Differences In BOLD Responses Research Articles

Brain activity during visuospatial working memory in congenital adrenal hyperplasia.

Patients with congenital adrenal hyperplasia (CAH) require life-long replacement of cortisol. Problems with cognitive function, especially working memory, have previously been identified, but the long-term effects of this disease on brain function are unknown. We investigate brain activity during working memory in CAH compared to controls. Twenty-nine individuals with CAH (17 females) and 40 healthy controls (24 females), 16-33 years, from a single research institute, underwent functional magnetic resonance imaging while doing a verbal and visuospatial working memory task. Individuals with CAH responded faster on the verbal task. Although we found no differences in BOLD response over the whole group, there were significant interactions with sex: CAH males had increased activity in the bilateral lateral superior occipital cortex, left supramarginal and angular gyri, left precuneus, left posterior cingulate cortex and bilateral cerebellum during decoding of the visuospatial task, while females showed decreased activity in these regions. Long-term cortisol imbalances do not seem to have a major impact on the functional brain responses during working memory in CAH. However, activity of the left dorsal visual stream in particular might be affected depending on sex. As the task employed may have been relatively easy, larger studies using more complex tasks are needed to further investigate this.

Effect of spinal anesthesia-induced deafferentation on pain processing in healthy male volunteers: A task-related fMRI study.

Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm. Twenty-two healthy subjects participated in the study. We performed a task-based fMRI study using a randomized crossover design. Subjects were scanned under two conditions (spinal anesthesia or control) at two-time points: before and after spinal anesthesia. Spinal anesthesia resulted in sensory loss up to dermatome Th6. Calibrated heat-pain stimuli were administered to the right forearm (C8-Th1) using a box-car design (blocks of 10s on/25s off) during MRI scanning. Pain perception was measured using a visual analogue scale (1-100) at the beginning and the end of each session. Generalized estimating equations were used to examine the effect of intervention by time by order on pain scores. Similarly, higher-level effects were tested with appropriate general linear models (accounting for within-subject variations in session and time) to examine: (1) Differences in BOLD response to pain stimulus under spinal anesthesia versus control; and (2) Effects of spinal anesthesia on pain-related modulation of the cerebral activation. Complete fMRI data was available for eighteen participants. Spinal anesthesia was associated with moderate pain score increase. Significant differences in brain response to noxious thermal stimuli were present in comparison of spinal versus control condition (post-pre). Spinal condition was associated with higher BOLD signal in the bilateral inferior parietal lobule and lower BOLD signal in bilateral postcentral and precentral gyrus. Within the angular regions, we observed a positive correlation between pain scores and BOLD signal. These observations were independent from order effect (whether the spinal anesthesia was administered in the first or the second visit). However, we did observe order effect on brain regions including medial prefrontal regions, possibly related to anticipation of the experience of spinal anesthesia. The loss of sensory and motor activity caused by spinal anesthesia has a significant impact on brain regions involved in the sensorimotor and cognitive processing of noxious heat pain stimuli. Our results indicate that the anticipation or experience of a strong somatosensory response to the spinal intervention might confound and contribute to increased sensitivity to cognitive pain processing. Future studies must account for individual differences in subjective experience of pain sensation within the experimental context.

Distinct patterns of altered quantitative T1ρ and functional BOLD response associated with history of suicide attempts in bipolar disorder.

Despite the high risk for suicide, relatively few studies have explored the relationship between suicide and brain imaging measures in bipolar disorder. In addition, fewer studies have explored the possibility that altered brain metabolism may be associated with suicide attempt. To begin to fill in these gaps, we evaluated functional (task based fMRI) and metabolic (quantitative T1ρ) differences associated with suicide attempt in participants with bipolar disorder. Thirty-nine participants with bipolar disorder underwent fMRI during a flashing checkerboard task and 27 also underwent quantitative T1ρ. The relationship between neuroimaging and history of suicide attempt was tested using multiple regression while adjusting for age, sex, and current mood state. Differences between two measures of suicide attempt (binary: yes/no and continuous: number of attempts) were quantified using the corrected Akaike Information Criterion. Participants who had attempted suicide had greater fMRI task-related activation in visual areas and the cerebellum. The number of suicide attempts was associated with a difference in BOLD response in the amygdala, prefrontal cortex, and cerebellum. Increased quantitative T1ρ was associated with number of suicide attempts in limbic, basal ganglia, and prefrontal cortex regions. This study is a secondary analysis with a modest sample size. Differences between measures of suicide history may be due to differences in statistical power. History of suicide was associated with limbic, prefrontal, and cerebellar alterations. Results comparing those with and without suicide attempts differed from results using number of suicide attempts, suggesting that these variables have different neurobiological underpinnings.

