Neurophysiological analysis of disadvantageous social inequity: Exploring emotional behavior changes and c-Fos expression in a male rat model.

Humans and other animals exhibit aversive behavioral and emotional responses to unequal reward distributions compared with their conspecifics. Despite the significance of this phenomenon, experimental animal models designed to investigate social inequity aversion and delve into the underlying neurophysiological mechanisms are limited. In this study, we developed a rat model to determine the effects of socially equal or unequal reward and stress on emotional changes in male rats. During the training session, the rats were trained to escape when a sound cue was presented, and they were assigned to one of the following groups: all escaping rats [advantageous equity (AE)], freely moving rats alongside a restrained rat [advantageous inequity (AI)], all restrained rats [disadvantageous equity (DE)], and a rat restrained in the presence of freely moving companions [disadvantageous inequity (DI)]. During the test session, rats in the advantageous group (AE and AI) escaped after the cue sound (expected reward acquisition), whereas rats in the disadvantageous group (DE and DI) could not escape despite the cue being presented (expected reward deprivation). Emotional alteration induced by exposure to restraint stress under various social interaction circumstances was examined using an open field test. Notably, the DI group displayed reduced exploration of the center zone during the open field tests compared with the other groups, indicating heightened anxiety-like behaviors in response to reward inequity. Immunohistochemical analysis revealed increased c-Fos expression in the medial prefrontal and orbitofrontal cortices, coupled with reduced c-Fos expression in the striatum and nucleus accumbens under DI conditions, in contrast to the other experimental conditions. These findings provide compelling evidence that rats are particularly sensitive to reward inequity, shedding light on the neurophysiological basis for distinct cognitive processes that manifest when individuals are exposed to social equity and inequity situations.

Antipsychotic drug use complicates assessment of gene expression changes associated with schizophrenia.

Recent postmortem transcriptomic studies of schizophrenia (SCZ) have shown hundreds of differentially expressed genes. However, the extent to which these gene expression changes reflect antipsychotic drug (APD) exposure remains uncertain. We compared differential gene expression in the prefrontal cortex of SCZ patients who tested positive for APDs at the time of death with SCZ patients who did not. APD exposure was associated with numerous changes in the brain transcriptome, especially among SCZ patients on atypical APDs. Brain transcriptome data from macaques chronically treated with APDs showed that APDs affect the expression of many functionally relevant genes, some of which show expression changes in the same directions as those observed in SCZ. Co-expression modules enriched for synaptic function showed convergent patterns between SCZ and some of the APD effects, while those associated with inflammation and glucose metabolism exhibited predominantly divergent patterns between SCZ and APD effects. In contrast, major cell-type shifts inferred in SCZ were primarily unaffected by APD use. These results show that APDs may confound SCZ-associated gene expression changes in postmortem brain tissue. Disentangling these effects will help identify causal genes and improve our neurobiological understanding of SCZ.

The Role of Molecular and Inflammatory Indicators in the Assessment of Cognitive Dysfunction in a Mouse Model of Diabetes.

The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1ß, IL-6, tumor necrosis factor-α (TNF-α) and genetic markers (Bdnf, Arc, Egr1) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased Arc and Egr1 mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in Arc and Egr1 gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.

Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression: A Randomized Clinical Trial.

Importance: A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder (MDD) within hours, but the mechanism of antidepressant effect is uncertain. Objective: To evaluate whether ketamine dose and brain glutamate and glutamine (Glx) and γ-aminobutyric acid (GABA) level responses to ketamine are related to antidepressant benefit and adverse effects. Design, Setting, and Participants: This randomized, parallel-group, triple-masked clinical trial included 38 physically healthy, psychotropic medication-free adult outpatients who were in a major depressive episode of MDD but not actively suicidal. The trial was conducted at Columbia University Medical Center. Data were collected from February 2012 to May 2015. Data analysis was conducted from January to March 2020. Intervention: Participants received 1 dose of placebo or ketamine (0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg) intravenously during 40 minutes of a proton magnetic resonance spectroscopy scan that measured ventro-medial prefrontal cortex Glx and GABA levels in 13-minute data frames. Main Outcomes and Measures: Clinical improvement was measured using a 22-item version of the Hamilton Depression Rating Scale (HDRS-22) 24 hours after ketamine was administered. Ketamine and metabolite blood levels were measured after the scan. Results: A total of 38 individuals participated in the study, with a mean (SD) age of 38.6 (11.2) years, 23 (60.5%) women, and 25 (65.8%) White patients. Improvement in HDRS-22 score at 24 hours correlated positively with ketamine dose (t36 = 2.81; P = .008; slope estimate, 19.80 [95% CI, 5.49 to 34.11]) and blood level (t36 = 2.25; P = .03; slope estimate, 0.070 [95% CI, 0.007 to 0.133]). The lower the Glx response, the better the antidepressant response (t33 = -2.400; P = .02; slope estimate, -9.85 [95% CI, -18.2 to -1.50]). Although GABA levels correlated with Glx (t33 = 8.117; P < .001; slope estimate, 0.510 [95% CI, 0.382 to 0.638]), GABA response did not correlate with antidepressant effect. When both ketamine dose and Glx response were included in a mediation analysis model, ketamine dose was no longer associated with antidepressant effect, indicating that Glx response mediated the relationship. Adverse effects were related to blood levels in men only (t5 = 2.606; P = .048; estimated slope, 0.093 [95% CI, 0.001 to 0.186]), but Glx and GABA response were not related to adverse effects. Conclusions and Relevance: In this study, intravenous ketamine dose and blood levels correlated positively with antidepressant response. The Glx response correlated inversely with ketamine dose and with antidepressant effect. Future studies are needed to determine whether the relationship between Glx level and antidepressant effect is due to glutamate or glutamine. Trial Registration: ClinicalTrials.gov Identifier: NCT01558063.

