Biomedical subjects

Richard S J Frackowiak

Publications and source records attributed to Richard S J Frackowiak.

At least 19 recordsLinked to original sources

PubMed2006

The effect of handedness on cortical motor activation during simple bilateral movements.

The neuronal correlates of handedness are still poorly understood. Here we used event-related functional magnetic resonance imaging to investigate the impact of handedness on neuronal activation of the primary sensorimotor cortex, supplementary motor area and dorsal premotor cortex during simple unilateral and bilateral finger movements. In 16 right-handed and 16 left-handed individuals, we mapped changes in regional neuronal activity while participants responded to four symbolic cues presented in a pseudorandom order. According to pre-specified cues, they pressed a button with their right, left or both index fingers or withheld a response. For unilateral right index finger button presses, reaction times, motor and premotor activity were the same for both right- and left-handers. Compared with right-handers, left-handers had shorter reaction times with unilateral left index finger button presses, along with greater activation of the supplementary motor area and right frontal opercular cortex. Simultaneous bilateral compared with unilateral button presses led to a relative increase of activity in the right and left dorsal premotor cortex and the right primary sensorimotor cortex in right but not left-handers. Neither right nor left-handers showed any tendency during bilateral button presses towards faster responses with the dominant hand and the reaction times were equal in the two groups. Therefore, we conclude that the relative increase of activity in dorsal premotor and right primary sensorimotor cortices in right-handers represents a genuine difference in bimanual motor control related to handedness.

Adult↗

PubMed2006

Acute changes in frontoparietal activity after repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex in a cued reaction time task.

Lesion and functional imaging studies in humans have suggested that the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and intraparietal sulcus (IPS) are involved in orienting attention. A functional magnetic resonance imaging study supplemented by a behavioral experiment examined the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) conditioning to the right and left DLPFC on reaction times and synaptic activity as indexed by changes in the blood oxygenation level-dependent (BOLD) signal during a cued choice reaction time task. Orienting precues were either correct (valid) or incorrect (invalid) with respect to the subsequent move cue. The effects of real and sham rTMS were compared for each site of stimulation. Invalid trials showed a significant increase in response times and increases in the BOLD signal in right frontal and parietal regions when compared with valid trials. Conditioning left DLPFC with rTMS led to decreased BOLD signal during performance of this reorienting task in areas including left VLPFC and left IPS. Comparing invalid to valid trials after right DLPFC conditioning revealed decreased BOLD signal in right VLPFC. Data from the behavioral study showed that right DLPFC rTMS selectively increases response times in invalid trials. This effect was only present in the first 10 min after rTMS conditioning. No effect was found in either validly or invalidly cued trials with left DLPFC conditioning. These results suggest that 5 Hz rTMS over right DLPFC exerts remote effects on the activity of areas that functionally interact with the DLPFC during attentional processes, particularly when the reorienting of attention is more demanding as in invalid trials.

Adult↗

PubMed2006

The functional anatomy of cerebral reorganisation after focal brain injury.

Stroke is a major cause of disability in all age groups. Although the value of specific rehabilitative therapies is now acknowledged, the mechanisms of impairment and recovery are not well understood. There is growing interest in the role that central nervous system reorganisation might play in the recovery process, and in particular whether this reorganisation can be manipulated to provide clinical benefits for patients. The careful use of non-invasive techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation allows the study of the working human brain, and studies in humans suggest that functionally relevant adaptive changes occur in cerebral networks following stroke. An understanding of how these changes influence the recovery process will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and will allow the delivery of specific therapies to appropriately targeted patients suffering from stroke.

Brain↗

PubMed2006

Non-invasive mapping of corticofugal fibres from multiple motor areas--relevance to stroke recovery.

