Incidental Activation Research Articles

Axonal stimulation affects the linear summation of single-point perception in three Argus II users.

Objective.Retinal implants use electrical stimulation to elicit perceived flashes of light ('phosphenes'). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation.Approach.We retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ('between-axon') and along axon bundles ('along-axon'). Statistical analyses were conducted using linear regression and partial correlation analysis.Main results.Simple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p < .001). Multiple regression revealed that paired-electrode phosphene shape was primarily predicted by stimulus amplitude and electrode-fovea distance (p < .05). Interestingly, the number of elicited phosphenes tended to increase with between-axon distance (p < .05), but not with along-axon distance, in two out of three participants.Significance.The shape of phosphenes elicited by paired-electrode stimulation was well predicted by the shape of their corresponding single-electrode phosphenes, suggesting that two-point perception can be expressed as the linear summation of single-point perception. The impact of the between-axon distance on the perceived number of phosphenes provides further evidence in support of the axon map model for epiretinal stimulation. These findings contribute to the growing literature on phosphene perception and have important implications for the design of future retinal prostheses.

Brown Adipose Tissue: A Protective Mechanism Against "Preprediabetes"?

Brown adipose tissue (BAT) is present in a significant number of adult humans and has been postulated to exert beneficial metabolic effects. Lean, nondiabetic patients undergoing clinical PET/CT imaging are more likely to exhibit incidental BAT activation. The aim of this study was to assess metabolic changes associated with the cold activation of BAT and to compare baseline blood metabolites in participants with varying amounts of active BAT. Methods: Serum blood samples were collected from healthy adult volunteers (body mass index, 18.0-25.0, and age ≤ 35 y) before and after 2 h of exposure to cold. 18F-FDG PET/CT imaging was performed immediately after cold exposure. Activated BAT was segmented, and fasting glucose, insulin, lipid, and other blood metabolite levels were correlated with volume and intensity of active BAT. Using a median cutoff, subjects were classified as high-BAT (BAThigh) or low-BAT (BATlow). Results: A higher volume of activated BAT was associated with significantly higher precooling glucose and insulin levels (P < 0.001 for each). Precooling thyroid-stimulating hormone and triglyceride levels were significantly higher in the BAThigh than the BATlow group (P = 0.002 and P < 0.001, respectively). Triglyceride levels tended to increase over the cooling period in both BAT groups but increased significantly more in the BAThigh group (15.7 ± 13.2 mg/dL; P < 0.001) than in the BATlow group (4.5 ± 12.2 mg/dL; P = 0.061). Conclusion: These findings may indicate that BAT is recruited to counteract incipient "preprediabetic" states, potentially serving as a first-line protective mechanism against very early metabolic or hormonal variations.

Optogenetic stimulation of pericytes lacking alpha smooth muscle actin produces a decrease in capillary blood flow in the living mouse brain

