In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.

Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.

The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan.

Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.

Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients.

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory > or = 19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.

Interactions of prefrontal cortex in relation to awareness in sensory learning.

In an associative learning paradigm, human subjects could be divided based on whether they were aware that one tone predicted a visual event and another did not. Only aware subjects acquired a differential behavioral response to the tones. Regional cerebral blood flow in left prefrontal cortex showed learning-related changes only in aware subjects. Left prefrontal cortex also showed changes in functional connectivity with contralateral prefrontal cortex, sensory association cortices, and cerebellum. Several of the interacting areas correlated with aware subjects' behavior. These results suggest cerebral processes underlying awareness are mediated through interactions of large-scale neurocognitive systems.

A SPECT study of sleep disturbance and Alzheimer's disease.

BACKGROUND/AIMS: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer's disease (AD). METHODS: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. (99m)Tc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. RESULTS: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). CONCLUSIONS: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.

A quantitative evaluation of human coordination interfaces for computer assisted surgery.

Computer assisted surgery (CAS) for tumor resection can assist the surgeon in locating the tumor margin accurately via some form of guidance method. A wide array of guidance methods can be considered, including model-based visual representations, symbolic graphical interfaces, and those based on other sensory cues such as sound. Given the variety of these guidance methods, it becomes increasingly important to test and analyze guidance methods for CAS in a quantitative and context-dependent manner to determine which is most suitable for a given surgical task. In this paper, we present a novel experimental methodology and analysis framework to test candidate guidance methods for CAS. Different viewpoints and stereographic, symbolic and auditory cues were tested in isolation or in combination in a set of virtual surgery experiments. A total of 28 participants were asked to circumscribe a virtual tumor with a magnetically tracked scalpel while measuring the surgical trajectory. This allowed measurement of surgical accuracy, speed, and the frequency with which the tumor margin was intersected, and enabled a quantitative comparison of guidance approaches. This study demonstrated that adding sound to pictorial guidance methods consistently improved accuracy, speed and margin intersection of the virtual surgery. However, the use of stereovision showed less benefit than expected. While guidance based on a combination of symbolic and pictorial cues enhanced accuracy, we found that speed could be substantially impaired. These studies demonstrate that optimal guidance combinations exist which would not be apparent by studying individual guidance methods in isolation. Our findings suggest that care is needed when using expensive and sometimes cumbersome virtual visualization technologies for CAS, and that simpler, non-stereo presentation may be sufficient for specific surgical tasks.

A reliable MR measurement of medial temporal lobe width from the Sunnybrook Dementia Study.

We studied the hippocampal angle and spatial relationships of medial temporal lobe (MTL) structures, using midbrain colliculi and inter-collicular sulcus (ICS) as landmarks, and measured MTL width on axial 3D-T1-weighted MRI at ICS level in 41 normal, aged participants. Mean hippocampal angle was 29 degrees (range 17-42 degrees ) caudal to the anterior-posterior commissure (AC-PC) line. The slice at the ICS, parallel to the long axis of the hippocampus, best revealed a longitudinal view of hippocampus and parahippocampal gyrus in 76% of participants, compared to only 7% when slices were 20 degrees caudal to orbitomeatal line (OML), an accepted technique used to examine MTL width in previous CT studies. The MTL width measured midway and at its thinnest between the anterior-posterior borders of the midbrain was highly reproducible (intraclass correlation coefficients >0.98) using these new methods. These simple decision rules, individualized orientation along the hippocampus and using a standardized landmark like the ICS, make these measures more comparable across subjects, and hence more useful in detecting and monitoring MTL atrophy in dementia.

Three brain SPECT region-of-interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras.

