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Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction in children with ADHD. Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPET 2 h after the intravenous administration of [(123)I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of ADHD symptoms in children with ADHD assessed with ADHD rating scale-IV and the specific/non-specific DAT binding ratio in the basal ganglia. Drug-naive children with ADHD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children. However, no significant correlation was found between the severity scores of ADHD symptoms in children with ADHD and the specific/non-specific DAT binding ratio in the basal ganglia. Our findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

Reserpine increases Fos activity in the rat basal ganglia via a quinpirole-sensitive mechanism.

Expression of the immediate early gene c-fos increases acutely following neuronal depolarization. c-fos and Fos protein have been widely used to investigate basal ganglia responses to changes in dopaminergic neurotransmission. Increased dopaminergic input to D1 receptors increases Fos synthesis in striatal neurons. The role of D2 receptors in regulating Fos activity has been more difficult to establish. Because dopamine is believed to excite striatal neurons via D1 receptors and inhibit them via D2 receptors, we hypothesized that acute dopamine depletion would increase Fos activity in basal ganglia circuits normally inhibited by dopaminergic input to D2 receptors. Rats were perfused after a single dose of the dopamine-depleting drug reserpine. The brains of rats perfused 3 h after reserpine displayed numerous Fos-like immunoreactive nuclei in the striatum, entopeduncular nucleus, nucleus accumbens shell, and ventral pallidum, and sparse Fos-like immunoreactive nuclei in the globus pallidus and nucleus accumbens core. Few or no Fos-like immunoreactive nuclei were seen following perfusion 30 min, 60 min, and 24 h after reserpine. In the 3-h paradigm, pretreatment with the selective D1 antagonist SCH 23390 did not change the pattern of Fos-like immunoreactivity; pretreatment with the selective D2 agonist quinpirole completely blocked increased Fos synthesis. Acute dopamine depletion, therefore, increases Fos activity in the basal ganglia by disinhibiting D2 circuits. These results support the parallel pathway model of basal ganglia function, and show that Fos can be used to investigate the role of D2 receptors in striatal function. The findings suggest anatomic correlates for the clinical effects of acute dopamine depletion in drug therapy and advanced Parkinson's disease in humans.

Animals↗

Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder.

OBJECTIVE: Accumulating evidence suggests an association between abnormalities of the basal ganglia and affective disorders. The authors hypothesized that patients with bipolar disorder would demonstrate smaller basal ganglia volumes and a greater number of hyperintensities on magnetic resonance imaging than comparison subjects who were matched on age, race, sex, and education. METHOD: Volumes of the caudate, putamen, and globus pallidus were measured in 30 patients with bipolar disorder and 30 matched normal comparison subjects. The presence, number, and location of hyperintensities were also assessed. RESULTS: Male patients with bipolar disorder demonstrated larger caudate volumes than male comparison subjects. Older, but not younger, patients with bipolar disorder demonstrated more hyperintensities than comparison subjects, primarily in frontal lobe white matter. CONCLUSIONS: These results are not consistent with those of previous studies showing reduced basal ganglia volume in subjects with affective disorders, but they are consistent with previous findings of increased white matter hyperintensities, especially in older patients with bipolar disorder. Considered together with results from other studies, the findings suggest that the nature of basal ganglia/subcortical white matter involvement may differ according to the type of depression (unipolar versus bipolar) and the age and sex of the patient.

Adult↗

Basal-ganglia 'projections' to the prefrontal cortex of the primate.

