Cerca de 50% dos pacientes portadores de transtorno afetivo bipolar (TAB) apresentam comorbidade com abuso ou dependência de álcool. A presença de alcoolismo nos pacientes com TAB está associada a manifestações clínicas mais graves e a uma pior resposta ao tratamento do transtorno de humor. Entretanto, as anormalidades neurobiológicas subjacentes à co-ocorrência de TAB e alcoolismo são desconhecidas. Neste estudo, nosso objetivo foi o de comparar o perfil neuroquímico do córtex pré-frontal dorsolateral esquerdo de pacientes portadores de TAB e diagnóstico prévio de alcoolismo ao de pacientes portadores de TAB não-alcoolistas e ao de indivíduos saudáveis, usando espectroscopia por ressonância magnética de hidrogênio. Para isso, obtivemos uma aquisição de espectroscopia de hidrogênio de voxel único e tempo de eco curto em campo magnético de 1,5 Tesla do córtex préfrontal dorsolateral esquerdo em 23 pacientes bipolares alcoolistas, 27 pacientes bipolares não-alcoolistas e 57 indivíduos saudáveis. Níveis absolutos de N-acetilaspartato (NAA), compostos de colina, creatina mais fosfocreatina, mio-inositol, glutamato mais glutamina (Glu+Gln), e glutamato foram determinados e comparados entre os três grupos. Pacientes bipolares alcoolistas apresentaram níveis menores de Glu+Gln (p = 0,06) e de glutamato (p = 0,03) do que pacientes bipolares nãoalcoolistas. Pacientes bipolares alcoolistas apresentaram níveis menores de NAA do que controles saudáveis (p = 0,06). Esses achados sugerem que anormalidades do sistema glutamatérgico, e, possivelmente, da integridade neuronal, estão presentes no córtex pré-frontal dorsolateral esquerdo de pacientes portadores de TAB em comorbidade com alcoolismo. Tais anormalidades podem caracterizar processos fisiopatológicos que seriam específicos da comorbidade entre TAB e alcoolismo. / About 50% of bipolar disorder (BD) patients present comorbidity with alcohol abuse or dependence. The presence of alcoholism in BD is associated with worse clínical manifestations and refractoriness to treatment of the mood disorder. Nevertheless, the neurochemical underpinnings that underlie the co-occurrence of bipolar disorder and alcoholism are unknown. In this study, we sought to compare the neurochemical profile of the left dorsolateral pre-frontal cortex of BD patients with a prior diagnosis of alcoholism to non-alcoholic BD patients and healthy controls (HC), using proton (1H) magnetic resonance spectroscopy. We obtained a short-TE, single-voxel 1H spectroscopy acquisition at 1.5 Tesla from the left dorsolateral pré-frontal córtex (DLFPC) of 23 alcoholic BD patients, 27 non-alcoholic BD patients and 57 HC. Absolute levels of N-acetyl-aspartate (NAA), choline-containing compounds, phosphocreatine plus creatine, myo-inositol, glutamato plus glutamina (Glu+Gln) and glutamato were determined and compared among the three groups. Alcoholic BD patients showed lower Glu+Gln (p = 0.06) and glutamate levels (p = 0.03) than non-alcoholic BD patients. Alcoholic BD patients tended to have lower NAA levels than HC (p = 0.06). These findings suggest that glutamatergic abnormalities, and possibly, neuronal integrity abnormalities, are present in the left DLPFC of BD patients with comorbid alcoholism. Such abnormalities may characterize pathophysiological processes that are specific for the comorbidity between BD and alcoholism.

<p>The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.</p>

The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.