UNLABELLED: The purpose of this study was to generate anatomically guided region-of-interest (ROI) brain SPECT templates based on scans of elderly healthy volunteers. We describe normal tracer uptake and hemispheric asymmetries for each of 3 camera systems and compare these characteristics among systems. METHODS: 99mTc-hexamethyl propyleneamine oxime SPECT scans were acquired from 28 elderly healthy volunteers (mean age [+/-SD], 70.3 +/- 6.5 y) on a single-head rotating gamma camera (n = 15) or on dual- (n = 18) or triple-head (n = 13) cameras. The average number of counts in each ROI was calculated and referenced to counts in a cerebellar ROI, providing semiquantitative regional cerebral blood flow (rCBF) ratios. For the templates and ROI map, base images of a healthy volunteer were obtained with each camera. Data from individuals scanned with 2 cameras on the same day (n = 15) were used to evaluate rCBF differences across cameras. For each camera, averaged SPECT templates were made using automated image registration. The base volunteer's T1-weighted MR image was converted to stereotactic space with dimensions similar to those of the SPECT templates, and 79 bilateral ROIs were defined. To obtain ROI rCBF ratios, we aligned individual images to their appropriate template and then to this modified MR image. RESULTS: The ROI coefficients of variation indicated that the fit of the ROIs was acceptable (0.07-0.35). Mean rCBF ratios ranged from 0.57 to 1.0, 0.67 to 1.01, and 0.63 to 1.00 for single-, dual-, and triple-head cameras, respectively. The cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus showed consistent hemispheric asymmetry (right side greater than left side in 83%-100% of individuals). Mean rCBF ratios did not differ between dual- and triple-head cameras, whereas the ratios for single- and dual-head cameras differed significantly (39 ROIs differed), even after smoothing and filtering the dual-head images to the level of the single-head images. CONCLUSION: The use of SPECT templates based on elderly healthy volunteers is an important feature of this technique because most available templates have used young individuals. Another important feature is the use of MR image-based ROIs. These procedures are versatile because they use more than 1 camera. They can easily be implemented in clinical and research settings to detect camera-specific, abnormal deviations in rCBF ROI ratios and asymmetry magnitudes in diseases associated with aging, such as stroke and dementia.

Sparing of patterned alternation but not partial reinforcement effect after infant and adult hippocampal lesions in the rat.

The effect of hippocampal lesions was assessed in patterned (single) alternation (PA) and the partial reinforcement extinction effect (PREE), the two reward-schedule effects that appear earliest in ontogeny. Three groups of rat pups, with appropriate controls, were tested for each effect: lesion as infant/test as infant, lesion as infant/test as adult, and lesion as adult/test as adult. Hippocampal lesions had no effect on PA in any of the three conditions except for a suggestion that the effect was mildly attenuated in the animals given lesions as infants and tested as adults: The pups were able to discriminate rewarded from nonrewarded trials and to inhibit responding on nonrewarded trials. On the other hand, the PREE was eliminated under all conditions of testing, in each case because of an increase in persistence following continuously reinforced acquisition. The results are discussed in terms of the functional maturation of the hippocampus and a possible dissociation of mechanisms that mediate response suppression in PA and in the PREE in infant rats.

Sparing of patterned alternation but not partial reinforcement extinction effect after prenatal chronic exposure to ethanol in infant rats.

The effects of in utero administration of ethanol on single patterned alternation (PA) and the partial reinforcement extinction effect (PREE) were studied in 15-day-old rat pups. This fetal-alcohol treatment had no effect on PA but eliminated the PREE by reducing persistence in extinction after partial reinforcement (PRF) training to its level after continuous reinforcement (CRF) training, which was not affected by the treatment. The results are discussed in terms of prenatal damage to the hippocampus and in relation to an earlier experiment (Lobaugh, Bootin, & Amsel, 1985), which found no effect of infant hippocampal lesions on PA but an elimination of the PREE, which, unlike the fetal-alcohol case, resulted from PRF-like persistence in extinction following CRF training.

Patterned (single) alternation in infant rats after combined or separate lesions of hippocampus and amygdala.

The role of the developing hippocampus and the amygdala on patterned (single) alternation (PA) in the infant rat was investigated in 4 experiments. In Experiments 1 and 2, pups were given 2 bilateral electrolytic hippocampal lesions or sham surgeries at 10 or 11 days of age and were trained 6 days later in a straight runway. In Experiment 1, there were 120 trials in 1 day, with an 8-, a 15-, or a 30-s intertrial interval (ITI). PA learning occurred in lesion and sham pups at the 8- and 15-s ITIs, but it was reduced in both groups at the 30-s ITI. In Experiment 2, training was extended to 240 trials over 2 days, with a 30- or 60-s ITI. Sham and lesion pups showed PA at the 30-s ITI, but the emergence of PA was delayed in the lesion pups at the 60-s ITI. In Experiment 3, amygdaloid lesions had no effect on PA learning at the 8-s ITI. However, when pups with hippocampal and amygdaloid lesions were trained at the 8-s ITI, the emergence of PA was delayed, and its size was reduced (Experiment 4). The results of these experiments argue for a role of the hippocampus in PA learning at long ITIs and suggest that, even in 16-day-old pups exposed to an 8-s ITI, the combined hippocampal and amygdaloid lesion produces a deficit greater than either the hippocampal or the amygdaloid lesion. The results are discussed in relation to current theories that distinguish between 2 levels of memory function.

Piracetam therapy does not enhance cognitive functioning in children with down syndrome.