Impaired cerebral blood flow contributes to the pathogenesis of numerous neurological diseases, ranging from dementia to traumatic brain injury. It is critical that we understand the cell types that control cerebral blood flow, so that we can target them to correct blood flow impairments and improve the trajectory of these diseases. Although it is accepted that vascular smooth muscle cells encircling arterioles can control blood flow, it is debated whether pericytes, which collectively adorn over 90% of the brain's vascular length, can also influence blood flow. To clarify the ability of pericytes to influence blood flow, we stimulated channelrhodopsin (ChR2) in individual pericytes using two photon illumination, as done previously (Hill, et al. Neuron 2015). Although we used mice that express ChR2 in both smooth muscle cells and pericytes, the spatial specificity of two photon excitation permitted selective optogenetic stimulation of individual pericytes, thus avoiding incidental activation of nearby vascular smooth muscle cells that also express ChR2. Simultaneously, with the same two photon laser used for excitation of ChR2 in pericytes, we measured capillary diameter and red blood cell velocity (RBCV) using intravenous dextrans. We found that pericyte excitation for 60 seconds produced a ~20% reduction in diameter and RBCV, indicating that pericytes can indeed influence blood flow. Surprisingly, the magnitude and kinetics of the decreases in diameter and RBCV were not different between pericytes with and without expression of alpha smooth muscle actin, a protein believed to be required for vascular contraction and blood flow control. Importantly, identical stimulation parameters did not produce hemodynamic changes in control mice with cytosolic YFP or membrane-bound GFP in smooth muscle cells and pericytes, indicating that our observed reductions in blood flow in ChR2 mice were not an artifactual result of light illumination, animal movement, or tissue damage. Further, the observed decrease in velocity and diameter in response to pericyte ChR2 stimulation was inhibited when we applied fasudil, a Rho kinase inhibitor and clinically-used vasodilator, to an intact dura (dose of 10 mM). Our results to date suggest that pericytes, even those without alpha smooth muscle actin, have the capacity to modulate blood flow. These findings will advance our understanding of vascular biology, and could be relevant for treating disease processes associated with deficits in capillary blood flow, such as dementia and traumatic brain injury. Support or Funding Information A.Y.S. thanks his support: NS085402, NS096997, NS097775, P20GM12345, NSF 1539034, AHA 14GRNT20480366, Alzheimer's Association, and CCAD. D.A.H. thanks his support: UL1 TR001450, TL1 TR001451, and F30NS096868. We optogenetically stimulated individual pericytes in vivo using two photon microscopy (A), and observed a significant decrease in the diameter and red blood cell flow in the underlying capillary (B). Surprisingly, similar responses were seen between pericytes with and without expression of alpha smooth muscle actin, an important protein in canonical vascular contraction mechanisms. Pericytes can therefore modulate blood flow using non-canonical mechanisms that can be targeted for therapies. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Arousal and Subjective Significance Shapes Stimuli Interpretation across Warmth Vs. Competence Dimensions

The current study sought to examine the impact of incidental activation defined as arousal and subjective significance, both represented in connotations of verbal materials, on social perception of unknown and thus ambiguous objects, in terms of two basic dimensions of social cognition: warmth and competence. Arousal was expected to promote interpretation of ambiguous stimuli in terms of warmth, while subjective significance in terms of competence. This means that both activation and social perception may be treated as examples dual-mind systems functioning. Sixty participants (30 women) were exposed to two subsequent tasks. The first involved memorizing 135 words (manipulation prepared in a factorial design contrasting 3 levels of arousal and 3 levels of subjective significance), and the second involved guessing the meaning of hexagram stimuli derived from Far East culture. An increasing level of arousal caused participants to interpret stimuli as increasingly related to warmth, while an increasing level of subjective significance led to interpretations more related to competence. This study shows that two distinct types of activation may trigger different interpretations of social stimuli, which means that there is a link between both types of processes. This finding is of great importance for the dual-mind approach, showing that a multitude of dualities indentified thus far may be related one another. Therefore, it is justified to treat them as emanations of more general mental systems.

Because they were there: Access, deliberation, and the mobilization of networks for support

When people need help, what is the process through which they decide whom in their network to turn to? Research on social support has described a process that is deliberative in nature: people determine their needs, assess who in their network has the needed attributes—such as skill, trustworthiness, intimacy, and accessibility—and then activate that tie. Nevertheless, research in behavioral economics and other fields has shown that people make many decisions not deliberatively but intuitively. We examine this possibility in the context of social support by focusing on one factor: accessibility. Although researchers have argued that people weigh the accessibility of potential helpers as they do any other attribute, accessibility may be not only an attribute of the helper but also a condition of the situation. We develop a framework to make this question tractable for survey research and evaluate competing hypotheses using original data on an analytically strategic sample of ∼2000 college students, probing concrete instances of social support. We identify and document not one but three decision processes, reflective, incidental, and spontaneous activation, which differ in the extent to which actors had deliberated on whether to seek help and on whom to approach before activating the tie. We find that while the process was reflective (consistent with existing theory) when skill or trustworthiness played a role, it was significantly less so (consistent with the alternative) when accessibility did. Findings suggest that actors decide whom in their network to mobilize through at least three systematically different processes, two of which are consistent less with either active “mobilization” or explicit “help seeking” than with responsiveness to opportunity and context.