Synchronized oscillations of ensembles of neurons in the brain underlie human cognition and behaviors. Neuronal network oscillations can be described by the physics of coupled dynamical systems. This dissertation examines the dynamic network activities in two distinct neurocognitive networks, the salience network (SN) and the ventral temporal cortex-dorsolateral prefrontal cortex (VTC-DLPFC) network, during perceptual decision-making (PDM). The key nodes of the SN include the right anterior insula (rAI), left anterior insula (lAI), and dorsal anterior cingulate cortex (dACC) in the brain. When and how a sensory signal enters and organizes within the SN before reaching the central executive network including the prefrontal cortex has been a mystery. Second, prior studies also report that perception of visual objects (face and house) involves a network of the VTC—the fusiform face area (FFA) and para-hippocampal place area (PPA)—and the DLPFC. How sensory information enters and organizes within the VTC-DLPFC network is not well understood, in milliseconds time-scale of human’s perception and decision-making. We used clear and noisy face/house image categorization tasks and scalp electroencephalography (EEG) recordings to study the dynamics of these networks. We demonstrated that beta (13–30 Hz) oscillation bound the SN, became most active around 100 ms after the stimulus onset, the rAI acted as a main outflow hub within the SN, and the SN activities were negatively correlated with the difficult tasks. We also uncovered that the VTC-DLPFC network activities were mediated by beta (13-30 Hz) and gamma (30-100 Hz) oscillations. Beta activities were enhanced in the time frame 125-250 ms after stimulus onset, the VTC acted as main outflow hub, and network activities were negatively correlated with the difficult tasks. In contrast, gamma activities were elevated in the time frame 0-125 ms, the DLPFC acted as a main outflow hub, and network activities—specifically the FFA-PPA pair—were positively correlated with the difficult tasks. These findings significantly enhance our understanding of how sensory information enters and organizes within the SN and the VTC-DLPFC network, respectively in PDM.

Des recherches, autant chez l’homme que chez l’animal, proposent qu’il existerait, au sein des réseaux cérébraux, une organisation anatomique parallèle de circuits qui coordonne l’activité des structures qui participent à la planification et à l’exécution d’une action. Dans cette foulée, un modèle émerge qui attribue au cortex préfrontal (CPF) latéral une spécificité anatomo-fonctionnelle basée sur les niveaux de traitement en mémoire de travail (MT). Il s’agit du modèle « niveaux de traitement-dépendant », qui accorde un rôle important au CPF latéral dans l’acquisition et la représentation de règles guidant nos comportements. Des études en neuroimagerie fonctionnelle, utilisant le Wisconsin Card Sorting Task (WCST) ont permis de corroborer ce modèle et de dissocier trois niveaux de traitement en MT non seulement au sein du CPF latéral mais encore aux structures sous- corticales, les ganglions de la base (GB). Ces études suggèrent que certains noyaux des GB seraient topographiquement organisés avec le CPF latéral et contriburaient, sous certaines conditions, à des processus cognitifs et moteurs semblables à leur homologue cortical. Le but de notre étude est d'explorer la généralisation de la contribution des GB et du CPF au modèle niveaux de traitement-dépendant afin de voir si ce dernier est indépendant de la nature des stimuli en mémoire de travail. À cet effet, nous avons modifié le WCST en l’appliquant à un autre domaine, celui du langage. Nous avons remplacé les pictogrammes par des mots et modifié les règles formes, couleurs, nombres, par des règles sémantiques et phonologiques. L’analyse des résultats a démontré que différentes parties des GB de concert avec différentes régions du CPF se différencient quant aux niveaux de traitement en MT et ce, indépendamment de la nature des stimuli. Une deuxième analyse a permis d’évaluer les patrons d’activations liés aux conditions sémantiques et phonologiques. Ces résultats ont mis en évidence que les réseaux préfrontaux semblent liés aux processus exécutifs nécessaires à la réalisation de la tâche, indépendamment de la condition tandis que les aires associatives se dissocient davantage et contiennent des réseaux propres à la sémantique et à la phonologie. / Researches in humans and animals have pointed out the possible existence of a parallel anatomic organization in the core of cerebral networks which could coordinate the activity of different brain regions involved in the planning and execution of an action. Within this framework, the emerging model ascribes an anatomic dissociation to the lateral prefrontal cortex (PFC) based on the level of complexity of the working memory (WM) treatment. This model, namely, the complexity-dependent model, gives an important role to the lateral PFC in the acquiring and representation of the rules guiding our behaviors. This model has been corroborated by functional neuroimaging studies using the Wisconsin Card Sorting Task (WCST). These studies allowed dissociating three levels of complexity of the WM treatment, not restricted to the lateral PFC but also including sub- cortical structures, the basal ganglia (BG), suggesting that some BG nuclei would be topographically organized with the lateral PFC and would contribute to the same cognitive and motor functions. The aim of our study was to investigate whether the BG and the PFC’S contribution to the complexity-dependent model generalizes to different types of stimuli or whether their functions are dependent on the nature of stimuli in WM. To do so, a language version of the WCST was developed to suit a different cognitive domain, i.e. language. The pictograms were replaced with words and rules concerning forms, colors and numbers were substituted with semantic and phonological rules. Data analysis showed that the BG along with the PFC have differential role at different levels of WM processing complexity. In a second analysis, the activation patterns linked to the semantic and phonological conditions were evaluated. Those results indicated that the prefrontal networks seem to be coupled with executive processes needed to perform each condition whereas the employment of different language rules (semantic and phonological) activates specific regions of the phonological and semantic network.