Functional magnetic resonance imaging study of working memory several years after pediatric concussion

ABSTRACT Primary objective: The neurophysiological effects of pediatric concussion several years after injury remain inadequately characterized. The objective of this study was to determine if a history of concussion was associated with BOLD response differences during an n-back working memory task in youth. Research Design: Observational, cross-sectional. Methods and Procedures: Participants include 52 children and adolescents (M = 15.1 years, 95%CI = 14.4–15.8, range = 9–19) with past concussion (n = 33) or orthopedic injury (OI; n = 19). Mean time since injury was 2.5 years (95%CI = 2.0–3.0). Measures included postconcussion symptom ratings, neuropsychological testing, and blood-oxygen-dependent-level (BOLD) functional magnetic resonance imaging (fMRI) during an n-back working memory task. Main Outcomes and Results: Groups did not differ on accuracy or speed during the three n-back conditions. They also did not differ in BOLD signal change for the 1- vs. 0-back or 2- vs. 0-back contrasts (controlling for task performance). Conclusions: This study does not support group differences in BOLD response during an n-back working memory task in youth who are on average 2.5 years post-concussion. The findings are encouraging from the perspective of understanding recovery after pediatric concussion.

Differences in BOLD responses in brain reward network reflect the tendency to assimilate a surprising flavor stimulus to an expected stimulus

External information can modify the subjective value of a tasted stimulus, but little is known about neural mechanisms underlying these behavioral modifications. This study used flavored drinks to produce variable degrees of discrepancy between expected and received flavor. During a learning session, 43 healthy young men learned 4 symbol-flavor associations. In a separate session, associations were presented again during an fMRI scan, but half of the trials introduced discrepancy with previously learned associations. Liking ratings of drinks were collected and were analyzed using a linear model to define the degree to which discrepant symbols affected liking ratings of the subjects during the fMRI session. Based on these results, a GLM analysis of fMRI data was conducted to determine neural correlates of observed behavior. Groups of subjects were composed based on their behavior in response to discrepant symbols, and comparison of brain activity between groups showed that activation in the PCC and the caudate nucleus was more potent in those subjects in which liking was not affected by discrepant symbols. These activations were not found in subjects who assimilated unexpected flavors to flavors preceeded by discrepant symbols. Instead, these subjects showed differences in the activity in the parietal operculum. The activity of reward network appears to be related to assimilation of received flavor to expected flavor in response to symbol-flavor discrepancy.

T69. PERFORMANCE OF PATIENTS WITH NMDAR-AB ENCEPHALITIS COMPARED TO PATIENTS WITH SCHIZOPHRENIA AND HEALTHY CONTROLS USING FUNCTIONAL MAGNETIC RESONANCE IMAGING (F-MRI) AND A WORKING MEMORY PARADIGM