BACKGROUND: Piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. Its efficacy, however, has not been rigorously assessed. OBJECTIVE: To determine whether 4 months of piracetam therapy (80-100 mg/kg per day) enhances cognitive function in children with Down syndrome. DESIGN: A randomized, double-blind, placebo-controlled crossover study. PARTICIPANTS AND METHODS: Twenty-five children with Down syndrome (aged 6.5-13 years) and their caregivers participated. After undergoing a baseline cognitive assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam-placebo or placebo-piracetam. MAIN OUTCOME MEASURE: The difference in performance while taking piracetam vs while taking placebo on tests assessing a wide range of cognitive functions, including attention, learning, and memory. RESULTS: Eighteen children completed the study, 4 withdrew, and 3 were excluded at baseline. Piracetam therapy did not significantly improve cognitive performance over placebo use but was associated with central nervous system stimulatory effects in 7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). CONCLUSION: Piracetam therapy did not enhance cognition or behavior but was associated with adverse effects.

Age-dependent effects of hippocampal muscarinic receptor blockade on memory-based learning in the developing rat.

The effects of ventral intrahippocampal injections of atropine sulfate on patterned single alternation (PSA), a discrimination task that requires intact short-to-intermediate-term memory, were examined in the developing rat at 16-17 and 28-32 days of age. Atropine treatment disrupted simple acquisition in some 16- to 17-day-old pups by interfering with approach to the goal, but did not eliminate PSA at either 8- or 15-s intertrial intervals when approach was normal. In the older rats, atropine treatment delayed the onset and reduced the magnitude of PSA, indicating a reduced memory-based discrimination. These results provide additional support for an increasing role of muscarinic receptors in learning and memory as this system matures in the developing rat, and suggest different mechanisms for PSA at the two ages.

Effects of prenatal ethanol exposure on learned persistence and hippocampal neuroanatomy in infant, weanling and adult rats.

The present experiment examined whether deficits in learned persistence, previously seen in 15-day-old infant rats prenatally exposed to ethanol, would be present in weanling and adult animals. Three prenatal treatments, EtOH, PAIR-FED, and LAB CHOW, were combined factorially with partial (PRF) or continuous (CRF) reinforcement training followed by extinction, at 21 days or 6 months of age. The results at 21 days were virtually the same as our earlier findings for 15-day-olds: we did not find the higher level of persistence in PRF-trained EtOH pups relative to CRF-trained EtOH pups, which characterizes the partial reinforcement extinction effect (PREE). The EtOH-PRF and EtOH-CRF animals extinguished at about the same rate, both faster than PRF controls. However, when tested as adults, the EtOH-exposed animals showed a normal PREE, with no deficits relative to controls. An analysis of CA1 pyramidal cells in midtemporal hippocampus demonstrated no significant differences in cell density or in CA1 area among the 3 prenatal diet conditions; however, there was a significant reduction in cell density with age for all groups. These results suggest that a developmental delay, unrelated to these neuroanatomical measures, is responsible for the lack of persistence in young rats exposed prenatally to ethanol.

Discrimination of single features and conjunctions by children.

Stimuli that are discriminated by a conjunction of features can show more rapid early processing in adults. To determine how this facilitation effect develops, the processing of visual features and their conjunction was examined in 7-12-year-old children. The children completed a series of tasks in which they made a target-non-target judgement as a function of shape only, colour only or shape and colour features, while event-related potentials were recorded. To assess early stages of feature processing the posteriorly distributed P1 and N1 were analysed. Attentional effects were seen for both components. P1 had a shorter latency and P1 and N1 had larger amplitudes to targets than non-targets. Task effects were driven by the conjunction task. P1 amplitude was largest, while N1 amplitude was smallest for the conjunction targets. In contrast to larger left-sided N1 in adults, N1 had a symmetrical distribution in the children. N1 latency was shortest for the conjunction targets in the 9-10-year olds and 11-12-year olds, demonstrating facilitation in children, but which continued to develop over the pre-teen years. These data underline the sensitivity of early stages of processing to both top-down modulations and the parallel binding of non-spatial features in young children. Furthermore, facilitation effects, increased speed of processing when features need to be conjoined, mature in mid-childhood, arguing against a hierarchical model of visual processing, and supporting a rapid, integrated facilitative model.

Visual search for features and conjunctions in development.

