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The perception of motor commands or effort during muscular paralysis.

An observation by Mach (1906) on the sense of effort during hemiplegia has been confirmed. Two patients, who became suddenly hemiplegic, without sensory symptoms, noted that attempts to move when first paralysed were not accompanied by a sense of effort, but that attempts to move when movement first returned were accompanied by distinct sensations of effort or heaviness. This absence of a sense of effort during upper motor neuron paralysis without sensory signs did not occur either in a group of patients with pure lower motor neuron paralysis or in patients with clinically complete spinal transection. Previous studies have suggested that signals of motor command or effort, which arise at levels rostral to spinal motoneurons, contribute to the estimation of weights and tensions (see McCloskey et al., 1974; Gandevia and McCloskey, 1977a). One interpretation of the return of a sensation of effort as hemiplegia progresses to paresis is that activity in corticofugal paths contributes to generation of the sense of effort. During complete hemiplegia there is no neural traffic in motor corticofugal paths below the internal capsule and a sense of effort is absent. But, during paresis, there is increased neural traffic in the uninterrupted corticofugal fibres and there is a strong sense of effort or heaviness. Alternatively, a subcortical structure with a critical ascending projection to motor cortical areas may co-operate in generation the sense of effort. Afferent information, while important for calibrating and scaling the sense of effort which usually signals force or weight, is not essential for generation of a crude signal of descending motor command or effort.

Adult↗

Crossed cerebellar diaschisis. Further studies.

To investigate further the topographical, clinical and temporal correlates of crossed cerebellar diaschisis (CCD) after supratentorial stroke, 55 patients suffering from a single unilateral ischaemic stroke in the carotid artery territory were studied with the quantitative oxygen-15 steady-state technique and positron tomography. Fourteen patients had one or more follow-up studies, contributing a total of 72 studies. The phenomenon of CCD, defined by depressed oxygen consumption in the contralateral cerebellum, was statistically significant in 58% of the studies. It was more prominent when the supratentorial infarct involved the internal capsule or the cortical mantle extensively, consistent with the hypothesis that it results from destruction of the corticopontocerebellar fibres. Although CCD was associated with the presence of hemiparesis, it also occurred in patients without hemiparesis and was not seen in all those with hemiparesis, suggesting that destruction of the pyramidal tract is neither necessary nor sufficient to induce CCD. Finally, CCD tended to persist over long periods of time after a stroke, pointing towards a transneuronal degeneration possibly akin to crossed cerebellar atrophy as a likely explanation for CCD. Nevertheless, CCD could be seen within hours of a stroke and sometimes disappeared within a few days, suggesting a temporal continuum between early, potentially reversible functional hypometabolism (diaschisis) and irreversible degeneration.

Adult↗

Infarction in the territory of the anterior choroidal artery. A clinical and computerized tomographic study of 16 cases.

Sixteen cases of the anterior choroidal artery syndrome are reported. In its completed form, this rare syndrome combines the triad of hemiplegia, hemianaesthesia, and homonymous hemianopia. CT examination confirms the diagnosis by revealing an area of reduced density situated in the posterior limb of the internal capsule, sparing the thalamus medially and encroaching upon the tip of the globus pallidus laterally, and corresponding to the distribution of the anterior choroidal artery. Incomplete forms of the syndrome are more frequent. Left-sided spatial neglect may accompany right-sided lesions, as may slight disorders of speech in left-sided lesions. Clinical-anatomical correlations are discussed.

Adult↗

The case of aphasia or neglect after striatocapsular infarction.

The occurrence of aphasia or neglect was related to anatomo-structural (CT/MRI), functional [regional cerebral blood flow (rCBF)] and pathogenetic features [duration of middle cerebral artery (MCA) occlusion and degree of cortical leptomeningeal anastomoses] in 57 cases (26 with and 31 without aphasia or neglect) with strictly subcortical infarcts of one defined type, i.e. striatocapsular infarcts. No distinct pattern of language disturbances was found. Aphasic syndromes did not differ in the amount of involvement of the putamen, pallidum, head of caudate nucleus and white matter. Patients with aphasia or neglect had larger infarcts than those without. However, there was no specific involvement of the basal ganglia, the internal capsule or the deep white matter in patients with aphasia or neglect. Patients with aphasia or neglect had a significantly longer duration of MCA occlusion and mostly poor leptomeningeal collaterals. The cortical rCBF was significantly decreased in the cortical MCA territory in the patients with aphasia or neglect only. The rCBF remained low at follow-up after 1 year and corresponded to focal cortical atrophy on MRI, although neglect had subsided completely in all patients and aphasia had improved considerably in almost 75% of the cases. Aphasia or neglect after striatocapsular infarcts are most likely due to selective neuronal loss of the cerebral cortex due to prolonged MCA occlusion and insufficient collateral blood flow. Individual differences in recovery from aphasia after striatocapsular infarction can be explained in terms of the number of surviving cortical neurons.