BackgroundN-methyl-D-aspartate receptor (NMDAR) encephalitis has prominent early psychotic features. It has been rarely misdiagnosed as schizophrenia. NMDAR encephalitis causes deficiencies in working memory in the short & long term. Early immunotherapy/tumour removal improves outcomes. Schizophrenia can cause significant cognitive performance deficits with working memory often severely affected.Clinical MRI in NMDAR encephalitis is usually normal, despite severe clinical course. Resting state fMRI studies have shown reduced functional connectivity of the left & right hippocampus. To date, to the best of our knowledge, functional neuroimaging utilising a working memory task such as the 1-back task (participant has to identify the number onscreen immediately before the number currently on screen) has not been utilised in NMDAR encephalitis. Potentially this may highlight alterations in brain regions through altered neuronal activity underlying working memory.We hypothesised that patients with NMDAR encephalitis would demonstrate a difference in BOLD response (a proxy for neuronal activity) compared to healthy controls during fMRI while performing the 1-back task. Additionally, we wished to compare task evoked BOLD response in patients with NMDAR-Ab encephalitis compared to patients with schizophrenia.MethodsUsing G*Power 3.1 software with effect size f (0.8), total sample size was calculated from data obtained from a previous study on working memory performance in NMDAR encephalitis for the 3 groups (NMDAR encephalitis, healthy controls & schizophrenia) (N=30). Following ethical approval, 12 individuals diagnosed with NMDAR encephalitis were recruited from neurological centres. Participants were trained in the 1-back task prior to scanning. Results were compared to previously collected data from cohorts of healthy controls (N=14) and schizophrenia (N=14). Cohorts were matched insofar as possible. Data was analysed using SPSS and ART toolbox.ResultsIn the NMDAR encephalitis (N=12) cohort, gender ratio F:M was (11:1), mean(s.d.) age 37.5(12.2) years. 50% identified ongoing memory problems. Schizophrenia cohort (N=14) gender ratio (7:7), mean (s.d.) age 39 (12.3) years. Healthy controls gender ratio (10.4) mean (s.d.) age 29.8 (6.5) years. There was no difference for gender, age or educational level between cohorts. FSIQ was higher (p<0.01) in controls & NMDAR encephalitis compared to schizophrenia cohorts. NMDAR encephalitis cohort had acute symptoms [mean (s.d.)] for 7.09 (2.43) weeks until treatment. 9 individuals were still on immunotherapy at time of entry.Duration since diagnosis to entry into this study was 55.18(23.13) months for NMDAR encephalitis and 12.6 (10.91) years for schizophrenia. There were no significant differences in number of ART motion outliers (p >0.05) between cohorts. Age & gender were added to second level analyses as covariates.One-way ANOVA was used to compare N-back accuracy & reaction time. There was a significant difference (p<0.01) between groups on accuracy but not reaction time, with only the schizophrenia group showing lower accuracy.1-back working memory condition was associated with significantly increased BOLD response across several brain regions that play a role in working memory, including the dorsolateral prefrontal cortex. However, there were no significant main effects on BOLD response for the 1-back task for any cohort.DiscussionPatients with NMDAR encephalitis report ongoing memory difficulties. However, in this study, there were no identifiable deficits compared to healthy controls using fMRI. This may relate to regeneration of NMDA receptors, the relatively long time until from diagnosis to follow up and early treatment with immunotherapy.

Decoupling of BOLD amplitude and pattern classification of orientation-selective activity in human visual cortex

Multivariate pattern analysis (MVPA) of fMRI data has allowed the investigation of neural representations of stimuli on the basis of distributed patterns of activity within a brain region, independently from overall brain activity. For instance, several studies on early visual cortex have reported reliable MVPA decoding of the identity of a stimulus representation that was kept in working memory or internally generated, despite the fact that the overall BOLD response was low or even at baseline levels. Here we ask how it is possible that reliable stimulus information can be decoded from early visual cortex even when the overall BOLD signal remains low. We reanalyzed a data set in which human participants (N = 24) imagined or kept in working memory an oriented visual grating. We divided voxels from V1, V2, and V3 into groups based on orientation preference, and compared the time course of mean BOLD responses to preferred and non-preferred orientations with the time course of the multivariate decoding performance.Decoding accuracy related to a numerically small, but reliable univariate difference in the mean BOLD response to preferred and non-preferred stimuli. The time course of the difference in BOLD responses to preferred and non-preferred orientations was highly similar to the time course of the multivariate pattern classification accuracy. The reliability of the classification strongly correlated with the magnitude of differences in BOLD signal between preferred and non-preferred stimuli. These activity differences were small compared to the large overall BOLD modulations. This suggests that a substantial part of the task-related BOLD response to visual stimulation might not be stimulus-specific. Rather, stimulus-evoked BOLD signals in early visual cortex during a task context may be an amalgam of small stimulus-specific responses and large task-related but non-stimulus-specific responses. The latter are not evident during the maintenance or internal generation of stimulus representations, but provide an explanation of how reliable stimulus information can be decoded from early visual cortex even though its overall BOLD signal remains low.