Recovery of motor function after subcortical stroke appears to be related to the integrity of descending connections from the ipsilesional cortical motor system, a view supported by the observation of greater than normal movement-related activation in ipsilesional motor regions in chronic subcortical stroke patients. This suggests that damage to the descending output fibres from one region of the cortical motor system may be compensated by activity in areas that retain corticofugal outputs. Though the trajectories of corticofugal fibres from each major component of the motor system through the corona radiata and internal capsule are well described in non-human primates, they have not been described fully in humans. Our study set out to map the trajectories of these connections in a group of healthy volunteers (8 male, 4 female; age range = 31-68 years, median = 48.5 years) and establish whether this knowledge can be used to assess stroke-induced disconnection of the cortical motor system and better interpret functional reorganization of the cortical motor system. We describe the trajectories of the connections from each major component of the motor system to the cerebral peduncle using diffusion-weighted imaging and probabilistic tractography in normal subjects. We observed good reproducibility of these connections over subjects. The comparative topography of these connections revealed many similarities between humans and other primates. We then inferred damage to corticofugal pathways in stroke patients (n = 3) by comparing the overlap between regions of subcortical white matter damage with the trajectories of the connections to each motor area. In a small series of case studies, we found that inferred disconnections could explain enhanced hand-grip-related responses, as assessed with functional MRI, in the ipsilesional motor system. These results confirm that selective disruption of motor corticofugal fibres influences functional reorganization and outcome in individual patients.

Adult↗

PubMed2006

Motor system activation after subcortical stroke depends on corticospinal system integrity.

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Adult↗

PubMed2006

Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.

CONTEXT: There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. OBJECTIVES: To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. DESIGN: Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. MAIN OUTCOME MEASURES: Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. RESULTS: The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal pole, hippocampus, and inferior temporal cortex. CONCLUSIONS: The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits.

Adult↗

PubMed2006

Posterior hypothalamic activation in paroxysmal hemicrania.

OBJECTIVE: Paroxysmal hemicrania (PH) is a severe, strictly unilateral headache that lasts 2 to 30 minutes, occurs more than five times daily, is associated with trigeminal autonomic symptoms, and is exquisitely responsive to indomethacin. The purpose of the study was to determine the brain structures active in PH. METHODS: Seven PH patients were studied using positron emission tomography (PET). Each patient was scanned in three states: (1) acute PH attack-off indomethacin; (2) pain-free-off indomethacin; and (3) pain-free after administration of intramuscular indomethacin 100 mg. The scan images were processed and analyzed using SPM99. RESULTS: The study showed no significant activations during state 1 compared with state 2, but there was relative activation of the pain neuromatrix in both states 1 and 2 compared with state 3. This suggests that there is persistent activation of the pain neuromatrix during acute PH attacks and during interictal pain-free states off indomethacin that is deactivated by the administration of indomethacin. In addition, the untreated PH state was associated with significant activation of the contralateral posterior hypothalamus and contralateral ventral midbrain, which extended over the red nucleus and the substantia nigra. INTERPRETATION: These activated subcortical structures may play a pivotal role in the pathophysiology of this syndrome.

Adult↗

PubMed2006

Longitudinal changes in cerebral response to proprioceptive input in individual patients after stroke: an FMRI study.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) provides an opportunity to study the relationship between cerebral reorganization and functional recovery after stroke. The authors set out to demonstrate the feasibility of using fMRI to investigate mechanisms of recovery in individual patients presenting with severe motor impairment. METHODS: fMRI was performed during passive movement at both affected and unaffected wrists separately in 2 patients with pure motor stroke. Six scanning sessions were performed in each patient over the first 4 months after stroke. Seven control subjects were also studied, 1 of them over 6 sessions. The authors examined for longitudinal changes in cerebral responses to proprioceptive afferent input that correlated with motor recovery. RESULTS: In control subjects, passive movement of either wrist led to relative increases in brain activation in the contralateral sensorimotor cortex and supplementary motor area, the bilateral inferior parietal cortex and secondary somatosensory areas, and the ipsilateral cerebellum. Increases in brain activation correlating with motor recovery were observed in both the ipsilesional primary sensory and primary motor cortex in 1 patient with good motor recovery but not in another patient with poor recovery. No longitudinal changes were seen in the control subject. CONCLUSIONS: These 2 case reports demonstrate that functionally relevant changes in cerebral organization can be identified in individual patients.

Adult↗

PubMed2005

Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex.

