Anhedonia and individual differences in orbitofrontal cortex sulcogyral morphology

Three types of orbitofrontal cortex (OFC) sulcogyral patterns that have been identified in the population, and the distribution of these three types in clinically diagnosed schizophrenic patients has been found to be distinct from the normal population. Schizophrenia is associated with increased levels of social and physical anhedonia. In this study, we asked whether variation in anhedonia in a neurologically normal population is associated with altered sulcogyral pattern frequency. OFC sulcogyral type was classified and anhedonia was measured in 58 normal young adults, and the relationship between OFC sulcogyral type and anhedonia was explored. In line with other studies conducted in chronic schizophrenia, individuals with higher levels of physical anhedonia demonstrated atypical sulcogyral patterns. Individuals with higher physical anhedonia showed a reduced incidence of Type I OFC and an increased incidence of Type II OFC in the left hemisphere compared to individuals with lower physical anhedonia. These findings support the notion that Type I OFC sulcogyral pattern is protective of anhedonia compared to Type II, even in individuals that are not schizophrenic. Overall, these results support the view that symptoms and neural indices typically associated with neuropsychiatric disorders actually reflect quantitative traits that are continuously distributed throughout the general population. Hum Brain Mapp 37:3873–3881, 2016. © 2016 Wiley Periodicals, Inc .     

Sexually dimorphic distribution of orbitofrontal sulcogyral pattern in schizophrenia

Aim: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by a remarkable inter‐individual variability that likely reflects neurobehavioral traits and genetic aspects of neurodevelopment. The aim of the present study was to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and healthy controls (HC) to determine group differences in OFC sulcogyral pattern as well as gender differences between groups. Methods: Forty‐seven SZ patients (M/F, 23/24) and forty‐seven HC (M/F, 17/30), matched on age and gender, were analyzed using magnetic resonance imaging. The sulcogyral pattern was classified into type I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous paper. Chi‐squared analysis was used to investigate group and gender differences in the sulcogyral pattern distribution, and categorical regression was used to explore clinical correlations. Results: The distribution of OFC sulcogyral pattern in HC replicated the results found in the previous study (left, χ² = 0.02, P = 0.989; right, χ² = 0.97, P = 0.616), in that there were no gender differences. Moreover, the distribution in SZ‐M was in accordance with that in the previous study (left, χ² = 1.59, P = 0.451; right, χ² = 0.14, P = 0.933). Additionally, within SZ‐M, patients with the type III pattern had a higher total positive and negative syndrome scale score (β = 0.902, F = 14.75, P = 0.001). In contrast, the distribution in the right hemisphere in the SZ‐F group differed significantly from that observed in SZ‐M (χ² = 6.017, P = 0.046), but did not differ from HC (χ² = 2.557, P = 0.110). Conclusion: OFC sulcogyral pattern is altered in SZ‐M but not in SZ‐F, possibly reflecting gender differences in early neurodevelopment.     

Altered orbitofrontal sulcogyral patterns in adult males with high-functioning autism spectrum disorders

Functions of the orbitofrontal cortex include diverse social, cognitive and affective processes, many of which are abnormal in autism spectrum disorders (ASDs). Recently, altered orbitofrontal sulcogyral patterns have been revealed in several psychiatric conditions, such as schizophrenia, indicating a possibility that altered orbitofrontal sulcogyral morphology reflects abnormal neurodevelopment. However, the presence of sulcal alterations in ASD remains unexplored. Using structural magnetic resonance imaging, subtypes of the ‘H-shaped’ sulcus (Type I, II and III, in order of frequency), posterior orbital sulcus (POS) and intermediate orbital sulcus were identified in each hemisphere of adult males with ASD (n = 51) and matched normal controls (n = 55) based on the study by Chiavaras and Petrides. ASD showed a significantly altered distribution of H-shaped sulcal subtypes in both hemispheres, with a significant increase of Type III. A significant alteration in the distribution of sulcal subtypes was also identified in the right hemisphere POS of ASD. Categorical regression analysis revealed that Type I and II expressions predicted a reduced total Autism-Spectrum Quotient score. Furthermore, Type I expression was associated with a reduced ‘attention to detail’ subscale score. The results demonstrate that altered sulcogyral morphology can be a marker for abnormal neurodevelopment leading to the increased risk of developing autism.     