Real-Time Value Integration during Economic Choice Is Regulated by Orbitofrontal Cortex.

Neural correlates implicate the orbitofrontal cortex (OFC) in value-based or economic decision making [1-3]. Yet inactivation of OFC in rats performing a rodent version of the standard economic choice task is without effect [4, 5], a finding more in accord with ideas that the OFC is primarily necessary for behavior when new information must be taken into account [6-9]. Neural activity in the OFC spontaneously updates to reflect new information, particularly about outcomes [10-16], and the OFC is necessary for adjustments to learned behavior only under these conditions [4, 16-26]. Here, we merge these two independent lines of research by inactivating lateral OFC during an economic choice that requires new information about the value of the predicted outcomes to be incorporated into an already established choice. Outcome value was changed by pre-feeding the rats one of two food options before testing. In control rats, this pre-feeding resulted in divergent changes in choice behavior that depended on the rats' prior preference for the pre-fed food. Optogenetic inactivation of the OFC disrupted this bi-directional effect of pre-feeding without affecting other measures that describe the underlying choice behavior. This finding unifies the role of the OFC in economic choice with its role in a host of other behaviors, causally demonstrating that the OFC is not necessary for economic choice per se-unless that choice incorporates new information about the outcomes.

Associations between cortical thickness and reasoning differ by socioeconomic status in development.

Although lower socioeconomic status (SES) is generally negatively associated with performance on cognitive assessments, some children from lower-SES backgrounds perform as well as their peers from higher-SES backgrounds. Yet little research has examined whether the neural correlates of individual differences in cognition vary by SES. The current study explored whether relationships between cortical structure and fluid reasoning differ by SES in development. Fluid reasoning, a non-verbal component of IQ, is supported by a distributed frontoparietal network, with evidence for a specific role of rostrolateral prefrontal cortex (RLPFC). In a sample of 115 4-7-year old children, bilateral thickness of RLPFC differentially related to reasoning by SES: thicker bilateral RLPFC positively correlated with reasoning ability in children from lower-SES backgrounds, but not in children from higher-SES backgrounds. Similar results were found in an independent sample of 59 12-16-year old adolescents. Furthermore, young children from lower-SES backgrounds with strong reasoning skills were the only group to show a positive relationship between RLPFC thickness and age. In sum, we found that relationships between cortical thickness and cognition differ by SES during development.

Adolescents' Neural Response to Tobacco Prevention Messages and Sharing Engagement.

INTRODUCTION: Interpersonal communication can reinforce media effects on health behavior. Recent studies have shown that brain activity in the medial prefrontal cortex during message exposure can predict message-consistent behavior change. Key next steps include examining the relationship between neural responses to ads and measures of interpersonal message retransmission that can be collected at scale. METHODS: Neuroimaging, self-report, and automated linguistic measures were utilized to investigate the relationships between neural responses to tobacco prevention messages, sharing engagement, and smoking-relevant belief changes. Thirty-seven adolescent nonsmokers viewed 12 ads from the U.S. Food and Drug Administration's "The Real Cost" campaign during a functional magnetic resonance imaging scan session (2015-2016). Data were analyzed between 2016 and 2017. The extent that participants talked in detail about the main message of the ads, or sharing engagement, was measured through transcripts of participants' subsequent verbal descriptions using automated linguistic coding. Beliefs about the consequences of smoking were measured before and after the main experiment using surveys. RESULTS: Increased brain activation in self- and value-related subregions of the medial prefrontal cortex during message exposure was associated with subsequent sharing engagement when participants verbally talked about the ads. In addition, sharing engagement was significantly associated with changes in participants' beliefs about the social consequences of smoking. CONCLUSIONS: Neural activity in self- and value-related subregions of the medial prefrontal cortex during exposure to "The Real Cost" campaign was associated with subsequent sharing engagement, which in turn was related to social belief change. These results provide new insights into the link between neurocognitive responses to ads, the content of interpersonal sharing, and downstream health-relevant outcomes. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Fifth Anniversary Retrospective of "The Real Cost," the Food and Drug Administration's Historic Youth Smoking Prevention Media Campaign, which is sponsored by the U.S. Food and Drug Administration.

