Cognitive functions related to interpersonal problem-solving skills in schizophrenic patients compared with healthy subjects

Subjects with schizophrenia have cognitive alterations. The functional consequences of these deficits need to be fully determined, in order to implement more effective rehabilitation programs for patients with schizophrenia. This research explores the relationships between cognitive functioning and social problem-solving skills in a group of 20 chronic schizophrenic patients compared with those found in a group of 20 healthy subjects. The following cognitive domains were evaluated: verbal memory (Rey Auditory-Verbal Test; RAVLT), visuo-spatial organization and visuo-spatial memory (Rey-Osterrieth complex figure test; RF), executive functioning (semantic verbal fluency test; VF, design fluency task; DF and Wisconsin Card Sorting Test; WCST), attention (d 2 cancellation test) and general intellectual ability (Standard Progressive Matrices of Raven; SPM). Social problem-solving skills were assessed with a video-based test; the Assessment of Interpersonal Problem-Solving Skills (AIPSS). As a group, patients performed significantly worse than control subjects on every cognitive variable and on AIPSS receiving, processing and sending constructs. Among schizophrenic patients, correlations between AIPSS constructs and neuropsychological tests were observed for VF, DF, d2 and SPM whilst these associations were not replicated in healthy subjects. However, in the whole sample, after adjusting for age, gender and education, SPM displayed significant associations with all three AIPSS constructs. Moreover, after taking SPM into account, neither diagnostic groups (patients versus control) nor cognitive variables, except d2, provided an additional contribution to AIPSS performance. Cognitive impaired performances, mainly frontal, have a deleterious effect on social problem-solving skills in the schizophrenic group. It is suggested that alterations in social problem-solving skills may reflect social anxiety and/or " theory of mind " impairment. These factors may explain the lack of association among healthy subjects. The results support the inclusion of cognitive remediation programs designed to enhance social skills for patients where a cognitive deficit is clearly ascertained.     

Increased temporal lobe glucose use in chronic schizophrenic patients

Temporal lobe glucose metabolic rate was assessed in 21 off-medication patients with schizophrenia and 19 normal controls by positron emission tomography with 18F-deoxyglucose. Patients with schizophrenia had significantly greater metabolic activity in the left than the right anterior temporal lobe, and the extent of this lateralization was in proportion to the severity of psychopathology.     

Cognitive performance of patients with mesial temporal lobe epilepsy and incidental calcified neurocysticercosis

OBJECTIVES: Although chronic calcified neurocysticercosis (NCC) has been considered a major cause of symptomatic epilepsy in developing countries, it can also be an incidental pathological finding in epileptic patients from endemic regions. The mechanisms of brain plasticity occurring in patients with NCC during and after the inflammatory process related to the parasite infection, death, degeneration, and calcification within the host brain might be an independent factor for cognitive impairment in patients with NCC and epilepsy. In order to assess this possibility cognitive performance of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) with and without NCC was investigated through structured neuropsychological testing. METHODS: Cognitive performance of long term MTLE-HS patients with (HS-NCC group, n = 32) and without NCC (HS only, n = 48) was compared. Imbalances between the two groups with respect to clinical, demographic, neuroimaging, and electrophysiological variables were adjusted by linear multiple regression analysis and Bonferroni correction for multiple tests. RESULTS AND CONCLUSIONS: There were no cognitive performance differences between HS-NCC and HS only patients, leading to the conclusion that chronic calcified NCC per se does not aggravate the cognitive performance of patients with long term MTLE-HS.     

The metyrapone test in schizophrenic patients and healthy subjects

The metyrapone test, a useful and reliable procedure for assessing hypothalamic-pituitary-adrenocortical (HPA) axis function, was applied to schizophrenic patients and healthy controls. 4 out of 18 patients had subnormal responses to metyrapone whereas there were no such cases in the 22 control subjects. 1 schizophrenic patient and 3 control subjects had high normal responses to metyrapone. The relationship with the dexamethasone suppression test was found to be complex. These preliminary results suggest that the HPA axis activity patterns in psychiatric illness may be more complicated than previously reported.     