Repetitive transcranial magnetic stimulation (rTMS) to the human primary motor cortex (M1) causes bidirectional changes in corticospinal excitability depending on the stimulation frequency used. We used functional brain imaging to compare the effects of 5 Hz and 1 Hz-rTMS on local and inter-regional connectivity within the motor system. Regional cerebral blood flow (rCBF) was measured as a marker of synaptic activity at rest and during freely selected finger movements. We hypothesized that increased cortical excitability induced by 5 Hz-rTMS over M1 has an opposite effect on the synaptic activity and the connectivity of the motor network from the decreased cortical excitability induced by 1 Hz-rTMS. rTMS at both frequencies induced similar changes in rCBF at the site of stimulation and within areas of the motor network engaged by the task. The two frequencies showed different effects on movement-related coupling between motor areas. Connectivity analyses also indicated a differential effect of 5 and 1 Hz-rTMS on motor network connectivity, suggesting a role for an inferomedial portion of left M1 and left dorsal premotor cortex in maintaining performance. These results suggest that rapid reorganization of the motor system occurs to maintain task performance during periods of altered cortical excitability. This reorganization differs according to the modulation of excitability which is a function of rTMS frequency. This study extends the work of Lee et al. (Lee, L., Siebner, H.R., Rowe, J.B., Rizzo, V. Rothwell, J.C. Frackowiak, R.S. Friston, K.J., 2003. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 5308-5318.) by providing evidence that the pattern of acute reorganization in the motor network following rTMS depends on the direction of conditioning.

Adult↗

PubMed2005

Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture.

Both specific and non-specific factors may play a role in acupuncture therapy for pain. We explored the cerebral consequences of needling and expectation with real acupuncture, placebo acupuncture and skin-prick, using a single-blind, randomized crossover design with 14 patients suffering from painful osteoarthritis, who were scanned with positron emission tomography (PET). The three interventions, all of which were sub-optimal acupuncture treatment, did not modify the patient's pain. The insula ipsilateral to the site of needling was activated to a greater extent during real acupuncture than during the placebo intervention. Real acupuncture and placebo (with the same expectation of effect as real acupuncture) caused greater activation than skin prick (no expectation of a therapeutic effect) in the right dorsolateral prefrontal cortex, anterior cingulate cortex, and midbrain. These results suggest that real acupuncture has a specific physiological effect and that patients' expectation and belief regarding a potentially beneficial treatment modulate activity in component areas of the reward system.

Acupuncture↗

PubMed2005

A positron emission tomographic study in spontaneous migraine.

BACKGROUND: Functional brain imaging in acute migraine has proved challenging because of the logistic problems associated with an episodic condition. Since the seminal observation of brainstem activation in migraine, there has been only a single case substantiating this finding. OBJECTIVE: To test the hypothesis that brainstem activation could be detected in migraine and to refine the anatomic localization with higher-resolution positron emission tomography than previously used. DESIGN: Using positron emission tomography with radioactive water (H(2)15O), we studied acute migraine attacks occurring spontaneously. Five patients underwent imaging in ictal and interictal states, and the differences were analyzed by means of statistical parametric mapping. SETTING: Tertiary referral center. PATIENTS: Six volunteers with episodic migraine were recruited from advertisements in migraine newsletters. One patient was excluded because of use of preventive medication. MAIN OUTCOME MEASURE: Brainstem activation during migraine state vs interictal state. RESULTS: Two patients had a typical migrainous aura before the onset of the headache. All of the attacks studied fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans with interictal scans, there was significant activation in the dorsal pons, lateralized to the left (small volume correction, P = .003). Activation was also seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus, insula, prefrontal cortex, and temporal lobes. There was an area of deactivation in the migraine phase also located in the pons, lateralized to the right. CONCLUSIONS: Our findings provide clear evidence of dorsal pontine activation in migraine and reinforce the view that migraine is a subcortical disorder modulating afferent neural traffic.

Adult↗

PubMed2005

Alzheimer's patients engage an alternative network during a memory task.

We conducted an event-related functional magnetic resonance imaging experiment to better understand the potentially compensatory alternative brain networks activated by a clinically relevant face-name association task in Alzheimer's disease (AD) patients and matched control subjects. We recruited 17 healthy subjects and 12 AD patients at an early stage of the disease. They underwent functional magnetic resonance imaging scanning in four sessions. Each of the sessions combined a "study" phase and a "test" phase. Face/name pairs were presented in each study phase, and subjects were asked to associate faces with names. In the test phase, a recognition task, faces seen in the study phase were presented each with four different names. The task required selection of appropriate previously associated names from the study phase. Responses were recorded for post hoc classification into those successfully or unsuccessfully encoded. There were significant differences between the groups in accuracy and reaction time. Comparison of correctly versus incorrectly encoded and recognized pairs in the two groups indicated bilateral hippocampal hypoactivation both when encoding and recognizing in the AD group. Moreover, patients showed bilateral hyperactivation of parts of the parietal and frontal lobes. We discuss whether hyperactivation of a frontoparietal network reflects compensatory strategies for failing associative memory in AD patients.

Aged↗

PubMed2004

The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour.

The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside prefrontal cortex. Structural equation modelling (SEM) of fMRI data was used to test the hypothesis that although the same regions of prefrontal cortex may be active in tasks within different domains, there is task-dependent effective connectivity between prefrontal cortex and non-prefrontal cortex. The SEM included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest that the functions of the prefrontal cortex may be defined not only by selection-specific rather than modality-specific processes, but also by changing patterns of effective connectivity from prefrontal cortex to motor and sensory cortices.

Adult↗

PubMed2004

The functional neuroanatomy of temporal discrimination.

Two identical stimuli, such as a pair of electrical shocks to the skin, are readily perceived as two separate events in time provided the interval between them is sufficiently long. However, as they are presented progressively closer together, there comes a point when the two separate stimuli are perceived as a single stimulus. Damage to posterior parietal cortex, peri-supplementary motor area (peri-SMA), and basal ganglia can disturb this form of temporal discrimination. Our aim was to establish, in healthy subjects, the brain areas that are involved in this process. During functional magnetic resonance imaging scanning, paired electrical pulses, separated by variable inter-stimulus intervals (5-110 msec), were delivered to different sites on one forearm (8-64 mm from the midline). Subjects were required to simply detect the stimulus (control task) or to identify a stimulus property. For temporal discrimination (TD), subjects reported whether they felt one or two stimuli. For spatial discrimination, they reported whether the stimuli were located on the right or left side of the forearm. Subjects reported their choice by pressing a button with the opposite hand. Our results showed that discrimination, as opposed to simply detection, activated several brain areas. Most were common to both discrimination tasks. These included regions of prefrontal cortex, right postcentral gyrus and inferior parietal lobule, basal ganglia, and cerebellum. However, activation of pre-SMA and anterior cingulate was found to be specific to the TD task. This suggests that these two frontal regions may play a role in the temporal processing of somatosensory events.

Adult↗

PubMed2004

The influence of time after stroke on brain activations during a motor task.

After stroke, the pattern of brain activation during performance of a motor task is related to outcome. Here, we compare this relationship in the early (10-14 days) and late (at least 3 months) phases after first-ever stroke. A negative linear relationship between task-related brain activation, as measured by functional magnetic resonance imaging, and outcome is seen in several identical primary and nonprimary motor regions that is independent of time after stroke. In other words, patients with poorer outcome scores recruit more widely within motor-related regions in both the early or late poststroke phase. However, in contralesional middle intraparietal sulcus, contralesional cerebellum, and ipsilesional rostral premotor cortex, this relationship is seen only in the early poststroke phase. Thus, patients with poorer outcome scores recruit these areas in only the early and not the late poststroke phase. These results suggest that there are differences in the cerebral implementation of action in patients with poor outcome that are dependent on the time since stroke. Thus, in those patients with the most to gain from rehabilitation, different therapeutic approaches may be required at different stages after stroke.

Adult↗

PubMed2004

Towards a new mapping of brain cortex function.

The aim of imaging neuroscience is to describe the functional organization of human brain at the level of large neuronal groupings, networks and systems. The systems level of description addresses how integrated brain functions are embodied in the physical structure of the brain. Magnetic resonance imaging is currently the technique of choice for the study of cerebral structure-function relationships and the analysis of structural and functional brain images can now be carried out automatically using statistical parametric mapping. The resultant ability to perform clinical-functional-anatomical correlative studies with complete objectivity and unparalleled sensitivity is providing powerful new opportunities for studying the relationship between structure and function, and how these parameters interact with pathology. One of the most exciting and dramatic observations to come from human brain mapping has been the dynamic plasticity of function in both normal brains and the brains of patients with neurological and neuropsychiatric disorders. Recent activation studies have provided interesting information about the brain's capacity to reorganize after injury and in association with practice and learning. The emerging studies of brain plasticity and its modulation by drugs and other therapies indicate potentially useful approaches to the rehabilitation of adults with brain damage, including damage resulting from cerebral ischaemia. Brain maps must therefore be viewed as dynamic, changing with development, disease progression, normal learning and in parallel with the recovery of function after acute injury. The dynamic plasticity of functional brain maps provides an exciting opportunity to study these processes.

Brain Mapping↗

PubMed2003

Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study.

Electrical stimulation of primary sensory afferents is known to have an antinociceptive effect. Animal and functional imaging studies suggest a role for supraspinal structures in this response. Eight patients with chronic migraine (> or =15 days per month of attacks of migraine without aura), who had shown a marked beneficial response to implanted bilateral suboccipital stimulators, were studied. Stimulation evoked local paraesthesia, the presence of which was a criterion of pain relief. On stimulation, the headache began to improve instantaneously and was completely suppressed within 30 min. On switching off the stimulation, the headache recurred instantly and peaked within 20 min. PET scans were performed using regional cerebral blood flow (rCBF) as a marker of neuronal activity. Each patient was scanned in the following three states: (1) stimulator at optimum settings: patient pain-free but with paraesthesia; (2) stimulator off: patient in pain and no paraesthesia; (3) stimulator partially activated: patient with intermediate levels of pain and paraesthesia. All scans were processed and analysed using Statistical Parametric Mapping (SPM) 99. There were significant changes in rCBF in the dorsal rostral pons, anterior cingulate cortex (ACC) and cuneus, correlated to pain scores, and in the ACC and left pulvinar, correlated to stimulation-induced paraesthesia scores. The activation pattern in the dorsal rostral pons is highly suggestive of a role for this structure in the pathophysiology of chronic migraine. The localization and persistence of activity during stimulation is exactly consistent with a region activated in episodic migraine, and with the persistence of activation of that area after successful treatment. The dorsal rostral pons may be a locus of neuromodulation by suboccipital stimulation. In addition, suboccipital stimulation modulated activity in the left pulvinar.

Adult↗

PubMed2003

Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans.

The amygdala, which plays a critical role in emotional learning and social cognition, is structurally and functionally sexually dimorphic in humans. We used magnetic neuroimaging and molecular genetic analyses with healthy subjects and patients possessing X-chromosome anomalies to find dosage-sensitive genes that might influence amygdala development. If such X-linked genes lacked a homologue on the Y-chromosome they would be expressed in one copy in normal 46,XY males and two copies in normal 46,XX females. We showed by means of magnetic neuroimaging that 46,XY males possess significantly increased amygdala volumes relative to normal 46,XX females. However, females with Turner syndrome (45,X) have even larger amygdalae than 46,XY males. This finding implies that haploinsufficiency for one or more X-linked genes influences amygdala development irrespective of a direct or indirect (endocrinological) mechanism involving the Y-chromosome. 45,X females also have increased grey matter volume in the orbitofrontal cortex bilaterally, close to a region implicated in emotional learning. They are as poor as patients with bilateral amygdalectomies in the recognition of fear from facial expressions. We attempted to localize the gene(s) responsible for these deficits in X-monosomy by means of a deletion mapping strategy. We studied female patients possessing structural X-anomalies of the short arm. A genetic locus (no greater than 4.96 Mb in size) at Xp11.3 appears to play a key role in amygdala and orbitofrontal structural and (by implication) functional development. Females with partial X-chromosome deletions, in whom this critical locus is deleted, have normal intelligence. Their fear recognition is as poor as that of 45,X females and their amygdalae are correspondingly enlarged. This 4.96 Mb region contains, among others, the genes for monoamine oxidase A (MAOA) and B (MAOB), which are involved in the oxidative deamination of several neurotransmitters, including dopamine and serotonin. Abnormal activity of these neurotransmitters has been implicated in the aetiology of several neurodevelopmental disorders in which social cognitive deficits are prominent. These associated deficits include a specific lack of fear recognition from facial expressions. We show that the thrombocytic activity of MAOB is proportionate to the number of X-chromosomes, and hypothesize that haploinsufficiency of this enzyme in 45,X females predisposes to their deficits in social cognition.

Adolescent↗