Comparison of the Neuroprotective and Anti-Inflammatory Effects of the Anthocyanin Metabolites, Protocatechuic Acid and 4-Hydroxybenzoic Acid.

Anthocyanins are being increasingly investigated for their neuroprotective and antineuroinflammatory effects; however, the overall bioavailability of many anthocyanins is relatively low. In contrast, phenolic acids, metabolites of many polyphenols, including anthocyanins, have been shown to accumulate in tissue at higher concentrations than those of parent compounds, suggesting that these metabolites may be the bioactive components of anthocyanin-rich diets. We examined the neuroprotective capacity of two common phenolic acids, 4-hydroxybenzoic acid (HBA) and protocatechuic acid (PCA), in primary cultures of cerebellar granule neurons. Both HBA and PCA are capable of mitigating oxidative stress induced by hydrogen peroxide, which is thought to contribute to neuronal cell death in neurodegeneration. Under conditions of nitrosative stress, which occur during inflammation in the central nervous system, only PCA was neuroprotective, despite similar structural characteristics between HBA and PCA. Intriguingly, this trend was reversed under conditions of excitotoxicity, in which only HBA was neuroprotective. Lastly, we explored the anti-inflammatory activity of these compounds in microglial cells stimulated with lipopolysaccharide. PCA was an effective anti-inflammatory agent, reducing nitric oxide production, while HBA had no effect. These data indicate that phenolic acids possess distinct neuroprotective and anti-inflammatory characteristics that could make them suitable for the treatment of neurodegeneration.

The psychology of HPA axis activation: Examining subjective emotional distress and control in a phobic fear exposure model.

The HPA axis plays a key role in mediating the effects of "stress" on health, but clarifying mechanisms requires an understanding of psycho-biological linkages. There has long been an implicit assumption that subjective emotional distress (e.g., fear) should activate the HPA axis. Although this assumption was challenged 25 years ago (Curtis, 1976), laboratory studies in humans are limited. In this study we sought to replicate Curtis' findings and extend it by investigating if presence or absence of stressor control shapes HPA axis reactivity in a phobic fear exposure model. We recruited 19-45-year-old specific phobia participants (n=32 spider/snake phobia; n=14 claustrophobia) and gradually exposed them to their feared object or situation while measuring hormonal (ACTH and cortisol) and subjective (emotional distress, perceived control) responses. Utilizing a dyadic yoked design, we compared HPA reactivity when the pace of exposure was controlled by participants to identical exposure given to matched participants in the absence of control. Results showed that phobic fear exposure generated intense emotional distress without a corresponding increase in HPA axis activity. Although our actual manipulation of control failed to impact HPA responses, perceived control during exposure was associated with lower cortisol, an effect that was moderated by actual availability of stressor control. Our findings replicate Curtis' findings and challenge the still common but unsupported assumption that HPA axis activity reflects subjective distress. These results also highlight the importance of both perceived and actual aspects of stressor control in understanding what is truly "stressful" to the HPA axis system.

P3b, consciousness, and complex unconscious processing.

How can perceptual consciousness be indexed in humans? Recent work with ERPs suggests that P3b, a relatively late component, may be a neural correlate of consciousness (NCC). This proposal dovetails with currently prevailing cognitive theory regarding the nature of conscious versus unconscious processes, which holds that the latter are simple and very brief, whereas consciousness is ostensibly required for more durable, complex cognitive processing. Using a P3b oddball paradigm, we instead show that P3b and even later, related slow wave activity occur under rigorously subliminal conditions. Additional principal component analysis (PCA) further differentiated the presence of both P3a and P3b components, demonstrating that the latter indeed occurred subliminally. Collectively, our results suggest that complex, sustained cognitive processing can occur unconsciously and that P3b is not an NCC after all.

Extremely rigorous subliminal paradigms demonstrate unconscious influences on simple decisions.

While showing unconscious influences on complex decisions is indeed difficult, relevant awareness in relatively simpler subliminal paradigms is more easily assessed. Utilizing objective detection (vs. more typical identification or classification) tasks to assess awareness overcomes longstanding residual methodological problems, and prior work using such methods (e.g., Snodgrass & Shevrin 2006) clearly shows unconscious influences on simple decisions.

Subliminal unconscious conflict alpha power inhibits supraliminal conscious symptom experience.

