The Qwantify app dataset: A remote experience sampling study of desire, emotion, and well-being.

Experiences of desire-the feeling of wanting to have, do, or experience something-are pervasive and varied. Recent theoretical advances draw attention to characterizing this variation. Thus, this study investigated experiences of desire in everyday life and co-occurring social, physical, and emotional states, including facets of emotional experiences known to be related to well-being (e.g., perceived loneliness and stress). The Qwantify app was designed to run a remote experience sampling study. Through the app, participants were randomly alerted during their daily life to report on their experience in the moment. During the data collection period, any individual could download the freely available Qwantify app and participate in the study, without providing identifying information or communicating with researchers. Similar to other remote experience sampling studies, an incentive for participants to engage in the study was unlocking visualizations of their own data. Over 600 participants downloaded the app, completed the sign-up process, and responded to at least one experience sampling alert. Approximately 40% of these participants went on to respond to 50 alerts. The purpose of this report is to describe this experience sampling dataset such that it can be used to test a variety of hypotheses, including hypotheses regarding individual differences.

Fruits of the Buddhism-science dialogue in contemplative research.

The modern mindfulness movement rests largely on the twin pillars of scientific investigation and Buddhist philosophy of mind. However, in its current form and application, the scientific study of meditation is celebrated while the Buddhist roots of these practices and modes of investigation are often obscured. This paper highlights the utility and value of Buddhist ideas in the context of studying the mind in various domains of contemplative science. The role of Buddhism in the development of this field is discussed, as well as major areas of current influence, including neurophenomenology, subjective experience, attention, self, and the cultivation of prosocial qualities.

The effect of antipsychotic medications on acoustic startle latency in schizophrenia.

Prepulse inhibition of the acoustic startle reflex (PPI) is extensively studied as a biomarker of schizophrenia (SCZ); however, antipsychotic medication can confound the measure. Latency, the time between the startling stimulus and the reflexive eye blink, provides an index of neural processing speed and is 90% heritable. SCZ subjects have slower latency than controls (CON). This study examined the effects of antipsychotic medication on startle latency. 108 CON and 132 SCZ subjects in three medication subgroups (94 on second-generation antipsychotics (SGA), 25 on first-generation antipsychotics (FGA), 13 unmedicated (NoMed)) were tested on a standard acoustic startle paradigm designed to measure startle magnitude, PPI, and latency. Latency was slower in SCZ compared to CON subjects (p=0.005). Latency did not differ between the three SCZ medication groups. When CON were added to that model, both the NoMed subjects (p=0.04) and the SGA subjects (p=0.003) were slower than CON subjects. For PPI, CON did not differ from SCZ analyzed as a single group. When SCZ subjects were divided into medication groups, PPI was lower in NoMed subjects than the CON group (p=0.03), the SGA group (p=0.02) and the FGA group (p=0.05). SCZ subjects on any medication did not differ from CON. Thus, latency was partially normalized by antipsychotic medication, but this did not obscure the slower latency in SCZ compared to CON. Therefore latency is both trait and state related, whereas medication normalized PPI and obscured any difference between SCZ and CON.

Toxoplasma gondii exposure affects neural processing speed as measured by acoustic startle latency in schizophrenia and controls.

The prevalence of Toxoplasma gondii (TOXO) infection in schizophrenia (SCZ) is elevated compared to controls (odds ratio=2.73). TOXO infection is associated with psychomotor slowing in rodents and non-psychiatric humans. Latency of the acoustic startle response, an index of neural processing speed, is the time it takes for a startling stimulus to elicit the reflexive response through a three-synapse subcortical circuit. We report a significant slowing of latency in TOXO seropositive SCZ vs. seronegative SCZ, and in TOXO seropositive controls vs. seronegative controls. Latency was likewise slower in SCZ subjects than in controls. These findings indicate a slowing of neural processing speed with chronic TOXO infection; the slowest startle latency was seen in the TOXO seropositive SCZ group.

Effects of meditation experience on functional connectivity of distributed brain networks.