The relation between craving and binge eating: Integrating neuroimaging and ecological momentary assessment

The role of craving in binge eating characteristic of bulimia nervosa (BN) is inconclusive. A network of regions associated with cue reactivity to food and substances has been identified, comprised of the amygdala, orbitofrontal cortex, insula, and striatum. The goal of this study was to examine individual differences in BOLD response in this appetitive network as moderators of the relationship between craving and binging in the natural environment in women with BN. Women with BN (N = 16) completed a baseline measure of craving and a fMRI scan, where they viewed neutral cues and food cues. After each run, craving for food was assessed. Participants then completed an ecological momentary assessment six times a day via smart phone and recorded binge eating and craving. Participants exhibited significantly increased BOLD response in the left amygdala in response to food cues compared to neutral cues. However, individual differences in BOLD response were not correlated with self-report craving throughout the scan. The relationship between craving and binging in everyday life was moderated by individual differences in activation in the caudate, insula, and amygdala. Women with greater activation in these regions demonstrated significant increases in craving prior to binge eating. Those who did not exhibit increases in activation did not exhibit increases in craving prior to binge eating in the natural environment. Craving may not underlie binge eating for all individuals with BN. However, these results indicate that neural response to food cues may affect individual differences in the daily experience of craving and binge eating.

Functional Changes of the Perigenual Part of the Anterior Cingulate Cortex after External Trigeminal Neurostimulation in Migraine Patients.

To explore the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of external trigeminal neurostimulation (eTNS) in migraine without aura (MwoA) patients between attacks. Using whole-brain BOLD-fMRI, functional response to THS at two different intensities (41 and 51°C) was investigated interictally in 16 adults MwoA patients before and after eTNS with the Cefaly® device. We calculated the percentage of patients having at least a 50% reduction of monthly migraine attacks and migraine days between baseline and the last month of eTNS. Secondary analyses evaluated associations between BOLD signal changes and clinical features of migraine. Before eTNS treatment, there was no difference in BOLD response between MwoA patients and healthy controls (HC) during low-innocuous THS at 41°C, whereas the perigenual part of the right anterior cingulate cortex (ACC) revealed a greater BOLD response to noxious THS at 51°C in MwoA patients when compared to HC. The same area demonstrated a significant reduced BOLD response induced by the noxious THS in MwoA patients after eTNS (p = 0.008). Correlation analyses showed a significant positive correlation between ACC BOLD response to noxious THS before eTNS treatment and the decrease of ACC BOLD response to noxious THS after eTNS. Moreover, a significant negative correlation in the migraine group after eTNS treatment between ACC functional activity changes and both the perceived pain ratings during noxious THS and pre-treatment migraine attack frequency has been found. Our findings suggest that eTNS treatment with the Cefaly® device induces a functional antinociceptive modulation in the ACC that is involved in the mechanisms underlying its preventive anti-migraine efficacy. Nevertheless, further observations to confirm whether the observed fMRI effects of eTNS are both related to clinical improvement and specific to antinociceptive modulation in migraine patients are mandatory.

Altered Brain Activation during Emotional Face Processing in Relation to Both Diagnosis and Polygenic Risk of Bipolar Disorder.

ObjectivesBipolar disorder (BD) is a highly heritable disorder with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the relation between reported brain functional abnormalities and underlying genetic risk remains elusive. This is the first cross-sectional study applying a whole-brain explorative approach to investigate potential influence of BD case-control status and polygenic risk on brain activation.MethodsA BD polygenic risk score (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control study, and assigned to each individual in our independent sample (N=85 BD cases and 121 healthy controls (HC)), all of whom participated in an fMRI emotional faces matching paradigm. Potential differences in BOLD response across diagnostic groups were explored at whole-brain level in addition to amygdala as a region of interest. Putative effects of BD PGRS on brain activation were also investigated.ResultsAt whole-brain level, BD cases presented with significantly lower cuneus/precuneus activation than HC during negative face processing (Z-threshold=2.3 as cluster-level correction). The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing. For amygdala activation, there were no correlations with diagnostic status or PGRS.ConclusionsThese findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD. While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.

Pretreatment Differences in BOLD Response to Emotional Faces Correlate with Antidepressant Response to Scopolamine.