Delta power in sleep in relation to neuropsychological performance in healthy subjects and schizophrenia patients

Delta power in sleep is of increasing interest because of its association with waking performance in neuropsychological tests. In schizophrenia, this link might be impaired because of a decrease in delta power in sleep and pronounced cognitive deficits. The authors analyzed delta power in sleep and neuropsychological performance in 16 patients with schizophrenia on stable medication with amisulpride and 17 healthy subjects. In healthy subjects, the authors found significant positive correlations between morning performance in declarative memory, procedural learning, and attention and delta power, especially in frontal channels. The authors interpret these results in terms of dysfunctions of thalamocortical and prefrontal networks in schizophrenia.     

Visual assessment of medial temporal lobe atrophy in demented and healthy control subjects: correlation with volumetry

The present study evaluated the validity of visual rating of medial temporal lobe atrophy on coronal magnetic resonance imaging scans in a population of demented and non-demented individuals. Medial temporal lobe atrophy in 194 subjects was visually rated from hard copies, using a 0–4 rating scale, and a comparison was made with the absolute volumes (ccm) of the medial temporal lobe as estimated with volumetry, using a stereological method. We found a highly significant correlation between the estimated and stereologically measured volumes. There was a 10-fold difference in time spent on rating medial temporal lobe atrophy (1–2 min) vs. time spent calculating the medial temporal lobe volume (10–12 min) on a single subject. The diagnostic accuracy of both methods showed that visual rating was more efficient than volumetry in differentiating Alzheimer’s disease from control subjects, We conclude that visual rating is a reliable and fast method to estimate medial temporal lobe atrophy in demented subjects in a clinical setting.     

MRI volume loss of subcortical structures in unilateral temporal lobe epilepsy

Few studies have examined the relative degree of brain volume loss in both the hippocampi and subcortical structures in unilateral temporal lobe epilepsy (TLE) and their association with clinical seizure correlates. In this study, quantitative MRI volumes were measured in the hippocampus, thalamus, caudate, putamen, and corpus callosum in 48 patients with unilateral TLE (26 right, and 22 left) and compared with the volumes of 29 healthy controls. The ipsilateral hippocampus, corpus callosum, and bilateral thalami exhibited the greatest volume loss, reflected by large to moderate effect size differences compared with controls. Bilaterally, the putamen showed the next highest volume reduction. The contralateral hippocampus and bilateral caudate nuclei showed the least volume reduction, characterized by small effect sizes. Furthermore, clinical seizure characteristics (e.g., duration of epilepsy) exhibited different patterns of association with the volume reductions observed across these structures. Findings suggest that distinct neurodevelopmental features may play a role in the volume abnormality observed in these regions.     

Cognitive strategies in patients with unilateral temporal lobe excisions

The performance of patients with surgical excisions of either the left or right temporal lobe and a normal control group was compared on a hypothesis test. Subjects in both temporal lobectomy groups solved fewer problems than controls; and there was no difference in the performance of left and right lobectomy patients. However, analyses of cognitive patterns revealed specific strategies associated with subjects having undergone left temporal lobe excisions. These patients formulated fewer hypotheses than controls and tended to shift from a given hypothesis even when it was indicated to be correct. Conversely, right temporal lobectomy patients tended to retain a given hypothesis which was indicated to be incorrect. The same results were found with and without memory assistance, indicating that these cognitive strategies occur independent of overt memory deficits.     

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.     

