Frontal and temporal volume size of grey and white matter in patients with schizophrenia

We previously performed a magnetic resonance imaging (MRI) parcellation study that showed smaller grey and white matter volumes of the temporal lobes and increased CSF volumes in the frontal and temporal lobe in men with schizophrenia. One question that arose from this earlier study was whether similar structural changes in the brain are found in a large group of schizophrenic patients consisting of both men and women. In the present study, MRI scans were acquired from 94 patients of both genders with schizophrenia and 101 healthy subjects. After the automatic segmentation of grey matter, white matter, and cerebrospinal fluid, the frontal, temporal, parietal, and occipital lobes were automatically parcellated according to the Talairach atlas. Compared with healthy subjects, schizophrenic patients showed significantly smaller volumes of grey matter in the temporal lobe and white matter in the frontal lobe. Schizophrenic patients had a greater CSF volume in the frontal and temporal lobes. These results suggest that volume reduction in the cerebrum is prominent in the frontal and temporal lobes in both men and women with schizophrenia.     

Auditory event-related potentials in the squirrel monkey: Parallels to human late wave responses

Event-related potentials (ERPs) were recorded from the brain surface in squirrel monkeys during the presentation of two auditory stimulus paradigms which have previously been utilized to elicit scalp-recorded ERPs in humans. In the first paradigm, inter-stimulus interval (ISI) was systematically varied during the presentation of a series of tone pips. The tones produced a negative (70 ms)-positive (130 ms) sequence of components similar in morphology to the human scalp-recorded N1-P2 'vertex' potential. The amplitude of the N70 and P130 components recorded from midline electrodes decreased with decreasing ISI, as previously shown for the human vertex potential. However, this amplitude change with ISI was not observed in ERPs recorded from lateral frontal and temporal electrodes. These results agree with previous studies of monkeys and humans which suggest at least two different sources contribute to N1-P2 components recorded in response to tones. The effects of stimulus probability and novelty on ERP morphology and amplitude were studied in the second paradigm. ERPs elicited by frequent (P = 0.92) and infrequent (P = 0.08) tone pips presented in an unpredictable order were compared. N70 - P130 components were produced by both stimuli, and the infrequent stimuli also elicited a broad, long latency (300 ms) positive complex that decreased in amplitude with repeated presentations. In humans the same infrequent auditory stimuli produce a frontally distributed late positive component that has been interpreted as indicating the activation of orientation mechanisms or of a 'mismatch detector'. These data suggest that in these paradigms squirrel monkeys exhibit ERPs which are similar in several respects to ERPs recorded to identical stimuli in humans.     

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.     

The cortical generators of P3a and P3b: a LORETA study

The P3 is probably the most well known component of the brain event-related potentials (ERPs). Using a three-tone oddball paradigm two different components can be identified: the P3b elicited by rare target stimuli and the P3a elicited by the presentation of rare non-target stimuli. Although the two components may partially overlap in time and space, they have a different scalp topography suggesting different neural generators. The present study is aimed at defining the scalp topography of the two P3 components by means of reference-independent methods and identifying their electrical cortical generators by using the low-resolution electromagnetic tomography (LORETA). ERPs were recorded during a three-tone oddball task in 32 healthy, right-handed university students. The scalp topography of the P3 components was assessed by means of the brain electrical microstates technique and their cortical sources were evaluated by LORETA. P3a and P3b showed different scalp topography and cortical sources. The P3a electrical field had a more anterior distribution as compared to the P3b and its generators were localized in cingulate, frontal and right parietal areas. P3b sources included bilateral frontal, parietal, limbic, cingulate and temporo-occipital regions. Differences in scalp topography and cortical sources suggest that the two components reflect different neural processes. Our findings on cortical generators are in line with the hypothesis that P3a reflects the automatic allocation of attention, while P3b is related to the effortful processing of task-relevant events.     

Abnormal CNV in chronic heavy drinkers.

