Spinal hemangioblastoma combined with pilocytic astrocytoma

The combination of vascular anomalies with gliomas is rarely seen in the CNS, and is defined as ‘angioglioma’. However, the definition, category, and histopathogenesis of angiogliomas remain controversial. Here, we present an unusual case of spinal hemangioblastoma (HB) combined with pilocytic astrocytoma (PA). Spinal MRI revealed lesions extending from T9 to T12 segments, in a “sandwich-like” fashion. After resection of the tumor, histopathologic study confirmed the diagnosis of HB as well as PA. A comprehensive review of the literature was further conducted. We describe a case of spinal HB combined with PA, in addition we discuss the clinicopathological relationship between HB and PA under these conditions, which may facilitate the understanding of the histogenesis of an angioglioma and guide its diagnosis and treatment.The association of gliomas with certain types of vascular anomalies has been designated as angioglioma, and is rarely seen in the CNS.1 Councilman2 for the first time coined the term of “angiogliomas” to describe a highly vascular cerebellar neoplasm with features that were later recognized as the cellular variant of hemangioblastoma. Angiogliomas are roughly defined as mixed neoplasms composed of a low-grade glioma and a vascular anomaly. The combination of glial component and vascular component can be diverse. The vascular anomalies may be associated with various glial components, including fibrillary astrocytoma, pilocytic astrocytoma (PA), xanthoastrocytoma, and so on. Whereas the glial tumors may be associated with arteriovenous malformation, cavernous angioma, and hemangioblastoma (HB), more seen in the first 2 types.1,3 The incidence of angioglioma is relatively low as a previous study found only 2 cases in 168 low-grade gliomas.3 Compared with their intracranial counterparts, spinal cord angiogliomas are less common, let alone those presenting as HBs with astrocytomas. Our objective in presenting this particular case is to report a spinal HB combined with PA extending from T9 to T12 levels, complicated by an extensive syrinx. The lesions were in a “sandwich-like” fashion both in MRI and surgical findings, and exhibited particular histopathologic characteristics. We also review the related literature and discuss the features related to this special type of angioglioma.     

“Venous congestion” as a cause of subcortical white matter T2 hypointensity on magnetic resonance images

Subcortical T2 hypointensity is an uncommon finding seen in very limited conditions such as multiple sclerosis, Sturge-Weber syndrome, and meningitis. Some of the conditions such as moyamoya disease, severe ischemic-anoxic insults, early cortical ischemia, and infarcts are of “arterial origin.” We describe two conditions in which “venous congestion” plays a major role in T2 hypointensity — cerebral venous sinus thrombosis (CVST) and dural arteriovenous fistula (dAVF). The third case is a case of meningitis, showing T2 hypointensity as well, and can be explained by the “venous congestion” hypothesis. The same hypothesis can explain few of the other conditions causing subcortical T2 hypointensity.     

Transcriptome profiling of five brain regions in a 6‐hydroxydopamine rat model of Parkinson’s disease

BackgroundParkinson''s disease (PD) is a neurodegenerative disease, and its pathogenesis is unclear. Previous studies mainly focus on the lesions of substantia nigra (SN) and striatum (Str) in PD. However, lesions are not limited. The olfactory bulb (OB), subventricular zone (SVZ), and hippocampus (Hippo) are also affected in PD.AimTo reveal gene expression changes in the five brain regions (OB, SVZ, Str, SN, and Hippo), and to look for potential candidate genes and pathways that may be correlated with the pathogenesis of PD.Materials and methodsWe established control group and 6‐hydroxydopamine (6‐OHDA) PD model group, and detected gene expressions in the five brain regions using RNA‐seq and real‐time quantitative polymerase chain reaction (RT‐qPCR). We further analyzed the RNA‐seq data by bioinformatics.ResultsWe identified differentially expressed genes (DEGs) in all five brain regions. The DEGs were significantly enriched in the “dopaminergic synapse” and “retrograde endocannabinoid signaling,” and Gi/o‐GIRK is the shared cascade in the two pathways. We further identified Ephx2, Fam111a, and Gng2 as the potential candidate genes in the pathogenesis of PD for further studies.ConclusionOur study suggested that gene expressions change in the five brain regions following exposure to 6‐OHDA. The “dopaminergic synapse,” “retrograde endocannabinoid signaling,” and Gi/o‐GIRK may be the key pathways and cascade of the synaptic damage in 6‐OHDA PD rats. Ephx2, Fam111a, and Gng2 may play critical roles in the pathogenesis of PD.     

Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches

Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models: (1) “the avoidance model”; (2) “the intolerance of uncertainty model”; (3) “the meta-cognitive model”; (4) “the emotion dysregulation model”; and (5) “the acceptance based model”. For depression, the following theoretical models are explicated: (1) “the cognitive model”; (2) “the behavioral activation model”; and (3) “the interpersonal model”. Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines (BZDs) are an important “bridging strategy” to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a “stacking approach” not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.     

Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding,with Associated Consequences for Hippocampal Spatial Memory

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology.SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.     

Looking at “thunderclap headache” differently? Circa 2016

The term “thunderclap headache” (TCH) was first coined in 1986 by Day and Raskin to describe headache that was the presenting feature of an underlying unruptured cerebral aneurysm. The term is now well established to describe the abrupt onset headache seen with many other conditions and is also now included in The International Classification of Headache Disorders 3^rd edition beta version rubric 4.4. An essential to label an acute headache as “TCH” and differentiate it from other “sudden onset, severe headaches” is the arbitrary time frame of 1 min from onset to peak intensity for “TCH.” What happens in practice, however, is that even those “sudden onset, severe headaches” that do not strictly fulfill the definition criteria are also labeled as “TCH” and investigated with the same speed and in the same sequence and managed based on the underlying cause. This article begins by questioning the validity and usefulness of this “one minute” arbitrary time frame to define “TCH,” particularly since this time frame is very difficult to assess in practice and is usually done on a presumptive subjective basis. The article concludes with suggestions for modification of the current investigation protocol for this emergency headache scenario. This proposal for “a change in practice methodology” is essentially based on (1) the fact that in the last two decades, we now have evidence for many more entities other than just subarachnoid hemorrhage that can present as “TCH” or “sudden onset, severe headache” and (2) the evidence from literature which shows that advances in imaging technology using higher magnet strength, better contrast, and newer acquisition sequences will result in a better diagnostic yield. It is therefore time now, in our opinion, to discard current theoretical time frames, use self-explanatory terminologies with practical implications, and move from “lumbar puncture (LP) first” to “LP last!”     

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood–brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: “symptomatic salvaged tissue” (SST) and “asymptomatic infarcted tissue” (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia–reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.     

Reduced cortical folding of the anterior cingulate cortex in obsessive–compulsive disorder

Background

Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive–compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls.

Methods

We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: “prominent,” “present” and “absent.” We classified the cingulate sulcus as “interrupted” or “continuous” according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology.

Results

Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a “prominent” or “present” paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls.

Limitations

Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates.

Conclusion

Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.     

Lists with and without Syntax: A New Approach to Measuring the Neural Processing of Syntax

In the neurobiology of syntax, a methodological challenge is to vary syntax while holding semantics constant. Changes in syntactic structure usually correlate with changes in meaning. We approached this challenge from a new angle. We deployed word lists—typically, the unstructured control in studies of syntax—as both test and control stimuli. Three-noun lists (“lamps, dolls, guitars”) were embedded in sentences (“The eccentric man hoarded lamps, dolls, guitars…”) and in longer lists (“forks, pen, toilet, rodeo, lamps, dolls, guitars…”). This allowed us to minimize contributions from lexical semantics and local phrasal combinatorics: the same words occurred in both conditions, and in neither case did the list items locally compose into phrases (e.g., “lamps” and “dolls” do not form a phrase). Crucially, the list partakes in a syntactic tree in one case but not the other. Lists-in-sentences increased source-localized MEG activity at ∼250–300 ms from each of the list item onsets in the left inferior frontal cortex, at ∼300–350 ms in the left anterior temporal lobe and, most reliably, at ∼330–400 ms in left posterior temporal cortex. In contrast, the main effects of semantic association strength, which we also varied, localized in the left temporoparietal cortex, with high associations increasing activity at ∼400 ms. This dissociation offers a novel characterization of the structure versus word meaning contrast in the brain: the frontotemporal network that is familiar from studies of sentence processing can be driven by the sheer presence of global sentence structure, while associative semantics has a more posterior neural signature.SIGNIFICANCE STATEMENT Human languages all have a syntax, which both enables the infinitude of linguistic creativity and determines what is grammatical in a language. The neurobiology of syntactic processing has, however, been challenging to characterize despite decades of study. One reason is pure manipulations of syntax are difficult to design. The approach here offers a novel control of two variables that are notoriously hard to keep constant when syntax is manipulated: word meaning and phrasal combinatorics. The same noun lists occurred inside longer lists and sentences, while semantic associations also varied. Our MEG results show that classic frontotemporal language regions can be driven by sentence structure even when local semantic contributions are absent. In contrast, the left temporoparietal junction tracks associative relationships.     