Adolescent↗

Leg weakness due to stroke. Site of lesions, weakness patterns and causes.

Among 1575 patients with an acute stroke, 63 (4%) were found to have a leg-predominant weakness. The cerebral lesions were situated in (i) the anterior cerebral artery (ACA) territory in 12 cases, including one patient with a thrombosis of the sagittal sinus; (ii) the middle cerebral artery (MCA) territory in nine cases; (iii) both territories (not watershed) in two cases; (iv) the internal capsule in 18 cases, of which six cases had lesions in the ponto-peduncular or pontine; (v) other brainstem regions in 10 cases; (iv) the thalamus in two cases. Four were not precisely classified. In short, 41 were hemispheric and 18 were in the brainstem or thalamus. Lesions restricted to the rear portion of the medial part of the precentral gyrus caused a contralateral predominantly distal leg weakness. The weakness was severe with little improvement. Lesions involving the medial part of the premotor cortex, the supplementary motor area (SMA) and the rear portion of the medial part of the precentral gyrus caused a contralateral, severe leg-predominant hemiplegia, distally predominant and a less severe proximal weakness of the arm. Recovery was much better for the arm than for the leg. Lesions affecting the medial part of the premotor cortex, the SMA and sparing the precentral gyrus caused a contralateral hemiparesis predominating on the leg but predominating proximally on both leg and arm. Recovery was good for leg and arm. There were 22 infarcts due to ACA or MCA occlusion, one due to superior sagittal sinus occlusion, 18 lacunes and five haemorrhages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The behavioural and motor consequences of focal lesions of the basal ganglia in man.

The behavioural and movement disorders reported in 240 patients described in the literature with lesions affecting the caudate nucleus, putamen and the globus pallidus (lentiform nucleus) have been analysed. Reports were classified into two groups: small or isolated lesions involving the said nuclei alone; and large lesions with additional involvement of the adjacent internal capsule and/or periventricular white matter. Amongst the 240 cases, dystonia was the most frequent movement disorder recorded (36%); chorea (8%) and parkinsonism (6%) or dystonia-parkinsonism (3%) were uncommon. The commonest behavioural disturbance was the syndrome of abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) (13%); disinhibition was rare (4%). Confusion usually was associated with intracerebral haemorrhage and depression was a relatively non-specific finding. Aphasia was extremely rare with lesions confined to these basal ganglia structures. Lesions of the caudate nucleus rarely caused motor disorders but were more likely to cause behavioural problems. Chorea has been described in only 6% of those with caudate lesions, and dystonia in only 9%. The most significant behavioural disturbance described in 28% of those with caudate lesions was the syndrome of abulia, sometimes alternating with disinhibition (11%). Lesions of the lentiform nuclei rarely caused abulia (10%) and did not produce disinhibition, but they commonly caused dystonia (49%), particularly when the putamen was involved (63%). Bilateral lesions of the lentiform nuclei, either of the globus pallidus or of the putamen, caused parkinsonism (19%) or dystonia-parkinsonism (6%) infrequently. The prominence of the behavioural disturbance of abulia with caudate lesions emphasizes the more complex cognitive role of this basal ganglia structure. The frequent occurrence of dystonia and less commonly of parkinsonism with lentiform lesions emphasize the motor roles of putamen and globus pallidus.

Basal Ganglia Diseases↗

Subcortical origin of visuomotor apraxia.

Visuomotor apraxia (VMA) is a clinical syndrome characterized by a failure to make use of visual information when performing a target-directed movement. Visuomotor apraxia has traditionally been assumed to result from a disconnection of cortico-cortical fibres between visual and motor areas following occipito-parietal lesions. We describe a patient who developed a permanent contralesional and a temporary ipsilesional visuomotor apraxia as part of a complex neurological syndrome after a right [corrected] thalamic haemorrhage. MRI showed that the suprathalamic white matter was not involved but the most caudal fibres of the internal capsule appeared to be interrupted. To our knowledge this is the first case of a VMA with a lesion restricted to a deep subcortical area indicating that VMA can result from damage to subcortical projections rather than interruption of cortico-cortical fibres.

Aged↗

The basal ganglia and apraxia.