MRI investigation of temporal lobe structures in bipolar patients

Previous anatomical MRI studies have suggested abnormalities in amygdala volumes in bipolar disorder, whereas hippocampus, temporal lobe (TL), and superior temporal gyri (STG) measures have been reported to be normal. This study further investigated the existence of anatomical abnormalities in these brain structures in bipolar subjects, to attempt to replicate previously reported findings. Twenty-four DSM-IV bipolar patients (mean age+/-S.D.=35+/-10 years) and 36 healthy controls (mean age+/-S.D.=37+/-10 years) were studied. 3D SPGR images were obtained with a 1.5T-GE Signa magnet (TR=25 ms, TE=5 ms, FOV=24 cm, slice-thickness=1.5 mm, matrix-size=256 x 192). Volumetric measurements of TL, hippocampus, amygdala, and STG were performed blindly, with a semi-automated software. Bipolar patients had significantly larger left amygdala volumes compared with controls (mean volumes+/-S.D.=2.57+/-0.69 vs. 2.17+/-0.58 ml, respectively; ANCOVA, age, gender, ICV as covariates; F=4.42, df=1/55, P=0.04). The volumes of the other temporal lobe structures did not differ significantly between the two groups (ANCOVA, age, gender, and ICV as covariates, P>0.05). Our findings of enlarged left amygdala in bipolar patients are in agreement with prior MRI studies, suggesting that abnormalities in this brain structure may be implicated in pathophysiology of the illness. Longitudinal studies in high-risk offspring and first-episode patients will be needed to examine whether such abnormalities precede the appearance of symptoms, or whether they may appear subsequently as a result of illness course.     

Visual assessment of medical temporal lobe atrophy in demented and healthy control subjects: correlation with volumetry.

The present study evaluated the validity of visual rating of medial temporal lobe atrophy on coronal magnetic resonance imaging scans in a population of demented and non-demented individuals. Medial temporal lobe atrophy in 194 subjects was visually rated from hard copies, using a 0-4 rating scale, and a comparison was made with the absolute volumes (ccm) of the medial temporal lobe as estimated with volumetry, using a stereological method. We found a highly significant correlation between the estimated and stereologically measured volumes. There was a 10-fold difference in time spent on rating medial temporal lobe atrophy (1-2 min) vs. time spent calculating the medial temporal lobe volume (10-12 min) on a single subject. The diagnostic accuracy of both methods showed that visual rating was more efficient than volumetry in differentiating Alzheimer's disease from control subjects, We conclude that visual rating is a reliable and fast method to estimate medial temporal lobe atrophy in demented subjects in a clinical setting.     

Olfactory bulb volume in patients with temporal lobe epilepsy

The study aimed to investigate the volume of the olfactory bulb (OB) in patients with temporal lobe epilepsy (TLE). Specifically, we wanted to see whether the olfactory deficit typically found in TLE patients also exerts a top-down influence on the OB. Twenty patients, and 20 age- and sex-matched healthy controls underwent olfactory testing by means of the Sniffin′ Sticks testing device (measurement of odor threshold, and identification abilities). In addition, they underwent an MR scan with 2-mm-thick T2-weighted fast spin-echo images without interslice gap in the coronal plane covering the anterior and middle segments of the base of the skull. Olfactory function was significantly impaired in TLE patients compared to healthy controls both at threshold level and for odor identification (p < 0.001); in addition, OB volumes were smaller than in controls (p = 0.013). The deficit seen at the level of the OB did not correlate with the side of the epileptic focus. Assuming that the olfactory deficit in TLE patients is due to the central nervous epileptic focus it appears that the OB volume is not only subject to changes in the periphery of the olfactory system, but also changes as a consequence to changes at a cortical level.     

Abnormal exploratory eye movements in schizophrenic patients vs healthy subjects

OBJECTIVE: We examined previously described exploratory eye movements abnormalities as biologic markers in schizophrenic patients in comparison with age-matched healthy subjects. MATERIAL AND METHODS: Using an eye-mark recorder, eye movements were analysed for mean gazing time, total number of gazing points, mean eye scanning length, total eye scanning length, and total gazing times as subjects viewed six simple pictures in preparation for copying them. RESULTS: In-patients, and to a lesser extent, out-patients, with schizophrenia showed a longer gazing time, fewer gazing points, a shorter mean and total eye scanning length. and longer gazing time than healthy subjects. In schizophrenic patients. negative symptom scores were positively correlated with mean gazing time (r = 0.33), and negatively correlated with the total number of gazing points (r = -0.29) as well as, the mean (r = -0.40) and total scanning length (r = -0.46). CONCLUSION: Exploratory eye movements are a biologic marker useful for evaluation of schizophrenia.     

