavioral performance as well as monotonously increasing magnitudes of the PFC activations. In addition, we found that when the subject performed the task as verbal material, the left ventrolateral PFC (VLPFC) and the bilateral dorsolateral PFC (DLPFC) were significantly activated, and when the subject performed the task as spatial material, the right VLPFC and the bilateral DLPFC were significantly activated. This result not only further substantiates previous view that cerebral information processing is lateralized to the left for verbal material and to the right for spatial material, not only provides an evidence that some collaboration mechanisms likely exist between bilateral hemispheres.

Information processing in severe disorders of consciousness: Vegetative state and minimally conscious state

Objective To study the presence of electrophysiological indicators of remaining cortical functions in patients with persistent vegetative state (PVS) and minimally conscious state (MCS). Previous electrophysiological and PET data indicated that some PVS patients have partially intact cortical processing functions. However, it remains unclear whether the reported patients were representative for PVS population or just some exceptional cases. Methods: Event-related brain responses to stimuli of different complexity levels, recorded in 98 patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four main indicators of cortical functions were: (i) N1–P2 complex as an index of simple, undifferentiated cortical processing; (ii) mismatch negativity as an index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave as an index of deep cortical analysis of physical stimuli, and (iv) brain responses to semantic stimuli. Results Cortical responses were found in all PVS patients with a background EEG activity >4 Hz. All responses investigated, including those to semantic stimuli that indicated comprehension of meaning, occurred significantly above chance, though less frequently than in patients with severe brain injuries who were conscious. Conclusions Cortical responses were lacking in most patients with severe EEG slowing (<4 Hz). Follow-up data revealed that the presence of a mismatch negativity, a short disease duration, and the traumatic etiology were related to a better outcome. Significance The data show that in a subpopulation of PVS patients with preserved thalamocortical feedback connections, remaining cortical information processing is a consistent finding and may even involve semantic levels of processing.

Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study

Voxel-based morphometry was used to assess the consistency among functional imaging and brain morphometry data in developmental dyslexia. Subjects, from three different cultural contexts (UK, France and Italy), were the same as those described in a previous PET activation paper, which revealed a common pattern of reduced activation during reading tasks in the left temporal and occipital lobes. We provide evidence that altered activation observed within the reading system is associated with altered density of grey and white matter of specific brain regions, such as the left middle and inferior temporal gyri and the left arcuate fasciculus. This supports the view that dyslexia is associated with both local grey matter dysfunction and with altered connectivity among phonological/reading areas. The differences were replicable across samples confirming that the neurological disorder underlying dyslexia is the same across the cultures investigated in the study.

Paget disease of bone

Purpose of review Paget disease of bone is a prevalent disorder of bone metabolism, described as the second most common bone disease to affect an aging population in the United States after osteoporosis. Although recent studies suggest a decrease in mortality rates in Great Britain between 1951 and 1970 and a decline in prevalence and severity from the 1970s to 1990s, Paget disease continues to affect an important segment of the population with progressive deformity of bone, pain, and impaired quality of life. This article reviews the theories of pathogenesis and examines some of the relevant epidemiologic data. The pivotal role of the osteoclast in mediating this disease is discussed, followed by a brief summary of the pathology, clinical features, the diagnostic approach to patients, and therapeutic experience with increasingly potent bisphosphonates. Recent findings The cause of the disorder remains elusive but may be a viral infection affecting osteoclasts in a genetically predisposed person. Recent advances in genetic research suggest that lesions affecting the signaling pathways of receptor for activation of nuclear factor-Kb (RANK) and its receptor are critical in the expression of familial and some sporadic Paget disease, but the environmental determinants and triggers remain controversial. Previous viral infections, pet ownership, and geographical differences are some of the features identified by epidemiologic studies that may play a causative role. Much progress is being made in characterizing pagetic osteoclasts further in terms of their altered structure and function and the likely role of cytokines and of the marrow microenvironment. Studies with nitrogen-containing bisphosphonates have demonstrated their efficacy in inducing clinical and skeletal improvement and biochemical remissions in most patients with Paget disease. Summary Although the cause of Paget disease remains enigmatic, progress continues in understanding of the pivotal role of the osteoclast in Paget disease, with an increasing number of factors now implicated in abnormal osteoclast structure and function. There have been major therapeutic advances with the availability of increasingly potent bisphosphonates with real potential for prevention of progressive changes and for long-lasting remissions in most patients with Paget disease.

Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.

