[Show abstract][Hide abstract] ABSTRACT: Previous studies have implicated several brain areas as subserving numerical approximation. Most studies have examined brain correlates of adult numerical approximation and have not considered individual differences in mathematical ability. The present study examined non-symbolic numerical approximation in two groups of 10-year-olds: Children with low and high mathematical ability. The aims of this study were to investigate the brain mechanisms associated with approximate numerosity in children and to assess whether individual differences in mathematical ability are associated with differential brain correlates during the approximation task. The results suggest that, similarly to adults, multiple and distributed brain areas are involved in approximation in children. Despite equal behavioral performance, there were differences in the brain activation patterns between low and high mathematical ability groups during the approximation task. This suggests that individual differences in mathematical ability are reflected in differential brain response during approximation.
PLoS ONE 02/2009; 4(2):e4587. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies have independently suggested that patients with schizophrenia are more likely to have an enlarged cavum septum pellucidum (CSP) and an absent adhesio interthalamica (AI), respectively. However, neither finding has been consistently replicated and it is unclear whether there is an association between these two midline brain abnormalities. Thus, we compared the prevalence of absent AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia and 38 healthy controls using magnetic resonance imaging (MRI). There were no between group differences in the presence or volume of CSP; however, an enlarged CSP was commoner among patients than controls. There was also a positive correlation between CSP ratings and volumes. No differences in the presence or absence of the AI were found between patients and controls; however, an absent AI was commoner in male patients with schizophrenia than females. There was absolutely no overlap between the presence of a large CSP and an absence of AI. In conclusion, our findings are in line with several case series and other MRI investigations that have shown a higher incidence of putatively developmental brain abnormalities in patients with schizophrenia, particularly in males, and support the neurodevelopmental model of this disorder.
European Psychiatry 08/2006; 21(5):291-9. · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.
[Show abstract][Hide abstract] ABSTRACT: We hypothesised that hippocampal volume would be reduced in underweight anorexia nervosa (AN) and associated with impaired hippocampus-dependent cognitive function. Hippocampal and whole brain volumes were measured in 16 women with AN and 16 matched healthy women using magnetic resonance imaging (MRI) and a manual tracing method. Participants also completed the Doors and People Test of hippocampus-dependent memory and an IQ test. After adjustment for total cerebral volume, there was significant bilateral reduction in hippocampal volume in the AN group (8.2% right; 7.5% left). There was no evidence of impaired hippocampus-dependent cognitive function and no evidence of a relationship between hippocampal volume and clinical features of AN. The reduced hippocampal volume in anorexia nervosa is not associated with changes in cognitive function. To understand the cause and consequence of hippocampal size and function, it will be important to integrate endocrine, neuropsychological and neuroimaging studies.
Psychiatry Research 04/2006; 146(2):117-25. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.
Psychiatry Research 03/2006; 141(2):129-39. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Women with Turner syndrome (TS; 45,X) lack a normal second X chromosome, and many are prescribed exogenous sex and growth hormones (GH). Hence, they allow us an opportunity to investigate genetic and endocrine influences on brain development.
We examined brain anatomy and metabolism in 27 adult monosomic TS women and 21 control subjects with volumetric magnetic resonance imaging and magnetic resonance spectroscopy.
In TS women, regional gray matter volume was significantly smaller in parieto-occipital cortex and caudate nucleus and larger in cerebellar hemispheres. White matter was reduced in the cerebellar hemispheres, parieto-occipital regions, and splenium of the corpus callosum but was increased in the temporal and orbitofrontal lobes and genui of corpus callosum. Women with TS had a significantly lower parietal lobe concentration of N-acetyl aspartate, and higher hippocampal choline. Also, among women with TS, there were significant differences in regional gray matter volumes and/or neuronal integrity, depending upon parental origin of X chromosome and oxandrolone and GH use.
X chromosome monosomy, imprinting and neuroendocrine milieu modulate human brain development-perhaps in a regionally specific manner.
