Implicit and explicit learning of Bayesian priors differently impacts bias during perceptual decision-making.

Knowledge without awareness, or implicit knowledge, influences a variety of behaviors. It is unknown however, whether implicit knowledge of statistical structure informs visual perceptual decisions or whether explicit knowledge of statistical probabilities is required. Here, we measured visual decision-making performance using a novel task in which humans reported the orientation of two differently colored translational Glass patterns; each color associated with different orientation probabilities. The task design allowed us to assess participants' ability to learn and use a general orientation prior as well as a color specific feature prior. Classifying decision-makers based on a questionnaire revealed that both implicit and explicit learners implemented a general orientation bias by adjusting the starting point of evidence accumulation in the drift diffusion model framework. Explicit learners additionally adjusted the drift rate offset. When subjects implemented a stimulus specific bias, they did so by adjusting primarily the drift rate offset. We conclude that humans can learn priors implicitly for perceptual decision-making and depending on awareness implement the priors using different mechanisms.

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.

Weight loss in early stage of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant disease with neurologic manifestations. In transgenic mouse models of HD, weight loss is recognized as a feature associated with the disease onset. It is unclear whether a similar pattern occurs in humans. METHODS: Data from the Huntington Study Group were used to evaluate whether HD is associated with lower body mass index (BMI) at the earliest stage of the disease. There were 361 case subjects in whom HD had been diagnosed with an independence scale rating of 100 (no special care needed), a total functional capacity score of >or=11, and HD duration of <4 years. For each case subject, five sex- and age-matched control subjects were selected from the National Heart, Lung, and Blood Institute Family Heart Study or the Framingham Offspring Study. RESULTS: Among case subjects, neither disease duration, nor dystonia, nor chorea score was significantly associated with BMI. BMI was significantly lower among case than among control subjects. Among men, age-adjusted BMI (+/-SE) was 25.90 +/- 0.34 kg/m(2) for case subjects with HD and 27.68 +/- 0.16 kg/m(2) for control subjects. Among women, corresponding values were 24.34 +/- 0.43 for case subjects with HD and 26.63 +/- 0.21 kg/m(2) for control subjects. CONCLUSIONS: At an early stage of the disease, subjects with Huntington's disease had lower body mass index than matched controls from the general population. The cause of weight loss is unknown but the parallel to observations in Huntington's disease transgenic mice suggests that it is a significant hallmark of Huntington's disease gene expression.

Reinforcer devaluation abolishes conditioned cue preference: evidence for stimulus-stimulus associations.

In the conditioned cue preference (CCP) task, the subject is presented with a cue paired with food reward, resulting in a preference for the paired cue when allowed to choose later. To clarify the learning involved, the authors devalued the reinforcer after training by inducing a taste aversion to the food. In five 30-min sessions, rats were confined in 1 arm of a radial arm maze and presented with food. These reinforced sessions alternated with 5 unreinforced sessions in a nonadjacent arm. Devaluation was then accomplished in 1 group by inducing taste aversion; controls received either saline or unpaired lithium chloride treatment. When tested later, both the saline group and the unpaired group preferred the previously reinforced arm, but the devalued group showed aversion to it. Thus, CCP is mediated by the stimulus-reinforcer association; when the reinforcer is devalued, the preference is also abolished.

Temporal allocation of visual attention in adult attention deficit hyperactivity disorder.

In two experiments, we examined the ability of adults with attention deficit hyperactivity disorder (ADHD) to process multiple targets appearing in a rapid serial visual presentation (RSVP) stream. Using a standard attentional blink (AB) task, subjects were required to both identify a target in the RSVP stream and detect a probe appearing in one of several posttarget serial positions. In Experiment 1, ADHD adults exhibited a protracted AB compared to controls, in that their probe detection did not improve as a function of increasing probe-to-target intervals (450-720 msec). In Experiment 2, the ADHD group performed as well as controls in detecting probes appearing immediately (i.e., 90 msec) after the target. Taken together, the results demonstrate that adults with ADHD exhibit a selective deficit in rapidly shifting attention between the target and the probe, when the two appear several hundred milliseconds apart. These results suggest that adults with ADHD can use automatic (reflexive) attention to detect items in close temporal proximity in the RSVP stream, but have difficulty allocating controlled attention to multiple stimuli separated by several hundred milliseconds.