OBJECTIVE: We used the contingent negative variation (CNV), a slow negative shift in the human electroencephalogram, to investigate the effects of heavy chronic alcohol use on frontal lobe function. METHODS: Event-related potentials (ERPs) were recorded from 30 heavy drinkers (HD) and 30 age-, sex-, and education-matched light or non-drinkers (LD), using a classical two-stimulus reaction time (RT) paradigm. Structural magnetic resonance images and neuropsychological tests were also administered. RESULTS: The amplitude of the late CNV was significantly reduced in HD relative to light drinkers. Moreover, diminished CNV amplitudes in HD appear to be closely related to the amount of recent alcohol consumption. There were no significant differences in neuropsychological measures of frontal lobe function and frontal lobe volume between light and HD. However, in HD, reduced late CNV amplitudes were associated with decreased frontal lobe gray matter volume and poor performance on the Trail Making Test B. In LD but not in HD, late CNV amplitude correlated positively with RT, suggesting that the late CNV reflects some aspect of motor and cognitive preparation. CONCLUSIONS: The inverse relationships between frontal lobe gray matter volume, performance on the Trail Making Test B, and late CNV amplitude in HD suggest that the ERP abnormalities observed in the current study may be indices of alcohol-related damage to the frontal lobe. The lack of a significant relationship between CNV amplitude and RT in HD suggests that chronic heavy alcohol use may disrupt response preparation.     

Volumetric analysis of regional cerebral development in preterm children

Preterm birth is frequently associated with both neuropathologic and cognitive sequelae. This study examined cortical lobe, subcortical, and lateral ventricle development in association with perinatal variables and cognitive outcome. High-resolution volumetric magnetic resonance imaging scans were acquired and quantified using advanced image processing techniques. Seventy-three preterm and 33 term control children ages 7.3-11.4 years were included in the study. Results indicated disproportionately enlarged parietal and frontal gray matter, occipital horn, and ventricular body, as well as reduced temporal and subcortical gray volumes in preterm children compared with control subjects. Birth weight was negatively correlated with parietal and frontal gray, as well as occipital horn volumes. Intraventricular hemorrhage was associated with reduced subcortical gray matter. Ventricular cerebrospinal fluid was negatively correlated with subcortical gray matter volumes but not with white matter volumes. Maternal education was the strongest predictor of cognitive function in the preterm group. Preterm birth appears to be associated with disorganized cortical development, possibly involving disrupted synaptic pruning and neural migration. Lower birth weight and the presence of intraventricular hemorrhage may increase the risk for neuroanatomic abnormality.     

Psychophysiological evidence for altered information processing in delusional misidentification syndromes

Recent research provides evidence that delusional misidentification syndromes (DMS) are associated with cognitive deficits. However, the underlying mechanisms of these deficits are not known. Since the P300 component of event-related potentials (ERPs) is related to fundamental aspects of working memory (WM), the present study is focused on P300 elicited during a WM test in DMS patients, as compared to those of healthy controls. Nine patients with DMS and 11 healthy controls, matched for age, sex and educational level were tested with a computerized version of the digit span test of the Wechsler batteries. Auditory ERPs were measured during the anticipatory period of the test. DMS patients showed significant reductions in P300 amplitude at the right frontal region compared to healthy controls. P300 latency in the central midline brain region was significantly prolonged in the DMS group. Each of these measures classified correctly 90% of the two groups. Moreover, the memory performance of the patient group was significantly lower, relatively to healthy controls. These findings provide evidence supporting the suggestion that DMS is associated with psychophysiological alterations occurring at the right frontal region, which mediates automatic processes, as well as with an irregular allocation of attentional resources, involving the interhemispheric circuitry, possibly due to gray matter degeneration. Finally, present work points to a need for further research investigating the characteristics, causes, course and treatment of severe cognitive deficits associated with DMS.     

MRI assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. METHOD: T(1)-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. RESULTS: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.     

Structural neuroimaging in adolescents with a first psychotic episode

OBJECTIVE: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. METHOD: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent inpatient unit and on 37 normal controls (13-18 years, 23 males, 14 females) matched for age, sex, and years of education. Diagnosis was made at baseline on the basis of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and confirmed after 12 months of follow-up. Total brain volume and gray matter, white matter, and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured bilaterally using a segmentation method based on the Talairach grid system. RESULTS: Male patients showed significantly larger volumes than did male controls in overall CSF and left frontal and right parietal sulci CSF. Male patients also showed significantly lower volumes of gray matter in the right and left frontal lobes. No significant volumetric differences were found in females. There were no differences between individuals with a diagnosis of schizophrenia at follow-up and the rest of the patients. CONCLUSIONS: This study suggests that larger CSF and lower gray matter volumes in the frontal lobes may be a nonspecific vulnerability marker for psychosis in male adolescents.     

Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research

The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age.     

Event-related potential dysfunction in posttraumatic stress disorder: the role of numbing

The purpose of this study was to examine the relationship between disturbance in event-related potentials (ERPs) and symptom clusters in posttraumatic stress disorder (PTSD). ERPs were recorded in 17 unmedicated civilian PTSD patients and 17 age- and sex-matched controls during a conventional auditory oddball task. PTSD symptom clusters (re-experiencing, active avoidance, numbing, hyperarousal) were correlated with ERP measures. The PTSD group showed ERP disturbances to target stimuli (reduced P200 and P300 and increased N200 amplitude, increased N200 and P300 latency) and reduced P200 amplitude to common stimuli compared to the control group. A significant negative correlation was found between the intensity of numbing symptoms and parietal P300 amplitude. This study replicates findings of disturbed N200 and P300 components in PTSD, reflecting impairments in stimulus discrimination and attention. The finding that numbing was associated with reduced attention processing (P300) is consistent with models positing a relationship between disordered arousal and attention in PTSD.     

Psychophysiological differences in schizophrenics with and without delusional misidentification syndromes: a P300 study

There is a debate on whether delusional misidentification syndromes (DMSs) and schizophrenia are distinct disorders. Information-processing deficits have been found in both. Since the P300 component of event-related potentials (ERPs) reflects attention and working memory (WM) mechanisms, the P300 elicited during a WM test was studied in schizophrenic patients with DMS in comparison to schizophrenic patients without DMS and controls. Nine schizophrenic patients with DMS, 11 without DMS and 11 healthy controls were tested with a computerized version of the digit span test of the Wechsler batteries. Auditory ERPs were measured during the anticipatory period of the test. P300 amplitude in prefrontal areas was found to be significantly reduced in schizophrenics without DMS and markedly less in DMS patients compared to controls. P300 latency in the central midline brain region was significantly prolonged in DMS patients compared to the other groups. Memory performance was significantly reduced in both patient groups as compared to healthy controls. The results may indicate abnormalities in both allocation of attentional resources and automatic orienting in schizophrenic patients with DSM. In contrast, even though schizophrenic patients without DMS exhibit partial similarities with patients suffering from DMS, they show excessive reduction of P300 amplitude located at the left frontal area. Future studies might clarify these issues.     

Smaller frontal lobe white matter volumes in depressed adolescents.

BACKGROUND: Prior studies have demonstrated reduced frontal lobe volumes in depressed adolescents. In this study, frontal lobe gray and white matter volumes in adolescents with major depressive disorder were evaluated. METHODS: Nineteen depressed and thirty-eight healthy comparison adolescents were recruited for a magnetic resonance imaging study. Images were segmented into gray matter, white matter, and cerebrospinal fluid. Morphometric measurements of the whole brain and frontal lobe region were completed. RESULTS: Whole brain volumes were significantly smaller in depressed subjects compared with the healthy comparison subjects. Significantly smaller frontal white matter volumes and significantly larger frontal gray matter volumes were found in the depressed subjects, after controlling for age and whole brain volume. CONCLUSIONS: These results are consistent with the hypothesis that a deficit in frontal volume exists during cortical development in adolescents with depression. Further studies are needed to assess whether volume differences resolve over time and the extent to which these differences influence response to treatment.     

Correlations between regional brain volumes and memory performance in anoxia

This study was aimed at investigating the quantitative relationship between regional brain volumes (hippocampus, amygdala, as well as cerebrum, frontal lobe, parietal lobe, temporal lobe) and performance on anterograde and retrograde memory tests in anoxic patients. We used high-resolution MRI to measure brain volumes in 13 anoxic patients. Neuropsychological testing was conducted contemporaneously with MRI. To control for age and sex, neuroanatomical volume residuals were calculated using regression equations derived from a group of 87 healthy comparison participants. We found that anoxic patients with severe amnesia had hippocampal volumes that were 36% smaller than normal, whereas patients with mild or no amnesia had normal hippocampal volumes. Regional gray matter volumes in severe amnesic anoxics were substantially smaller than expected. Performances on anterograde memory tests were significantly correlated with hippocampal and regional gray matter volume residuals. There was a significant correlation between white matter volume (but not hippocampal volume) and performance on the Visual Retention Test, a multi-dimensional test of cognitive function. There were no significant correlations between neuroanatomical measures and performance on a retrograde memory test. Our results indicate a strong quantitative relationship between performance on anterograde memory tests and hippocampal and regional gray matter volume residuals. Correlations between white matter volume residuals and performance on the VRT were found to be independent of hippocampal volume. Given the strong correlation between hippocampal volume and total gray matter volume residuals, a quantitative, normalized measure of total gray matter volume may provide a good indication of clinical outcome in anoxia.     

