A tutorial review of electrical neuroimaging from group-average to single-trial event-related potentials.

This tutorial review details some of the recent advances in signal analyses applied to event-related potential (ERP) data. These "electrical neuroimaging" analyses provide reference-independent measurements of response strength and response topography that circumvent statistical and interpretational caveats of canonical ERP analysis methods while also taking advantage of the greater information provided by high-density electrode montages. Electrical neuroimaging can be applied across scales ranging from group-averaged ERPs to single-subject and single-trial datasets. We illustrate these methods with a tutorial dataset and place particular emphasis on their suitability for studies of clinical and/or developmental populations.

In-vivo brain neuroimaging provides a gateway for integrating biological and clinical biomarkers of Alzheimer's disease.

PURPOSE OF REVIEW: Only 5% of the Alzheimer's cases are explained by genetic mutations, whereas the remaining 95% are sporadic. The pathophysiological mechanisms underlying sporadic Alzheimer's disease are not well understood, suggesting a complex multifactorial cause. This review summarizes the recent findings on research aiming to show how biomarkers can be used for revealing the underlying mechanisms of preclinical stage Alzheimer's disease and help in their diagnosis. RECENT FINDINGS: The undisputed successful publicly accessible repositories provide longitudinal brain images, clinical, genetic and proteomic information of Alzheimer's disease. By combining with increasingly sophisticated data analysis methods, it is a great opportunity for searching new biomarkers. Innovative studies validated theoretical models of disease progression demonstrating the sequential ordering of well-established biomarkers. Novel observations shed light on the interaction between biomarkers to confirm that disease progression is related to multiple pathological factors. A typical example is the tau-associated neuronal toxicity that can be additionally potentiated by amyloid β peptides. To increase further the complexity, studies report specific impact of common genetic variants that can be traced from childhood through middle age up to the symptomatic onset of Alzheimer's disease. SUMMARY: The discovery of efficient therapies to prevent the disease or modify the progression of disease requires a more thorough understanding of the underlying biological processes. Neuroimaging, genetic and proteomic biomarkers for Alzheimer's disease are critically discussed and proposed to be included in clinical descriptions and diagnostic guidelines.

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

Quantitative functional neuroimaging of cerebral physiology in healthy aging

Les études d’imagerie par résonance magnétique fonctionnelle (IRMf) ont pour prémisse générale l’idée que le signal BOLD peut être utilisé comme un succédané direct de l’activation neurale. Les études portant sur le vieillissement cognitif souvent comparent directement l’amplitude et l’étendue du signal BOLD entre des groupes de personnes jeunes et âgés. Ces études comportent donc un a priori additionnel selon lequel la relation entre l’activité neurale et la réponse hémodynamique à laquelle cette activité donne lieu restent inchangée par le vieillissement. Cependant, le signal BOLD provient d’une combinaison ambiguë de changements de métabolisme oxydatif, de flux et de volume sanguin. De plus, certaines études ont démontré que plusieurs des facteurs influençant les propriétés du signal BOLD subissent des changements lors du vieillissement. L’acquisition d’information physiologiquement spécifique comme le flux sanguin cérébral et le métabolisme oxydatif permettrait de mieux comprendre les changements qui sous-tendent le contraste BOLD, ainsi que les altérations physiologiques et cognitives propres au vieillissement. Le travail présenté ici démontre l’application de nouvelles techniques permettant de mesurer le métabolisme oxydatif au repos, ainsi que pendant l’exécution d’une tâche. Ces techniques représentent des extensions de méthodes d’IRMf calibrée existantes. La première méthode présentée est une généralisation des modèles existants pour l’estimation du métabolisme oxydatif évoqué par une tâche, permettant de prendre en compte tant des changements arbitraires en flux sanguin que des changements en concentrations sanguine d’O2. Des améliorations en terme de robustesse et de précisions sont démontrées dans la matière grise et le cortex visuel lorsque cette méthode est combinée à une manipulation respiratoire incluant une composante d’hypercapnie et d’hyperoxie. Le seconde technique présentée ici est une extension de la première et utilise une combinaison de manipulations respiratoires incluant l’hypercapnie, l’hyperoxie et l’administration simultanée des deux afin d’obtenir des valeurs expérimentales de la fraction d’extraction d’oxygène et du métabolisme oxydatif au repos. Dans la deuxième partie de cette thèse, les changements vasculaires et métaboliques liés à l’âge sont explorés dans un groupe de jeunes et aînés, grâce au cadre conceptuel de l’IRMf calibrée, combiné à une manipulation respiratoire d’hypercapnie et une tâche modifiée de Stroop. Des changements de flux sanguin au repos, de réactivité vasculaire au CO2 et de paramètre de calibration M ont été identifiés chez les aînés. Les biais affectant les mesures de signal BOLD obtenues chez les participants âgés découlant de ces changements physiologiques sont de plus discutés. Finalement, la relation entre ces changements cérébraux et la performance dans la tâche de Stroop, la santé vasculaire centrale et la condition cardiovasculaire est explorée. Les résultats présentés ici sont en accord avec l’hypothèse selon laquelle une meilleure condition cardiovasculaire est associée à une meilleure fonction vasculaire centrale, contribuant ainsi à l’amélioration de la santé vasculaire cérébrale et cognitive.