Retrograde amnesia.

In humans, the phenomenon of temporally graded retrograde amnesia has been described in the clinic and the laboratory for more than 100 years. In the 1990s, retrograde amnesia began to be studied prospectively in experimental animals. We identified 13 published studies in which animals were given equivalent training at two or more separate times before damage to the fornix or hippocampal formation. Eleven of these studies found temporally graded retrograde amnesia, with the extent of amnesia ranging from several days to a month or two. We consider these studies and also suggest why temporally graded retrograde amnesia has sometimes not been observed. Although the evidence in favor of temporally graded retrograde amnesia is substantial, the inference from this work, that memory is reorganized as time passes, is rather vague and depends on mechanisms yet to be identified. It is therefore encouraging that many opportunities exist for moving beyond purely descriptive studies to studies that involve treatments or manipulations directed toward yielding information about mechanisms.

Hemispheric differences in object identification.

Although the right hemisphere is thought to be preferentially involved in visuospatial processing, the specialization of the two hemispheres with respect to object identification is unclear. The present study investigated the effects of hemifield presentation on object and word identification by presenting objects (Experiment 1) and words (Experiment 2) in a rapid visual stream of distracters. In Experiment 1, object images presented in the left visual field (i.e., to the right hemisphere) were identified with shorter display times. In addition, the left visual field advantage was greater for inverted objects. In Experiment 2, words presented in the right visual field (i.e., to the left hemisphere) under similar conditions were identified with shorter display times. These results support the idea that the right hemisphere is specialized with regard to object identification.

Family-based association tests for qualitative and quantitative traits using single-nucleotide polymorphism and microsatellite data.

Using the Genetic Analysis Workshop 12 simulated data, we contrasted results for association tests in nuclear families and extended pedigrees using single-nucleotide polymorphism (SNP) data, and we compared results for different trait definitions, for outbred and isolate populations, and for SNP and microsatellite data. SNPs in major genes 1 and 6 were analyzed using transmission disequilibrium testing (TDT) [Spielman et al., Am J Hum Genet 52:506-16, 1993], sibship disequilibrium testing (SDT) [Horvath and Laird, Am J Hum Genet 63:1886-97, 1998], family-based association testing (FBAT) [Horvath et al., Eur J Hum Genet 9:301-6, 2001], and a chi-square analysis of founders. TDT and SDT were applied in a sample of independent nuclear families, while FBAT was applied in extended pedigrees. SNPs and microsatellites were analyzed with dichotomous and quantitative trait definitions using FBAT in the isolate and outbred populations. The results of the TDT, SDT, and FBAT analyses are comparable using SNP data to identify the disease gene. However, these tests of association were not helpful in discriminating between functional and non-functional SNPs in disequilibrium. SNP data were able to identify association with affection status in a gene that influences the liability directly (MG6), but did not perform as well when assessing association with affection status in a gene that influences the outcome only through a quantitative trait (MG1). Association with MG1 was observed using the SNP data when the outcome was defined quantitatively. Microsatellite data were relatively unsuccessful in identifying association with the markers in the region of a major gene. The magnitude of the associations between SNPs and the dichotomous or quantitative trait definitions were similar in the outbred and isolated populations.

Influence of marker heterozygosity and genetic heterogeneity on fine mapping.

The purpose of the current study was to utilize the Genetic Analysis Workshop 12 simulated data to evaluate fine-mapping strategies for quantitative traits. We approached the analysis as if it was a follow-up to a genome scan that had identified two regions of interest and used the provided 1-cM density microsatellite typing data to mimic fine mapping of these regions. As these investigators knew the true locations of the putative genes under study, we explored the effects of the informativeness of microsatellite markers (marker heterozygosity) and the effects of genetic heterogeneity across families for ten replicates of the data. These results shed a cautionary light on the reliability of fine-mapping efforts on refining mapping locations as the position and the strength of the lod score can be markedly affected by the sampling of the population, the amount of variation accounted for by the gene, and the informativeness of the marker. Our studies did not reveal a large effect of unlinked families on the shape of the lod score peak.

