Correspondence between the alcohol-P3 event-related potential and alcohol reward phenotypes among young adults.

BACKGROUND: Behavioral economic theory suggests that the value of alcohol depends upon elements of the choice context, such that increasing constraints on alternatives (e.g., price) or increasing the benefits of alcohol (e.g., social context) may result in greater likelihood of heavy drinking. The P3 event-related potential elicited by alcohol-related cues, a proposed marker of incentive salience, may be an electrophysiological parallel for behavioral economic alcohol demand. However, these indices have not been connected in prior research, and studies typically do not disaggregate social influences in the context of alcohol cue reactivity. METHOD: The current study recruited heavy drinking young adults (N = 81) who completed measures of alcohol use and alcohol demand, in addition to a 2 (social/nonsocial) × 2 (alcohol/nonalcohol) visual oddball task to elicit the P3. RESULTS: In multilevel models controlling for demographic characteristics, P3 reactivity was greater to alcohol (p < 0.001) and social (p < 0.001) cues than to nonalcohol and nonsocial cues, but without a significant interaction. Higher alcohol consumption (p = 0.02) and lower elasticity of demand (p = 0.01) were associated with greater P3 response to alcohol than nonalcohol cues. CONCLUSIONS: The results highlight a brain-behavior connection that may be an important marker for alcohol reward across units of analysis and may be sensitive to changes in the economic choice contexts that influence the likelihood of alcohol use.

A Phosphatidylserine Source of Docosahexanoic Acid Improves Neurodevelopment and Survival of Preterm Pigs.

The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P's < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems.

Auditory Event-Related Potentials in the Interictal Phase of Migraine Indicate Alterations in Automatic Attention.

Migraine has been characterized by interictal cortical hyperresponsivity. We compared event-related brain potentials (ERPs) to unattended tone pairs in migraineurs (interictal) versus non-headache controls, with particular interest in attention-related activity (i.e., the N1 component). Electroencephalograms were recorded from 11 interictal migraineurs and 14 headache-free controls while they watched a silent video. Pairs of 50-ms tones with 500-ms inter-tone intervals were presented with inter-pair intervals of 1 or 5 s. P1, N1, P2, and N2 components were analyzed. N1 peak amplitudes were larger in migraineurs than in controls, especially after the 5-s inter-pair interval. However, there was no difference between groups in the attenuation of the N1 (i.e., no interaction). P2 peak amplitudes were larger in migraineurs, but only after the first tone in the pair. The three migraineurs without aura had larger N1s than the eight with aura. Our findings are consistent with interictal hyperresponsivity of cortical generators of these ERPs in migraineurs. However, areas that inhibit the responses with stimulus repetition do not seem to be affected.

Behavioral therapy: emotion and pain, a common anatomical background.

Emotion and pain are closely intertwined in the brain, as the human experience of pain includes both affective and nociceptive components. Although each of these components relies on a different system in the brain, the two systems converge on the anterior cingulate and insular cortices, which interact with the prefrontal cortex and other frontal structures to influence behavior. Both emotional and physical pain elicit activity in these common areas, and conditions that affect one system (e.g., drugs, neural plasticity) may affect the function of the other-ultimately altering the experience of pain. Changes in these areas and their connections may even contribute to the chronification of pain. This relationship should not be overlooked in the treatment of painful conditions, including headache. Nonpharmacological therapies, such as cognitive behavioral therapy, yoga, biofeedback, and meditation, that are often used for enhancing emotional regulation, are increasingly being turned to for augmenting management of migraine and pain. Because of the overlap between emotion and pain, these therapies are likely acting through similar mechanisms, and emotional cues can be sensitive indicators of treatment-related changes in patients.

Cognitive Neuroscience and Single-Word Processing.