What neuroimaging and perceptions of self-other similarity can tell us about the mechanism underlying mentalizing

Carruthers' "mindreading is prior" model postulates one unitary mindreading mechanism working identically for self and other. While we agree about shared mindreading mechanisms, there is also evidence from neuroimaging and mentalizing about dissimilar others that suggest factors that differentially affect self-versus-other mentalizing. Such dissociations suggest greater complexity than the mindreading is prior model allows.

From dichotic listening to the irrelevant sound effect: a behavioural and neuroimaging analysis of the processing of unattended speech

The assumption that ignoring irrelevant sound in a serial recall situation is identical to ignoring a non-target channel in dichotic listening is challenged. Dichotic listening is open to moderating effects of working memory capacity (Conway et al., 2001) whereas irrelevant sound effects (ISE) are not (Beaman, 2004). A right ear processing bias is apparent in dichotic listening, whereas the bias is to the left ear in the ISE (Hadlington et al., 2004). Positron emission tomography (PET) imaging data (Scott et al., 2004, submitted) show bilateral activation of the superior temporal gyrus (STG) in the presence of intelligible, but ignored, background speech and right hemisphere activation of the STG in the presence of unintelligible background speech. It is suggested that the right STG may be involved in the ISE and a particularly strong left ear effect might occur because of the contralateral connections in audition. It is further suggested that left STG activity is associated with dichotic listening effects and may be influenced by working memory span capacity. The relationship of this functional and neuroanatomical model to known neural correlates of working memory is considered.

Combined neurostimulation and neuroimaging in cognitive neuroscience: past, present, and future

Modern neurostimulation approaches in humans provide controlled inputs into the operations of cortical regions, with highly specific behavioral consequences. This enables causal structure–function inferences, and in combination with neuroimaging, has provided novel insights into the basic mechanisms of action of neurostimulation on dis- tributed networks. For example,more recent work has established the capacity of transcranialmagnetic stimulation (TMS) to probe causal interregional influences, and their interaction with cognitive state changes. Combinations of neurostimulation and neuroimaging now face the challenge of integrating the known physiological effects of neu- rostimulationwith theoretical and biologicalmodels of cognition, for example,when theoretical stalemates between opposing cognitive theories need to be resolved. This will be driven by novel developments, including biologically informedcomputational network analyses for predicting the impactofneurostimulationonbrainnetworks, as well as novel neuroimaging and neurostimulation techniques. Such future developments may offer an expanded set of tools withwhich to investigate structure–function relationships, and to formulate and reconceptualize testable hypotheses about complex neural network interactions and their causal roles in cognition

Does neural input or processing play a greater role in the magnitude of neuroimaging signals?

An important constraint on how hemodynamic neuroimaging signals such as fMRI can be interpreted in terms of the underlying evoked activity is an understanding of neurovascular coupling mechanisms that actually generate hemodynamic responses. The predominant view at present is that the hemodynamic response is most correlated with synaptic input and subsequent neural processing rather than spiking output. It is still not clear whether input or processing is more important in the generation of hemodynamics responses. In order to investigate this we measured the hemodynamic and neural responses to electrical whisker pad stimuli in rat whisker barrel somatosensory cortex both before and after the local cortical injections of the GABAA agonist muscimol. Muscimol would not be expected to affect the thalamocortical input into the cortex but would inhibit subsequent intra-cortical processing. Pre-muscimol infusion whisker stimuli elicited the expected neural and accompanying hemodynamic responses to that reported previously. Following infusion of muscimol, although the temporal profile of neural responses to each pulse of the stimulus train was similar, the average response was reduced in magnitude by ∼79% compared to that elicited pre-infusion. The whisker-evoked hemodynamic responses were reduced by a commensurate magnitude suggesting that, although the neurovascular coupling relationships were similar for synaptic input as well as for cortical processing, the magnitude of the overall response is dominated by processing rather than from that produced from the thalamocortical input alone.

Differentiating core and co-opted mechanisms in calculation: The neuroimaging of calculation in aphasia

The role of language in exact calculation is the subject of debate. Some behavioral and functional neuroimaging investigations of healthy participants suggest that calculation requires language resources. However, there are also reports of individuals with severe aphasic language impairment who retain calculation ability. One possibility in resolving these discordant findings is that the neural basis of calculation has undergone significant reorganization in aphasic calculators. Using fMRI, we examined brain activations associated with exact addition and subtraction in two patients with severe agrammatic aphasia and retained calculation ability. Behavior and brain activations during two-digit addition and subtraction were compared to those of a group of 11 healthy, age-matched controls. Behavioral results confirmed that both patients retained calculation ability. Imaging findings revealed individual differences in processing, but also a similar activation pattern across patients and controls in bilateral parietal cortices. Patients differed from controls in small areas of increased activation in peri-lesional regions, a shift from left fronto-temporal activation to the contralateral region, and increased activations in bilateral superior parietal regions. Our results suggest that bilateral parietal cortex represents the core of the calculation network and, while healthy controls may recruit language resources to support calculation, these mechanisms are not mandatory in adult cognition.

Are power calculations useful? A multicentre neuroimaging study

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources.