Reward Learning as a Potential Mechanism for Improvement in Schizophrenia Spectrum Disorders Following Cognitive Remediation: Protocol for a Clinical, Nonrandomized, Pre-Post Pilot Study.

BACKGROUND: Cognitive impairment is common with schizophrenia spectrum disorders. Cognitive remediation (CR) is effective in improving global cognition, but not all individuals benefit from this type of intervention. A better understanding of the potential mechanism of action of CR is needed. One proposed mechanism is reward learning (RL), the cognitive processes responsible for adapting behavior following positive or negative feedback. It is proposed that the structure of CR enhances RL and motivation to engage in increasingly challenging tasks, and this is a potential mechanism by which CR improves cognitive functioning in schizophrenia. OBJECTIVE: Our primary objective is to examine reward processing in individuals with schizophrenia before and after completing CR and to compare this with a group of matched clinical controls. We will assess whether RL mediates the relationship between CR and improved cognitive function and reduced negative symptoms. Potential differences in social RL and nonsocial RL in individuals with schizophrenia will also be investigated and compared with a healthy matched control group. METHODS: We propose a clinical, nonrandomized, pre-post pilot study comparing the impact of CR on RL and neurocognitive outcomes. The study will use a combination of objective and subjective measures to assess neurocognitive, psychiatric symptoms, and neurophysiological domains. A total of 40 individuals with schizophrenia spectrum disorders (aged 18-35 years) will receive 12 weeks of CR therapy (n=20) or treatment as usual (n=20). Reward processing will be evaluated using a reinforcement learning task with 2 conditions (social reward vs nonsocial reward) at baseline and the 12-week follow-up. Functional magnetic resonance imaging responses will be measured during this task. To validate the reinforcement learning task, RL will also be assessed in 20 healthy controls, matched for age, sex, and premorbid functioning. Mixed-factorial ANOVAs will be conducted to evaluate treatment group differences. For the functional magnetic resonance imaging analysis, computational modeling will allow the estimation of learning parameters at each point in time, during each task condition, for each participant. We will use a variational Bayesian framework to measure how learning occurred during the experimental task and the subprocesses that underlie this learning. Second-level group analyses will examine how learning in patients differs from that observed in control participants and how CR alters learning efficiency and the underlying neural activity. RESULTS: As of September 2023, this study has enrolled 15 participants in the CR group, 1 participant in the treatment-as-usual group, and 11 participants in the healthy control group. Recruitment is expected to be completed by September 2024. Data analysis is expected to be completed and published in early 2025. CONCLUSIONS: The results of this study will contribute to the knowledge of CR and RL processes in severe mental illness and the understanding of the systems that impact negative symptoms and cognitive impairments within this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52505.

Routine assessment of gastrointestinal symptom using a validated questionnaire in the clinical setting to assess the probability of organic or functional gastrointestinal diseases.

BACKGROUND: Patients presenting with gastrointestinal symptoms can be challenging in terms of determining etiology and management strategies. Identifying likely organic pathology is important since it can be treated and may result in further, long-term harm to the patient if not treated. Currently, organic pathology is often identified via invasive procedures such as endoscopy or referral to a medical imaging service. We report on an approach that offers a first step at identifying patients with an organic gastrointestinal disease based on the SAGIS, a validated symptom questionnaire. METHODS: 8,922 patients referred to a tertiary care hospital were classified as having either functional gastrointestinal disease or an organic gastrointestinal disease. A model was developed to distinguish organic from functional symptoms on one random split half of the sample and validated on the other half. The incremental benefit of including psychological conditions and extra-gastrointestinal conditions was also evaluated. KEY RESULTS: Functional gastrointestinal patients scored higher on average than organic patients on all dimensions of the SAGIS and reported higher rates of psychological and extra-gastrointestinal conditions. All five dimensions of the SAGIS provided statistically independent discrimination of organic from functional diagnoses with good overall discrimination (AUC = 0.75). However, there was no noticeable incremental benefit of adding either psychological or extra-gastrointestinal conditions. Model performance was highly reproducible. CONCLUSIONS AND INFERENCES: The proposed algorithm for identifying likely organic gastrointestinal disease applied to symptoms as recorded in the SAGIS questionnaire provides a useful tool for the clinician in deciding what or if further diagnostic testing is required.

Improving the Quality of Bowel Preparation: Rewarding Patients for Success or Intensive Patient Education?