Orexin 1 receptors in the anterior cingulate and orbitofrontal cortex regulate cost and benefit decision-making.

Orexin neurons are discretely localized within the lateral hypothalamus and have widespread projections into all areas of the brain. In addition, several lines of evidence specify that orexins may also participate in the regulation of a variety of affective and cognitive processes. The Orexin-1 receptor (OX1r) is distributed extensively throughout the prefrontal cortex (PFC). Delay-based decision- making is mediated largely by the orbitofrontal cortex (OFC) while effort- based decision-making is controlled by the anterior cingulated cortex (ACC). Hence, in the present study, a series of experiments were conducted to clarify the role of OX1r in the mPFC (ACC and/or OFC) in cost and benefit decision-making. The rats were trained in a delay and/or effort-based form of cost-benefit T-maze decision-making task. Two goal arms were different in the amount of accessible reward and cost. Before surgery, all animals were selecting the high reward arm and pay the cost on almost every trial. During the test days, the rats received local injections of either DMSO 20% /0.5 µl, as a vehicle, or SB334867 (3, 30 and 300 nM/0.5 µl), as a selective OX1r antagonist, within the ACC and/or OFC. The results of this study showed that the bilateral microinjection of SB334867 into ACC and/or OFC changed the preference to a low reward arm with no cost, indicating the role of OX1 receptors in cost and benefit decision- making. From these results, it can be implied that OX1 receptors in the mPFC play a crucial role for allowing the animal to evaluate and pay the cost to acquire greater rewards.

Postnatal impoverished housing impairs adolescent risk-assessment and increases risk-taking: A sex-specific effect associated with histone epigenetic regulation of Crfr1 in the medial prefrontal cortex.

While increasing evidence posits poor decision-making as a central feature of mental disorders, very few studies investigated the effects of early-life stress (ELS) on specific components of reward-related choice behaviors. Risk-taking (RT) involves the exposure to some danger, or negative consequences, in order to achieve a goal-directed behavior. Such behaviors are likely to be preceded by risk-assessment (RA), which is a dynamic cognitive process involving the acquisition of information in potentially dangerous situations. Here, we investigated the effects of being raised in impoverished housing conditions during early life (P2-P9) on RT, RA and dopaminergic and corticotrophinergic gene expression of adolescent male and female mice. Phenotypes were assessed by two protocols: the elevated plus-maze (EPM) and the predator-odor risk-taking (PORT). We found decreased RA in mice exposed to impoverished housing in the absence of a reward (EPM), with a more pronounced effect among females. Moreover, when exposed to a predatory olfactory cue, increased RT was observed in these females in a reward-related task (PORT), as well as decreased HPA axis responsivity. This sex-specific behavioral effect was associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC) and higher levels of the histone mark H3R2me2s, a histone modification known to be involved in transcriptional activation, within the promoter of the Crfr1 gene. These findings revealed that ELS exposure can impair the acquisition of environmental information in dangerous situations and increase RT in reward-related scenarios among females, with an important role regarding epigenetic regulation of the Crfr1 gene.

No Evidence for Recent Selection at FOXP2 among Diverse Human Populations.

FOXP2, initially identified for its role in human speech, contains two nonsynonymous substitutions derived in the human lineage. Evidence for a recent selective sweep in Homo sapiens, however, is at odds with the presence of these substitutions in archaic hominins. Here, we comprehensively reanalyze FOXP2 in hundreds of globally distributed genomes to test for recent selection. We do not find evidence of recent positive or balancing selection at FOXP2. Instead, the original signal appears to have been due to sample composition. Our tests do identify an intronic region that is enriched for highly conserved sites that are polymorphic among humans, compatible with a loss of function in humans. This region is lowly expressed in relevant tissue types that were tested via RNA-seq in human prefrontal cortex and RT-PCR in immortalized human brain cells. Our results represent a substantial revision to the adaptive history of FOXP2, a gene regarded as vital to human evolution.