Investigation of Blood-Flow Changes During Cognitive Task Activation using CASL

Functional perfusion imaging (p-fMRI) was applied for the first time to a cognitive paradigm that produces activations in a number of brain regions. An adapted single-trial version of the color-word Stroop interference task was used as a paradigm. This experiment is known to produce robust activations in the lateral prefrontal, the fronto-median, and parietal cortices. Perfusion contrast was created by continuous arterial spin labeling (CASL) of the blood in the left common carotid artery, and was applied for all repetitions of the functional run in a quasi-continuous fashion, i.e., it was interrupted only during image acquisition. For imaging, a spin-echo (SE) echo planar imaging (EPI) sequence with a 64×36 acquisition matrix was used. A short echo time of TE=13 ms was employed in order to suppress blood oxygen level dependent (BOLD) signals. For comparison, BOLD contrast was detected using conventional gradient-echo (GE) or SE-EPI. Positive activations in BOLD imaging appear in p-fMRI as negative signal changes corresponding to an enhanced transport of inverted water spins into the region of interest (i.e., increased cerebral blood flow [CBF]). Negative BOLD responses (areas of deactivation) appear as positive signal changes in p-fMRI indicating areas with decreased CBF. p-fMRI was capable of reproducing most of the GE-BOLD-fMRI activations and deactivations as signal changes of opposite sign. The localization of the local maxima of p-fMRI agreed reasonably with SE-BOLD-fMRI and GE-BOLD-fMRI. Significant shifts between the covered areas of each contrast were also detected. In certain areas, p-fMRI yielded a low sensitivity compared to BOLD-fMRI. The quantification of CBF changes during cognitive task activation is demonstrated for several well-separated cortical areas. The observation of a decreased CBF during the Stroop task in the parietomedian cortex confirms previous PET results which showed decreases of CBF in well-separated cortical regions related to a decrease in neuronal activity.

Imaging a cognitive model of apraxia: the neural substrate of gesture-specific cognitive processes.

The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using H2 15O PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis of the visual analysis of gestures. First, we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture imitation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;33:63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to-be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature.

Use of fluorodeoxyglucose positron emission tomography scans in patients with advanced germ cell tumour following chemotherapy: single-centre experience with long-term follow up.

Fluorodeoxyglucose positron emission tomography (FDG-PET) may detect residual or recurrent malignancy in patients with germ cell tumours (GCT) following chemotherapy. The objective of the present study was to evaluate the use of FDG-PET in the setting of advanced GCT, and to determine the influence of FDG-PET on subsequent patient management. A computerized search of the patient database of the Department of Medical Oncology, Guy's Hospital, London, United Kingdom, and a manual search of medical records, were conducted. All male patients with metastatic or extragonadal GCT treated with chemotherapy between July 1996 and June 1999 inclusive were identified. Data from patients that had a PET scan following chemotherapy were analysed. Reported PET scan findings were compared with subsequent clinical management and patient outcome. A total of 30 patients with metastatic testicular GCT and three patients with extragonadal GCT were treated with chemotherapy. Of these, 15 patients (12 testicular; three extragonadal; 10 non-seminoma; and five seminoma) were investigated following chemo-therapy with at least one FDG-PET scan. Seven patients had two or more PET scans, and a total of 26 FDG-PET scans was performed. The most frequent indication for PET scan was evaluation of a residual mass (11 patients). Three patients had an FDG-PET to evaluate thymic prominence. Minimum follow up from first PET scan was 18 months. Three of 26 PET scans had false positive findings. Four PET scans yielded findings of equivocal significance with repeat PET scan recommended. Relapse of disease occurred in three patients; two of whom had normal previous PET scans and one had a previous equivocal result. PET had an impact on patient management in only one case where it 'prompted' surgical excision of a residual mass. Normal PET scans provided reassurance in patients with residual small masses but did not alter their subsequent -management. A residual mass was the most common indication for PET. For the majority of patients PET did not have a discernible influence on clinical management. Oncologists should exercise caution in their interpretation of PET scan findings and guidelines for the appropriate use of PET in testicular cancer management need to be developed. Prospective trials are required to define the clinical role of PET in this setting.

Dual representation of pain in the operculo-insular cortex in humans.

We report the response properties of the suprasylvian opercular and insular cortices to a painful stimulation delivered by a CO(2) laser recorded by depth intracerebral electrodes in epileptic patients. We defined two cortical areas of activation in the operculo-insular cortex in response to a painful laser stimulation: a suprasylvian opercular area, where we recorded responses peaking 140-170 ms after a painful stimulation (N140-P170), and a deeper insular area, where responses with a similar pattern peaked 180-230 ms after the stimulus (N180-P230). The average delay of 50 ms measured between the opercular and insular responses may reflect either sequential activation of the suprasylvian cortex then of the insula via corticocortical connections, or direct activation of the insula by inputs conveyed via thalamocortical projections through distinct fibres with different conduction times. We also recorded similar insular and opercular responses in the hemisphere ipsilateral to the stimulation, peaking 15 ms later than contralateral responses; this delay is compatible with transcallosal input transmission between these cortices. The mean stereotactic coordinates of the suprasylvian opercular N140-P170 and insular N180-P230 responses were found to be very similar to those of the maximal blood-flow responses to pain reported by previous PET and functional MRI studies in these cortical areas. We were able to distinguish the suprasylvian opercular and insular cortices in terms of response latencies evoked by a painful stimulus and in terms of stereotactic coordinates of the sources of these responses. The sequential timing of activation of the suprasylvian and insular cortices shown in this study thus complements in the time domain the spatial information provided by neuroimaging studies of the cortical processing of pain. It strongly suggests that these cortical areas are those responding with the shortest latency to peripheral pain inputs in the human brain.