The Effect of Incidental Semantic Activation on Hypothesis Generation: Exclusive vs Compatible Hypotheses

The Effect of Incidental Semantic Activation on Hypothesis Generation: Exclusive vs Compatible Hypotheses

Abnormal dynamics of activation of object use information in apraxia: Evidence from eyetracking

Action representations associated with object use may be incidentally activated during visual object processing, and the time course of such activations may be influenced by lexical–semantic context (e.g., Lee, Middleton, Mirman, Kalénine, & Buxbaum (2012). Journal of Experimental Psychology: Human Perception and Performance, 39(1), 257–270). In this study we used the “visual world” eye-tracking paradigm to examine whether a deficit in producing skilled object-use actions (apraxia) is associated with abnormalities in incidental activation of action information, and assessed the neuroanatomical substrates of any such deficits. Twenty left hemisphere stroke patients, ten of whom were apraxic, performed a task requiring identification of a named object in a visual display containing manipulation-related and unrelated distractor objects. Manipulation relationships among objects were not relevant to the identification task. Objects were cued with neutral (“S/he saw the….”), or action-relevant (“S/he used the….”) sentences. Non-apraxic participants looked at use-related non-target objects significantly more than at unrelated non-target objects when cued both by neutral and action-relevant sentences, indicating that action information is incidentally activated. In contrast, apraxic participants showed delayed activation of manipulation-based action information during object identification when cued by neutral sentences. The magnitude of delayed activation in the neutral sentence condition was reliably predicted by lower scores on a test of gesture production to viewed objects, as well as by lesion loci in the inferior parietal and posterior temporal lobes. However, when cued by a sentence containing an action verb, apraxic participants showed fixation patterns that were statistically indistinguishable from non-apraxic controls. In support of grounded theories of cognition, these results suggest that apraxia and temporal–parietal lesions may be associated with abnormalities in incidental activation of action information from objects. Further, they suggest that the previously-observed facilitative role of action verbs in the retrieval of object-related action information extends to participants with apraxia.

Using Neural Pattern Classifiers to Quantify the Modularity of Conflict-Control Mechanisms in the Human Brain

Resolving conflicting sensory and motor representations is a core function of cognitive control, but it remains uncertain to what degree control over different sources of conflict is implemented by shared (domain general) or distinct (domain specific) neural resources. Behavioral data suggest conflict-control to be domain specific, but results from neuroimaging studies have been ambivalent. Here, we employed multivoxel pattern analyses that can decode a brain region's informational content, allowing us to distinguish incidental activation overlap from actual shared information processing. We trained independent sets of "searchlight" classifiers on functional magnetic resonance imaging data to decode control processes associated with stimulus-conflict (Stroop task) and ideomotor-conflict (Simon task). Quantifying the proportion of domain-specific searchlights (capable of decoding only one type of conflict) and domain-general searchlights (capable of decoding both conflict types) in each subject, we found both domain-specific and domain-general searchlights, though the former were more common. When mapping anatomical loci of these searchlights across subjects, neural substrates of stimulus- and ideomotor-specific conflict-control were found to be anatomically consistent across subjects, whereas the substrates of domain-general conflict-control were not. Overall, these findings suggest a hybrid neural architecture of conflict-control that entails both modular (domain specific) and global (domain general) components.

Incidental and context-responsive activation of structure- and function-based action features during object identification.