Visual search performance was examined in three groups of children 7 to 12 years of age and in young adults. Colour and orientation feature searches and a conjunction search were conducted. Reaction time (RT) showed expected improvements in processing speed with age. Comparisons of RT's on target-present and target-absent trials were consistent with parallel search on the two feature conditions and with serial search in the conjunction condition. The RT results indicated searches for feature and conjunctions were treated similarly for children and adults. However, the youngest children missed more targets at the largest array sizes, most strikingly in conjunction search. Based on an analysis of speed/accuracy trade-offs, we suggest that low target-distractor discriminability leads to an undersampling of array elements, and is responsible for the high number of misses in the youngest children.

Age and dose-related effects of hippocampal ibotenic acid on lesion size, mortality, and nonspatial working memory in infant rats.

Three experiments are presented in which the neural and behavioral consequences of multiple ibotenic acid (IBO) injections into the hippocampus were examined in Sprague-Dawley rat pups. Rat pups were 11 or 15 days of age at the time of surgery (SURG11, SURG15), the dose of IBO was either 1 microgram in 1 microliter, 2.5 micrograms in 0.5 microliters, or 5 micrograms in 1 microliter for each of four injections, and pups were allowed to survive for 3 or 7 days after the lesion was made. The Fink-Heimer silver stain was used in Experiment 1 to examine the extent of neural damage following unilateral lesions and showed that the degeneration was primarily located in the hippocampus. The magnitude of the damage was greatest in younger pups and in those which received the higher of the two concentrations (injection volume was not a factor). Degenerating fibers were seen in the columns of the fornix as well as precommissural fornix fibers, but only in SURG15 animals when damage extended into the dorsal subiculum. Mortality rates following multiple IBO injections were very high in infant rats, in some cases as high as 60%. Experiments 2 and 3 examined the effects of bilateral lesions on neuroanatomy and behavior. Bilateral lesions were somewhat smaller than unilateral lesions, and as for unilateral lesions, degeneration in pre- and postcommissural fornix was seen only in SURG15 animals. The behavioral task used in Experiments 2 and 3 was patterned single alteration, a memory-based appetitive learning discrimination. Earlier work has shown that damage to the infant hippocampus results in moderate deficits in this task at 30-s intervals and more substantial deficits at 60-s intertrial intervals. This was not the case in the present studies: regardless of age at surgery or time postlesion, all infant rats tested learned this discrimination at the two intertrial intervals. As has been recently reported for adult rats, excitotoxic lesions of the hippocampus in infant rats do not produce the same patterns of behavioral deficits as electrolytic lesions.

Analysis of neural interactions explains the activation of occipital cortex by an auditory stimulus.

Analysis of neural interactions explains the activation of occipital cortex by an auditory stimulus. J. Neurophysiol. 80: 2790-2796, 1998. Large-scale neural interactions were characterized in human subjects as they learned that an auditory stimulus signaled a visual event. Once learned, activation of left dorsal occipital cortex (increased regional cerebral blood flow) was observed when the auditory stimulus was presented alone. Partial least-squares analysis of the interregional correlations (functional connectivity) between the occipital area and the rest of the brain identified a pattern of covariation with four dominant brain areas that could have mediated this activation: prefrontal cortex (near Brodmann area 10, A10), premotor cortex (A6), superior temporal cortex (A41/42), and contralateral occipital cortex (A18). Interactions among these regions and the occipital area were quantified with structural equation modeling to identify the strongest sources of the effect on left occipital activity (effective connectivity). Learning-related changes in feedback effects from A10 and A41/42 appeared to account for this change in occipital activity. Influences from these areas on the occipital area were initially suppressive, or negative, becoming facilitory, or positive, as the association between the auditory and visual stimuli was acquired. Evaluating the total effects within the functional models showed positive influences throughout the network, suggesting enhanced interactions may have primed the system for the now-expected visual discrimination. By characterizing both changes in activity and the interactions underlying sensory associative learning, we demonstrated how parts of the nervous system operate as a cohesive network in learning about and responding to the environment.

Spatiotemporal analysis of experimental differences in event-related potential data with partial least squares.

One challenge in the analysis of event-related potentials (ERPs) is to identify task-related differences in scalp topography. The multivariate Partial Least Squares (PLS) analysis was used to identify the spatiotemporal distribution of ERP differences related to experimental manipulations. Two simulations included latency shifts and amplitude changes at peaks with temporal overlap. PLS identified effects only at modeled timepoints and electrodes. In contrast, principal components analysis identified differences at most timepoints. We also demonstrated that PLS identified combinations of waveform differences, not isolated sources. ERP components in an auditory oddball task were also assessed with PLS. The primary distinction was between ERPs on hit and correct rejection trials, expressed at multiple timepoints and electrodes. PLS provides a mechanism to describe experimental differences in ERP waveforms, simultaneously across the head.