Ever since Liepmann's original descriptions at the beginning of the century apraxia has usually been attributed to damage confined to the cerebral cortex and/or cortico-cortical connecting pathways. However, there have been suggestions that apraxia can be due to deep subcortical lesions, which raises the question as to whether damage to the basal ganglia or thalamus can cause apraxia. We therefore analysed 82 cases of such 'deep' apraxias reported in the literature. These reports consisted of a small number (n=9) of cases studied neuropathologically, and a much larger group (n=73) in which CT or MRI was used to identify the size and extent of the lesion. The reports were subdivided into (i) those with small isolated lesions which involved nuclei of the basal ganglia or thalamus only, and not extending to involve periventricular or peristriatal white matter; (ii) those with large lesions which involved two or more of the nuclei, or one or more of these deep structures plus damage to closely adjacent areas including the internal capsule, periventricular or peristriatal white matter; and (iii) lesions sparing basal ganglia and thalamus but involving adjacent white matter. The main conclusions to be drawn from this meta-analysis are that lesions confined to the basal ganglia (putamen, caudate nucleus and globus pallidus) rarely, if ever, cause apraxia. Lesions affecting the lenticular nucleus or putamen nearly always intruded into the adjacent lateral white matter to involve association fibres, in particular those of the superior longitudinal fasciculus and frontostriatal connections. Apraxia occurred with deep lesions of the basal ganglia apparently sparing white matter in only eight out of the 82 cases. Apraxia was most commonly seen when there were lesions in the lenticular nucleus or putamen (58 out of 72 cases) with additional involvement of capsular, and particularly of periventricular or peristriatal, white matter. Lesions of the globus pallidus (no cases) or caudate nucleus (three cases) rarely caused apraxia. The caudate lesions also had white matter involvement. Indeed, involvement of periventricular white matter alone caused apraxia. The vast majority of cases described with apraxia associated with deep lesions were in the left, dominant hemisphere. Ideomotor apraxia was described in most reports (72 out of 82 cases). Orofacial apraxia was less common (37 cases), usually with ideomotor apraxia. Ideational apraxia was rare (five cases), all with ideomotor apraxia. Apraxia was either bilateral or involved the left hand if there was a right hemiparesis, in those cases where descriptions were available. Lesions of the thalamus can sometimes cause apraxia (26 cases), even if there is no apparent involvement of white matter (12 cases). Small lesions confined to the thalamus can also sometimes cause apraxia (eight cases). The role of the thalamus in higher order motor control and apraxia remains to be determined. It is suggested that the term limb-kinetic apraxia should be retained to describe motor deficits in planning 'what to do', 'how to do it' and 'when to do it'; decisions which appear to involve activation of a complex distributed network of dorsolateral prefrontal cortex, supplementary motor areas, anterior cingulate regions and lateral premotor cortex. Such deficits need to be quantified. If they are present in patients with basal ganglia disease, over and above classical akinesia, bradykinesia and hypokinesia, then such patients could be said to exhibit limb-kinetic apraxia.

Apraxias↗

Cerebral control of eye movements. I. The relationship between cerebral lesion sites and smooth pursuit deficits.

We investigated smooth pursuit eye movements in 72 patients with focal cerebral lesions using a sinusoidal pursuit task at multiple target frequencies and amplitudes. Twenty patients had normal pursuit gain and symmetry at all target frequencies, 12 had strictly ipsilesional pursuit deficit, 19 had symmetric bi-directional pursuit deficit, 18 had asymmetric bi-directional pursuit deficit (the deficit being more severe on the side of the lesion) and three had more severe contra-directional deficit. Normal pursuit gain was found in patients whose lesions were limited to the frontal, temporal and occipital poles, or the primary somaesthetic areas. Predominant ipsilesional pursuit deficit occurred in a long band of lesion overlap areas that run from the V5 occipito-temporal areas posteriorly, through the internal sagittal stratum, the posterior and anterior limbs of the internal capsule with adjacent striatum, to the dorsomedial frontal cortex anteriorly. Symmetric bi-directional deficit was associated with lesions involving the regions of the cortico-limbic-reticular network for directed attention, including the frontal eye fields, the posterior parietal cortex and the thalamus. Asymmetric bi-directional deficit resulted from lesions that penetrated into the underlying/adjacent white matter from the frontal eye field, posterior parietal cortex and thalamus. Varying combinations of lesions in the areas associated with uni-directional and symmetric bi-directional deficits produced a graded continuum from strict ipsi-directional pursuit deficit, through asymmetric bi-directional deficit, to symmetric bi-directional deficit. The striatum was identified as the area of lesion overlap in patients with large phase errors. Patients with lesions involving the right posterior parietal cortex and/or right dorsolateral frontal cortex had significantly more severe impairments than their counterparts with left-sided lesions. All pursuit deficits were more pronounced at high frequencies.