The Motor Basis for Misophonia

Misophonia is a common disorder characterized by the experience of strong negative emotions of anger and anxiety in response to certain everyday sounds, such as those generated by other people eating, drinking, and breathing. The commonplace nature of these “trigger” sounds makes misophonia a devastating disorder for sufferers and their families. How such innocuous sounds trigger this response is unknown. Since most trigger sounds are generated by orofacial movements (e.g., chewing) in others, we hypothesized that the mirror neuron system related to orofacial movements could underlie misophonia. We analyzed resting state fMRI (rs-fMRI) connectivity (N = 33, 16 females) and sound-evoked fMRI responses (N = 42, 29 females) in misophonia sufferers and controls. We demonstrate that, compared with controls, the misophonia group show no difference in auditory cortex responses to trigger sounds, but do show: (1) stronger rs-fMRI connectivity between both auditory and visual cortex and the ventral premotor cortex responsible for orofacial movements; (2) stronger functional connectivity between the auditory cortex and orofacial motor area during sound perception in general; and (3) stronger activation of the orofacial motor area, specifically, in response to trigger sounds. Our results support a model of misophonia based on “hyper-mirroring” of the orofacial actions of others with sounds being the “medium” via which action of others is excessively mirrored. Misophonia is therefore not an abreaction to sounds, per se, but a manifestation of activity in parts of the motor system involved in producing those sounds. This new framework to understand misophonia can explain behavioral and emotional responses and has important consequences for devising effective therapies.SIGNIFICANCE STATEMENT Conventionally, misophonia, literally “hatred of sounds” has been considered as a disorder of sound emotion processing, in which “simple” eating and chewing sounds produced by others cause negative emotional responses. Our data provide an alternative but complementary perspective on misophonia that emphasizes the action of the trigger-person rather than the sounds which are a byproduct of that action. Sounds, in this new perspective, are only a “medium” via which action of the triggering-person is mirrored onto the listener. This change in perspective has important consequences for devising therapies and treatment methods for misophonia. It suggests that, instead of focusing on sounds, which many existing therapies do, effective therapies should target the brain representation of movement.     

“Excessive Thinking” as Explanatory Model for Schizophrenia: Impacts on Stigma and “Moral” Status in Mainland China

Although psychiatric stigma in China is particularly pervasive and damaging, rates of high expressed emotion (“EE” or family members'' emotional attitudes that predict relapse) are generally lower than rates found in Western countries. In light of this seemingly incongruous juxtaposition and because Chinese comprise approximately one-fifth of the world''s mentally ill, we examine how one of the most widely held causal beliefs of schizophrenia—excessive thinking (xiang tai duo)—may powerfully shape how those exhibiting psychotic symptoms pass from “normal” status to stigmatized “other.” Using a framework by which stigma threatens an actor''s capacity to participate in core everyday engagements, we examine how expressions of excessive thinking intersect with psychotic symptoms and how this idiom reduces stigma by preserving essential moral standing. Four focus groups with family members (n = 34 total) of schizophrenia outpatients, who had participated in psychoeducation, were conducted in Beijing. Open coding was conducted by 2 bilingual coders achieving high interrater agreement. Common expressions of excessive thinking—taking things too hard that is perceived as a causal factor and unwarranted suspicion that is used to benignly interpret paranoid symptoms encapsulated disruptive behaviors that closely overlapped with psychotic symptoms. Because excessive thinking is understood to occur universally, this idiom encourages socially accommodating behavior that signifies acceptance of these individuals as full-status community members. In contrast, due to beliefs implying moral contamination, those labeled mentally ill are threatened with both subtle and outright social exclusion. We discuss implications of this idiom for EE and the detection of schizophrenia “prodrome” in China.     