This study sought to examine the effect of meditation experience on brain networks underlying cognitive actions employed during contemplative practice. In a previous study, we proposed a basic model of naturalistic cognitive fluctuations that occur during the practice of focused attention meditation. This model specifies four intervals in a cognitive cycle: mind wandering (MW), awareness of MW, shifting of attention, and sustained attention. Using subjective input from experienced practitioners during meditation, we identified activity in salience network regions during awareness of MW and executive network regions during shifting and sustained attention. Brain regions associated with the default mode were active during MW. In the present study, we reasoned that repeated activation of attentional brain networks over years of practice may induce lasting functional connectivity changes within relevant circuits. To investigate this possibility, we created seeds representing the networks that were active during the four phases of the earlier study, and examined functional connectivity during the resting state in the same participants. Connectivity maps were then contrasted between participants with high vs. low meditation experience. Participants with more meditation experience exhibited increased connectivity within attentional networks, as well as between attentional regions and medial frontal regions. These neural relationships may be involved in the development of cognitive skills, such as maintaining attention and disengaging from distraction, that are often reported with meditation practice. Furthermore, because altered connectivity of brain regions in experienced meditators was observed in a non-meditative (resting) state, this may represent a transference of cognitive abilities "off the cushion" into daily life.

Mind wandering and attention during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states.

Studies have suggested that the default mode network is active during mind wandering, which is often experienced intermittently during sustained attention tasks. Conversely, an anticorrelated task-positive network is thought to subserve various forms of attentional processing. Understanding how these two systems work together is central for understanding many forms of optimal and sub-optimal task performance. Here we present a basic model of naturalistic cognitive fluctuations between mind wandering and attentional states derived from the practice of focused attention meditation. This model proposes four intervals in a cognitive cycle: mind wandering, awareness of mind wandering, shifting of attention, and sustained attention. People who train in this style of meditation cultivate their abilities to monitor cognitive processes related to attention and distraction, making them well suited to report on these mental events. Fourteen meditation practitioners performed breath-focused meditation while undergoing fMRI scanning. When participants realized their mind had wandered, they pressed a button and returned their focus to the breath. The four intervals above were then constructed around these button presses. We hypothesized that periods of mind wandering would be associated with default mode activity, whereas cognitive processes engaged during awareness of mind wandering, shifting of attention and sustained attention would engage attentional subnetworks. Analyses revealed activity in brain regions associated with the default mode during mind wandering, and in salience network regions during awareness of mind wandering. Elements of the executive network were active during shifting and sustained attention. Furthermore, activations during these cognitive phases were modulated by lifetime meditation experience. These findings support and extend theories about cognitive correlates of distributed brain networks.

Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls.

The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning.

Lack of relationship between acoustic startle and cognitive variables in schizophrenia and control subjects.

Measures of acoustic startle such as prepulse inhibition (PPI) and startle latency have been found to be impaired in schizophrenia, and are commonly thought to be related to cognitive deficits in this disease. However, findings about the relationship between startle variables and cognitive performance have been equivocal. In this study, we examined correlations between startle measures (baseline startle magnitude, latency, habituation and PPI) and cognitive performance (using the Benton Visual Retention Test, Conner's Continuous Performance Test, California Verbal Learning Test, Finger Tapping Test, and Wisconsin Card Sort Test) in 107 schizophrenia patients and 94 healthy controls. Overall, there was a lack of any significant relationship between these constructs in both populations when correcting for multiple comparisons. This suggests that alterations in startle measures seen in schizophrenia may not reflect elements of information processing that cause cognitive deficits in the disease.

Altered engagement of attention and default networks during target detection in schizophrenia.

Recent studies have implicated inappropriate engagement of functional brain networks in schizophrenia. This fMRI study examined task-induced activations and deactivations in 10 schizophrenia patients with prominent negative symptoms and 10 healthy controls during a simple target detection task. Group comparison revealed recruitment of distinct attentional networks during this task, with schizophrenia subjects activating the dorsal attention system and controls activating the executive network. Further, schizophrenia patients failed to deactivate posterior cingulate regions during the task, supporting recent studies of altered default mode processing. These findings support theories of dysfunctional recruitment of large-scale brain networks in schizophrenia.

Spatiotemporal dynamics of low frequency BOLD fluctuations in rats and humans.

