Abstract• Introduction• Results• Discussion• Methods• References• Acknowledgments• ... more Abstract• Introduction• Results• Discussion• Methods• References• Acknowledgments• Author information• Supplementary information Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre''post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not inbetween sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestiv...
SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutation... more SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volum...
The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic af... more The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic afferents and forms an essential component of the neural circuitry regulating impulsive behaviour. This structure represents a primary target of psychostimulant medication, the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), and is biochemically modified by these drugs in animals. However, the effects of stimulants on the human VStr remain to be determined. We acquired anatomical brain MRI scans from 23 never-medicated adult patients with ADHD, 31 adult patients with a history of stimulant treatment and 32 control subjects, and VStr volumes were determined using individual rater-blinded region of interest delineation on high-resolution neuroanatomical scans. Furthermore, we also extracted VStr volumes before and after methylphenidate treatment in a subsample of the medication-naïve adult patients as well as in 20 never-medicated children with ADHD. We observed s...
Spontaneous fluctuations can be measured in the brain that reflect dissociable functional network... more Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task-positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention-deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication-naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC-DMN coherence also surfaced in a whole-...
European Archives of Psychiatry and Clinical Neuroscience
The aim of this study was to determine brain activation during facial emotion discrimination in f... more The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment ...
Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disord... more Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility. Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging. Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis. Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.
It is known that there is a high prevalence of certain anxiety disorders among schizophrenic pati... more It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitof...
The aim of the study is to present a new method for the segmentation of the caudate nucleus and u... more The aim of the study is to present a new method for the segmentation of the caudate nucleus and use it to compare the caudate heads and bodies of an attention deficit-hyperactivity disorder (ADHD) group with those of a control group. We used a 1.5-T system to acquire magnetic resonance brain scans from 39 children with ADHD, as defined by DSM-IV TR, and 39 age, handedness and IQ matched controls. The new method for caudate head and body segmentation was applied to obtain semi-automatic volumes and asymmetric patterns. Bilateral volumetric measures of the head, body, and head-body of the caudate nuclei were compared within groups and between ADHD and control groups. Although the group factor was not significant, there were first and second order interactions. The analysis of simple effects showed that the right body and right head+body of the ADHD group was significantly smaller than in the control group, although the ADHD right caudate head was bigger. No ADHD within-group caudate differences were found. Controls showed a significantly larger left caudate head and a significantly bigger caudate right body and right head+body. Our new method for segmenting the caudate nucleus detected differential abnormalities of the right caudate head and body in the ADHD group, explaining previous heterogeneous findings in the literature.
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inat... more Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.
We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar... more We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention deficit/hyperactivity disorder) medicated children and a group of 17 control children matched for laterality, gender and age. As we had found decreased gray matter volume in the right prefrontal region and the left cerebellar hemisphere in a previous voxel-based morphometry study conducted on an independent ADHD sample, we tested the hypothesis that these regions should show neurometabolite abnormalities. MRI (magnetic resonance imaging) was performed with a 1.5 T system; spectral acquisition was performed with a single-voxel technique and a PRESS sequence. Two volumes of interest were selected in the right prefrontal region and the left cerebellar hemisphere. NAA (N-acetylaspartate), Cre (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine) resonance intensities were absolutely quantified. In the left cerebellar hemisphere, ADHD children showed significant decreased MI and NAA absolute concentrations with high effect sizes (p=0.004, ES=1.184; p=0.001, ES=1.083). The diminished absolute concentration of the NAA could be related to a gray matter volume decrease in the same cerebellar region found in the previous voxel-based morphometry MRI study, while the reduced MI absolute concentration could express a decreased glial density. This is the first proton MR spectroscopic study examining the cerebellum and it provides additional support for the role of cerebellum in the ADHD neurobiology.
Abstract• Introduction• Results• Discussion• Methods• References• Acknowledgments• ... more Abstract• Introduction• Results• Discussion• Methods• References• Acknowledgments• Author information• Supplementary information Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre''post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not inbetween sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestiv...
SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutation... more SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volum...
The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic af... more The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic afferents and forms an essential component of the neural circuitry regulating impulsive behaviour. This structure represents a primary target of psychostimulant medication, the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), and is biochemically modified by these drugs in animals. However, the effects of stimulants on the human VStr remain to be determined. We acquired anatomical brain MRI scans from 23 never-medicated adult patients with ADHD, 31 adult patients with a history of stimulant treatment and 32 control subjects, and VStr volumes were determined using individual rater-blinded region of interest delineation on high-resolution neuroanatomical scans. Furthermore, we also extracted VStr volumes before and after methylphenidate treatment in a subsample of the medication-naïve adult patients as well as in 20 never-medicated children with ADHD. We observed s...
Spontaneous fluctuations can be measured in the brain that reflect dissociable functional network... more Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task-positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention-deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication-naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC-DMN coherence also surfaced in a whole-...
European Archives of Psychiatry and Clinical Neuroscience
The aim of this study was to determine brain activation during facial emotion discrimination in f... more The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment ...
Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disord... more Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility. Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging. Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis. Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.
It is known that there is a high prevalence of certain anxiety disorders among schizophrenic pati... more It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitof...
The aim of the study is to present a new method for the segmentation of the caudate nucleus and u... more The aim of the study is to present a new method for the segmentation of the caudate nucleus and use it to compare the caudate heads and bodies of an attention deficit-hyperactivity disorder (ADHD) group with those of a control group. We used a 1.5-T system to acquire magnetic resonance brain scans from 39 children with ADHD, as defined by DSM-IV TR, and 39 age, handedness and IQ matched controls. The new method for caudate head and body segmentation was applied to obtain semi-automatic volumes and asymmetric patterns. Bilateral volumetric measures of the head, body, and head-body of the caudate nuclei were compared within groups and between ADHD and control groups. Although the group factor was not significant, there were first and second order interactions. The analysis of simple effects showed that the right body and right head+body of the ADHD group was significantly smaller than in the control group, although the ADHD right caudate head was bigger. No ADHD within-group caudate differences were found. Controls showed a significantly larger left caudate head and a significantly bigger caudate right body and right head+body. Our new method for segmenting the caudate nucleus detected differential abnormalities of the right caudate head and body in the ADHD group, explaining previous heterogeneous findings in the literature.
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inat... more Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.
We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar... more We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention deficit/hyperactivity disorder) medicated children and a group of 17 control children matched for laterality, gender and age. As we had found decreased gray matter volume in the right prefrontal region and the left cerebellar hemisphere in a previous voxel-based morphometry study conducted on an independent ADHD sample, we tested the hypothesis that these regions should show neurometabolite abnormalities. MRI (magnetic resonance imaging) was performed with a 1.5 T system; spectral acquisition was performed with a single-voxel technique and a PRESS sequence. Two volumes of interest were selected in the right prefrontal region and the left cerebellar hemisphere. NAA (N-acetylaspartate), Cre (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine) resonance intensities were absolutely quantified. In the left cerebellar hemisphere, ADHD children showed significant decreased MI and NAA absolute concentrations with high effect sizes (p=0.004, ES=1.184; p=0.001, ES=1.083). The diminished absolute concentration of the NAA could be related to a gray matter volume decrease in the same cerebellar region found in the previous voxel-based morphometry MRI study, while the reduced MI absolute concentration could express a decreased glial density. This is the first proton MR spectroscopic study examining the cerebellum and it provides additional support for the role of cerebellum in the ADHD neurobiology.
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Papers by Susanna Carmona