[Show abstract][Hide abstract] ABSTRACT: Diffusion tensor magnetic resonance imaging (DT-MRI) has been used to examine the microstructure of individual white matter tracts, often in neuropsychiatric conditions without identifiable focal pathology. However, the voxel-based group-mapping and region-of-interest (ROI) approaches used to analyse the data have inherent conceptual and practical difficulties. Taking the example of the genu of the corpus callosum in a sample of schizophrenic patients, we discuss the difficulties in attempting to replicate a voxel-based finding of reduced anisotropy using two ROI methods. Firstly we consider conventional ROIs; secondly, we present a novel tractography-based approach. The problems of both methods are explored, particularly of high variance and ROI definition. The potential benefits of the tractographic method for neuropsychiatric conditions with subtle and diffuse pathology are outlined.
Psychiatry Research 02/2006; 146(1):73-82. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abnormalities in perception and evaluation of body shape are a hallmark of eating disorders.
Brain responses to line drawings of underweight, normal weight, and overweight female bodies were measured with functional magnetic resonance imaging in 9 women with bulimia nervosa, 13 with anorexia nervosa, and 18 healthy women. Participants rated the stimuli for fear and disgust.
In the three groups, the lateral fusiform gyrus, inferior parietal cortex, and lateral prefrontal cortex were activated in response to body shapes compared with the control condition (drawings of houses). The responses in the lateral fusiform gyrus and in the parietal cortex were less strong in patients with eating disorders compared with healthy control subjects. Patients with eating disorders rated the body shapes in all weight categories as more aversive than did healthy women. In the group with eating disorders, the aversion ratings correlated positively with activity in the right medial apical prefrontal cortex.
Processing of female body shapes engages a distributed neural network, parts of which are underactive in women with eating disorders. The considerable variability in subjective emotional reaction to body shapes in patients with eating disorders is associated with differential activity in the prefrontal cortex.
[Show abstract][Hide abstract] ABSTRACT: Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra-motor cerebral and cognitive change in this disorder.
Journal of Neurology 04/2005; 252(3):321-31. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sexually dimorphic cognitive performance in men (n=42) and women (n=42) was related to testosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin, measured in 10-ml blood samples collected between 0900 and 1030 and, among women, during the follicular phase of the menstrual cycle. Significant sex differences favored men on spatial tasks (Mental Rotation and Judgment of Line Orientation) and on an inhibition task and favored women on a verbal task (category fluency). However, there were no significant relationships between any of the hormones and cognitive performance, suggesting that there are few, if any, consistent, substantial relationships between endogenous, nonfluctuating levels of gonadal hormones or gonadotropins and these cognitive abilities in men or women.
[Show abstract][Hide abstract] ABSTRACT: Expanded trinucleotide repeats are associated with several neuropsychiatric disorders, including fragile X syndrome (FraX) which is the most common inherited form of mental retardation. It is currently thought that FraX results from having >200 CGG trinucleotide repeats, with consequent methylation of the fragile X mental retardation gene (FMR1) and loss of FMR1 protein (FMRP). Pre-mutation carriers of FraX (with 55-200 CGG trinucleotide repeats) were originally considered unaffected, although recent studies challenge this view. However, there are few studies on the effect of pre-mutation trinucleotide repeat expansion on the male human brain using quantitative MRI. Also the results of prior investigations may be confounded because people were selected on the basis of clinical and neurological features, and not genetic phenotype. We compared the brain anatomy of 20 adult male pre-mutation members of known FraX families with 20 healthy male controls. The two groups did not differ significantly in age, intelligence quotient (IQ) or handedness. We also investigated whether any observed effects were associated with: (i) ageing; (ii) expansion of pre-mutation CGG trinucleotide repeats; (iii) reduction in the percentage of lymphocytes staining with anti-FMRP antibodies [%FMRP(+) lymphocytes]; and (iv) elevation of FMR1 mRNA levels. Male pre-mutation carriers of FraX, compared with matched controls, had significantly less voxel density in several brain regions, including the cerebellum, amygdalo-hippocampal complex and thalamus. Within pre-mutation carriers of FraX, ageing, increases in the number of CGG trinucleotide repeats and decreases in %FMRP(+) lymphocytes were associated with decreasing voxel density of regions previously identified as decreased relative to controls. Regional grey and white matter density is significantly affected in male pre-mutation carriers of FraX recruited on the basis of genetic, not clinical, phenotype. The association of voxel density reduction and ageing is consistent with observations of a subgroup of older pre-mutation males who present with cognitive decline. Moreover, our findings suggest, for the first time, an association between voxel density reduction and genetic variation in FraX.