Central to human intelligence, visual categorization is a skill that is both remarkably fast and accurate. Although there have been numerous studies in primates regarding how information flows in inferiortemporal (ITC) and prefrontal (PFC) cortices during online discrimination of visual categories, there has been little comparable research on the human cortex. To bridge this gap, this thesis explores how visual categories emerge in prefrontal cortex and the ventral stream, which is the human homologue of ITC. In particular, cortical spatiotemporal plasticity in visual category learning was investigated using behavioral experiments, magnetoencephalographic (MEG) imaging, and statistical machine learning methods. From a theoretical perspective, scientists from work on non-human primates have posited that PFC plays a primary role in the encoding of visual categories. Much of the extant research in the cognitive neuroscience literature, however, emphasizes the role of the ventral stream. Despite their apparent incompatibility, no study has evaluated these theories in the human cortex by examining the roles of the ventral stream and PFC in online discrimination and acquisition of visual categories. To address this question, I conducted two learning experiments using visually-similar categories as stimuli and recorded cortical response using MEG—a neuroimaging technique that offers a millisecond temporal resolution. Across both experiments, categorical information was found to be available during the period of cortical activity. Moreover, late in the learning process, this information is supplied increasingly in the ventral stream but less so in prefrontal cortex. These findings extend previous theories by suggesting that the ventral stream is crucial to long-term encoding of visual categories when categorical perception is proficient, but that PFC jointly encodes visual categories early on during learning. From a methodological perspective, MEG is limited as a technique because it can lead to false discoveries in a large number of spatiotemporal regions of interest (ROIs) and, typically, can only coarsely reconstruct the spatial locations of cortical responses. To address the first problem, I developed an excursion algorithm that identified ROIs contiguous in time and space. I then used a permutation test to measure the global statistical significance of the ROIs. To address the second problem, I developed a method that incorporates domainspecific and experimental knowledge in the modeling process. Utilizing faces as a model category, I used a predefined “face” network to constrain the estimation of cortical activities by applying differential shrinkages to regions within and outside this network. I proposed and implemented a trial-partitioning approach which uses trials in the midst of learning for model estimation. Importantly, this renders localizing trials more precise in both the initial and final phases of learning. In summary, this thesis makes two significant contributions. First, it methodologically improves the way we can characterize the spatiotemporal properties of the human cortex using MEG. Second, it provides a combined theory of visual category learning by incorporating the large time scales that encompass the course of the learning.