INTRODUCTION AND OBJECTIVES: The quality of the bowel preparation is a critical parameter for the outcome of colonoscopies. It is well established that the bowel preparation modality (e.g., split or larger volume preparation) significantly improves the quality of the bowel preparation. Patient compliance is another important factor impacting on the quality of bowel preparations that receives relatively little research attention. We aimed to explore if intensified education or a lottery ticket as reward for good bowel preparation could improve outcomes. METHODS: After informed consent, all patients received a standardized printed information booklet. In a randomized fashion, patients were offered (a) a lottery scratchy ticket with an opportunity to win $25,000 as "reward" for good bowel preparation, (b) an education session delivered over the phone by a trained nurse, or (c) no additional measure. RESULTS: Overall, the quality of the bowel preparation was rated good or very good in 69.1% (95% CI 61.7-75.7%) of patients. Reward intervention did not influence the quality of bowel preparation (OR 0.42, 95% CI 0.09-1.91, p = 0.260); however, bowel preparation quality decreased in patients randomized to receive the additional education (OR 0.28, 95% CI 0.08-0.96, p = 0.042). Neither intervention significantly impacted on polyp detection rates. CONCLUSIONS: Contrasting general beliefs, additional interventions (e.g., incentives or phone consultation) did not improve the quality of the bowel preparation. The unexpected result shows that utilizing extra resources must be balanced against real-world outcomes and may not always provide the expected result.

Serial MRI studies over 12 months using manual and atlas-based region of interest in patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper and lower motor neurons. There is a need for an imaging biomarker to track disease progression. Previously, magnetic resonance imaging (MRI) has shown loss of grey and white matter in the brain of patients with ALS compared to controls. We performed serial diffusion tractography imaging (DTI) study of patients with ALS looking for changes over time. METHODS: On all subjects (n = 15), we performed three MRI studies at 6 month intervals. DTI changes were assessed with tract-based spatial statistics (TBSS) and region of interest (ROI) studies. Cortic-spinal tract (CST) was selected for our ROI at the upper level; the posterior limb of internal capsule (PLIC), and a lower level in the pons. RESULTS: There was no significant change in DTI measures over 12 months of observation. Better correlation of manual and atlas-based ROI methods was found in the posterior limb of the internal capsule than the pons. CONCLUSION: While previous DTI studies showed significant differences between ALS subjects and controls, within individual subjects there is little evidence of progression over 12 months. This suggests that DTI is not a suitable biomarker to assess disease progression in ALS.

Tract integrity in amyotrophic lateral sclerosis: 6-month evaluation using MR diffusion tensor imaging.

BACKGROUND: This study was performed to assess changes in diffusion tensor imaging (DTI) over time in patients with amyotrophic lateral sclerosis (ALS). METHODS: We performed DTI in 23 ALS patients who had two magnetic resonance imaging (MRI) scans at 6 month intervals and to correlate results with clinical features. The revised ALS functional rating scale (ALSFRS-R) was administered at each clinical visit. Data analysis included voxel-based white matter tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analysis of fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: With TBSS, there were no significant changes between the two scans. The average change in FA and MD in the ROIs over 6 months was small and not significant after allowing for multiple comparisons. After allowing for multiple comparisons, there was no significant correlation of FA or MD with ALSFRS-R. CONCLUSION: This study shows that there is little evidence of progressive changes in DTI over time in ALS. This could be because white matter is already substantially damaged by the time of onset of symptoms of ALS.

Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases.

BACKGROUND: In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn's disease. METHODS: We examined 9 patients with Crohn's disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge. RESULTS: Following anti-TNFα treatment, ratings of 'fullness' following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings. CONCLUSION: In patients with Crohn's disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.

Altered functional connectivity in mesial temporal lobe epilepsy.

Growing evidence of altered functional connectivity suggests that mesial temporal lobe epilepsy (mTLE) alters not only hippocampal networks, but also a number of resting state networks. These highly coherent, yet functionally distinct brain circuits interact dynamically with each other in order to mediate consciousness, memory, and attention. However, little is currently known about the modulation of these networks by epileptiform activity, such as interictal spikes and seizures. The objective of the study was to use simultaneous EEG-fMRI to investigate functional connectivity in three resting state networks: default mode network (DMN), salience network (SN), and dorsal attentional network (DAN) in patients with mTLE compared to a healthy cohort, and in relation to the onset of interictal spikes and the period immediately prior to the spikes. Compared to the healthy participants, mTLE patients showed significant alterations in functional connectivity of all three resting state networks, generally characterized by a lack of functional connectivity to prefrontal areas and increased connectivity to subcortical and posterior areas. Critically, prior to the onset of interictal spikes, compared to resting state, mTLE patients showed a lack of functional connectivity to the DMN and decreased synchronization within the SN and DAN, demonstrating alterations in functional coherence that may be responsible for the generation of epileptiform activity. Our findings demonstrate mTLE-related alterations of connectivity during the resting state as well as in relation to the onset of interictal spikes. These functional changes may underlie epilepsy-related cognitive abnormalities, because higher cognitive functions, such as memory or attention, rely heavily on the coordinated activity of all three resting state networks.