Early neuroimaging research on language-related function is useful for teaching cognitive neuroscience. In these studies, researchers used relatively simple experimental designs in an attempt to break down complex cognitive processes. In addition, the hypotheses tested in these studies were based on models derived from non-imaging observations, such as lesion studies. Thus, students at all levels may find the research accessible in its simplicity and engaging in its attempt to test existing theories in novel ways. Raichle (1996) describes a series of such studies that used what were, at the time, novel applications of relatively young imaging methods to measure brain activity related to single-word processing. In a short, readable article, he places the studies in their historical context (i.e., models of language function based largely on case studies of patients with brain lesions) and describes the methods and designs used in the research. He summarizes the results and the main takeaways from the research and its practical implications for research and medicine in the future. This paper touches on many important features of cognitive neuroscience, as well as psychology and neuroscience more broadly. It can serve as a springboard into discussion of many topics in many course contexts.

Sex differences in response to amphetamine in adult Long-Evans rats performing a delay-discounting task.

The use of animal models to investigate experimental questions about impulsive behavior can provide valuable insight into problems that affect human health. The delay-discounting paradigm involves subjects choosing between smaller reinforcers delivered immediately and larger reinforcers that are delivered after a delay. This is an important experimental paradigm for examining impulsive choice in both laboratory species and humans. However, a shortcoming of previously published delay-discounting studies in animals is that typically only males were studied, reducing the applicability of these studies to human populations. In the present study, both female and male adult Long-Evans rats were trained to perform a delay-discounting task, with delays of 0, 5, 10, 20 and 40 s before delivery of the larger reinforcer. Because dopaminergic signaling is important in mediating this task, the effects of d-amphetamine and the dopamine receptor antagonist, cis-flupenthixol, on task performance were then examined. The main experimental measure was percent larger-reinforcer choice, which was defined as the percentage of experimental trials at each delay in which the delayed, larger reinforcer was chosen. There was no sex difference in percent larger-reinforcer choice during baseline performance of the task. However, d-amphetamine administration disrupted choice in females, as evidenced by <80% larger-reinforcer choice in half of the females, but none of the males, at 0.5 mg/kg. D-Amphetamine also differentially altered the latency to choose between immediate versus delayed reinforcers in females compared to males. In contrast, cis-flupenthixol did not have a sex-related effect on percent larger-reinforcer choice. These findings parallel the sex differences in response to amphetamine seen in human delay-discounting studies and underscore the importance of evaluating sex-based differences in baseline performance and in response to pharmacologic agents when utilizing animal models.

Attention-deficit hyperactivity disorder reduces automatic attention in young adults.

Previous ERP studies have provided mixed information about ADHD, especially in adults and when conscious attention to stimuli is not required. We used the auditory N1 to assess automatic attention in adults with and without ADHD. While participants watched a silent video, trains of 5 tones (400-ms onset-to-onset time) were presented with intertrain intervals (ITIs) of 1 or 5 s. The P1, N1, P2, and N2 were analyzed. Compared to controls, participants with ADHD had relatively little N1 attenuation after the 5-s ITI, which was driven by uniformly small N1s to all tones. However, after the 1-s ITI, the ADHD group had relatively large N2s to all 5 tones in the train. The reduced N1 in adults with ADHD indicated reduced automatic attention to salient sound stimuli, which may be due to reduced function of brain-stem arousal mechanisms. However, the increased N2 in these participants suggests they had developed certain compensatory mechanisms.

Effects of alcohol on sequential information processing: evidence for temporal myopia.

Alcohol Myopia Theory (AMT) posits that alcohol restricts the focus of attention, such that behaviors are determined only by highly salient environmental cues. While AMT is most commonly understood in terms of spatial attention, the present study tested the effects of alcohol in the temporal domain of attention. Seventy-one participants consumed either a placebo beverage or one of two doses of alcohol (0.40g/kg or 0.80g/kg ETOH) before performing an auditory discrimination task while event-related potentials (ERPs) were recorded. Consistent with typical sequential effects, placebo participants showed increased P300 amplitude and slowed behavioral responses when the current target differed from the two-back tone. In contrast, alcohol caused increased P300 and response slowing when the target tone differed from the one-back tone. These findings suggest that alcohol increases the salience of more recently encountered information, consistent with the general tenets of AMT.