We used retrograde transneuronal transport of the McIntyre-B strain of herpes simplex virus type 1 to examine the extent and organization of basal-ganglia-thalamocortical projections to five regions of prefrontal cortex in the cebus monkey (Cebus apella): medial and lateral area 9 (9m and 9l), dorsal and ventral area 46 (46d and 46v) and lateral area 12 (12l). All of these prefrontal areas were found to be targets of basal-ganglia output that originated in the internal segment of the globus pallidus (GPi) and/or the pars reticulata of the substantia nigra (SNpr). Approximately one-third of the total volume of these nuclei was directed toward prefrontal cortex, a volume comparable to that directed at the cortical motor areas. The origins of the outputs to different prefrontal areas were topographically organized. Different portions of SNpr (the rostral and caudal thirds) projected to areas 9m and 12l. Similarly, different output nuclei (GPi and SNpr) projected to adjacent portions of the same cytoarchitectonic field (46d and 46v). Furthermore, the outputs to prefrontal areas were segregated from those to motor areas of cortex. Thus, basal-ganglia outputs to prefrontal cortex are both extensive and topographically organized, forming a rich anatomical substrate for basal-ganglia influences on the cognitive operations of the frontal lobe.

Animals↗

Development of somatosensory responsiveness in the basal ganglia in awake cats.

Single-unit activity was recorded from the caudate nucleus (CD), globus pallidus, and entopeduncular nucleus (GP-ENTO) in awake, partially restrained kittens. The purpose of this experiment was to assess the ability of developing basal ganglia structures to process natural facial somatosensory information and compare this function to that observed in the adult. Somatosensory responsiveness in the CD and GP-ENTO developed slowly during the first three postnatal months. Somatosensory responsiveness had three major developmental trends in these nuclei: 1) The proportion of neurons responding to facial sensory stimulation increased with age; 2) proportionally, the area of face encompassing a receptive field of a neuron was smaller in adults than in young kittens; 3) qualitatively, adultlike responses to sensory stimulation did not appear until approximately three months of age. Units responsive to facial somatosensory stimulation in kittens under three months of age were very limited in the types of information they received. No specific stimuli parameters were encoded by these neurons. At approximately three months of age, units began to respond to varied stimuli (i.e., indentation of the skin as well as to brushing stimuli) and began to encode specific stimulus parameters such as direction of movement and relative location on the face. Kitten units responsive to skin indentation showed no evidence of encoding stimulus magnitude information. This was also true for the majority of adult basal ganglia neurons tested. The present findings suggest that the functions of the basal ganglia may be altered significantly during development. With increasing age, the basal ganglia may change from primarily a relay area for relatively nonspecific sensory information to an active processor of complex afferent information.

Animals↗

[Lesions of the basal ganglia in mumps. Clinical and neuroradiological development in a case].

Among mumps complications, encephalitis is the most frequent. Involvement of the basal ganglia has been previously reported associated to some other encephalic lesions. In one case, changes were confined to basal ganglia and occurred at the 10th day of evolution of mumps. Clinically a bilateral extrapyramidal syndrome was present without other neurological disorders. CT scan showed bilateral lesions in the area of the basal ganglia. The course was favorable. The neurological examination and CT scan were normal 6 months later. Such complications should be prevented by vaccination.

Basal Ganglia Diseases↗

Diffuse basal ganglia or thalamus hyperechogenicity in preterm infants.

OBJECTIVE: To determine the incidence and factors associated with diffuse basal ganglia or thalamus hyperechogenicity (BGTH) in preterm infants. STUDY DESIGN: (1) Review of serial neurosonograms among neonates with gestational age (GA) <34 weeks born at Weiler Hospital during a 21-month period; (2) Color Doppler flow imaging; (3) Case-control study using GA group-matched controls; and (4) Blind reading of CT scans or MRIs in patients with BGTH. RESULTS: Among 289 infants, 24 (8.3%) had diffuse BGTH. Color Doppler flow imaging was normal in nine patients. The incidence of diffuse BGTH was inversely related to GA (P<0.01). Logistic regression (n=96) showed that diffuse BGTH was significantly associated with requirement of high-frequency oscillation (HFO) (P=0.031), severe intraventricular hemorrhage (IVH) (P=0.004), hypotension requiring vasopressors (P=0.040), hypoglycemia (P=0.031) and male gender (P=0.014). Most patients with diffuse BGTH had normal basal ganglia and thalamus on CT/MRI, one had a hemorrhage, and one had an ischemic infarction. CONCLUSIONS: In our series, diffuse BGTH occurred in 8.3%, and was associated with factors similar to those previously reported. In contrast, several series have reported almost exclusively linear or punctuate hyperechoic foci, corresponding to hyperechogenicity of the lenticulostriate vessels. Our data provide further evidence to suggest that diffuse BGTH and hyperechogenicity of the lenticulostriate vessels are two different entities. Additional studies are required to determine the long-term significance of diffuse BGTH.