[Show abstract][Hide abstract] ABSTRACT: Velocardiofacial syndrome is associated with interstitial deletions of chromosome 22q11, mild to borderline learning disability, characteristic dysmorphology, and a high prevalence of schizophrenia. The biological basis for this increased risk for schizophrenia is unknown, but people with velocardiofacial syndrome may have genetically determined differences in brain anatomy that predispose to the development of schizophrenia.
To determine whether there are differences in brain structure between subjects with velocardiofacial syndrome with and without schizophrenia.
A cross-sectional quantitative structural magnetic resonance imaging study in 39 adult subjects.
Referrals were made through medical genetics clinics and psychiatric services throughout the United Kingdom.
Thirteen subjects with velocardiofacial syndrome and schizophrenia, 12 with velocardiofacial syndrome without history of a psychosis, and 14 healthy controls volunteered to participate after screening for eligibility.
Total and regional brain volumes were analyzed by means of manual tracing, and gray- and white-matter densities were obtained by computerized voxel-based methods.
People with velocardiofacial syndrome and schizophrenia, compared with both controls and nonschizophrenic patients with velocardiofacial syndrome, had a significant (P<.05) reduction in volume of whole-brain (white + gray) matter and whole-brain white matter, and an increase in total and sulcal cerebrospinal fluid volume. Both velocardiofacial syndrome groups had a reduced cerebellar volume compared with controls.
Within velocardiofacial syndrome, schizophrenia is associated with generalized differences in brain anatomy, but white matter may be particularly implicated. Studies with larger samples are needed to replicate our findings.
Archives of General Psychiatry 12/2004; 61(11):1085-96. · 13.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The authors sought to identify neural correlates of eating disorders in order to contribute to the debate on the genesis and classification of eating disorders and provide endophenotypes for genetic research.
Twenty-six female patients with eating disorders (10 with bulimia nervosa, 16 with anorexia nervosa) and 19 healthy female comparison subjects matched for age and education were presented with food and aversive emotional images while brain activity was recorded with functional magnetic resonance imaging.
Women with eating disorders identified the food stimuli as threatening and disgusting. In response to these stimuli, the women with eating disorders had greater activation in the left medial orbitofrontal and anterior cingulate cortices and less activation in the lateral prefrontal cortex, inferior parietal lobule, and cerebellum, relative to the comparison group. In addition, women with bulimia nervosa had less activation in the lateral and apical prefrontal cortex, relative to the comparison group. Between-group differences in response to nonspecific emotional stimuli were found in the occipital cortex, parietal cortex, and cerebellum.
A medial prefrontal response to symptom-provoking stimuli was identified as a common feature of anorexia and bulimia nervosa. This finding supports a conceptualization of eating disorders as being transdiagnostic at the neural level. The abnormal prefrontal reaction is associated with symptom-related material, whereas the occipital and cerebellar differences are nonspecific. An abnormal propensity to activate medial prefrontal circuits in response to inappropriate stimuli is common to eating, obsessive-compulsive, and addictive disorders and may account for the compulsive features of behavior in these conditions.
American Journal of Psychiatry 08/2004; 161(7):1238-46. · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While cortical processing of visceral sensation has been described, the role that cognitive factors play in modulating this processing remains unclear.
To investigate how selective and divided attention modulate the cerebral processing of oesophageal sensation.
In seven healthy volunteers (six males, mean age 33 years; ranging from 24 to 41 years old) from the general community, phasic visual and oesophageal (non-painful balloon distension) stimuli were presented simultaneously. During the selective attention task, subjects were instructed to press a button either to a change in frequency of oesophageal or visual stimuli. During a divided attention task, subjects received simultaneous visual and oesophageal stimuli and were instructed to press a button in response to a change in frequency of both stimuli.
Selectively focussing attention on oesophageal stimuli activated the visceral sensory and cognitive neural networks (primary and secondary sensory cortices and anterior cingulate cortex respectively) while selective attention to visual stimuli primarily activated the visual cortex. When attention was divided between the two sensory modalities, more brain regions in the sensory and cognitive domains were utilised to process oesophageal stimuli in comparison to those employed to process visual stimuli (p=0.003).
Selective and divided attention to visceral stimuli recruits more neural resources in both the sensory and cognitive domains than attention to visual stimuli. We provide neurobiological evidence that demonstrates the biological importance placed on visceral sensations and demonstrate the influence of cognitive factors such as attention on the cerebral processing of visceral sensation.