Effect of lesions on cortical-generalized seizures in the kindled rat: Spinal transections

The convulsions which accompany cortical-generalized seizures in the kinkled rat commonly consist of three separate components: “early” clonus, “tonus,” and “late” clonus. Previous studies indicated that the first two of these can be differentially suppressed by selective brain lesions. In the present study, a series of partial and total sections of the spinal cord was carried out in an attempt to relate the various elements of the tripartite convulsion to specific spinal tracts. It was easily established that the tonic element of the convulsion could be suppressed by section of the dorsolateral cord, presumably due to interruption of the rubrospinal tract. Early and late clonus, however, survived every manipulation short of complete transection of the cord. Even contralateral hemisections placed a few millimeters apart did not diminish these elements of the cortical-generalized convulsive response. This unexpected result seems to suggest that early and late clonus depend not on direct descending connections from the brain, but rather on the activation of some sort of nonspecific neuronal pool within the cord itself.     

Photoreceptor Disc Enclosure Is Tightly Controlled by Peripherin-2 Oligomerization

Mutations in the PRPH2 gene encoding the photoreceptor-specific protein PRPH2 (also known as peripherin-2 or rds) cause a broad range of autosomal dominant retinal diseases. Most of these mutations affect the structure of the light-sensitive photoreceptor outer segment, which is composed of a stack of flattened “disc” membranes surrounded by the plasma membrane. The outer segment is renewed on a daily basis in a process whereby new discs are added at the outer segment base and old discs are shed at the outer segment tip. New discs are formed as serial membrane evaginations, which eventually enclose through a complex process of membrane remodeling (completely in rods and partially in cones). As disc enclosure proceeds, PRPH2 localizes to the rims of enclosed discs where it forms oligomers which fortify the highly curved membrane structure of these rims. In this study, we analyzed the outer segment phenotypes of mice of both sexes bearing a single copy of either the C150S or the Y141C PRPH2 mutation known to prevent or increase the degree of PRPH2 oligomerization, respectively. Strikingly, both mutations increased the number of newly forming, not-yet-enclosed discs, indicating that the precision of disc enclosure is regulated by PRPH2 oligomerization. Without tightly controlled enclosure, discs occasionally over-elongate and form large membranous “whorls” instead of disc stacks. These data show that the defects in outer segment structure arising from abnormal PRPH2 oligomerization are manifested at the stage of disc enclosure.SIGNIFICANCE STATEMENT The light-sensitive photoreceptor outer segment contains a stack of flattened “disc” membranes that are surrounded, or “enclosed,” by the outer segment membrane. Disc enclosure is an adaptation increasing photoreceptor light sensitivity by facilitating the diffusion of the second messenger along the outer segment axes. However, the molecular mechanisms by which photoreceptor discs enclose within the outer segment membrane remain poorly understood. We now demonstrate that oligomers of the photoreceptor-specific protein peripherin-2, or PRPH2, play an active role in this process. We further propose that defects in disc enclosure because of abnormal PRPH2 oligomerization result in major structural abnormalities of the outer segment, ultimately leading to loss of visual function and cell degeneration in PRPH2 mutant models and human patients.     

Detection of Alzheimer's Disease using cortical diffusion tensor imaging

The aim of this research was to test a novel in‐vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer''s Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the “Discovery” cohort, the second as the “Test” cohort and the last “ATN” (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADNI 3 cohort, comparing to amyloid and Tau PET. The method can detect altered quality of cortical grey matter in AD patients, providing an additional tool to assess AD, distinguishing between these and healthy controls with an accuracy range between good and excellent. These new measurements could be used within the “ATN” framework as an index of cortical microstructure quality and a marker of Neurodegeneration. Further development may aid diagnosis, patient selection, and quantification of the “Neurodegeneration” component in response to therapies in clinical trials.     

Neuronal Firing and Waveform Alterations through Ictal Recruitment in Humans

Analyzing neuronal activity during human seizures is pivotal to understanding mechanisms of seizure onset and propagation. These analyses, however, invariably using extracellular recordings, are greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the “noise”; all three factors confound attempts to detect and classify single neurons. To address these analytical difficulties, we developed a novel template-matching-based spike sorting method, which enabled identification of 1239 single neurons in 27 patients (13 female) with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing with widespread intense activation and stereotyped action potential alterations in tissue that was invaded by the seizure: neurons displayed increased waveform duration (p < 0.001) and reduced amplitude (p < 0.001), consistent with prior animal studies. By contrast, neurons in “penumbral” regions (those receiving intense local synaptic drive from the seizure but without neuronal evidence of local seizure invasion) showed stable waveforms. All neurons returned to their preictal waveforms after seizure termination. We conclude that the distinction between “core” territories invaded by the seizure versus “penumbral” territories is evident at the level of single neurons. Furthermore, the increased waveform duration and decreased waveform amplitude are neuron-intrinsic hallmarks of seizure invasion that impede traditional spike sorting and could be used as defining characteristics of local recruitment.SIGNIFICANCE STATEMENT Animal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proven difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude as the neurons are recruited to the seizure, while penumbral tissue shows stable action potentials, in keeping with the “dual territory” model of seizure dynamics.     