The Sensory Gating Inventory as a potential diagnostic tool for attention-deficit hyperactivity disorder.

Diagnoses of attention-deficit hyperactivity disorder (ADHD) are often made rapidly in physicians' offices without thorough assessment. We examined whether adults diagnosed with ADHD would score differently from controls on a modified Sensory Gating Inventory (SGI: Hetrick et al. in Schizophr Bull 38:178-191, 2012; Kisley et al. in Psychophysiol 41:604-612, 2004), which would facilitate rapid and easy preliminary assessment of ADHD status. The modified SGI was administered to 22 controls and 22 adults with physician diagnoses of ADHD. Analysis was performed on the 17 SGI items and the three categories to which they belong (Perceptual Modulation, Distractibility, and Over-Inclusion). The Distractibility category, and its individual items, showed large group differences. In spite of a relatively small sample size, we found large effect sizes between those with and without ADHD diagnoses. The SGI is a simple, quick, paper/pencil method that may be used to facilitate accurate diagnosis of individuals experiencing ADHD symptoms, which may be especially useful when evaluations are made in settings such as physicians' offices.

Recording invertebrate nerve activation with modulated light changes.

Optical scattering techniques have the potential to provide noninvasive measurements of neural activity with good spatial and temporal resolution. We used the lobster nerve as a model system to investigate and record event-related optical signals with a modulated light source and heterodyne detection system. We observed changes in the transmitted birefringent light intensity, corresponding with electrophysiological measurements of the action potential. The photon delay was below the detection threshold, in part due to the small size of the nerve bundle. Our system allowed us to place an upper bound on the magnitude of the phase change of 0.01 degrees. The physiological stability of the preparation allows comprehensive characterization of biological and instrumentation noise sources for testing optical measurement systems.

Optical imaging of temporal integration in human auditory cortex.

Behavioral and physiological studies have indicated the existence of a temporal window of auditory integration (TWI), within which similar sounds are perceptually grouped. The current study exploits the combined temporal and spatial resolution of fast optical imaging (the event-related optical signal, EROS) to show that brain activity elicited by sounds within and outside the TWI differs in location and latency. In a previous event-related brain potential (ERP) study [Sable, Gratton, and Fabiani (2003) European Journal of Neuroscience, 17, 2492-2496], we found that the mismatch negativity (MMN; a brain response to acoustic irregularities) elicited by deviations in stimulus onset asynchronies (SOAs) had a unique shape when the deviant SOA was within the TWI. In the present study, we extended these ERP results using EROS. Participants heard trains of five tones. The first four tones had SOAs of 96, 192, 288 or 384 ms. The SOA of the fourth and fifth tones was either the same (standard) or one of the other three (deviant) SOAs. With a deviant SOA of 96 ms, the cortical response was approximately 2 cm anterior to responses to longer SOA deviants, and was followed by a later response that was absent in the other conditions. Similarly to the electrical MMN, the optical mismatch response amplitudes were proportional to the magnitude of interval deviance. These results, in combination with our previous findings, indicate that the temporal integration of sounds is reflected in cortical mismatch responses that differ from the typical response to interval deviance.

Reduced suppression or labile memory? Mechanisms of inefficient filtering of irrelevant information in older adults.