An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment.

Objectives: To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs). Methods: PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine. Results: Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05). Conclusions: Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine. Clinical Trial Registration: Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853. Trial Identification Number: 12612000050853.

Behavioral differences of male Wistar rats from different vendors in vulnerability and resilience to chronic mild stress are reflected in epigenetic regulation and expression of p11.

Outbred rat lines such as Wistar rats are commonly used for models of depressive disorders. Such rats arise from random mating schedules. Hence, genetic drift occurs in outbred populations which could lead to genotypic and phenotypic heterogeneity between rats from different vendors. Additionally, vendor specific rearing conditions could contribute to intrastrain variability. In the present study differences in behavioral responses to the chronic mild stress (CMS) model of depression within Wistar rat strains from different vendors are described. DNA methylation studies and mRNA expression analysis of p11 revealed that the behavioral differences between the substrains are reflected at the epigenetic and genetic level. The results suggest that there are breeder-dependent differences in vulnerability to stress in the CMS model of depression, which might bear on the validity of the model and contribute to contradictory findings and difficulties of replication between laboratories. P11 mRNA expression seems to be differently regulated depending on the quality of the stress response evoked by CMS exposure.

Neuroanatomical distribution of oxytocin receptor binding in the female rabbit forebrain: Variations across the reproductive cycle.

Oxytocin receptors (OTR) have been characterized in the brains of several mammals, including rodents, carnivores, and primates. Their species-specific distribution in the brain has been associated with species differences in social organization, including mating strategy and parenting behavior. In several species, the density of OTR binding in specific brain regions varies according to reproductive condition, including ovarian cycle, pregnancy and lactation. Rabbits are induced ovulators, polygamous, and monoparental but their distribution and regulation of brain OTR has not been described. Here we used receptor autoradiography to quantitatively characterize OTR binding in the brains of estrous, ovariectomized, late pregnant, and lactating does. Intense binding occurred in the prefrontal cortex (PFC), preoptic area (POA), lateral septum (LS; dorsal and ventral), hippocampus, and medial amygdala. Variations among the experimental groups were seen only in PFC, POA, LS. Ovariectomy increased OTR density in PFC but had the opposite effect in POA. Lactating does had significantly reduced OTR density, relative to late pregnancy, in PFC and POA. Our results are consistent with a possible role of OT in modulating social and maternal behavior in rabbits since the brain regions sensitive to OT have been implicated in social interaction, learning and memory, olfactory processing and maternal behavior.

Diffusion imaging and transcranial magnetic stimulation assessment of transcallosal pathways in chronic stroke.

OBJECTIVE: To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke. METHODS: Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated. RESULTS: Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p<0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p<0.01). Both transcallosal prefrontal tract FA (ΔR(2)=0.12, p=0.04) and NL-iSPmean (ΔR(2)=0.09, p=0.04) accounted for unique variance in motor impairment level. CONCLUSIONS: Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke. SIGNIFICANCE: Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke.

Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment.

The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid ß (Aß), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aß (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn(2+) modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD.

Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games.

Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance--catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase--modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function--dopamine transporter and D2 receptors--was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.

Assessment of dynamic cerebral autoregulation and cerebrovascular CO2 reactivity in ageing by measurements of cerebral blood flow and cortical oxygenation.

With ageing, cerebral blood flow velocity (CBFV) decreases; however, to what extent dynamic cerebral autoregulation and cerebrovascular CO2 reactivity are influenced by ageing is unknown. The aim was to examine the dynamic responses of CBFV and cortical oxygenation to changes in blood pressure (BP) and arterial CO2 across different ages. Fifty-eight participants in three age groups were included, as follows: young (n = 20, 24 ± 2 years old), elderly (n = 20, 66 ± 1 years old), and older elderly (n = 18, 78 ± 3 years old). The CBFV was measured using transcranial Doppler ultrasound, simultaneously with oxyhaemoglobin (O2Hb) using near-infrared spectroscopy and beat-to-beat BP measurements using Finapres. Postural manoeuvres were performed to induce haemodynamic fluctuations. Cerebrovascular CO2 reactivity was tested with hyperventilation and CO2 inhalation. With age, CBFV decreased (young 59 ± 12 cm s(-1), elderly 48 ± 7 cm s(-1) and older elderly 42 ± 9 cm s(-1), P < 0.05) and cerebrovascular resistance increased (1.46 ± 0.58, 1.81 ± 0.36 and 1.98 ± 0.52 mmHg cm(-1) s(-1), respectively, P < 0.05). Normalized gain (autoregulatory damping) increased with age for BP-CBFV (0.88 ± 0.18, 1.31 ± 0.30 and 1.06 ± 0.34, respectively, P < 0.05) and CBFV-O2Hb (0.10 ± 0.09, 0.12 ± 0.04 and 0.17 ± 0.08, respectively, P < 0.05) during the repeated sit-stand manoeuvre at 0.05 Hz. Even though the absolute changes in CBFV and cerebrovascular resistance index during the cerebrovascular CO2 reactivity were higher in the young group, the percentage changes in CBFV, cerebrovascular resistance index and O2Hb were similar in all age groups. In conclusion, there was no decline in dynamic cerebral autoregulation and cerebrovascular CO2 reactivity with increasing age up to 86 years. Despite the decrease in cerebral blood flow velocity and increase in cerebrovascular resistance with advancing age, CBFV and cortical oxygenation were not compromised in these elderly humans during manoeuvres that mimic daily life activities.