Imaging of the 5-HT 2A system: age-, gender-, and Alzheimer’s disease-related findings

Serotonin (5-HT) and more specifically the 5-HT 2A receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimer’s disease (AD). The objective was to assess the 5-HT 2A binding potential (BP) in healthy volunteers and AD with SPECT and 123 I -5-I-R91150, a selective radio-iodinated 5-HT 2A receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT 2A receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD.

Pets, parental atopy, and asthma in adults

Background: Studies of exposure to pets and the risk of asthma have provided conflicting results. Objective: We conducted a population-based incident case-control study to assess the relationship of current and previous pet keeping with the risk of adult-onset asthma. We also investigated whether genetic propensity as a result of parental atopy modifies these relations. Methods: From the source population of 441,000 inhabitants of a geographically defined area in South Finland, we systematically recruited, during a 2.5-year period, all new cases of asthma in 21- to 63-year-old adults and randomly selected control subjects. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and a control series of 932 control subjects. Information on current and past exposure to hairy pets was collected by using a self-administered questionnaire. Results: In logistic regression analysis the risk of asthma was lower among subjects with pets during the past 12 months (adjusted odds ratio [OR], 0.74; 95% confidence interval [CI], 0.57-0.96) but higher among subjects with pets more than 12 months previously (adjusted OR, 1.39; 95% CI, 1.05-1.84). Parental atopy increased the risk of asthma (OR, 1.88; 95% CI, 1.47-2.41), but there was no interaction between parental atopy and pet exposure. Conclusions: The present results are consistent with the hypothesis that both keeping furry pets and parental atopy increase the risk of asthma development in adulthood. Parental atopy does not modify the effects of pet exposure. The negative association between current pets and the risk of asthma is consistent with selective avoidance of these pets by symptomatic individuals. (J Allergy Clin Immunol 2002;109:784-8.)

FMRI in patients implanted with a vagal nerve stimulator

Objective: To demonstrate the feasibility and safety of using functional magnetic resonance imaging (fMRI) to determine the blood oxygen level dependent changes (BOLD) in patients undergoing vagal nerve stimulation (VNS) for the treatment of epilepsy.Methods: Four patients with an implanted vagus nerve stimulator had fMRI images acquired during several cycles of intermittent VNS. Blood oxygen level dependent changes were detected. These regions were then superimposed upon the patients’ structural MR images.Results: Patients undergoing VNS tolerated fMRI without difficulty. No complications with the implanted stimulators were encountered. Areas of activation were noted in several cortical regions, including frontal, temporal, parietal, and occipital cortices.Conclusion: Our study in four patients shows fMRI can be performed safely in patients with an implanted vagal nerve stimulator. The successful use of fMRI during VNS offers potential advantages over PET imaging by allowing rapid image acquisition and the ability to repeatedly study patients over time. Our preliminary results differ from previous PET or SPECT studies in failing to detect changes in subcortical areas. This finding could be due to the smaller n in this study compared with the other studies.

Multiple-dipole analysis of visual event-related potentials during oddball paradigms

Visual event-related potentials (ERPs) during oddball paradigms with button pressing, silent counting and movement imagery tasks were recorded in right-handed subjects from 32 scalp electrodes. By incorporating the knowledge deduced from the task relevance of the P300 into equivalent current dipole source localization (ECDL), stable multiple ECD solutions with goodness-of-fit (GOF) of more than 90% and confidence limits (CLs) of less than 1 mm were estimated for all the three target P300s. The obtained frontal dipoles were discussed in terms of visual working memory, sustained attention and higher motor control in reference to the previous PET, fMRI and MEG studies. The distributed multiple ECDs may suggest that P300 should be interpreted as being the embodiment of the cortico-limbic-thalamic network accomplishing various cognitive functions.

Evidence for asymmetric frontal-lobe involvement in episodic memory from functional magnetic resonance imaging and patients with unilateral frontal-lobe excisions

Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.

Mapping Transient, Randomly Occurring Neuropsychological Events Using Independent Component Analysis

The feasibility of mapping transient, randomly occurring neuropsychological events using independent component analysis (ICA) was evaluated in an auditory sentence-monitoring fMRI experiment, in which prerecorded short sentences of random content were presented in varying temporal patterns. The efficacy of ICA on fMRI data with such temporal characteristics was assessed by a series of simulation studies, as well as by human activation studies. The effects of contrast-to-noise ratio level, spatially varied hemodynamic response within a brain region, time lags of the responses among brain regions, and different simulated activation locations on the ICA were investigated in the simulations. Component maps obtained from the auditory sentence-monitoring experiments in each subject using ICA showed distinct activation in bilateral auditory and language cortices, as well as in superior sensorimotor cortices, consistent with previous PET studies. The associated time courses in the activated brain regions matched well to the timing of the sentence presentation, as evidenced by the recorded button-press response signals. Methods for ICA component ordering that may rank highly the components of primary interest in such experiments were developed. The simulation results characterized the performance of ICA under various conditions and may provide useful information for experimental design and data interpretation.