Cognitive aging theories emphasize the decrease in efficiency of inhibitory processes and attention control in normal aging, which, in turn, may result in reduction of working memory function. Accordingly, some of these age-related changes may be due to faster sensory memory decay or to inefficient filtering of irrelevant sensory information (sensory gating). Here, event-related brain potentials and the event-related optical signal were recorded in younger and older adults passively listening to tone trains. To determine whether age differentially affects decay of sensory memory templates over short intervals, trains were separated by delays of either 1 or 5 sec. To determine whether age affects the suppression of responses to unattended repeated stimuli, we evaluated the brain activity elicited by successive train stimuli. Some trains started with a shorter-duration stimulus (deviant trains). Results showed that both electrical and optical responses to tones were more persistent with repeated stimulation in older adults than in younger adults, whereas the effects of delay were similar in the two groups. A mismatch negativity (MMN) was elicited by the first stimulus in deviant trains. This MMN was larger for 1- than 5-sec delay, but did not differ across groups. These data suggest that age-related changes in sensory processing are likely due to inefficient filtering of repeated information, rather than to faster sensory memory decay. This inefficient filtering may be due to, or interact with, reduced attention control. Furthermore, it may increase the noise levels in the information processing system and thus contribute to problems with working memory and speed of processing.

Latent inhibition mediates N1 attenuation to repeating sounds.

Sound repetition typically reduces auditory N1 amplitudes, more so at higher rates. This has been attributed to refractoriness of N1 generators. However, evidence that N1 attenuation is delayed 300-400 ms after the first occurrence of a repeated sound suggests an alternative process, such as inhibition, that requires 300-400 ms to become fully operational. We examined the N1 to trains of fixed-interval (100, 200, 300, 400 ms) tones for evidence of effects predicted by models of refractoriness and of latent inhibition. Regardless of interval, latency of the eliciting tone from train onset determined N1 amplitudes during the first 400 ms of the train, which decreased in this window. The results show that N1 attenuation cannot be due simply to refractoriness, which would elicit the smallest N1 to the second tone. An inhibitory neural circuit can account for these and previous results, and may be important to auditory perceptual processing.

The event-related optical signal to electrical stimulation of the median nerve.

The event-related optical signal (EROS) uses near-infrared light to study changes in neuronal optical properties in response to stimuli and endogenous events. EROS responses to electrical stimulation of the median nerve at 1, 5, and 8 Hz were collected from 80 channels in 7 subjects. Optical recording channels were spatially aligned by co-registering the digitized fiber locations with structural magnetic resonance images (MRI) for each subject separately. The co-registered data sets were then transformed into Talairach space to permit alignment across subjects. After alignment, data from channels underlying pixels of a surface projection were combined to produce maps of Z statistics. Waveforms associated with voxels within an a priori region of interest (ROI) over the hand area of primary somatosensory (SI) cortex were compared across the three stimulus frequencies. Reliable early increases in light propagation time (i.e., increased phase delay) were found in SI as early as 16-32 ms of poststimulus for all three frequency conditions, and both an increase in phase delay and a decrease in signal intensity were observed over SI at longer latencies. A split-half analysis of the 8 Hz condition demonstrated the replicability of the response. This represents the first direct comparison of intensity and delay measures of these components of the somatosensory response; further, it shows that these early cortical components are replicable across subjects and correspond well to individual subjects' anatomical landmarks for SI.

Sound presentation rate is represented logarithmically in human cortex.

The encoding of temporal information is critical to auditory processing. Since the mismatch negativity component of the auditory event-related brain potential is thought to reflect properties of auditory sensory memory, we used it to examine the representation of acoustic time intervals in the human cortex. The mismatch negativity occurs in response to deviations in acoustic regularities, which are stored in sensory memory. We used 16 stimulus conditions, randomly presenting short trains of tones with fixed onset-to-onset intervals of 100, 200, 300 or 400 ms (all tones in the study were identical). The first four intervals between the tones established the acoustic regularity on each train (i.e. the 'standard'). The fifth tone in each train was preceded by an interval that varied randomly among the same four intervals. If this interval was different from the standard for that trial, it violated the acoustic regularity (i.e. it was a 'deviant'). The mismatch response to the fifth tone differed significantly among stimulus conditions and was proportional to the absolute value of the logarithm of the deviant/standard interval ratio. This indicates that short acoustic time intervals are represented with a ratio scale in the human cortex. When the fifth tone occurred 100 ms after the fourth, it elicited a somewhat different, although proportional response, supporting the hypothesis that a special integration mechanism may exist for very short time intervals.