Adult↗

Directional defects in pursuit and motion perception in humans with unilateral cerebral lesions.

We tested motion perception and smooth pursuit in 26 patients with unilateral cerebral hemispheric lesions. We used random dot cinematograms to test motion direction discrimination. We measured pursuit gain as they followed a predictable sinusoidal target moving horizontally at three different frequencies, and an unpredictable horizontal step-ramp target in the ipsilateral hemi-field. Six patients had defects in motion perception when the targets were moving towards the side of the lesions ('ipsi-directional' defects) and two had bi-directional defects. Motion perception defects occurred with lesions of the junction of Brodmann areas 19 and 37, a putative human homologue of the monkey V5 complex. Seven patients had ipsi-directional pursuit defects, five of whom had damage to the posterior limb of the internal capsule. Only two patients had ipsi-directional defects of both motion perception and sinusoidal smooth pursuit. Four patients had ipsi-directional defects of motion perception alone, and five patients had ipsi-directional pursuit defects alone. The two patients with bi-directional defects in motion perception had normal sinusoidal smooth pursuit. Patients with lesions at the 19/37 junction and defects of motion perception alone had normal pursuit of unpredictable step-ramp targets in the ipsilateral hemi-field. In contrast, patients with ipsi-directional sinusoidal pursuit defects had decreased ipsi-directional and increased contra-directional velocities with step-ramp targets. No patient group had a motion-specific directional defect in saccadic accuracy. We conclude that neither predictable nor unpredictable pursuit is necessarily impaired by lesions of the 19/37 junction that cause ipsi-directional defects of motion perception. These dissociations between smooth pursuit and motion perception provide evidence that the pursuit system operates as an interconnected network with parallel pathways, rather than as a simple sequential hierarchy of cortical areas.

Adult↗

Thalamic haemorrhage.

Thalamic haemorrhage is usually considered a single entity although the thalamus is composed of anatomically as well as functionally discrete subregions receiving blood from different arteries. The clinical features vary according to the intrathalamic location of the haematomas and the bleeding artery. We investigated the impact of haematoma location and vascular territory on the clinical symptoms and signs, neuro-imaging findings and clinical courses of patients with thalamic haemorrhages by a retrospective analysis of 175 consecutive patients with thalamic haemorrhage. Based on the neuro-imaging findings we classified thalamic haematomas into four regional types and one global type according to the primary bleeding sites: (i) anterior type occurring in the territory of the tuberothalamic arteries, (ii) posteromedial type occurring in the territory of the thalamic-subthalamic paramedian arteries, (iii) posterolateral type occurring in the territory of the thalamogeniculate arteries. (iv) dorsal type occurring in the territory of the posterior choroidal arteries and (v) global type occupying the entire area of the thalamus. We studied the clinical and neuroimaging characteristics of each type. Eleven patients (7%) had the anterior type: these were the smallest haematomas and often ruptured into the anterior horn of the lateral ventricle. The major clinical signs were acute behavioural abnormalities: the clinical course was usually benign. Twenty-four patients (14%) had the posteromedial type in which haematomas often ruptured into the third ventricle, causing marked hydrocephalus, and often extended mediocaudally, involving the mesencephalon. The prognoses of this type depended on the presence of mesencephalic involvement which was associated with the worst outcome among the types even if the size of the haematoma itself was not large. The posterolateral type was most frequent (77 patients, 44%) and was characterized by large haematomas, rupture into the posterior horn of the lateral ventricle and frequent extension into the posterior limb of the internal capsule. Clinical signs included marked sensory and motor signs, hemineglect in right-side haematomas and language abnormalities with left-side haematomas. The case fatality with this type was relatively high (35%) and permanent neurologic sequelae frequently resulted. In the dorsal type (32 patients, 18%) haematomas were best visualized at the level of the body of the lateral ventricle on CT scans. The size was moderate and haematomas often extended posterolaterally into the adjacent subcortical white matter. Sensory and motor signs were common and about one third of the patients were first misdiagnosed as having lacunar infarcts. The prognoses were excellent. The global type (31 patients, 18%) of thalamic haemorrhage was clinically and radiologically very similar to the posterolateral type except that the haematomas were too large to define the bleeding focus. Severe sensory and motor signs were almost always present. In this type 25 patients died (the case fatality was 81%).

Adolescent↗

Impaired cortico-bulbar tract function in dysarthria due to hemispheric stroke. Functional testing using transcranial magnetic stimulation.