Most studies involving spontaneous fluctuations in the BOLD signal extract connectivity patterns that show relationships between brain areas that are maintained over the length of the scanning session. In this study, however, we examine the spatiotemporal dynamics of the BOLD fluctuations to identify common patterns of propagation within a scan. A novel pattern finding algorithm was developed for detecting repeated spatiotemporal patterns in BOLD fMRI data. The algorithm was applied to high temporal resolution T2*-weighted multislice images obtained from rats and humans in the absence of any task or stimulation. In rats, the primary pattern consisted of waves of high signal intensity, propagating in a lateral to medial direction across the cortex, replicating our previous findings (Majeed et al., 2009a). These waves were observed primarily in sensorimotor cortex, but also extended to visual and parietal association areas. A secondary pattern, confined to subcortical regions consisted of an initial increase and subsequent decrease in signal intensity in the caudate-putamen. In humans, the most common spatiotemporal pattern consisted of an alteration between activation of areas comprising the "default-mode" (e.g., posterior cingulate and anterior medial prefrontal cortices) and the "task-positive" (e.g., superior parietal and premotor cortices) networks. Signal propagation from focal starting points was also observed. The pattern finding algorithm was shown to be reasonably insensitive to the variation in user-defined parameters, and the results were consistent within and between subjects. This novel approach for probing the spontaneous network activity of the brain has implications for the interpretation of conventional functional connectivity studies, and may increase the amount of information that can be obtained from neuroimaging data.

Heritability of acoustic startle magnitude, prepulse inhibition, and startle latency in schizophrenia and control families.

Prepulse inhibition (PPI) is an acoustic startle paradigm that has been used as an operational measure of sensorimotor gating. Many patients with schizophrenia have impaired PPI, and several lines of evidence suggest that PPI may represent a heritable endophenotype in this disease. We examined startle magnitude and latencies in 40 schizophrenia patients, 58 first-degree relatives of these patients, and 100 healthy controls. After removing low-startlers, we investigated PPI and startle habituation in 34 schizophrenia patients, 43 relatives, and 86 control subjects. Heritability analyses were conducted using a variance-component approach. We found significant heritability of 45% for PPI at the 60-ms interval and 67% for startle magnitude. Onset latency heritability estimates ranged between 39% and 90% across trial types, and those for peak latency ranged from 29% to 68%. Heritability of startle habituation trended toward significance at 31%. We did not detect differences between controls and either schizophrenia patients or their family members for PPI, startle magnitude, or habituation. Startle latencies were generally longer in schizophrenia patients than controls. The heritability findings give impetus to applying genetic analyses to PPI variables, and suggest that startle latency may also be a useful measure in the study of potential endophenotypes for schizophrenia.

Ethanol self-administration modulation of NMDA receptor subunit and related synaptic protein mRNA expression in prefrontal cortical fields in cynomolgus monkeys.

BACKGROUND: Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR) complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication, and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in the alcohol-addicted state. METHODS AND RESULTS: The effects of chronic ethanol self-administration on glutamate receptor ionotropic NMDA (GRIN), as well as GRIN1 splice variant mRNA expression was studied in the orbitofrontal cortex (OFC; Area 13), dorsolateral prefrontal cortex (DLPFC; Area 46) and anterior cingulate cortex (ACC; Area 24) of male cynomolgus monkeys. Chronic ethanol self-administration resulted in significant changes in the expression of NMDA subunit mRNA expression in the DLPFC and OFC, but not the ACC. In DLPFC, the overall expression of NMDA subunits was significantly decreased in ethanol treated monkeys. Slight but significant changes were observed for synaptic associated protein 102 kD (SAP102) and neuronal nitric oxide synthase (nNOS) mRNAs. In OFC, the NMDAR1 variant GRIN1-1 was reduced while GRIN1-2 was increased. Furthermore, no significant changes in GFAP protein levels were observed in either the DLPFC or OFC. CONCLUSION: Results from these studies provide the first demonstration of posttranscriptional regulation of iGluR subunits in the primate brain following long-term ethanol self-administration. Furthermore, changes in these transcripts do not appear to reflect changes in glial activation or loss. Further studies examining the expression and cellular localization of subunit proteins and receptor pharmacology would shed more light on the findings reported here.

Differences in startle reflex and prepulse inhibition in European-Americans and African-Americans.

The acoustic startle reflex and its modulation by a prepulse are psychophysiological phenomena that are commonly studied to evaluate various aspects of information processing. Recent reports in human populations suggest that subjects from disparate racial backgrounds may have significant differences in the startle response. To determine if this pattern could be observed in our subject population and whether it extended to prepulse inhibition (PPI), we evaluated baseline startle parameters and PPI in 53 African-Americans (AA) and 38 European-Americans (EA). In AA compared to EA, mean startle magnitude and probability of blink response were lower, with no difference in habituation. PPI was greater in AA than EA when groups were matched on baseline startle magnitude. These findings support the idea of racial differences in startle response. Implications for study design are highlighted, and possible environmental and genetic influences are considered.