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.     

Morphometric MRI alterations and postoperative seizure control in refractory temporal lobe epilepsy

Refractory mesial temporal lobe epilepsy (mTLE) is a debilitating condition potentially amenable to resective surgery. However, between 40 and 50% patients continue to experience postoperative seizures. The development of imaging prognostic markers of postoperative seizure outcome is a crucial objective for epilepsy research. In the present study, we performed analyses of preoperative cortical thickness and subcortical surface shape on MRI in 115 of patients with mTLE and radiologically defined hippocampal sclerosis being considered for surgery, and 80 healthy controls. Patients with excellent (International League Against Epilepsy outcome (ILAE) I) and suboptimal (ILAE II–VI) postoperative outcomes had a comparable distribution of preoperative atrophy across the cortex, basal ganglia, and amygdala. Conventional volumetry of whole hippocampal and extrahippocampal subcortical structures, and of global gray and white matter, could not differentiate between patient outcome groups. However, surface shape analysis revealed localized atrophy of the thalamus bilaterally and of the posterior/lateral hippocampus contralateral to intended resection in patients with persistent postoperative seizures relative to those rendered seizure free. Data uncorrected for multiple comparisons also revealed focal atrophy of the ipsilateral hippocampus posterior to the margins of resection in patients with persistent seizures. This data indicates that persistent postoperative seizures after temporal lobe surgery are related to localized preoperative shape alterations of the thalamus bilaterally and the hippocampus contralateral to intended resection. Imaging techniques that have the potential to unlock prognostic markers of postoperative outcome in individual patients should focus assessment on a bihemispheric thalamohippocampal network in prospective patients with refractory mTLE being considered for temporal lobe surgery. Hum Brain Mapp 36:1637–1647, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Surgery in temporal lobe epilepsy patients without cranial MRI lateralization

High resolution MRI is very important in the evaluations of patients with intractable temporal lobe epilepsy in preoperative investigations. Morphologic abnormalities on cranial MRI usually indicate the epileptogenic focus. Intractable TLE patients who have normal cranial MRI or bilateral hippocampal atrophy may have a chance for surgery if a certain epileptogenic focus is determined. We evaluated the patients who were monitorized in Gazi University Medical Faculty Epilepsy Center from October 1997 to April 2004. Seventy three patients, who had a temporal epileptogenic focus, underwent anterior temporal lobectomy at Ankara University Medical Faculty Department of Neurosurgery. Twelve of them (16, 4%), did not have any localizing structural lesion on cranial MRI. Of the 12 patients examined 6 had normal findings and 6 had bilateral hippocampal atrophy. Of these 12 patients, 6 (50%) were women and 6 (50%) were men. The ages of patients ranged from 7 to 37 (mean: 24.5). Preoperatively long-term scalp video-EEG monitoring, cranial MRI, neuropsychological tests, and Wada test were applied in all patients. Five patients, whose investigations resulted in conflicting data, underwent invasive monitoring by the use of subdural strips. The seizure outcome of patients were classified according to Engel with postsurgical follow-up ranging from 11 to 52 (median: 35.7) months. Nine patients (75%) were classified into Engel's Class I and the other 3 patients (25%) were placed into Engel's Class II. One patient who was classified into Engel's Class II had additional psychiatric problems. The other patient had two different epileptogenic foci independent from each other in her ictal EEG. One of them localized in the right anterior temporal area, the other was in the right frontal lobe. She was classified in Engel's Class II and had no seizure originating from temporal epileptic focus, but few seizures originating from the frontal region continued after the surgery. In conclusion, surgery was successful in all 12 patients. We think that patients with no MRI lateralizing or localizing lesion should undergo epilepsy surgery after detailed presurgical evaluations, including invasive monitoring.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI

BackgroundIncreased MRI T2 signal is commonly present not only in the hippocampus but also in other temporal structures of patients with temporal lobe epilepsy (TLE), and it is associated with histological abnormalities related to the epileptogenic lesion.ObjectiveThis study aimed to verify the distribution of T2 increased signal in temporal lobe structures and its correlations with clinical characteristics of TLE patients with (TLE-HS) or without (TLE-NL) MRI signs of hippocampal sclerosis.MethodsWe selected 203 consecutive patients: 124 with TLE-HS and 79 with TLE-NL. Healthy controls (N = 59) were used as a comparison group/comparative group. T2 multiecho images obtained via a 3-T MRI were evaluated with in-house software. T2 signal decays were computed from five original echoes in regions of interest in the hippocampus, amygdala, and white matter of the anterior temporal lobe. Values higher than 2 standard deviations from the mean of controls were considered as abnormal.ResultsT2 signal increase was observed in the hippocampus in 78% of patients with TLE-HS and in 17% of patients with TLE-NL; in the amygdala in 13% of patients with TLE-HS and in 14% of patients with TLE-NL; and in the temporal lobe white matter in 22% of patients with TLE-HS and in 8% of patients with TLE-NL. Group analysis demonstrated a significant difference in the distribution of the T2 relaxation times of the hippocampus (ANOVA, p < 0.0001), amygdala (p = 0.003), and temporal lobe white matter (p < 0.0001) ipsilateral to the epileptogenic zone for patients with TLE-HS compared with controls but only for the amygdala (p = 0.029) and temporal lobe white matter (ANOVA, p = 0.025) for patients with TLE-NL compared with controls. The average signal from the hippocampus ipsilateral to the epileptogenic zone was significantly higher in patients with no family history of epilepsy (two-sample T-test, p = 0.005).ConclusionIncreased T2 signal occurs in different temporal structures of patients with TLE-HS and in patients with TLE-NL. The hippocampal hyperintense signal is more pronounced in patients without family history of epilepsy and is influenced by earlier seizure onset. These changes in T2 signal may be associated with structural abnormalities related to the epileptogenic zone or to the nature of the initial precipitating injury in patients with TLE.     

Cognitive prognosis in chronic temporal lobe epilepsy

OBJECTIVE: First, to determine whether patients with chronic temporal lobe epilepsy have a different cognitive trajectory compared to control subjects over a prospective 4-year interval; second, to determine the proportion of patients who exhibit abnormal cognitive change and their profile of demographic, clinical epilepsy, and baseline quantitative magnetic resonance imaging characteristics; and third, to determine the most vulnerable cognitive domains. METHODS: Participants with chronic temporal lobe epilepsy (n = 46) attending a tertiary referral clinic and healthy control subjects (n = 65) underwent neuropsychological assessment and reevaluation 4 years later. Analysis of test-retest patterns identified individual patients with adverse cognition outcomes. RESULTS: The prospective cognitive trajectory of patients with chronic temporal lobe epilepsy differs from age- and sex-matched healthy control subjects. Lack of practice effects is common, but frank adverse cognitive outcomes are observed in a subset of patients (20-25%), particularly in vulnerable cognitive domains that include memory. Cognitive declines are associated with a profile of abnormalities in baseline quantitative magnetic resonance volumetrics, lower baseline intellectual capacity, as well as longer duration of epilepsy and older chronological age. INTERPRETATION: Cognitive prognosis is poor for a subset of patients characterized by chronicity of epilepsy, older age, lower intellectual ability, and more baseline abnormalities in quantitative magnetic resonance volumetrics.