Orbitofrontal sulcogyral patterns are related to temperamental risk for psychopathology

There are marked individual differences in the pattern of cortical (sulcogyral) folding in the orbitofrontal cortex (OFC), and there is a growing literature suggesting that these individual differences are associated with risk for psychotic disorders. To date, however, no study has investigated whether OFC folding patterns are associated with broader risk factors relevant to a range of psychopathology. This study helps address this knowledge gap by examining whether OFC sulcogyral folding patterns are associated with putative risk factors, specifically affective temperament and psychiatric symptoms, in a large community sample (N = 152) of adolescents. Results showed that the most common pattern of folding (‘Type I’, marked by discontinuity of the medial orbital sulcus and continuity of the lateral orbital sulcus) was associated with low levels of Surgency, high levels of Negative Affectivity (in girls) and higher depressive symptoms. This pattern was also associated with reduced thickness of OFC gray matter. Overall, the findings, combined with previous work, suggest some specificity of neurodevelopmental risk for different types of psychopathology. Thus, these results have the potential to inform the early identification of at-risk individuals.     

Orbitofrontal morphology in people at high risk of developing schizophrenia

BackgroundAbnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.MethodsHundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.ResultsWe refined Chiavaras’ classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.ConclusionsOur results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.     

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (− 1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.     

Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder

Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3‐D high‐spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age‐ and gender‐matched healthy controls. Optimized voxel‐based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism‐Extraversion‐Openness Personality Inventory scores. Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait‐Anxiety (β = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait‐Anxiety (β = ?0.394, F = 5.341, P = 0.032) and Neuroticism trait (β = ?0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.     

Prevalence and length of the adhesio interthalamica in schizophrenia spectrum disorders

We used magnetic resonance imaging to investigate the prevalence and length of the adhesio interthalamica (AI) in 72 schizophrenia patients, 47 schizotypal disorder patients, and 81 healthy controls. The AI was more often absent and shorter in both disorders than in controls, possibly reflecting common neurodevelopmental abnormalities in the schizophrenia spectrum.     

Olfactory cortex and Olfactory bulb volume alterations in patients with post-infectious Olfactory loss

Upper respiratory tract infection (URI) is one of the most common etiology of olfactory loss. Previous studies demonstrated that both olfactory bulb (OB) volume and sulcus (OS) depth decreased in patients with post-infectious olfactory loss (PIOL) compared to normal controls. The aim of our study was to observe alterations of central olfactory pathways in patients with PIOL. T1 weighted magnetic resonance images were acquired in 19 PIOL patients and 19 age- and sex-matched control subjects on a 3 T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. We also analyzed OB volume in coronal T2-weighted images. Whole-brain analysis revealed a significant gray matter volume loss in the right orbitofrontal cortex (OFC) in patients group. Further analysis with region of interest exhibited a significant negative correlation between gray matter volume in right OFC as well as OB volume and the duration of olfactory loss in these patients (r = -0.566 and r = -0.535 both P?<?0.05, respectively). In conclusion, the morphological alterations in the right OFC and OB might contribute to the pathogenic mechanism of olfactory dysfunction after upper respiratory tract infection.     

Hyperintentionality during automatic perception of naturalistic cooperative behavior in patients with schizophrenia

Social cognition and the corresponding functionality of involved brain networks are essential for effortless social interaction. Patients with schizophrenia exhibit impaired social functioning. In this study, we focused on the neural networks involved in the automatic perception of cooperative behavior and their alterations in schizophrenia.

We performed a functional magnetic resonance imaging study of 19 schizophrenia patients and 19 healthy matched controls. Participants watched a set of short videos with two actors manipulating objects, either with (C+) or without cooperation (C–). Additionally, we assessed delusional symptoms in patients using the Scales for the Assessment of Positive Symptoms and psychosis proneness in healthy controls using the brief schizotypal personality questionnaire.

The observed group-by-condition interaction revealed a contrasting activation pattern for patients versus healthy controls in the medial and lateral prefrontal cortex, the middle cingulate cortex, and the left angular gyrus. Furthermore, increased activation of the middle prefrontal areas, left angular gyrus, and the posterior sulcus temporalis superior in response to the noncooperative condition (C–) was positively correlated with delusional symptoms in patients.

Our findings suggest an overactivated “theory of mind” network in patients for the processing of noncooperative behavior. Thus, “overmentalizing” might be based on delusions and altered processing of cooperative behavior in patients with schizophrenia.     

Olfactory sulcal depth and olfactory bulb volume in patients with schizophrenia: an MRI study

The current report used structural magnetic resonance imaging (MRI) to objectively measure olfactory bulb volume and olfactory sulcal depth in patients diagnosed with chronic schizophrenia and healthy controls. Additional measures were obtained to assess olfactory function. The olfactory bulb and sulcus were manually traced on structural 3T MRIs for 25 right-handed male patients diagnosed with chronic schizophrenia and 25 matched male healthy controls. A sub-set of subjects received the University of Pennsylvania Smell Identification Test (UPSIT). Olfactory bulb volume was significantly decreased in patients with schizophrenia compared to healthy controls, as was their performance on the UPSIT. Additionally, a positive correlation was seen in patients between right bulb volume and UPSIT scores. Overall, our findings support earlier research studies showing morphometric and functional changes in the olfactory system in patients with schizophrenia.     

Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum

Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal pole (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis.     

Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder

Lack of normal structural asymmetry of the anterior cingulate gyrus (ACG) in patients with schizophrenia has been reported in our previous study. However, to our knowledge, no morphological studies of the brain have examined changes in ACG volume in patients with schizotypal features. We investigated the volume of the gray matter and the white matter of the ACG by three-dimensional magnetic resonance imaging (MRI) in 24 patients who met the ICD-10 criteria for schizotypal disorder (12 males, 12 females) in comparison with 48 age- and gender-matched healthy control subjects (24 males, 24 females) and 40 patients with schizophrenia (20 males, 20 females). As we reported previously, right ACG gray matter volume was significantly reduced in the female patients with schizophrenia compared with the female controls. On the other hand, the gray and white matter volume of the ACG in the patients with schizotypal disorder did not differ significantly from the values in the healthy controls or the patients with schizophrenia. However, the female patients with schizotypal disorder showed a lack of right-greater-than-left asymmetry of the ACG gray and white matter found in the female controls. These results suggest that both schizotypal and schizophrenic subjects share, at least in part, the same cerebral asymmetry abnormalities. Received: 28 May 2002 / Accepted: 30 October 2002 Correspondence to T. Takahashi     

The use of the orbitofrontal H‐sulcus as a reference frame for value signals

Understanding the factors that drive organization and function of the brain is an enduring question in neuroscience. Using functional magnetic resonance imaging (fMRI), structure and function have been mapped in primary sensory cortices based on knowledge of the organizational principles that likely drive a given region (e.g., aspects of visual form in primary visual cortex and sound frequency in primary auditory cortex) and knowledge of underlying cytoarchitecture. The organizing principles of higher‐order brain areas that encode more complex signals, such as the orbitofrontal cortex (OFC), are less well understood. One fundamental component that underlies the many functions of the OFC is the ability to compute the reward or value of a given object. There is evidence of variability in the spatial location of responses to specific categories of objects (or value of said objects) within the OFC, and several reference frames have been proposed to explain this variability, including topographic spatial gradients that correspond to axes of primary versus secondary rewards and positive versus negative reinforcers. One potentially useful structural morphometric reference frame in the OFC is the “H‐sulcus,” a pattern formed by medial orbital, lateral orbital and transverse orbital sulci. In 48 human subjects, we use a structural morphometric tracing procedure to localize functional activation along the H‐sulcus for face and food stimuli. We report the novel finding that food‐selective responses are consistently found within the caudal portion of the medial orbital sulcus, but no consistency within the H‐sulcus for response to face stimuli. These results suggest that sulcogyral anatomy of the H‐sulcus may be an important morphological metric that contributes to the organizing principles of the OFC response to certain stimulus categories, including food.     

Brain morphologic changes in early stages of psychosis: Implications for clinical application and early intervention

To date, a large number of magnetic resonance imaging (MRI) studies have been conducted in schizophrenia, which generally demonstrate gray matter reduction, predominantly in the frontal and temporo‐limbic regions, as well as gross brain abnormalities (e.g., a deviated sulcogyral pattern). Although the causes as well as timing and course of these findings remain elusive, these morphologic changes (especially gross brain abnormalities and medial temporal lobe atrophy) are likely present at illness onset, possibly reflecting early neurodevelopmental abnormalities. In addition, longitudinal MRI studies suggest that patients with schizophrenia and related psychoses also have progressive gray matter reduction during the transition period from prodrome to overt psychosis, as well as initial periods after psychosis onset, while such changes may become almost stable in the chronic stage. These active brain changes during the early phases seem to be relevant to the development of clinical symptoms in a region‐specific manner (e.g., superior temporal gyrus atrophy and positive psychotic symptoms), but may be at least partly ameliorated by antipsychotic medication. Recently, increasing evidence from MRI findings in individuals at risk for developing psychosis has suggested that those who subsequently develop psychosis have baseline brain changes, which could be at least partly predictive of later transition into psychosis. In this article, we selectively review previous MRI findings during the course of psychosis and also refer to the possible clinical applicability of these neuroimaging research findings, especially in the diagnosis of schizophrenia and early intervention for psychosis.     