Content matters: neuroimaging investigation of brain and behavioral impact of televised anti-tobacco public service announcements.

Televised public service announcements are video ads that are a key component of public health campaigns against smoking. Understanding the neurophysiological correlates of anti-tobacco ads is an important step toward novel objective methods of their evaluation and design. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain and behavioral effects of the interaction between content ("argument strength," AS) and format ("message sensation value," MSV) of anti-smoking ads in humans. Seventy-one nontreatment-seeking smokers viewed a sequence of 16 high or 16 low AS ads during an fMRI scan. Dependent variables were brain fMRI signal, the immediate recall of the ads, the immediate change in intentions to quit smoking, and the urine levels of a major nicotine metabolite cotinine at a 1 month follow-up. Whole-brain ANOVA revealed that AS and MSV interacted in the inferior frontal, inferior parietal, and fusiform gyri; the precuneus; and the dorsomedial prefrontal cortex (dMPFC). Regression analysis showed that the activation in the dMPFC predicted the urine cotinine levels 1 month later. These results characterize the key brain regions engaged in the processing of persuasive communications and suggest that brain fMRI response to anti-smoking ads could predict subsequent smoking severity in nontreatment-seeking smokers. Our findings demonstrate the importance of the quality of content for objective ad outcomes and suggest that fMRI investigation may aid the prerelease evaluation of televised public health ads.

Assessment of pain due to lumbar spine diseases using MR spectroscopy: a preliminary report.

BACKGROUND DATA: There is a considerable difference in pain perception among individuals. In patients with chronic pain, recent studies using fMRI, PET and SPECT have shown that functional changes mainly occurred in the anterior cingulate cortex (ACC), prefrontal cortex (PFC) and thalamus. Brain magnetic resonance spectroscopy (MRS) can evaluate brain chemistry by measuring metabolites such as N-acetyl aspartate (NAA). The purpose of this study was to analyze whether brain MRS could assess pain due to lumbar spine diseases. METHODS: NAA levels were determined relative to the concentration of creatine/phosphocreatine complex (Cr) and choline (Cho), which is commonly used as an internal standard. The NAA/Cr and NAA/Cho ratios in the ACC, PFC and thalamus were compared between six patients with unilateral pain (left side) and six control patients without pain. RESULTS: In the right thalamus (contralateral side to symptom), the NAA/Cr in the patients with pain was statistically significantly lower compared with the control patients (p < 0.05). Also, in the right thalamus, the NAA/Cho in pain patients was significantly lower compared with controls (p < 0.01). When considering just the right thalamus, there were statistically significant correlations between the numerical rating scale for pain (NRS) and NAA values. CONCLUSIONS: Lumbar pain can be assessed indirectly by analyzing the decrease in NAA concentration in the thalamus.

From neural responses to population behavior: neural focus group predicts population-level media effects.

Can neural responses of a small group of individuals predict the behavior of large-scale populations? In this investigation, brain activations were recorded while smokers viewed three different television campaigns promoting the National Cancer Institute's telephone hotline to help smokers quit (1-800-QUIT-NOW). The smokers also provided self-report predictions of the campaigns' relative effectiveness. Population measures of the success of each campaign were computed by comparing call volume to 1-800-QUIT-NOW in the month before and the month after the launch of each campaign. This approach allowed us to directly compare the predictive value of self-reports with neural predictors of message effectiveness. Neural activity in a medial prefrontal region of interest, previously associated with individual behavior change, predicted the population response, whereas self-report judgments did not. This finding suggests a novel way of connecting neural signals to population responses that has not been previously demonstrated and provides information that may be difficult to obtain otherwise.