Our approach is based on a tri-partite method of integrating psychodynamic hypotheses, cognitive subliminal processes, and psychophysiological alpha power measures. We present ten social phobic subjects with three individually selected groups of words representing unconscious conflict, conscious symptom experience, and Osgood Semantic negative valence words used as a control word group. The unconscious conflict and conscious symptom words, presented subliminally and supraliminally, act as primes preceding the conscious symptom and control words presented as supraliminal targets. With alpha power as a marker of inhibitory brain activity, we show that unconscious conflict primes, only when presented subliminally, have a unique inhibitory effect on conscious symptom targets. This effect is absent when the unconscious conflict primes are presented supraliminally, or when the target is the control words. Unconscious conflict prime effects were found to correlate with a measure of repressiveness in a similar previous study (Shevrin et al., 1992, 1996). Conscious symptom primes have no inhibitory effect when presented subliminally. Inhibitory effects with conscious symptom primes are present, but only when the primes are supraliminal, and they did not correlate with repressiveness in a previous study (Shevrin et al., 1992, 1996). We conclude that while the inhibition following supraliminal conscious symptom primes is due to conscious threat bias, the inhibition following subliminal unconscious conflict primes provides a neurological blueprint for dynamic repression: it is only activated subliminally by an individual's unconscious conflict and has an inhibitory effect specific only to the conscious symptom. These novel findings constitute neuroscientific evidence for the psychoanalytic concepts of unconscious conflict and repression, while extending neuroscience theory and methods into the realm of personal, psychological meaning.

Subliminal affect valence words change conscious mood potency but not valence: is this evidence for unconscious valence affect?

Whether or not affect can be unconscious remains controversial. Research claiming to demonstrate unconscious affect fails to establish clearly unconscious stimulus conditions. The few investigations that have established unconscious conditions fail to rule out conscious affect changes. We report two studies in which unconscious stimulus conditions were met and conscious mood changes measured. The subliminal stimuli were positive and negative affect words presented at the objective detection threshold; conscious mood changes were measured with standard manikin valence, potency, and arousal scales. We found and replicated that unconscious emotional stimuli produced conscious mood changes on the potency scale but not on the valence scale. Were positive and negative affects aroused unconsciously, but reflected consciously in potency changes? Or were the valence words unconscious cognitive causes of conscious mood changes being activated without unconscious affect? A thought experiment is offered as a way to resolve this dilemma.

Access is mainly a second-order process: SDT models whether phenomenally (first-order) conscious states are accessed by reflectively (second-order) conscious processes.

Access can either be first-order or second-order. First order access concerns whether contents achieve representation in phenomenal consciousness at all; second-order access concerns whether phenomenally conscious contents are selected for metacognitive, higher order processing by reflective consciousness. When the optional and flexible nature of second-order access is kept in mind, there remain strong reasons to believe that exclusion failure can indeed isolate phenomenally conscious stimuli that are not so accessed. Irvine's [Irvine, E. (2009). Signal detection theory, the exclusion failure paradigm and weak consciousness-Evidence for the access/phenomenal distinction? Consciousness and Cognition.] partial access argument fails because exclusion failure is indeed due to lack of second-order access, not insufficient phenomenally conscious information. Further, the enable account conforms with both qualitative differences and subjective report, and is simpler than the endow account. Finally, although first-order access may be a distinct and important process, second-order access arguably reflects the core meaning of access generally.

Unconscious inhibition and facilitation at the objective detection threshold: replicable and qualitatively different unconscious perceptual effects.

Although the veridicality of unconscious perception is increasingly accepted, core issues remain unresolved [Jack, A., & Shallice, T. (2001). Introspective physicalism as an approach to the science of consciousness. Cognition, 79, 161-196], and sharp disagreement persists regarding fundamental methodological and theoretical issues. The most critical problem is simple but tenacious-namely, how to definitively rule out weak conscious perception as an alternative explanation for putatively unconscious effects. Using a direct task and objectively undetectable stimuli, the current experiments demonstrate clearly reliable unconscious perceptual effects, which differ qualitatively from weakly conscious effects in fundamental ways. Most importantly, the current effects correlate negatively with stimulus detectability, directly rebutting the exhaustiveness, null sensitivity, and exclusiveness problems [Reingold, E., & Merikle, P. (1988). Using direct and indirect measures to study perception without awareness. Perception & Psychophysics, 44, 563-575; Reingold, E., & Merikle, P. (1990). On the inter-relatedness of theory and measurement in the study of unconscious processes. Mind and Language, 5, 9-28)], which all predict positive correlations. Moreover, the current effects are entirely bidirectional [Katz, (2001). Bidirectional experimental effects. Psychological Methods, 6, 270-281)] and radically uncontrollable, including below-chance performance despite intentions to facilitate. In contrast, weakly conscious effects on direct measures are unidirectional, facilitative, and potentially controllable. Moreover, these qualitative differences also suggest that objective and subjective threshold phenomena are fundamentally distinct, rather than the former simply being a weaker version of the latter [Merikle, P., Smilek, D., Eastwood, J. (2001). Perception without awareness: Perspectives from cognitive psychology. Cognition, 79, 115-134]. Accordingly, it is important to distinguish between rather than conflate these methods. Further, the current effects reinforce recent work [e.g. Naccache, L., Blandin, E., & Dehaene, S. (2002). Unconscious masked priming depends on temporal attention. Psychological Science, 13, 416-424] demonstrating that unconscious effects, although not selectively controllable, are nonetheless mediated by strategic and individual difference factors, rather than being immune to such influences as long thought.

