Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Multiple theories of Attention-Deficit/Hyper- activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.     

Hemispheric visual atentional imbalance in patients with traumatic brain injury

We find a spatially asymmetric allocation of attention in patients with traumatic brain injury (TBI) despite the lack of obvious asymmetry in neurological indicators. Identification performance was measured for simple spatial patterns presented briefly to a locus 5 degrees into the left or right hemifield, after precuing attention to the same (ipsilateral) or opposite (cross-hemifield) side. Though the cue was non-predictive of target location overall, performance was significantly slower for cross than for ipsilateral trials in both patients and controls. We tested 21 TBI patients without overt focal brain damage and nine control subjects. Only patients demonstrated significantly worse performance for left side presentation in the ipsilateral condition. Furthermore, in the cross-hemifield condition, the left-right difference seen in TBI patients was significantly larger-reflecting a failure in producing a leftward attention shift. Again no significant difference was found in controls. These hemifield effects suggest an asymmetry in the ability of TBI patients in shifting attention to the left hemifield, whether from central fixation or from a cue in the contra-lateral hemifield. The results support basic hypotheses regarding visual attention: Attentional control may be asymmetric and attention may be a distributed, rather than localized cortical function.     

神经经济学:迈向脑科学的决策科学

神经经济学是一门应用神经科学技术来确定经济决策的神经机制的新兴学科。文章首先概述了神经经济学这一学科,说明了经济学、心理学和神经科学与神经经济学之间的关系并主要介绍决策与奖惩系统和情绪在神经经济学中的研究发现及相关理论。文章最后评价了神经经济学在发展中的问题。     

Is word perception in a second language more vulnerable than in one's native language? Evidence from brain potentials in a dual task setting

We assessed the effect of additional tasks on language perception in second-language and native speakers. The N400 component of the event-related potential was recorded to spoken nouns that had to be judged for synonymity with a preceding word, while additional choice responses were required to visual stimuli. In both participant groups N400 was delayed as a function of temporal overlap with the additional task. In second-language speakers there was a global delay of N400 independent of additional task load and a decrease of accuracy at highest overlap. These findings are interpreted within a single channel account of language perception.     

Sequential Memory: A Developmental Perspective on Its Relation to Frontal Lobe Functioning

The multidimensional nature of the frontal lobes serves to organize and coordinate brain functionings playing a central and pervasive role in human cognition. The executive processes implicated in complex cognition such as novel problem solving, modifying behavior as appropriate in response to changes in the environment, inhibiting prepotent or previous responses, and the implementation of schemas that organize behavior over time are believed to be mediated by the frontal regions of the brain. Overall, the functioning of the frontal lobes assists individuals in goal directed and self-regulatory behavior. Additional theories of frontal lobe functioning have focused on its involvement in temporal, or time-related domains. The organizational and strategic nature of frontal lobe functioning affects memory processes by enhancing the organization of to-be-remembered information. Among the specific memory systems presumed to be based on anterior cerebral structures is the temporal organization of memory. An essential component of memory that involves temporal organization is sequential ordering entailing the ability to judge which stimuli were seen most recently and the temporal ordering of events in memory. Focal lesion studies have demonstrated the importance of the frontal lobes on retrieval tasks in which monitoring, verification, and placement of information in temporal and spatial contexts of critical importance. Similarly, frontal lobe damage has been associated with deficits in memory for the temporal ordering, or sequencing, of events. The acquisition of abilities thought to be mediated by the frontal lobes, including sequential memory, unfolds throughout childhood, serving to condition patterns of behavior for the rest of the brain. Development of the frontal regions of the brain is known to continue through late adolescence and into early adulthood, in contrast to the earlier maturation of other cortical regions. The developmental patterns of the frontal lobes are thought to involve a hierarchical, dynamic, and multistage process.     