Previous studies suggest that action representations are activated during object processing, even when task-irrelevant. In addition, there is evidence that lexical-semantic context may affect such activation during object processing. Finally, prior work from our laboratory and others indicates that function-based ("use") and structure-based ("move") action subtypes may differ in their activation characteristics. Most studies assessing such effects, however, have required manual object-relevant motor responses, thereby plausibly influencing the activation of action representations. The present work uses eyetracking and a Visual World Paradigm task without object-relevant actions to assess the time course of activation of action representations, as well as their responsiveness to lexical-semantic context. In two experiments, participants heard a target word and selected its referent from an array of four objects. Gaze fixations on nontarget objects signal activation of features shared between targets and nontargets. The experiments assessed activation of structure-based (Experiment 1) or function-based (Experiment 2) distractors, using neutral sentences ("S/he saw the....") or sentences with a relevant action verb (Experiment 1: "S/he picked up the...."; Experiment 2: "S/he used the...."). We observed task-irrelevant activations of action information in both experiments. In neutral contexts, structure-based activation was relatively faster-rising but more transient than function-based activation. Additionally, action verb contexts reliably modified patterns of activation in both Experiments. These data provide fine-grained information about the dynamics of activation of function-based and structure-based actions in neutral and action-relevant contexts, in support of the "Two Action System" model of object and action processing (e.g., Buxbaum & Kalénine, 2010).

Damage to temporo-parietal cortex decreases incidental activation of thematic relations during spoken word comprehension

Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to examine incidental activation of taxonomic and thematic relations during spoken word comprehension in participants with aphasia. Three groups of participants were tested: neurologically intact control participants (N=14), individuals with aphasia resulting from lesions in left hemisphere BA 39 and surrounding temporo-parietal cortex regions (N=7), and individuals with the same degree of aphasia severity and semantic impairment and anterior left hemisphere lesions (primarily inferior frontal gyrus and anterior temporal lobe) that spared BA 39 (N=6). The posterior lesion group showed reduced and delayed activation of thematic relations, but not taxonomic relations. In contrast, the anterior lesion group exhibited longer-lasting activation of taxonomic relations and did not differ from control participants in terms of activation of thematic relations. These results suggest that taxonomic and thematic semantic knowledge are functionally and neuroanatomically distinct, with the temporo-parietal cortex playing a particularly important role in thematic semantics.

A Combination of Thematic and Similarity-Based Semantic Processes Confers Resistance to Deficit Following Left Hemisphere Stroke

Semantic knowledge may be organized in terms of similarity relations based on shared features and/or complementary relations based on co-occurrence in events. Thus, relationships between manipulable objects such as tools may be defined by their functional properties (what the objects are used for) or thematic properties (e.g., what the objects are used with or on). A recent study from our laboratory used eye-tracking to examine incidental activation of semantic relations in a word–picture matching task and found relatively early activation of thematic relations (e.g., broom–dustpan), later activation of general functional relations (e.g., broom–sponge), and an intermediate pattern for specific functional relations (e.g., broom–vacuum cleaner). Combined with other recent studies, these results suggest that there are distinct semantic systems for thematic and similarity-based knowledge and that the “specific function” condition drew on both systems. This predicts that left hemisphere stroke that damages either system (but not both) may spare specific function processing. The present experiment tested these hypotheses using the same experimental paradigm with participants with left hemisphere lesions (N = 17). The results revealed that, compared to neurologically intact controls (N = 12), stroke participants showed later activation of thematic and general function relations, but activation of specific function relations was spared and was significantly earlier for stroke participants than controls. Across the stroke participants, activation of thematic and general function relations was negatively correlated, further suggesting that damage tended to affect either one semantic system or the other. These results support the distinction between similarity-based and complementarity-based semantic relations and suggest that relations that draw on both systems are relatively more robust to damage.

Conceptual and non-conceptual repetition priming in category exemplar generation: Evidence from bilinguals

One measure of conceptual implicit memory is repetition priming in the generation of exemplars from a semantic category, but does such priming transfer across languages? That is, do the overlapping conceptual representations for translation equivalents provide a sufficient basis for such priming? In Experiment 1 (N=96) participants carried out a deep encoding task, and priming between languages was statistically reliable, but attenuated, relative to within-language priming. Experiment 2 (N=96) replicated the findings of Experiment 1 and assessed the contributions of conceptual and non-conceptual processes using a levels-of-processing manipulation. Words that underwent shallow encoding exhibited within-language, but not between-language, priming. Priming in shallow conditions cannot therefore be explained by incidental activation of the concept. Instead, part of the within-language priming effect, even under deep-encoding conditions, is due to increased availability of language-specific lemmas or phonological word forms.