Longitudinal changes in the fronto-striatal network are associated with executive dysfunction and behavioral dysregulation in Huntington's disease: 30 months IMAGE-HD data.

Neuropsychiatric disturbance-particularly executive dysfunction and behavioral dysregulation-is a common feature of Huntington's disease (HD), with implications for functional capacity and quality of life. No study to date has ascertained whether longitudinal change in brain activity is associated with neuropsychiatric deficits in HD. We used a set-response-shifting task together with functional magnetic resonance imaging to investigate 30-month longitudinal blood-oxygen level dependent (BOLD) signal changes in the fronto-striatal attentional control network in premanifest and symptomatic HD (pre-HD and symp-HD, respectively), relative to healthy control participants. We also assessed the extent to which changes in the BOLD signal over time were related to neuropsychiatric measures in the domains of executive dysfunction and behavioral dysregulation. Associations were also evaluated with clinical and disease severity. We found no longitudinal BOLD differences between pre-HD and controls over 30 months. In contrast, reduction in BOLD response over time was greater in symp-HD, relative to controls, in task-related areas (e.g., anterior cingulate cortex and striatum) and in regions from the default mode network (e.g., medial prefrontal cortex and posterior cingulate/precuneus). Moreover, when considered across both premanifest and symptomatic stages, longitudinal BOLD signal decline in the right dorsolateral prefrontal cortex and putamen was associated with executive dysfunction and behavioral dysregulation measures. In addition, longitudinal reduction in BOLD signal, in fronto-striatal and default mode networks, correlated with disease severity. These results suggest that longitudinal change in fronto-striatal and default mode networks may be useful in understanding the biological underpinnings of functional decline in HD. Such findings offer new avenues for targeted treatments in terms of minimizing psychiatric impairment and potentially maximizing cognitive function.

Neuroanatomical substrates for the volitional regulation of heart rate.

The control of physiological arousal can assist in the regulation of emotional state. A subset cortical and subcortical brain regions are implicated in autonomic control of bodily arousal during emotional behaviors. Here, we combined human functional neuroimaging with autonomic monitoring to identify neural mechanisms that support the volitional regulation of heart rate, a process that may be assisted by visual feedback. During functional magnetic resonance imaging (fMRI), 15 healthy adults performed an experimental task in which they were prompted voluntarily to increase or decrease cardiovascular arousal (heart rate) during true, false, or absent visual feedback. Participants achieved appropriate changes in heart rate, without significant modulation of respiratory rate, and were overall not influenced by the presence of visual feedback. Increased activity in right amygdala, striatum and brainstem occurred when participants attempted to increase heart rate. In contrast, activation of ventrolateral prefrontal and parietal cortices occurred when attempting to decrease heart rate. Biofeedback enhanced activity within occipito-temporal cortices, but there was no significant interaction with task conditions. Activity in regions including pregenual anterior cingulate and ventral striatum reflected the magnitude of successful task performance, which was negatively related to subclinical anxiety symptoms. Measured changes in respiration correlated with posterior insula activation and heart rate, at a more lenient threshold, change correlated with insula, caudate, and midbrain activity. Our findings highlight a set of brain regions, notably ventrolateral prefrontal cortex, supporting volitional control of cardiovascular arousal. These data are relevant to understanding neural substrates supporting interaction between intentional and interoceptive states related to anxiety, with implications for biofeedback interventions, e.g., real-time fMRI, that target emotional regulation.

Slow breathing and hypoxic challenge: cardiorespiratory consequences and their central neural substrates.

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.

Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study.

Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5-10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients.

Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study.

We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2-BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD.

Identification of pre-spike network in patients with mesial temporal lobe epilepsy.