Diagnosis and repair of negative polarity constructions in the light of symbolic resonance analysis

In a post hoc analysis, we investigate differences in event-related potentials of two studies (Drenhaus et al., 2004, Drenhaus et al., to appear, Saddy et al., 2004a and Saddy et al., 2004b) by using the symbolic resonance analysis (Beim Graben & Kurths, 2003). The studies under discussion, examined the failure to license a negative polarity item (NPI) in German: Saddy et al. (2004a) reported an N400 component when the NPI was not accurately licensed by negation; Drenhaus et al., 2004 and Drenhaus et al., to appear considered additionally the influence of constituency of the licensor in NPI constructions. A biphasic N400-P600 response was found for the two induced violations (the lack of licensor and the inaccessibility of negation in a relative clause). The symbolic resonance analysis (SRA) revealed an effect in the P600 time window for the data in Saddy et al., which was not found by using the averaging technique. The SRA of the ERPs in Drenhaus et al., showed that the P600 components are distinguishable concerning the amplitude and latency. It was smaller and earlier in the condition where the licensor is inaccessible, compared to the condition without negation in the string. Our findings suggest that the failure in licensing NPIs is not exclusively related to semantic integration costs (N400). The elicited P600 components reflect differences in syntactic processing. Our results confirm and replicate the effects of the traditional voltage average analysis and show that the SRA is a useful tool to reveal and pull apart ERP differences which are not evident using the traditional voltage average analysis.     

ERP correlates of auditory negative priming

Negative priming refers to slowed down reactions when the distractor on one trial becomes the target on the next. Following two popular accounts, the effect might be due either to inhibitory processes associated with the frontal cortex, or to an ambiguity in the retrieval of episodic information. We used event-related brain potentials (ERPs) to identify the processing stage primarily associated with negative priming. In an auditory categorization task, reactions in negative priming trials were compared to reactions in a standard control (unrelated primes and probes) and a repetition control (attended prime=ignored probe) condition. Reactions were slower for negative priming than for standard control (Delta32 ms) and repetition control trials (Delta64 ms). The corresponding ERP effect was reflected in an attenuation of a sustained parietal positivity extending from 300 to 600 ms. Because corresponding ERP components were found to be sensitive to stimulus recognition and familiarity, the results may be interpreted to support an episodic retrieval account of negative priming.     

Group Intervention Studies in the Cognitive Rehabilitation of Individuals with Traumatic Brain Injury: Challenges Faced by Researchers

There are many factors to consider in designing and interpreting group studies. These include both analytic considerations, such as the selection of valid and reliable outcome measures, and subjective considerations, such as the selection of outcomes that are perceived to be important to participants and researchers. In this paper, we review key issues to consider in the design of group studies in neurorehabilitation, using problem-solving studies in traumatic brain injury as an example.     

The P600 as an indicator of syntactic ambiguity

In a study using event-related brain potentials, we show that the current characterization of the P600 component as an indicator of revision processes (reanalysis and repair) in sentence comprehension must be extended to include the recognition of syntactic ambiguity. By comparing the processing of ambiguous and unambiguous sentence constituents in German, we show that the P600 is elicited when our language processing system has syntactic alternatives at a certain item given in the input string. That the P600 is sensitive to syntactic ambiguity adds crucial evidence to current debates in psycholinguistic modelling, as the results clearly favour parallel models of syntactic processing which assume that ambiguity is recognized and costly.     

Grammar overrides frequency: evidence from the online processing of flexible word order

We show that online processing difficulties induced by word order variations in German cannot be attributed to the relative infrequency of the constructions in question, but rather appear to reflect the application of grammatical principles during parsing. Event-related brain potentials revealed that dative-marked objects in the initial position of an embedded sentence do not elicit a neurophysiologically distinct response from subjects, whereas accusative-marked objects do. These differences are predictable on the basis of grammatical distinctions (i.e. underlying linguistic properties), but not on the basis of frequency information (i.e. a superficial linguistic property). We therefore conclude that the former, but not the latter, guides syntactic integration during online parsing.