We investigated cortico-lingual and cortico-orofacial tract function utilizing transcranial magnetic stimulation in 18 consecutive patients with dysarthria due to hemispheric stroke. Delayed responses (conduction time > mean + 2.5 SD of that of 43 controls) or absent responses were considered abnormal. In all patients, motor-cortex stimulation of the lesion side demonstrated absent (13 patients) or delayed (five patients) responses to the tongue bilaterally (17 patients) or unilaterally (one patient). In 14 patients the contralateral orofacial responses were either absent (13 patients) or delayed (one patient). According to the electrophysiological findings, all lesions revealed by CT or MRI, were located within the pyramidal tract at the lower motor cortex (n = 4), the corona radiata (n = 7), and the genu of the internal capsule (n = 3) or its posterior limb (n = 4). We conclude that interruption of the cortico-bulbar tract fibres to muscles involved in articulation is a frequent cause of dysarthria in hemispheric stroke.

Aged↗

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease.

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Aged↗

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism.

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Adolescent↗

Brain damage and axonal injury in a Scottish cohort of neonatal deaths.

Despite the clinical and medicolegal significance attached to perinatal asphyxia, the neuropathological basis of this condition remains obscure. There are very few studies in the literature which correlate the pathological findings in neonatal brains with detailed epidemiological data, and none which are population based. In a Scotland-wide study of neonatal deaths, 70 brains have been examined. On the basis of glial and macrophage reactions, we previously identified infants with putative antepartum brain damage in this cohort and have related these reactions to signs of birth asphyxia. The present study explores the extent of neuronal/axonal injury in these infants since this is likely to be the basis for neurological deficits in surviving infants. We have also investigated these brains for beta-amyloid precursor protein (betaAPP) positivity to determine whether this is a useful marker of neuronal injury in neonates. Neuronal eosinophilia and karyorrhexes were detected in 43% and 27% of the cohort, respectively; maximally in the subiculum and ventral pons, but often present elsewhere. White matter damage was detected in 24% of cases but without classic cystic lesions of periventricular leucomalacia. betaAPP positivity was present in neuronal soma in 52% of cases and, in axons, in 27% of cases, and was seen from as early as 25-weeks gestation. Axonal bulbs were clearly delineated by betaAPP positivity and were usually located in the cerebral white matter and internal capsule, and infrequently in the brain stem. Although white matter damage and betaAPP axonal positivity were often detected in the same cases (P = 0.034), these features also occurred independently of each other. Both neuronal karyorrhexes and white matter betaAPP positivity were significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both betaAPP and glial fibrillary acidic protein proved useful in detecting neuropathological features which escaped detection on routine examination, particularly in preterm infants. The presence together of recent and older damage in individual brains suggests that there is an ongoing neuronal response to cerebral insults. We find that betaAPP is a useful marker of white matter damage in the neonatal brain. Immunopositivity for betaAPP in these circumstances is not attributable to inflicted or accidental trauma. While birth-related trauma cannot be ruled out, hypoxia/ischaemia is a likely cause in these infants. However, the exact pathogenesis of neuronal/axonal injury in the neonatal brain remains unclear.

Amyloid beta-Protein Precursor↗

Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study.

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.

Adolescent↗

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↗

Unconscious vision: new insights into the neuronal correlate of blindsight using diffusion tractography.

The existence of several types of unconscious vision, or 'blindsight', has convincingly been demonstrated in numerous studies, and their neuronal correlates have been hypothesized according to the nature of the residual vision observed. We used diffusion tensor imaging (DTI) tractography to demonstrate an association between the presence of 'Type I'- blindsight or 'attention blindsight' and reconstructed superior colliculi (SC) fibre tracts in hemispherectomized subjects, in support of the hypothesis that this subcortical structure plays a pivotal role in this type of blindsight. Before the DTI study, 'Type I' blindsight was identified in two of four hemispherectomized subjects by using a spatial summation effect paradigm, an indirect behavioural method, in which subjects were unaware of a stimulus presented in their blind visual field and were required to respond to an identical stimulus presented simultaneously in their intact field. SC tracts were then reconstructed in six control subjects, the two hemispherectomized subjects with blindsight and the two hemispherectomized subjects without blindsight. Whereas control subjects demonstrated mainly ipsilateral connections to visual association areas, parietal cortex, prefrontal areas and to an area close to the frontal eye fields, hemispherectomized subjects with blindsight showed ipsi- and contralateral connections from the SC to visual association areas, primary visual areas, parietal areas, prefrontal areas and to the posterior part of the internal capsule. In contrast, no projections from the SC on the hemispherectomized side were observed in hemispherectomized subjects without blindsight, in support of a key role of this structure in 'Type-I' or 'attention blindsight'.

Adult↗