Relation of neurological soft signs to psychiatric symptoms in schizophrenia.

INTRODUCTION: Although several studies have identified abnormal rates of neurological soft signs (NSS) as a manifestation of CNS dysfunction in schizophrenia, differences in sample populations have contributed to a discrepancy in empirical findings. Furthermore, little is known about the potential of NSS to predict a clinical response to antipsychotic medications. The present study tests the associations between NSS and schizophrenia symptomatology and examines NSS as a potential marker for predicting treatment response. METHODS: Nineteen unmedicated male schizophrenia patients were treated prospectively with haloperidol for six weeks. The subjects were assessed for pre and post-treatment NSS and schizophrenia symptomatology (Brief Psychiatric Rating Scale, BPRS). RESULTS: NSS at baseline were significantly associated with baseline symptoms on the Positive, Negative, and Psychological Discomfort BPRS subscales. NSS showed a strong trend toward improvement during six weeks of a prospective haloperidol trial. Hierarchical linear regression analyses indicated that more severe baseline NSS predicted poorer response to haloperidol treatment as measured by post-treatment BPRS Total subscale scores. DISCUSSION: NSS at untreated baseline are associated with baseline symptom severity, and elevated NSS are predictive of a smaller degree of improvement in symptoms after antipsychotic treatment. These findings are consistent with the hypothesis that NSS are linked to the neuropathology that underlies schizophrenia symptomatology and course.

Region specific regulation of NR1 in rhesus monkeys following chronic antipsychotic drug administration.

BACKGROUND: Altered NMDA receptor subunit protein levels have been reported in various regions of the schizophrenic brain; however, chronic antipsychotic administration in schizophrenic subjects may confound interpretation. METHODS: The effects of chronic antipsychotic drug administration (haloperidol and clozapine) on protein levels of NR1, NR2A and NR2B proteins were evaluated in the nucleus accumbens (NAc), putamen (PUT), dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), and entorhinal cortex (EC) of rhesus monkeys using Western blot analysis. RESULTS: Haloperidol administration significantly decreased NR1 expression in the DLPFC. In contrast, NR2B expression was not affected by antipsychotic administration in any brain region examined. NR2A was not reliably detected in any of the brain regions. CONCLUSIONS: Results indicate that the NR1 subunit in the DLPFC may be a substrate for antipsychotic action and that glutamatergic hypofunction in the DLPFC commonly associated with cognitive dysfunction in schizophrenia may be associated with haloperidol administration.

Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemia.

Hypertrophy is one mechanism of pancreatic beta-cell growth and is seen as an important compensatory response to insulin resistance. We hypothesized that the induction of protective genes contributes to the survival of enlarged (hypertrophied) beta-cells. Here, we evaluated changes in stress gene expression that accompany beta-cell hypertrophy in islets from hyperglycemic rats 4 weeks after partial pancreatectomy (Px). A variety of protective genes were upregulated, with markedly increased expression of the antioxidant genes heme oxygenase-1 and glutathione peroxidase and the antiapoptotic gene A20. Cu/Zn-superoxide dismutase (SOD) and Mn-SOD were modestly induced, and Bcl-2 was modestly reduced; however, several other stress genes (catalase, heat shock protein 70, and p53) were unaltered. The increases in mRNA levels corresponded to the degree of hyperglycemia and were reversed in Px rats by 2-week treatment with phlorizin (treatment that normalized hyperglycemia), strongly suggesting the specificity of hyperglycemia in eliciting the response. Hyperglycemia in Px rats also led to activation of nuclear factor-kappaB in islets. The profound change in beta-cell phenotype of hyperglycemic Px rats resulted in a reduced sensitivity to the beta-cell toxin streptozotocin. Sensitivity to the toxin was restored, along with the beta-cell phenotype, in islets from phlorizin-treated Px rats. Furthermore, beta-cells of Px rats were not vulnerable to apoptosis when further challenged in vivo with dexamethasone, which increases insulin resistance. In conclusion, beta-cell adaptation to chronic hyperglycemia and, hence, increased insulin demand is accompanied by the induction of protective stress genes that may contribute to the survival of hypertrophied beta-cells.