Lack of normal gender differences of the perigenual cingulate gyrus in schizophrenia spectrum disorders

Abstract. We have previously reported a lack of normal gender differences of the perigenual cingulate gyrus in patients with schizophrenia. The purpose of this study was to examine the perigenual cingulate gyrus morphology in patients with schizotypal disorder. We investigated volume of the gray and white matter of the perigenual cingulate gyrus in 26 patients with schizotypal disorder (14 males, 12 females) in comparison with 61 age- and gender-matched healthy controls (30 males, 31 females) and 58 schizophrenia patients (31 males, 27 females) using magnetic resonance imaging. The volumetric measures of the perigenual cingulate gyrus were compared among the three groups that were entered into the same multiple analysis of variance model. The gray and white matter volume of the perigenual cingulate gyrus in the schizotypal patients did not differ significantly from the values in the healthy controls or the schizophrenia patients. Similar to schizophrenia, however, the schizotypal patients showed a lack of normal gender differences of the perigenual cingulate gray matter seen in the healthy controls (females > males). These results suggest that both schizotypal and schizophrenia patients may share the same disruption of the normal pattern of gender differences of the perigenual cingulate gyrus.     

Interactive decision-making in people with schizotypal traits: A game theory approach

Studies that have investigated whether deficits in social cognition observed in schizophrenia are also present in schizotypal individuals have largely been inconclusive, and none of these studies have examined social interactive behavior. Here, we investigated interactive decision-making behavior in individuals differing in the amount of schizotypal symptoms using tasks derived from Game Theory. In total 1691 undergraduate students were screened with the Schizotypal Personality Questionnaire-Brief version. We selected 69 people distributed across the full schizotypal continuum to participate in Ultimatum and Dictator Games in which they played against human and non-human, computer partners. The results showed that higher levels of schizotypal symptoms, particularly positive and disorganized schizotypy, were related to proposing higher offers to all partners. Additionally, the amount of interpersonal schizotypal symptoms was associated with an increased acceptance rate of very unfair offers from human partners, possibly reflecting a blunted emotional response to such offers. We conclude that positive and disorganized schizotypal symptoms are associated with less adequate bargaining behavior, similar to what has been recently observed in patients with schizophrenia. The observed similarities on Ultimatum Game behavior between patients with schizophrenia and individuals with more schizotypal symptoms contribute to the growing evidence that social cognitive deficits may represent a marker of vulnerability to schizophrenia.     

Visual perception and working memory in schizotypal personality disorder

OBJECTIVE: Patients affected by schizophrenia show deficits in both visual perception and working memory. The authors tested early-stage vision and working memory in subjects with schizotypal personality disorder, which has been biologically associated with schizophrenia. METHOD: Eleven subjects who met DSM-III-R criteria for schizotypal personality disorder and 12 normal comparison subjects were evaluated. Performance thresholds were obtained for tests of visual discrimination and working memory. Both form and trajectory processing were evaluated for each task. RESULTS: Subjects with schizotypal personality disorder showed intact discrimination of form and trajectory but were impaired on working memory tasks. CONCLUSIONS: These data suggest that subjects with schizotypal personality disorder, unlike patients affected by schizophrenia, have relatively intact visual perception. Subjects with schizotypal personality disorder do show specific deficits on tasks of comparable difficulty when working memory demands are imposed. Schizotypal personality disorder may be associated with a more specific visual processing deficit than schizophrenia, possibly reflecting disruption of frontal lobe systems subserving visual working memory operations.     

Schizophrenia patients demonstrate a distinctive pattern of decision-making impairment on the Iowa Gambling Task

Although dorsolateral prefrontal cortex (DLPFC) abnormalities in schizophrenia are well established, several lines of evidence suggest the orbitofrontal cortex (OFC) may also be dysfunctional in this disorder. We examined the performance of schizophrenia patients and nonpatient controls on the Iowa Gambling Task [Cognition 50 (1994) 7], a decision-making task sensitive to OFC damage that involves a series of selections from four decks of cards that vary in their reward/punishment profiles. Patients also completed neuropsychological tests assessing DLPFC functions and clinical symptom assessments. The schizophrenic patients demonstrated a pattern of impaired performance that differed both from healthy controls and from the "non-conservative" pattern typically found in patients with OFC lesions. The patients selected from the two card decks that had low frequency and high magnitude punishments significantly more often than the decks with high frequency and low magnitude punishments. Performance on the task was not strongly related to tests sensitive to DLPFC dysfunction but was correlated with negative symptoms. Results suggest that individuals with schizophrenia display a pattern of compromised decision-making that is somewhat distinct from that found in OFC lesion patients and that may be linked to certain clinical symptoms.     

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval = 2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, − 2.6%/year; right, − 2.3%/year) compared with schizotypal patients (left: − 0.4%/year; right: − 0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.