Background:Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine.Methods:Healthy participants (n=15) and unmedicated-depressed major depressive disorder patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 μg/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder.Results:Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (P<.02) and middle occipital cortices (P<.02).Conclusions:The magnitude and direction of differential blood oxygen-level– dependent response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine.

Differences in BOLD responses to intragastrically infused glucose and saccharin in rats.

The postingestive effect is different between caloric and noncaloric sweeteners. The gut administration of glucose induces a preference for flavored water which is paired with the intragastric infusion of glucose. However, a comparison of the brain response to the gut glucose and saccharin stimuli still remains to be demonstrated. Here, using functional magnetic resonance imaging, we investigated the blood oxygenation level-dependent signal response to gut glucose and saccharin in the brain of conscious rats. Glucose induced a positive signal increase in the amygdala and nucleus accumben, both of which receive dopaminergic input from the ventral tegmental area. In contrast, saccharin administration did not activate these areas. Both glucose and saccharin increased the blood oxygenation level-dependent signal intensity in the insular cortex and the nucleus of the solitary tract. These results show that there were significant differences between postingestive glucose and saccharin-induced increases in the blood oxygenation level-dependent signal in rats. Together with previous findings, these results suggest distinct activation patterns in the brain for both glucose and saccharin, which is partially due to different changes of internal signals, including the blood glucose and insulin levels.

Synaesthesia or vivid imagery? A single case fMRI study of visually induced olfactory perception.

The most common form of synaesthesia is grapheme-colour synaesthesia. However, rarer forms of synaesthesia also exist, such as word-gustatory and olfactory-gustatory synaesthesia, whereby a word or smell will induce a specific. In this study we describe a single individual (LJ) who experiences a concurrent olfactory stimulus when presented with congruent visual images. For some visual stimuli, he perceives a strong and automatic olfactory percept, which has existed throughout his life. In this study, we explore whether his experiences are a new form of synaesthesia or simply vivid imagery. Unlike other forms of synaesthesia, the concurrent odour is congruent to the visual inducer. For example, a photograph of dress shoes will elicit the smell of leather. We presented LJ and several control participants with 75 images of everyday objects. Their task was to indicate the strength of any perceived odours induced by the visual images. LJ rated several of the images as inducing a concurrent odour, while controls did not have any such percept. Images that LJ reported as inducing the strongest odours were used, along with colour-matched control images, in the context of an fMRI experiment. Participants were given a one-back task to maintain attention. A block-design odour localizer was presented to localize the piriform cortex (primary olfactory cortex). We found an increased BOLD response in the piriform cortex for the odour-inducing images compared to the control images in LJ. There was no difference in BOLD response between these two stimulus types in the control participants. A subsequent olfactory imagery task did not elicit enhanced activity in the piriform cortex in LJ, suggesting his perceptual experiences may not be based on olfactory imagery.

Error processing in current and former cocaine users

Deficits in response inhibition and error processing can result in maladaptive behavior, including failure to use past mistakes to inform present decisions. A specific deficit in inhibiting a prepotent response represents one aspect of impulsivity and is a prominent feature of addictive behaviors in general, including cocaine abuse/dependence. Brain regions implicated in cognitive control exhibit reduced activation in cocaine abusers. The purposes of the present investigation were (1) to identify neural differences associated with error processing in current and former cocaine-dependent individuals compared to healthy controls and (2) to determine whether former, long-term abstinent cocaine users showed similar differences compared with current users. The present study used an fMRI Go/No-Go task to investigate differences in BOLD response to correct rejections and false alarms between current cocaine users (n = 30), former cocaine users (n = 29), and healthy controls (n = 35). Impulsivity trait measures were also assessed and compared with BOLD activity. Nineteen regions of interest previously implicated in errors of disinhibition were queried. There were no group differences in the correct rejections condition, but both current and former users exhibited increased BOLD response relative to controls for false alarms. In current users, the pregenual cingulate gyrus and left angular/supramarginal gyri overactivated. In former users, the right middle frontal/precentral gyri, right inferior parietal lobule, and left angular/supramarginal gyri overactivated. Overall, our results support a hypothesis that neural activity in former users differs more from healthy controls than that of current users due to cognitive compensation that facilitates abstinence.