[Show abstract][Hide abstract] ABSTRACT: The course of anorexia nervosa varies from rapid recovery to a chronic debilitating illness. This study aimed to identify functional neural correlates associated with differential outcomes.
Brain reactions to food and emotional visual stimuli were measured with functional magnetic resonance imaging in nine women who had long-term recovery from restricting anorexia nervosa. These were compared with age- and education-matched groups of eight women chronically ill with restricting anorexia nervosa and nine healthy control women.
In response to food stimuli, increased medial prefrontal and anterior cingulate activation, as well as a lack of activity in the inferior parietal lobule, differentiated the recovered group from the healthy control subjects. Increased activation of the right lateral prefrontal, apical prefrontal, and dorsal anterior cingulate cortices differentiated these recovered subjects from chronically ill patients. Group differences were specific to food stimuli, whereas processing of emotional stimuli did not differ between groups.
Separate neural correlates underlie trait and state characteristics of anorexia nervosa. The medial prefrontal response to disease-specific stimuli may be related to trait vulnerability. Lateral and apical prefrontal involvement is associated with a good outcome.
[Show abstract][Hide abstract] ABSTRACT: Cortico-striato-thalamic (CST) systems are anatomical substrates for many motor and executive functions and are implicated in diverse neuropsychiatric disorders. Electrophysiological studies in rats, monkeys and patients with Parkinson's disease have shown that power and coherence of low frequency oscillations in CST systems can be profoundly modulated by dopaminergic drugs. We combined functional MRI with correlational and path analyses to investigate functional and effective connectivity, respectively, of a prefronto-striato-thalamic system activated by object location learning in healthy elderly human subjects (n = 23; mean age = 72 years). Participants were scanned in a repeated measures, randomized, placebo-controlled design to measure modulation of physiological connectivity between CST regions following treatment with drugs which served both to decrease (sulpiride) and increase (methylphenidate) dopaminergic transmission, as well as non-dopaminergic treatments (diazepam and scopolamine) to examine non-specific effects. Functional connectivity of caudate nucleus was modulated specifically by dopaminergic drugs, with opposing effects of sulpiride and methylphenidate. The more salient effect of sulpiride was to increase functional connectivity between caudate and both thalamus and ventral midbrain. A path diagram based on prior knowledge of unidirectional anatomical projections between CST components was fitted satisfactorily to the observed inter-regional covariance matrix. The effect of sulpiride was defined more specifically in the context of this model as increased strength of effective connection from ventral midbrain to caudate nucleus. In short, we have demonstrated enhanced functional and effective connectivity of human caudate nucleus following sulpiride treatment, which is compatible both with the anatomy of ascending dopaminergic projections and with electrophysiological studies indicating abnormal coherent oscillations of CST neurons in parkinsonian states.
[Show abstract][Hide abstract] ABSTRACT: Sensory experience is influenced by emotional context. Although perception of emotion and unpleasant visceral sensation are associated with activation within the insula and dorsal and ventral anterior cingulate gyri (ACG), regions important for attention to and perception of sensory and emotional information, the neural mechanisms underlying the effect of emotional context upon visceral sensation remain unexplored. Using functional MRI, we examined neural responses to phasic, non-painful oesophageal sensation (OS) in eight healthy subjects (seven male; age range 27-36 years) either during neutral or negative emotional contexts produced, respectively, by presentation of neutral or fearful facial expressions. Activation within right insular and bilateral dorsal ACG was significantly greater (P < 0.01) during OS with fearful than with neutral faces. In a second experiment, we measured anxiety, discomfort and neural responses in eight healthy male subjects (age range 22-41 years) to phasic, non-painful OS during presentation of faces depicting either low, moderate or high intensities of fear. Significantly greater (P < 0.01) discomfort, anxiety and activation predominantly within the left dorsal ACG and bilateral anterior insulae occurred with high-intensity compared with low-intensity expressions. Clusters of voxels were also detected in this region, which exhibited a positive correlation between subjective behaviour and blood oxygenation level-dependent effect (P < 0.05). We report the first evidence for a modulation of neural responses, and perceived discomfort during, non-painful visceral stimulation by the intensity of the negative emotional context in which the stimulation occurs, and suggest a mechanism for the effect of negative context on symptoms in functional pain disorders.
[Show abstract][Hide abstract] ABSTRACT: Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.