Basal Ganglia↗

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.

Adolescent↗

Lesions of the basal ganglia, thalamus, and deep white matter: differential effects on language functions.

Forty-five patients with unilateral demarcated vascular lesions in the basal ganglia, the thalamus and the deep white matter were investigated with an "aphasia battery." Patients with basal ganglia lesions performed worse than both other groups in tests of articulation, syntax, and lexical functions. The deficit of patients with basal ganglia lesions on all expressive language modalities was lateralized to the left hemisphere. Patients with left thalamic lesions showed impairments of speech fluency and in the Token Test. Patients with white matter lesions alone showed no effect of laterality in tests of language functions. The results are discussed on the basis of a recent theory of the participation of the deep nuclei in language processing.

Adult↗

The significance of traumatic haematoma in the region of the basal ganglia.

Computed tomography demonstrated a haematoma in the region of the basal ganglia in 61 of 2000 head injured patients. In 41 the haematoma occurred as an isolated lesion while in 20 there was another associated intracranial haematoma. Clinical and radiological differences within these groups are discussed. The patients with basal ganglia haematoma were more severely injured than those in a group who had an intracranial haematoma evacuated by craniotomy and the findings closely resembled those of a group of patients who had sustained diffuse brain damage. They share many features with those of patients with diffuse white matter injury and have a worse prognosis than other traumatic intracranial haematomas.

Adolescent↗

Radiologic correlates of antidepressant-induced delirium: the possible significance of basal-ganglia lesions.

Antidepressant-induced delirium in five of 60 (8%) patients over the age of 45 is reported. In each case, delirium developed within two weeks of beginning the antidepressant and appeared to be completely reversible once the medication was discontinued. Brain magnetic resonance imaging revealed basal-ganglia lesions in each patient who developed delirium. This finding indicates that patients with basal-ganglia lesions may be more vulnerable to antidepressant-induced delirium and is consistent with recent data from the neurologic and psychiatric literature that implicate the basal ganglia in the development of other types of delirium.

Aged↗

Amphetamine-induced preprodynorphin mRNA expression and kappa-opioid receptor binding in basal ganglia of adult rats after prenatal exposure to diazepam.

In order to obtain information on the functional state of basal ganglia following prenatal benzodiazepine exposure, preprodynorphin mRNA expression and kappa-opioid receptors were studied in offspring of timed-pregnant Long Evans rats treated with diazepam (1.25 mg/kg/day) on gestational days 14 to 20. Preprodynorphin mRNA was localised by in situ hybridization using a 33P-labeled oligonucleotide. Relative optical density (ROD) was quantified by image analysis in four quadrants of caudate putamen, in nucleus accumbens and olfactory tubercle of adult male rats. Six hours after functional challenge by injection of D-amphetamine (8 mg/kg s.c.), prenatally vehicle-exposed rats exhibited increased preprodynorphin mRNA (ROD) levels in caudate putamen (dorsolateral 187%, dorsomedial 150%, ventrolateral 153%, ventromedial 140% of control), nucleus accumbens (142%) and olfactory tubercle (213%). Prenatal diazepam exposure attenuated the effect of amphetamine in all regions; statistically significant differences between ROD levels of prenatally vehicle/adult amphetamine-treated and prenatally diazepam/adult amphetamine-treated groups were seen in ventrolateral caudate putamen, nucleus accumbens and olfactory tubercle. Baseline levels and topographical distribution of preprodynorphin mRNA remained unchanged. kappa-opioid receptor binding was analyzed in membrane from nucleus accumbens + olfactory tubercle, caudate putamen, and midbrain of male and female offspring using [3h]U69593. Bmax was reduced in nucleus accumbens + olfactory tubercle, but not in caudate putamen or midbrain of adult, prenatally diazepam-exposed male offspring, This effect was not yet seen at earlier postnatal stages (14 and 28 days), and was also absent in females. These data indicate that prenatal exposure to diazepam results in a delayed change in the functional state of dynorphin-containing neurons in several parts of the basal ganglia of adult male offspring. The decreased responsiveness to enhanced dopaminergic transmissions may impair the function of basal ganglia circuitry.