Brain activation patterns during visual episodic memory processing among first-degree relatives of schizophrenia subjects

Episodic memory deficits are proposed as a potential intermediate phenotype of schizophrenia. We examined deficits in visual episodic memory and associated brain activation differences among early course schizophrenia (n=22), first-degree relatives (n=16) and healthy controls without personal or family history of psychotic disorders (n=28). Study participants underwent functional magnetic resonance imaging on a 3T scanner while performing visual episodic memory encoding and retrieval task. We examined in-scanner behavioral performance evaluating response time and accuracy of performance. Whole-brain BOLD response differences were analyzed using SPM5 correcting for multiple comparisons. There was an incremental increase in response time among the study groups (healthy controls<first-degree relatives<schizophrenia) with no differences in accuracy for encoding. Response time for retrieval was significantly increased in schizophrenia subjects compared to healthy controls with no difference in accuracy. Although there were no significant differences in BOLD responses for the encoding task, we noted increased BOLD response to retrieval in the prefrontal regions (Brodmann areas 9 and 8), thalamus and insula among the schizophrenia subjects compared to healthy controls, and first-degree relatives. Familial risk for schizophrenia may be associated with qualitatively similar but quantitatively milder abnormalities in visual episodic memory retrieval but not for encoding in the prefrontal cortex and thalamus.

Congruent and Incongruent Cues in Highly Familiar Audiovisual Action Sequences: An ERP Study

In a previous fMRI study we found significant differences in BOLD responses for congruent and incongruent semantic audio-visual action sequences (whole-body actions and speech actions) in bilateral pSTS, left SMA, left IFG, and IPL (Meyer, Greenlee, & Wuerger, JOCN, 2011). Here, we present results from a 128-channel ERP study that examined the time-course of these interactions using a one-back task. ERPs in response to congruent and incongruent audio-visual actions were compared to identify regions and latencies of differences. Responses to congruent and incongruent stimuli differed between 240–280 ms, 340–420 ms, and 460–660 ms after stimulus onset. A dipole analysis revealed that the difference around 250 ms can be partly explained by a modulation of sources in the vicinity of the superior temporal area, while the responses after 400 ms are consistent with sources in inferior frontal areas. Our results are in line with a model that postulates early recognition of congruent audiovisual actions in the pSTS, perhaps as a sensory memory buffer, and a later role of the IFG, perhaps in a generative capacity, in reconciling incongruent signals.

Implementation of spin‐echo blood oxygen level‐dependent (BOLD) functional MRI in birds

The advent of high-field MRI systems has allowed the implementation of blood oxygen level-dependent functional MRI (BOLD fMRI) on small animals. An increased magnetic field improves the signal-to-noise ratio and thus allows an improvement in the spatial resolution. However, it also increases susceptibility artefacts in the commonly acquired gradient-echo images. This problem is particularly prominent in songbird MRI because of the presence of numerous air cavities in the skull of birds. These T(2)*-related image artefacts can be circumvented using spin-echo BOLD fMRI. In this article, we describe the implementation of spin-echo BOLD fMRI in zebra finches, a small songbird of 15-25 g, extensively studied in the behavioural neurosciences of birdsong. Because the main topics in this research domain are song perception and song learning, the protocol implemented used auditory stimuli. Despite the auditory nature of the stimuli and the weak contrast-to-noise ratio of spin-echo BOLD fMRI compared with gradient-echo BOLD fMRI, we succeeded in detecting statistically significant differences in BOLD responses triggered by different stimuli. This study shows that spin-echo BOLD fMRI is a viable approach for the investigation of auditory processing in the whole brain of small songbirds. It can also be applied to study auditory processing in other small animals, as well as other sensory modalities.