Remembering episodes: a selective role for the hippocampus during retrieval.

Some memories are linked to a specific time and place, allowing one to re-experience the original event, whereas others are accompanied only by a feeling of familiarity. To uncover the distinct neural bases for these two types of memory, we measured brain activity during memory retrieval using event-related functional magnetic resonance imaging. We show that activity in the hippocampus increased only when retrieval was accompanied by conscious recollection of the learning episode. Hippocampal activity did not increase for items recognized based on familiarity or for unrecognized items. These results indicate that the hippocampus selectively supports the retrieval of episodic memories.

Long-term retinotopic priming in object identification.

An important result in perception research is that priming in an object naming task is invariant with translation and left-right reflection. A more sensitive object recognition paradigm was used in three experiments in order to investigate the extent to which priming of object identification is affected by changes in left-right orientation and position. In a prime phase, participants viewed consecutively presented object images. In a subsequent probe phase, participants identified familiar objects in rapid visual streams of nonobject distractors. In Experiment 1, images previously viewed in the same left-right orientation were primed more than images previously viewed in the opposite orientation (i.e., a left-right reflection). This reflection-sensitive priming was replicated in Experiment 2 using a brief (300-msec) prime exposure. In Experiment 3, when the retinal locations of prime and probe images matched, reflection-sensitive priming was also obtained, but when the retinal locations of prime and probe images differed, no reflection-sensitive priming was observed. These results suggest that a single prime exposure can produce long-term priming that is sensitive to left-right reflection, but that this priming is specific to a retinal location.

Effects of US devaluation on win-stay and win-shift radial maze performance in rats.

Previous studies have shown double dissociations between win-stay and win-shift radial maze learning in terms of their underlying neural substrates. To examine the content of the associations formed in the two tasks, the authors devalued the food unconditioned stimulus (US) by taste aversion to differentiate stimulus-stimulus(CS-US) and stimulus-response (CS-CR) learning. US devaluation was performed in rats that were over- or undertrained on the win-stay task. Devaluation substantially reduced food consumption on the maze but failed to disrupt choice accuracy, regardless of the amount of training. Devaluation did not affect latency in overtrained rats but did increase latency in undertrained rats. In the win-shift task, devaluation caused rats to reject the reinforcer, yet they continued to accurately win-shift, but with significantly longer latencies (Experiment 3). The results suggest that an S-R association may mediate performance after extended win-stay training. In contrast, a US representation appears to be recalled during early win-stay and win-shift performance.

Dissociating the effects of featural and conceptual interference on multiple target processing in rapid serial visual presentation.

Attentional blink (AB) describes the finding that, when subjects attend to a specified target in a rapidly presented visual stream, they show a decreased ability to process a subsequent probe item for up to 600 msec. In the present study, the roles of featural and conceptual interference in the processing of targets and probes in a rapid serial visual presentation stream were examined. In Experiment 1, featurally more complex T + 1 items produced larger AB even when the physical energy of the stimulus (e.g., the number of pixels) was held constant. In Experiment 2, the conceptual category of the T + 1 item affected target identification but not AB magnitude. These result suggest that featural interference is a major determinant of AB magnitude, whereas featural and conceptual interference both affect target identification.

Effects of paired and unpaired eye-blink conditioning on Purkinje cell morphology.

This experiment addressed (1) the importance of conjunctive stimulus presentation for morphological plasticity of cerebellar Purkinje cells and inhibitory interneurons and (2) whether plasticity is restricted to the spiny branches of Purkinje cells, which receive parallel fiber input. These issues were investigated in naive rabbits and in rabbits that received paired or unpaired presentations of the conditioned stimulus (CS) and unconditioned stimulus (US). To direct CS input to the cerebellar cortex, pontine stimulation served as the CS. Air puffs to the cornea served as the US. Paired condition rabbits received pontine stimulation for 350 msec paired with a coterminating 100-msec air puff. Unpaired condition rabbits received the same stimuli in a pseudorandom order at 1- to 32-sec intervals. Rabbits were trained for a mean of 12 days. Naive rabbits received no treatment. In Golgi-stained Purkinje neurons in lobule HVI, total dendritic length, main branch length, total spiny branch length, and number of spiny branch arbors were all greater in the naive group than in the paired and unpaired groups, which did not differ. No differences were found between the hemispheres ipsilateral and contralateral to the trained eye. The dendritic length and number of branches for inhibitory interneurons did not differ across groups. The Purkinje cell morphological changes detected with these methods do not appear to be uniquely related to the conjunctive activation of the CS and US in the paired condition.