BACKGROUND: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) affect a network of brain regions rather than a single epileptic focus. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a focus, or conversely the activation of a network linked to spike generation remains unknown. The functional connectivity (FC) changes prior to spikes may provide information about the connectivity changes that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes immediately prior to the appearance of interictal spikes on EEG in patients with MTLE. METHODS/PRINCIPAL FINDINGS: Fifteen patients with MTLE underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were defined relative to spike onset: spike (0-10 s), pre-spike (-10 to 0 s), and rest (-20 to -10 s, with no previous spikes in the preceding 45s). Significant spike-related activation in the hippocampus ipsilateral to the seizure focus was found compared to the pre-spike and rest epochs. The peak voxel within the hippocampus ipsilateral to the seizure focus was used as a seed region for FC analysis in the three conditions. A significant change in FC patterns was observed before the appearance of electrographic spikes. Specifically, there was significant loss of coherence between both hippocampi during the pre-spike period compared to spike and rest states. CONCLUSION/SIGNIFICANCE: In keeping with previous findings of abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings specifically link reduced connectivity to the period immediately before spikes. This brief decoupling is consistent with a deficit in mutual (inter-hemispheric) hippocampal inhibition that may predispose to spike generation.

Superficial amygdala and hippocampal activity during affective music listening observed at 3 T but not 1.5 T fMRI.

The purpose of this study was to compare 3 T and 1.5 T fMRI results during emotional music listening. Stimuli comprised of psychoacoustically balanced instrumental musical pieces, with three different affective expressions (fear, neutral, joy). Participants (N=32) were split into two groups, one subjected to fMRI scanning using 3 T and another group scanned using 1.5 T. Whole brain t-tests (corrected for multiple comparisons) compared joy and fear in each of the two groups. The 3 T group showed significant activity differences between joy and fear localized in bilateral superficial amygdala, bilateral hippocampus and bilateral auditory cortex. The 1.5 T group showed significant activity differences between joy and fear localized in bilateral auditory cortex and cuneus. This is the first study to compare results obtained under different field strengths with regard to affective processes elicited by means of auditory/musical stimulation. The findings raise concern over false negatives in the superficial amygdala and hippocampus in affective studies conducted under 1.5 T and caution that imaging improvements due to increasing magnetic field strength can be influenced by region-specific characteristics.

Fear from the heart: sensitivity to fear stimuli depends on individual heartbeats.

Cognitions and emotions can be influenced by bodily physiology. Here, we investigated whether the processing of brief fear stimuli is selectively gated by their timing in relation to individual heartbeats. Emotional and neutral faces were presented to human volunteers at cardiac systole, when ejection of blood from the heart causes arterial baroreceptors to signal centrally the strength and timing of each heartbeat, and at diastole, the period between heartbeats when baroreceptors are quiescent. Participants performed behavioral and neuroimaging tasks to determine whether these interoceptive signals influence the detection of emotional stimuli at the threshold of conscious awareness and alter judgments of emotionality of fearful and neutral faces. Our results show that fearful faces were detected more easily and were rated as more intense at systole than at diastole. Correspondingly, amygdala responses were greater to fearful faces presented at systole relative to diastole. These novel findings highlight a major channel by which short-term interoceptive fluctuations enhance perceptual and evaluative processes specifically related to the processing of fear and threat and counter the view that baroreceptor afferent signaling is always inhibitory to sensory perception.

Emotional valence and arousal affect reading in an interactive way: neuroimaging evidence for an approach-withdrawal framework.

A growing body of literature shows that the emotional content of verbal material affects reading, wherein emotional words are given processing priority compared to neutral words. Human emotions can be conceptualised within a two-dimensional model comprised of emotional valence and arousal (intensity). These variables are at least in part distinct, but recent studies report interactive effects during implicit emotion processing and relate these to stimulus-evoked approach-withdrawal tendencies. The aim of the present study was to explore how valence and arousal interact at the neural level, during implicit emotion word processing. The emotional attributes of written word stimuli were orthogonally manipulated based on behavioural ratings from a corpus of emotion words. Stimuli were presented during an fMRI experiment while 16 participants performed a lexical decision task, which did not require explicit evaluation of a word's emotional content. Results showed greater neural activation within right insular cortex in response to stimuli evoking conflicting approach-withdrawal tendencies (i.e., positive high-arousal and negative low-arousal words) compared to stimuli evoking congruent approach vs. withdrawal tendencies (i.e., positive low-arousal and negative high-arousal words). Further, a significant cluster of activation in the left extra-striate cortex was found in response to emotional than neutral words, suggesting enhanced perceptual processing of emotionally salient stimuli. These findings support an interactive two-dimensional approach to the study of emotion word recognition and suggest that the integration of valence and arousal dimensions recruits a brain region associated with interoception, emotional awareness and sympathetic functions.

FMRI scanner noise interaction with affective neural processes.

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes.

Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome.

Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD.

Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study.

IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington's disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (<15 years) and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.