Neural correlates of S-ketamine induced psychosis during overt continuous verbal fluency

The glutamatergic N-methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Administered to healthy volunteers, a subanesthetic dose of the non-competitive NMDA receptor antagonist ketamine leads to psychopathological symptoms similar to those observed in schizophrenia. In patients with schizophrenia, ketamine exacerbates the core symptoms of illness, supporting the hypothesis of a glutamatergic dysfunction.In a counterbalanced, placebo-controlled, double-blind study design, healthy subjects were administered a continuous subanesthetic S-ketamine infusion while differences in BOLD responses measured with fMRI were detected. During the scanning period, subjects performed continuous overt verbal fluency tasks (phonological, lexical and semantic). Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).Ketamine elicited psychosis like psychopathology. Post-hoc t-tests revealed significant differences between placebo and ketamine for the amounts of words generated during lexical and semantic verbal fluency, while the phonological domain remained unaffected. Ketamine led to enhanced cortical activations in supramarginal and frontal brain regions for phonological and lexical verbal fluency, but not for semantic verbal fluency.Ketamine induces activation changes in healthy subjects similar to those observed in patients with schizophrenia, particularly in frontal and temporal brain regions. Our results provide further support for the hypothesis of an NMDA receptor dysfunction in the pathophysiology of schizophrenia.

FMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer's disease

Background We adapted an event-related brain potential word repetition paradigm, sensitive to early Alzheimer's disease (AD), for functional MRI (fMRI). We hypothesized that AD would be associated with reduced differential response to New/Old congruous words. Methods Fifteen mild AD patients (mean age = 72.9) and 15 normal elderly underwent 1.5T fMRI during a semantic category decision task. Results We found robust between-groups differences in BOLD response to congruous words. In controls, the New > Old contrast demonstrated larger responses in much of the left-hemisphere (including putative P600 generators: parahippocampal, cingulate, fusiform, perirhinal, middle temporal (MTG) and inferior frontal gyri (IFG)); the Old > New contrast showed modest activation, mainly in right parietal and prefrontal cortex. By contrast, there were relatively few regions of significant New > Old responses in AD patients, mainly in the right-hemisphere, and their Old > New contrast did not demonstrate a right-hemisphere predominance. Across subjects, the spatial extent of New > Old responses in left medial temporal lobe (MTL) correlated with subsequent recall and recognition ( r's ≥ 0.60). In controls, the magnitude of New–Old response in left MTL, fusiform, IFG, MTG, superior temporal and cingulate gyrus correlated with subsequent cued recall and/or recognition (0.51 ≤ r's ≤ 0.78). Conclusions A distributed network of mostly left-hemisphere structures, which are putative P600 generators, appears important for successful verbal encoding (with New > Old responses to congruous words in normal elderly). This network appears dysfunctional in mild AD patients, as reflected in decreased word repetition effects particularly in left association cortex, paralimbic and MTL structures.

Trait cheerfulness modulates BOLD response in lateral cortical but not limbic brain areas—A pilot fMRI study

Having a good “sense of humor” is an important personality characteristic that significantly influences social communication and may represent an important coping strategy. To take things “with humor” does not only represent a state characteristic but also a personality trait that can reliably be assessed with questionnaires like the “state–trait–cheerfulness–inventory” (STCI) by Ruch [Ruch et al., Assessing the “humorous temperament”: construction of the facet and standard trait forms of the state–trait–cheerfulness–inventory—STCI, Humor 9 (1996) 303–339]. Substantial inter-individual differences among study subjects are a key feature of almost all functional magnetic resonance imaging studies on higher cognitive functions. Usually, they are considered as “statistical noise” and are not recommended for the data analysis, although they can have a high intra-individual stability. However, a number of recent fMRI studies found robust correlations between inter-individual differences in BOLD response and personality traits such as extraversion. The aim of this pilot exploratory study was to localise regions where the BOLD response was predicted by “humor personality” scores. 10 healthy male subjects viewed funny or non-funny versions of Gary Larson cartoons while BOLD response was measured with functional magnetic resonance imaging (fMRI). Data were collected from the whole brain (28 slices, slice thickness 4 mm, 1 mm gap, TR = 3 s). SPM 99 software was used. A simple regression analysis with the sub-score cheerfulness from the STCI was applied. Higher cheerfulness in the STCI predicted brain activation in the right inferior parietal lobule (Tal X, Y, Z: 45, −77, 29), but not in limbic and prefrontal brain areas. We conclude that neural correlates of cheerfulness are correlated with BOLD response in lateral cortical rather than limbic brain areas. Likely the activated region is important for a readiness or tendency to be amused, whereas the regions previously shown to be activated in humor appreciation studies are related to the understanding of the joke and the emotional reaction.