The relationship between remembering and knowing: a cognitive neuroscience perspective.

Cognitive neuroscience has provided strong support for the idea that there are multiple memory systems. Recent evidence suggests that remembering and knowing may be two types of recognition with different neural substrates. The remember/know distinction is not equivalent to the explicit/implicit distinction because both remembering and knowing are impaired after damage to medial temporal lobe structures. A number of converging lines of evidence suggest that the relationship between remembering and knowing is one redundancy, with "knowing" processes also active during remembering. Remembering appears to depend additionally on frontal lobe functioning.

Dissociable properties of memory systems: differences in the flexibility of declarative and nondeclarative knowledge.

Amnesic patients (n = 8), who have severely impaired declarative memory, learned a probabilistic classification task at the same rate as normal subjects (n = 16) but subsequently were impaired on transfer tests that required flexible use of their task knowledge. A second group of controls (n = 20) rated the questions on the transfer tests according to whether the questions simply reinstated the training conditions or required flexible use of task knowledge. The amnesic patients tended to be impaired on the same items that were rated as requiring indirect or flexible use of knowledge. Thus, control subjects acquired declarative knowledge about the task that could be applied flexibly to the transfer tests. The nondeclarative memory available to amnesic patients was relatively inflexible and available only in conditions that reinstantiated the conditions of training. These findings show that declarative memory has different operating characteristics than nondeclarative memory.

A neostriatal habit learning system in humans.

Amnesic patients and nondemented patients with Parkinson's disease were given a probabilistic classification task in which they learned which of two outcomes would occur on each trial, given the particular combination of cues that appeared. Amnesic patients exhibited normal learning of the task but had severely impaired declarative memory for the training episode. In contrast, patients with Parkinson's disease failed to learn the probabilistic classification task, despite having intact memory for the training episode. This double dissociation shows that the limbic-diencephalic regions damaged in amnesia and the neostriatum damaged in Parkinson's disease support separate and parallel learning systems. In humans, the neostriatum (caudate nucleus and putamen) is essential for the gradual, incremental learning of associations that is characteristic of habit learning. The neostriatum is important not just for motor behavior and motor learning but also for acquiring nonmotor dispositions and tendencies that depend on new associations.

Artificial grammar learning depends on implicit acquisition of both abstract and exemplar-specific information.

The contributions of exemplar-specific and abstract knowledge to artificial grammar learning were examined in amnesic patients and controls. In Experiment 1, grammatical rule adherence and chunk strength exerted separate effects on grammaticality judgments. Amnesic patients exhibited intact classification performance, demonstrating the same pattern of results as controls. In Experiment 2, amnesic patients exhibited impaired declarative memory for chunks. In Experiment 3, both amnesic patients and controls exhibited transfer when tested with a letter set different than the one used for training, although performance was better when the same letter sets were used at training and test. The results suggest that individuals learn both abstract information about training items and exemplar-specific information about chunk strength and that both types of learning occur independently of declarative memory.

Learning about categories in the absence of memory.

A fundamental question about memory and cognition concerns how information is acquired about categories and concepts as the result of encounters with specific instances. We describe a profoundly amnesic patient (E.P.) who cannot learn and remember specific instances--i.e., he has no detectable declarative memory. Yet after inspecting a series of 40 training stimuli, he was normal at classifying novel stimuli according to whether they did or did not belong to the same category as the training stimuli. In contrast, he was unable to recognize a single stimulus after it was presented 40 times in succession. These findings demonstrate that the ability to classify novel items, after experience with other items in the same category, is a separate and parallel memory function of the brain, independent of the limbic and diencephalic structures essential for remembering individual stimulus items (declarative memory). Category-level knowledge can be acquired implicitly by cumulating information from multiple training examples in the absence of detectable conscious memory for the examples themselves.