Unconscious perception: a model-based approach to method and evidence.

Unconscious perceptual effects remain controversial because it is hard to rule out alternative conscious perception explanations for them. We present a novel methodological framework, stressing the centrality of specifying the single-process conscious perception model (i.e., the null hypothesis). Various considerations, including those of SDT (Macmillan & Creelman, 1991), suggest that conscious perception functions hierarchically, in such a way that higher level effects (e.g., semantic priming) should not be possible without lower level discrimination (i.e., detection and identification). Relatedly, alternative conscious perception accounts (as well as the exhaustiveness, null sensitivity, and exclusiveness problems-Reingold & Merikle, 1988, 1990) predict positive relationships between direct and indirect measures. Contrariwise, our review suggests that negative and/or nonmonotonic relationships are found, providing strong evidence for unconscious perception and further suggesting that conscious and unconscious perceptual influences are functionally exclusive (cf. Jones, 1987), in such a way that the former typically override the latter when both are present. Consequently, unconscious perceptual effects manifest reliably only when conscious perception is completely absent, which occurs at the objective detection (but not identification) threshold.

Characterization of event related potentials using information theoretic distance measures.

Analysis of event-related potentials (ERPs) using signal processing tools has become extremely widespread in recent years. Nonstationary signal processing tools such as wavelets and time-frequency distributions have proven to be especially effective in characterizing the transient phenomena encountered in event-related potentials. In this paper, we focus on the analysis of event-related potentials collected during a psychological experiment where two groups of subjects, spider phobics and snake phobics, are shown the same set of stimulus: A blank stimulus, a neutral stimulus and a spider stimulus. We introduce a new approach, based on time-frequency distributions, for analyzing the ERPs. The difference in brain activity before and after a stimulus is presented is quantified using distance measures as adapted to the time-frequency plane. Three different distance measures, including a new information theoretic distance measure, are applied on the time-frequency plane to discriminate between the responses of the two groups of subjects. The results illustrate the effectiveness of using distance measures combined with time-frequency distributions in differentiating between the two classes of subjects and the different regions of the brain.

The dissociation paradigm and its discontents: how can unconscious perception or memory be inferred?

Erdelyi does us all a great service by his customarily incisive discussion of the various ways in which our field tends to neglect, confuse, and misunderstand numerous critical issues in attempting to differentiate conscious from unconscious perception and memory. Although no single commentary could hope to comprehensively assess these issues, I will address Erdelyi's three main points: (1) How (and if) the dissociation paradigm can be used to validly infer unconscious perception; (2) The implications of below-chance effects; and (3) The role of time. I suggest that (a) significant progress on construct validity issues is possible; (b) below-chance effects are part of a more general bidirectional phenomenon, very likely unconscious, and do not threaten absolute subliminality; and (c) practice/learning effects pose potential difficulties for time-based dissociation paradigms.

Disambiguating conscious and unconscious influences: do exclusion paradigms demonstrate unconscious perception?

Does exclusion failure--responding with previously presented words despite instructions to avoid doing so--demonstrate unconscious influences? This article examines exclusion-based evidence for unconscious perception. I propose an alternative signal detection theory (SDT) framework that can account for exclusion failure and ostensibly convergent qualitative differences without positing additional unconscious perceptual mechanisms. In the proposed SDT model, exclusion failure is a criterion artifact, similar to classic SDT-based critiques of subjective threshold approaches. However, it is suggested that exclusion approaches do demonstrate that response strategies are applied only to above-criterion stimuli and thereby illustrate important qualitative differences between two conscious processes: phenomenal awareness itself and higher-order (i.e., metacognitive) decision processes.