In vivo intracranial microdialysis is a valuable technique yielding novel and useful insight into normal or pathological neurochemical processes in the brain by means of sampling of interstitial fluid of cells in a living animal. It's most important advantage is that it can continuously monitor time-related changes in the concentration of neurotransmitters and their metabolites, other neuromodulators, energy substrates, as well as exogenous drugs in the extracellular fluid of specific brain areas of interest. While the development and standardization of the intracranial microdialysis technique in our laboratory was the main aim of the current study, a pilot application study was also performed during which the effect of several locally administered pharmacological agents on brain glutamate levels in a genetic rat model of depression was investigated. Abnormal neuronal glutamate levels have been implicated in various psychiatric conditions including major depressive disorder. The Flinders Sensitive Line (FSL) is a genetic line of Sprague-Dawley rat that displays various behavioral and neurochemical traits akin to that observed in depression. The Flinders Resistant Line (FRL) rat is used as the normal control. The prefrontal cortex is an important brain area involved in the neuropathology of depression. Prefrontal cortical glutamate levels in a small number of FSL and FRL rats were therefore compared at baseline and following local administration of potassium chloride (100 mM), the latter in order to study changes in evoked glutamate release. Ketamine hydrochloride (9 mM) and fluoxetine (30 μM) respectively were also administered via reverse dialysis. Prior to initiating the microdialysis studies, an HPLC-fluorescence method was developed to analyze the levels of glutamate in the microdialysate. As part of the development and standardization of the microdialysis technique, a number of validation studies were performed. This included refining the stereotaxic surgery procedure, determining the most appropriate anesthesia protocol, and standardizing the microdialysis procedure with regard to perfusion fluid, flow rate, sample volume, duration of dialysis, and anatomical verification of probe location. The HPLC-fluorescence method for the analysis of glutamate was also developed and validated. This technique proved to be sensitive and specific for the determination of glutamate with a linearity of 0.991 in the concentration range of standards tested (0.1 – 10 μM) and an intra-assay repeatability (precision value) yielding relative standard deviations of less than 10.5%, Mean elution time was between 24 and 26 minutes for glutamate in the microdialysis sample and the limit of detection and quantification was both 0.1 μM. Results from the application study indicated that baseline values of glutamate in the prefrontal cortex did not differ between FRL and FSL rats during the 1 hour period of dialysis. However, potassium chloride-evoked glutamate release was greater in FSL vs. FRL rats, although this difference was not statistically significant. Local perfusion by reverse dialysis of ketamine hydrochloride produced statistically significant increases in glutamate concentrations at certain time points in FSL rats. Although glutamate levels were also increased in FRL rats in response to ketamine, it was not statistically different compared to baseline levels. Fluoxetine perfusion did not affect glutamate release in either of the two rat groups. In conclusion, we have successfully developed and established an intracranial in vivo microdialysis procedure in our laboratory, as well as standardized and validated a sensitive method to analyze glutamate in microdialysate samples. These techniques were then applied in a small number of FSL vs. FRL rats in order to confirm their application in a typical research scenario. Although the data were too limited to make any valid conclusions about glutamate concentrations in an animal model of depression or the effect of drugs on the release thereof, these novel techniques and analyses will be valuable in future studies. / Thesis (MSc (Pharmacology))--North-West University, Potchefstroom Campus, 2013.

