Effects of early energy intake on neonatal cerebral growth of preterm newborn: an observational study

Current guidelines for preterm newborns recommend high energy nutrition soon after birth in order to limit growth retardation. However, long-term effects of this nutritional approach are still debated, and it has been demonstrated that cerebral growth depends on protein intake in early life. A negative impact of early high energy intake by parenteral nutrition (PN) has been reported for patients in critically ill conditions, observed in intensive care unit. We aimed at evaluating the impact of energy intake on cerebral growth in preterm neonates early in life. We included preterm newborns with gestational age < 32 weeks or birth weight (BW) < 1500 g. Measurement of cerebral structures was performed by cranial Ultrasonography (cUS) between 3 and 7 days of life (DOL, T0) and at 28 DOL (T1). We evaluated the relation between energy intake and cerebral growth in the first 28 DOL. We observed in 109 preterm newborns a significant (p < 0.05) negative correlation between energy intake received by PN and right caudate head growth (r = − 0.243*) and a positive correlation between total energy intake and transverse cerebellum diameter (r = 0.254*). Multivariate analysis showed that energy intake administered by enteral nutrition (EN), independently increased growth of left caudate head (β = 0.227*) and height cerebellar vermis (β = 0.415*), while PN independently affected growth of both right and left caudate head (β = − 0.164* and β = − 0.228*, respectively) and cerebellum transverse diameter (β = − 0.849*). The route of energy administration may exert different effects on cerebral growth in early life. High energy intake administered through EN seems to be positively correlated to cerebral growth; conversely, PN energy intake results in a poorer cerebral growth evaluated with cUS.

Single caudate neurons encode temporally discounted value for formulating motivation for action

The term ‘temporal discounting’ describes both choice preferences and motivation for delayed rewards. Here we show that neuronal activity in the dorsal part of the primate caudate head (dCDh) signals the temporally discounted value needed to compute the motivation for delayed rewards. Macaque monkeys performed an instrumental task, in which visual cues indicated the forthcoming size and delay duration before reward. Single dCDh neurons represented the temporally discounted value without reflecting changes in the animal’s physiological state. Bilateral pharmacological or chemogenetic inactivation of dCDh markedly distorted the normal task performance based on the integration of reward size and delay, but did not affect the task performance for different reward sizes without delay. These results suggest that dCDh is involved in encoding the integrated multidimensional information critical for motivation.

Whole-brain 3D MR fingerprinting brain imaging: clinical validation and feasibility to patients with meningioma

Purpose MR fingerprinting (MRF) is a MR technique that allows assessment of tissue relaxation times. The purpose of this study is to evaluate the clinical application of this technique in patients with meningioma. Materials and methods A whole-brain 3D isotropic 1mm3 acquisition under a 3.0T field strength was used to obtain MRF T1 and T2-based relaxometry values in 4:38 s. The accuracy of values was quantified by scanning a quantitative MR relaxometry phantom. In vivo evaluation was performed by applying the sequence to 20 subjects with 25 meningiomas. Regions of interest included the meningioma, caudate head, centrum semiovale, contralateral white matter and thalamus. For both phantom and subjects, mean values of both T1 and T2 estimates were obtained. Statistical significance of differences in mean values between the meningioma and other brain structures was tested using a Friedman’s ANOVA test. Results MR fingerprinting phantom data demonstrated a linear relationship between measured and reference relaxometry estimates for both T1 (r2 = 0.99) and T2 (r2 = 0.97). MRF T1 relaxation times were longer in meningioma (mean ± SD 1429 ± 202 ms) compared to thalamus (mean ± SD 1054 ± 58 ms; p = 0.004), centrum semiovale (mean ± SD 825 ± 42 ms; p < 0.001) and contralateral white matter (mean ± SD 799 ± 40 ms; p < 0.001). MRF T2 relaxation times were longer for meningioma (mean ± SD 69 ± 27 ms) as compared to thalamus (mean ± SD 27 ± 3 ms; p < 0.001), caudate head (mean ± SD 39 ± 5 ms; p < 0.001) and contralateral white matter (mean ± SD 35 ± 4 ms; p < 0.001) Conclusions Phantom measurements indicate that the proposed 3D-MRF sequence relaxometry estimations are valid and reproducible. For in vivo, entire brain coverage was obtained in clinically feasible time and allows quantitative assessment of meningioma in clinical practice.