Self-regulatory cognition and immune reactivity: idiographic success and failure feedback effects on the natural killer cell

Inducing depressed and anxious individuals to write about their personal goals decreases natural killer (NK) cell activity, revealing a psychobiological pathway whereby experiences of failure can influence health ( Strauman et al., 1993). However, it is unclear whether similar effects also occur in non-distressed individuals. This study used the same writing task to examine the acute physiological effects of presenting idiographic success and failure feedback by priming self-congruencies or self-discrepancies on three occasions (including a control condition). Blood samples were collected after each writing session to determine NK activity, and the number and type of lymphocytes in circulation were enumerated to help explain the cytolytic changes. The two self-relevant priming conditions were associated with significant alterations in immunity, and the high self-discrepant participants were more responsive. Both self-congruent (success) and self-discrepant (failure) priming induced significant shifts in mood, which partially mediated immune alterations but did not account for them completely. If repeated and sustained over time, incidental activation of self-discrepancies and self-congruencies could account for individual variation in immune responses.

Oxidative stress and cardiovascular injury: Part II: animal and human studies.

This review so far has considered the role of vascular cells in the generation of reactive oxygen species (ROS) and novel approaches to their detection in integrated systems such as animal models of vascular disease and humans. We now turn attention to evidence consistent with a role for ROS in models of human disease and in discrete patient populations. We also briefly comment on the outcomes of clinical trials of antioxidants. Mainly, these have been disappointing. However, it is premature to conclude that the oxidation hypothesis of disease causality has been adequately tested. Animal studies, for the most part, support a fundamental role for ROS in cardiovascular disease. Any controversy could in part reflect the use of ineffective antioxidants and the selection of models in which ROS generation is of marginal relevance to the measured outcome. Both of these issues require a quantitatively accurate measurement of drug effect (ie, antioxidant capacity) before hypotheses relating to the role of oxidant stress can be addressed rationally. These issues pertain to clinical trials also, as we will discuss. However, animal studies permit administration of much more powerful antioxidants (eg, rate constant for interaction of superoxide dismutase (SOD) with O2·− ≈1.6×109 · mol/L−1 · s−1) than is possible in humans (eg, rate constant for vitamin E ≈0.59 mol/L−1 · s−1) or, like in the case of vitamin E, doses of the antioxidant in excess of those usually applied in clinical research. ### Atherosclerosis Animal models of atherosclerosis have documented that all the constituents of the plaque produce and use ROS. Lesion formation is associated with the accumulation of lipid peroxidation products1,2 and induction of inflammatory genes,3 inactivation of NO·resulting in endothelial dysfunction, 4,5 activation of matrix metalloproteinases,6 and increased smooth muscle cell growth.7 …

Phonological Activation in Anaphoric Lexical Access (ALA)

Simner and Smyth (1998) propose that anaphoric lexical access (ALA) occurs at an anaphor and targets the lexical entry (specifically, the lemma) of the antecedent. Since the word frequency effect (e.g., Rubenstein et al., 1970) resides at the lexeme (Jescheniak & Levelt, 1994) Simner and Smyth predict, and subsequently illustrate, that ALA exhibits no frequency effect. A problem arises, however: if ALA does not access the lexeme, how do we account for phonological priming at anaphor sites (e.g., Tanenhaus et al., 1985)? We claim that this is the result of “incidental” lemma-to-lexeme activation. Furthermore, we argue that since lexeme activation is not crucial to anaphor comprehension, anaphor reading times indicate lemma search times only (therefore there is no frequency effect).An experiment is presented demonstrating that lemma-access during ALA can cause incidental lexeme activation without invoking a frequency effect.