In vivo intracranial microdialysis is a valuable technique yielding novel and useful insight into normal or pathological neurochemical processes in the brain by means of sampling of interstitial fluid of cells in a living animal. It's most important advantage is that it can continuously monitor time-related changes in the concentration of neurotransmitters and their metabolites, other neuromodulators, energy substrates, as well as exogenous drugs in the extracellular fluid of specific brain areas of interest. While the development and standardization of the intracranial microdialysis technique in our laboratory was the main aim of the current study, a pilot application study was also performed during which the effect of several locally administered pharmacological agents on brain glutamate levels in a genetic rat model of depression was investigated. Abnormal neuronal glutamate levels have been implicated in various psychiatric conditions including major depressive disorder. The Flinders Sensitive Line (FSL) is a genetic line of Sprague-Dawley rat that displays various behavioral and neurochemical traits akin to that observed in depression. The Flinders Resistant Line (FRL) rat is used as the normal control. The prefrontal cortex is an important brain area involved in the neuropathology of depression. Prefrontal cortical glutamate levels in a small number of FSL and FRL rats were therefore compared at baseline and following local administration of potassium chloride (100 mM), the latter in order to study changes in evoked glutamate release. Ketamine hydrochloride (9 mM) and fluoxetine (30 μM) respectively were also administered via reverse dialysis. Prior to initiating the microdialysis studies, an HPLC-fluorescence method was developed to analyze the levels of glutamate in the microdialysate. As part of the development and standardization of the microdialysis technique, a number of validation studies were performed. This included refining the stereotaxic surgery procedure, determining the most appropriate anesthesia protocol, and standardizing the microdialysis procedure with regard to perfusion fluid, flow rate, sample volume, duration of dialysis, and anatomical verification of probe location. The HPLC-fluorescence method for the analysis of glutamate was also developed and validated. This technique proved to be sensitive and specific for the determination of glutamate with a linearity of 0.991 in the concentration range of standards tested (0.1 – 10 μM) and an intra-assay repeatability (precision value) yielding relative standard deviations of less than 10.5%, Mean elution time was between 24 and 26 minutes for glutamate in the microdialysis sample and the limit of detection and quantification was both 0.1 μM. Results from the application study indicated that baseline values of glutamate in the prefrontal cortex did not differ between FRL and FSL rats during the 1 hour period of dialysis. However, potassium chloride-evoked glutamate release was greater in FSL vs. FRL rats, although this difference was not statistically significant. Local perfusion by reverse dialysis of ketamine hydrochloride produced statistically significant increases in glutamate concentrations at certain time points in FSL rats. Although glutamate levels were also increased in FRL rats in response to ketamine, it was not statistically different compared to baseline levels. Fluoxetine perfusion did not affect glutamate release in either of the two rat groups. In conclusion, we have successfully developed and established an intracranial in vivo microdialysis procedure in our laboratory, as well as standardized and validated a sensitive method to analyze glutamate in microdialysate samples. These techniques were then applied in a small number of FSL vs. FRL rats in order to confirm their application in a typical research scenario. Although the data were too limited to make any valid conclusions about glutamate concentrations in an animal model of depression or the effect of drugs on the release thereof, these novel techniques and analyses will be valuable in future studies. / Thesis (MSc (Pharmacology))--North-West University, Potchefstroom Campus, 2013.

The purpose of this thesis was to explore the potential of near-infrared spectroscopy (NIRS) as an access channel by establishing reliable signal detection to verify the existence of signal differences associated with changes in activity. This thesis focused on using NIRS to measure brain activity from the prefrontal cortex during an auditory Go-No-Go task. A singular spectrum analysis change-point detection algorithm was applied to identify transition points where the NIRS signal properties varied from previous data points in the signal, indicating a change in brain activity. With this algorithm, latency values for change-points detected ranged from 6.44 s to 9.34 s. The averaged positive predictive values over all runs were modest (from 49.41% to 67.73%), with the corresponding negative predictive values being generally higher (48.66% to 78.80%). However, positive and negative predictive values up to 97.22% and 95.14%, respectively, were achieved for individual runs. No hemispheric differences were found.

The purpose of this thesis was to explore the potential of near-infrared spectroscopy (NIRS) as an access channel by establishing reliable signal detection to verify the existence of signal differences associated with changes in activity. This thesis focused on using NIRS to measure brain activity from the prefrontal cortex during an auditory Go-No-Go task. A singular spectrum analysis change-point detection algorithm was applied to identify transition points where the NIRS signal properties varied from previous data points in the signal, indicating a change in brain activity. With this algorithm, latency values for change-points detected ranged from 6.44 s to 9.34 s. The averaged positive predictive values over all runs were modest (from 49.41% to 67.73%), with the corresponding negative predictive values being generally higher (48.66% to 78.80%). However, positive and negative predictive values up to 97.22% and 95.14%, respectively, were achieved for individual runs. No hemispheric differences were found.