Childhood ischaemic stroke in the basal ganglia can lead to fine motor and anxiety disorders: a retrospective analysis and follow-up of 109 cases

Background Stroke in children easily causes long-term dysfunction. Whether the prognoses of motor and anxiety disorders are related to the affected stroke area has not been reported. Methods One hundred nine cases of children with ischaemic stroke were reviewed and divided into three groups: lenticular nucleus lesions only (lenticular nucleus group), lenticular nucleus and caudate head lesions (caudate head group), and lenticular nucleus and thalamus lesions (thalamus group). Overall prognosis was evaluated by the mRS score. The SCAS-P was used to evaluate anxiety in children aged ≥6 years. Results mRS scores were ≤ 2 points (mean: 0.62), no significant difference among groups. 3/21 (14.2%) patients in the caudate head group changed handedness, which is significantly higher than other groups. Patients with lesions in thalamus group had significantly higher SCAS-P scores. Conclusions The overall prognosis of children with basal ganglia ischaemic stroke is good. However, hand preference changes and anxiety disorders may develop. Patients in the caudate head groups are more likely to suffer from fine motor disorders and changes in handedness. Patients within the thalamus group are more prone to anxiety than patients in the other groups. Anxiety disorders should be noted in children with basal ganglia stroke.

Childhood ischaemic stroke in the basal ganglia can lead to fine motor and anxiety disorders: a retrospective analysis and follow-up of 109 cases

Backgroud:Stroke in children easily causes long-term dysfunction. Whether the prognoses of motor and anxiety disorders are related to the affected stroke area has not been reported. Methods: 109 cases of children with ischaemic stroke were reviewed and divided into three groups: lenticular nucleus lesions only (lenticular nucleus group), lenticular nucleus and caudate head lesions (caudate head group), and lenticular nucleus and thalamus lesions (thalamus group). Overall prognosis was evaluated by the mRS score. The SCAS-P was used to evaluate anxiety in children aged ≥6 years. Results: mRS scores were ≤2 points (mean: 0.62), no significant difference among groups. 3/21 (14.2%) patients in the caudate head group changed handedness, which is significantly higher than other groups. Patients with lesions in thalamus group had significantly higher SCAS-P scores. Conclusions: The overall prognosis of children with basal ganglia ischaemic stroke is good. However, hand preference changes and anxiety disorders may develop. Patients in the caudate head groups are more likely to suffer from fine motor disorders and changes in handedness. Patients within the thalamus group are more prone to anxiety than patients in the other groups. Anxiety disorders should be noted in children with basal ganglia stroke.

Single caudate neurons encode temporally discounted value for formulating motivation for action

Temporal discounting captures both choice preferences and motivation for delayed rewards. While temporally discounted value for choice is represented in brain areas including the dorsolateral prefrontal cortex (DLPFC) and the striatum, the neural process of motivation for delayed rewards remains unidentified. Here we show that neuronal activity of the dorsal part of the primate caudate head (dCDh) — a striatal region receiving projection from the DLPFC — signals temporally discounted value essential for computing motivation for delayed rewards. Macaque monkeys performed an instrumental task, in which a visual cue indicated the forthcoming size and delay duration before reward. Single dCDh neurons represented the temporally discounted value without reflecting changes in the animal’s physiological state. Bilateral pharmacological or chemogenetic inactivation of dCDh specifically distorted a normal motivational performance based on the integration of reward size and delay. These results suggest a major contribution of dCDh to encoding a temporally discounted value, the integrated multidimensional information critical for formulating the motivation for action.

Human caudate nucleus subdivisions in tinnitus modulation

OBJECTIVEThe object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.METHODSSix awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.RESULTSAcute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).CONCLUSIONSAcute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia–centric neuromodulation approach to treat medically refractory tinnitus.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov)

Multiple neuronal circuits for variable object–action choices based on short- and long-term memories

At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.

Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis

The neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.