The intracranial topography of the P3 event-related potential elicited during auditory oddball.

In order to isolate the anatomical locus of neural activity primarily responsible for generating the scalp-recorded P3 (or P300), the topography of event-related potentials (ERPs) elicited during an auditory oddball task was compared between medial-to-lateral aspects of the frontal, parietal, and temporal lobes in 10 epileptic patients undergoing stereoelectroencephalography for seizure localization. Evidence of local ERP generation was obtained from each of these areas. Small amplitude P3-type potentials were sometimes observed to invert polarity across recording contacts in the frontal lobe. Large amplitude positive polarity P3-type components were observed in the lateral neocortex of the inferior parietal lobule (IPL), that rapidly attenuated in amplitude at more anterior, posterior, superior, inferior, and medial recording contacts. Large amplitude polarity inverting P3-type components were also observed to be highly localized to hippocampal contacts of temporal lobe electrodes. These data are discussed in the context of other recent studies of lesion effects, scalp topography, and intracranial recordings, and it is concluded that activity generated in the IPL is likely to make the major contribution to the scalp-recorded P3, with smaller contributions from these other sources. Finally, salient topographical differences between the intracranial distribution of the P3 and those of the N2 (or N200) and slow wave (SW) suggest that the generators of these components are not identical.     

Markers from event-related potential subcomponents and reaction time for information processing dysfunction in schizophrenia

Event-related potentials (ERPs) can serve as markers for cognitive processing stages. Identification of those ERPs altered in schizophrenia offer information about cognitive dysfunction. Auditory evoked potentials (AEPs) were elicited within an oddball paradigm in 35 schizophrenic patients and compared with 35 healthy controls. N100 and P200, as well as N200, frontal P300 and parietal P300 subcomponents, were separated using dipole source analysis. The amplitudes of the N100 and the parietal P300 measured in schizophrenics were diminished. The input-related processing stages (N100 and P200) were not altered, whereas later, the deviant and task-related processes (N200, frontal P300, parietal P300 and reaction time) were significantly prolonged in schizophrenia. Received: 28 September 1998 / Accepted: 1 October 1998     

Structural changes in patients with primary generalized tonic and clonic seizures

We conducted MR volumetry and voxel-based morphometry in 19 patients who had idiopathic generalized epilepsy (IGE) with tonic clonic seizures as the only seizure type and 52 control subjects. Patients exhibited elevated frontal lobe fraction of CSF and reduced fraction of gray matter in the frontal, parietal, temporal cortex, thalamus, and cerebellum. The thalamus and cerebellum also showed reduced volumes, as did the caudate and putamen. Contrary to current diagnostic criteria, regional tissue abnormalities may be present in IGE.     

Thought disorder and frontotemporal volumes in pediatric epilepsy

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5–16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl’s gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl’s gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.     

Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.     

Memory and executive function in older adults: relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities

Forty-eight healthy adults aged 65-85 were recruited for structural magnetic resonance scans after an extensive neuropsychological battery that ensured a high degree of variability across the sample in performance on long-term memory tests, and on tests traditionally thought to rely on prefrontal cortex. Gray matter volumes were measured for three gyri in the frontal lobe (superior, middle, inferior), six gyri in the temporal lobe (superior, middle, inferior, fusiform, parahippocampal, and hippocampus), and the occipital lobe. Gray matter volumes declined across the age range evaluated, but with substantial regional variation--greatest in the inferior frontal, superior temporal, and middle temporal gyri but negligible in the occipital lobe. Both memory performance and executive function declined as the number of hyperintense regions in the subcortical white matter increased. Memory performance was also significantly correlated with gray matter volumes of the middle frontal gyrus (MFG), and several regions of temporal neocortex. However, the correlations were all in the negative direction; better memory performance was associated with smaller volumes. Several previous reports of significant negative correlations between gray matter volumes and memory performance are described, so that the possible reasons for this surprising finding are discussed.