Age Factors↗

The Basal Ganglia and involuntary movements: impaired inhibition of competing motor patterns.

The basal ganglia are organized to facilitate voluntary movements and to inhibit competing movements that might interfere with the desired movement. Dysfunction of these circuits can lead to movement disorders that are characterized by impaired voluntary movement, the presence of involuntary movements, or both. Current models of basal ganglia function and dysfunction have played an important role in advancing knowledge about the pathophysiology of movement disorders, but they have not contained elements sufficiently specific to allow for understanding the fundamental differences among different involuntary movements, including chorea, dystonia, and tics. A new model is presented here, building on existing models and data to encompass hypotheses of the fundamental pathophysiologic mechanisms underlying chorea, dystonia, and tics.

Basal Ganglia↗

Radiotherapy of germinomas involving the basal ganglia and thalamus.

Nine patients with histologically confirmed germinomas of the basal ganglia and thalamus (GBT) were treated by radiotherapy. The average dose of 52.5 Gy was delivered to the tumor bed, 37 Gy to the whole brain and 24.8 Gy to the CNS axis. The local control, which was verified by CT scan, was achieved in all patients. All patients are alive 11 to 96 months after radiotherapy. As with other intracranial germinomas, geminomas of the basal ganglia and thalamus respond well to radiotherapy and the prognosis is good after treatment.

Adolescent↗

A computational model of action selection in the basal ganglia. II. Analysis and simulation of behaviour.

In a companion paper a new functional architecture was proposed for the basal ganglia based on the premise that these brain structures play a central role in behavioural action selection. The current paper quantitatively describes the properties of the model using analysis and simulation. The decomposition of the basal ganglia into selection and control pathways is supported in several ways. First, several elegant features are exposed--capacity scaling, enhanced selectivity and synergistic dopamine modulation--which might be expected to exist in a well designed action selection mechanism. The discovery of these features also lends support to the computational premise of selection that underpins our model. Second, good matches between model globus pallidus external segment output and globus pallidus internal segment and substantia nigra reticulata area output, and neurophysiological data, have been found which are indicative of common architectural features in the model and biological basal ganglia. Third, the behaviour of the model as a signal selection mechanism has parallels with some kinds of action selection observed in animals under various levels of dopaminergic modulation.

Animals↗

Extrinsic connections of the basal ganglia.

Recent neuroanatomical studies undertaken with various powerful neural tracing methods have radically changed our concept of the organization of the basal ganglia. This paper briefly reviews some of the findings that have led to the conclusion that the major components of the basal ganglia can no longer be considered as single undifferentiated entities. Instead, each of these structures is characterized by several distinct afferent and efferent chemospecific subsystems by which they can modulate and convey the multifarious information that flows through the basal ganglia. This paper focuses mainly on data obtained in primates, but also stresses the importance of comparison with non-primate species.

Animals↗

Hemolytic uremic syndrome with particular involvement of basal ganglia and favorable outcome.

Two children with hemolytic uremic syndrome and extrapyramidal complications are presented. Neuroimaging studies demonstrated bilateral basal ganglia (striatal) involvement with favorable recovery in both patients. The pathophysiology of the neurologic complications in hemolytic uremic syndrome are probably multifactorial. Our patients suggest a reversible process because both patients recovered clinically and radiographically. Neurologic complications do not always portend a poor prognosis and, in general, involvement of the basal ganglia is associated with favorable outcome.

Basal Ganglia↗