Viewing Ambiguous Social Interactions Increases Functional Connectivity between Frontal and Temporal Nodes of the Social Brain

Social behavior is coordinated by a network of brain regions, including those involved in the perception of social stimuli and those involved in complex functions, such as inferring perceptual and mental states and controlling social interactions. The properties and function of many of these regions in isolation are relatively well understood, but less is known about how these regions interact while processing dynamic social interactions. To investigate whether the functional connectivity between brain regions is modulated by social context, we collected fMRI data from male monkeys (Macaca mulatta) viewing videos of social interactions labeled as “affiliative,” “aggressive,” or “ambiguous.” We show activation related to the perception of social interactions along both banks of the superior temporal sulcus, parietal cortex, medial and lateral frontal cortex, and the caudate nucleus. Within this network, we show that fronto-temporal functional connectivity is significantly modulated by social context. Crucially, we link the observation of specific behaviors to changes in functional connectivity within our network. Viewing aggressive behavior was associated with a limited increase in temporo-temporal and a weak increase in cingulate-temporal connectivity. By contrast, viewing interactions where the outcome was uncertain was associated with a pronounced increase in temporo-temporal, and cingulate-temporal functional connectivity. We hypothesize that this widespread network synchronization occurs when cingulate and temporal areas coordinate their activity when more difficult social inferences are being made.SIGNIFICANCE STATEMENT Processing social information from our environment requires the activation of several brain regions, which are concentrated within the frontal and temporal lobes. However, little is known about how these areas interact to facilitate the processing of different social interactions. Here we show that functional connectivity within and between the frontal and temporal lobes is modulated by social context. Specifically, we demonstrate that viewing social interactions where the outcome was unclear is associated with increased synchrony within and between the cingulate cortex and temporal cortices. These findings suggest that the coordination between the cingulate and temporal cortices is enhanced when more difficult social inferences are being made.     

Need for Ethnic and Population Diversity in Psychosis Research

This article aims to evaluate “racial”, ethnic, and population diversity—or lack thereof—in psychosis research, with a particular focus on socio-environmental studies. Samples of psychosis research remain heavily biased toward Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. Furthermore, we often fail to acknowledge the lack of diversity, thereby implying that our findings can be generalized to all populations regardless of their social, ethnic, and cultural background. This has major consequences. Clinical trials generate findings that are not generalizable across ethnicity. The genomic-based prediction models are far from being applicable to the “Majority World.” Socio-environmental theories of psychosis are solely based on findings of the empirical studies conducted in WEIRD populations. If and how these socio-environmental factors affect individuals in entirely different geographic locations, gene pools, social structures and norms, cultures, and potentially protective counter-factors remain unclear. How socio-environmental factors are assessed and studied is another major shortcoming. By embracing the complexity of environment, the exposome paradigm may facilitate the evaluation of interdependent exposures, which could explain how variations in socio-environmental factors across different social and geographical settings could contribute to divergent paths to psychosis. Testing these divergent paths to psychosis will however require increasing the diversity of study populations that could be achieved by establishing true partnerships between WEIRD societies and the Majority World with the support of funding agencies aspired to foster replicable research across diverse populations. The time has come to make diversity in psychosis research more than a buzzword.     

2012 CCNP Innovations Award Paper: Antipsychotic dosing: found in translation

In the field of schizophrenia research, as in other areas of psychiatry, there is a sense of frustration that greater advances have not been made over the years, calling into question existing research strategies. Arguably, many purported gains claimed by research have been “lost in translation,” resulting in limited impact on diagnosis and treatment in the clinical setting. There are exceptions; for example, we would argue that different lines of preclinical and clinical research have substantially altered how we look at antipsychotic dosing. While this story remains a work in progress, advances “found in translation” have played an important role. Detailing these changes, the present paper speaks to a body of evidence that has already shifted clinical practice and raises questions that may further alter the manner in which antipsychotics have been administered over the last 6 decades.