Functional Characterization of the Ocular Prostaglandin F2α (PGF2α) Receptor: ACTIVATION BY THE ISOPROSTANE, 12-iso-PGF2α

Prostaglandin F2alpha (PGF2alpha) is a product of cyclooxygenase-catalyzed metabolism of arachidonic acid. Recently, PGF2alpha analogs have been hypothesized to reduce intraocular pressure via relaxation of the ciliary muscle. To investigate the molecular basis of PGF2alpha receptor (FP) activation in the eye, we cloned the FP from a human ciliary body (hcb) cDNA library. The open reading frame of the hcb-FP cDNA was identical to the uterine FP cDNA. The hcb-FP appeared to be predominantly membrane-localized, as visualized by an FP-specific peptide antibody, and coupled to inositol phosphate formation when stably expressed in HEK 293 cells. Interestingly, the hcb-FP could also be activated by the F2 isoprostane, 12-iso-PGF2alpha, in addition to its cognate ligand, PGF2alpha. 12-iso-PGF2alpha was less potent (EC50 = 5 microM) than PGF2alpha (EC50 = 10 nM) in generating inositol phosphates via the hcb-FP in HEK 293 cells. Both ligands also stimulated mitogenesis in NIH 3T3 cells. Although 12-iso-PGF2alpha caused a dose-dependent activation of the FP, it failed to activate the recombinant human prostacyclin receptor and caused only minimal activation of the thromboxane receptor isoforms stably expressed in HEK 293 cells. Four additional F2 isoprostanes, 8-iso-PGF2alpha, IPF2alpha-I, IPF2alpha-III, and 9beta,11beta-PGF2, caused trivial, or no, activation of the FP. Consistent with these observations, only PGF2alpha and 12-iso-PGF2alpha caused rapid homologous desensitization of FP and also exhibited cross-desensitization, with PGF2alpha resulting in a maximum of approximately 60% desensitization. The human FP may thus be activated specifically, by the free radical-catalyzed F2 isoprostane, 12-iso-PGF2alpha, in addition to the cyclooxygenase product, PGF2alpha. Incidental receptor activation by isoprostanes may complement the actions of PGF2alpha in clinical syndromes where oxidant stress and augmented prostaglandin biosynthesis coincide.

Local Amplification of Platelet Function by 8-Epi Prostaglandin F2α Is Not Mediated by Thromboxane Receptor Isoforms

8-epi-Prostaglandin (PG) F2alpha may be formed by cyclooxygenases 1 and 2 or by a free radical catalyzed process as an isoprostane. Concentrations of 8-epi-PGF2alpha in the range 1 nM to 1 microM induce a dose-dependent increase in platelet shape change, in calcium release from intracellular stores [Ca2+]iand in inositol phosphates; it also causes irreversible platelet aggregation, dependent on thromboxane generation, when incubated with subthreshold concentrations of ADP, thrombin, collagen, and arachidonic acid. Much higher concentrations of 8-epi-PGF2alpha (10-20 microM) alone induce weak, reversible aggregation. Although these effects are prevented by pharmacological thromboxane receptor antagonists, they are unlikely to be mediated by thromboxane receptors. Thus, 8-epi-PGF2alpha does not compete for binding at the stably expressed placental or endothelial isoforms of the thromboxane receptor or for binding of thromboxane ligands to human platelets. Furthermore, the response to 8-epi PGF2alpha exhibits structural specificity versus 8-epi PGF3alpha and PGF2alpha. Concentrations in the range that evoke its effects on platelets do not desensitize the aggregation response stimulated by thromboxane or PGH2 analogs. Unlike primary prostaglandins, which are rapidly metabolized to inactive products, 8-epi PGF2alpha circulates in plasma. However, the systemic concentrations found in healthy volunteers (median 48 pmol/liter) and in patients with hepatic cirrhosis (median 147 pmol/liter), a syndrome of oxidant stress in vivo, fall well below those which modulate platelet function. 8-Epi PGF2alpha may amplify the response to platelet agonists in syndromes where oxidant stress and platelet activation coincide. Despite blockade by thromboxane antagonists, 8-epi PGF2alpha does not activate either of the thromboxane receptor isoforms described in platelets. Activation of a distinct receptor would be consistent with the enzymatic formation of 8-epi PGF2alpha by cyclooxygenases. However, incidental activation of such a receptor by systemic concentrations of 8-epi PGF2alpha is unlikely to occur, even in syndromes of excessive free radical generation in vivo.