Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.

The anatomy and functional role of the inferior fronto-occipital fascicle (IFOF) remain poorly known. We accurately analyze its course and the anatomical distribution of its frontal terminations. We propose a classification of the IFOF in different subcomponents. Ten hemispheres (5 left, 5 right) were dissected with Klingler's technique. In addition to the IFOF dissection, we performed a 4-T diffusion tensor imaging study on a single healthy subject. We identified two layers of IFOF. The first one is superficial and antero-superiorly directed, terminating in the inferior frontal gyrus. The second is deeper and consists of three portions: posterior, middle and anterior. The posterior component terminates in the middle frontal gyrus (MFG) and dorso-lateral prefrontal cortex. The middle component terminates in the MFG and lateral orbito-frontal cortex. The anterior one is directed to the orbito-frontal cortex and frontal pole. In vivo tractography study confirmed these anatomical findings. We suggest that the distribution of IFOF fibers within the frontal lobe corresponds to a fine functional segmentation. IFOF can be considered as a "multi-function" bundle, with each anatomical subcomponent subserving different brain processing. The superficial layer and the posterior component of the deep layer, which connects the occipital extrastriate, temporo-basal and inferior frontal cortices, might subserve semantic processing. The middle component of the deep layer could play a role in a multimodal sensory-motor integration. Finally, the anterior component of the deep layer might be involved in emotional and behavioral aspects.

To explore brain areas involved in basic numerical computation, functional magnetic imaging (fMRI) scanning was performed on college students during performance of three tasks; simple arithmetic, numerical magnitude judgment, and a perceptual-motor control task. For the arithmetic relative to the other tasks, results for all eight subjects revealed bilateral activation in Brodmann's area 44, in dorsolateral prefrontal cortex (areas 9 and 10), in inferior and superior parietal areas, and in lingual and fusiform gyri. Activation was stronger on the left for all subjects, but only at Brodmann's area 44 and the parietal cortices. No activation was observed in the arithmetic task in several other areas previously implicated for arithmetic, including the angular and supramarginal gyri and the basal ganglia. In fact, angular and supramarginal gyri were significantly deactivated by the verification task relative to both the magnitude judgment and control tasks for every subject. Areas activated by the magnitude task relative to the control were more variable, but in five subjects included bilateral inferior parietal cortex. These results confirm some existing hypotheses regarding the neural basis of numerical processes, invite revision of others, and suggest productive lines for future investigation.

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (+/-standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.

Background and Objectives:To investigate the natural history and outcomes following treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri).Methods:A multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria, recruited through the iCAβ International Network, in the period January 2013 - March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, GRE-T2*, fluid-suppressed T2-weighted (FLAIR), and T1 post-gadolinium contrast-enhancement images aquired on 1.5T MRI, was employed at 3, 6, 12, 24-months follow-up. Centralized reads of MRI images were performed blinded to clinical, therapeutic, and time-points information. Main outcomes were survival, clinical and radiological recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri.Results:The study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri), mean age 72.9 years, 43.4% female, 37.1% APOEε4 carriers. 36.3% had a history of Alzheimer’s disease, 33.6% of ICH. A history of ICH, as well as the occurrence of new ICH at follow-up, was more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%; p< 0.0001 and 19.3% vs 3.6%; p<0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% CI, 61.6-78.5) and 84.1% (95% CI, 76.2-90.6) clinically recovered within three and twelve months, followed by radiological recovery in 45.1% (95% CI, 36.4 - 54.8) and 77.4% (95% CI, 67.7 - 85.9), respectively. After clinicoradiological resolution of the first-ever episode, 38,3% (95% CI, 22.9 - 59.2) had at least one recurrence within the following 24 months. Recurrence was more likely if intravenous high dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering-off (Hazard Ratio 4.68; 95% CI, 1.57-13.93; p=0.006).Discussion:These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiological acute manifestations of the disease and the effectiveness of slow oral tapering-off after intravenous corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in Aβ-driven diseases, including treatment-related ARIA in Alzheimer’s disease patients exposed to immunotherapy drugs.

BackgroundIn the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond.ResultsAn RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 ± 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates.ConclusionAlthough the basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved.

These results in healthy subjects further expand previous findings from animal and human studies by providing an in vivo functional demonstration of the involvement of the orbitofrontal cortex in the expression of aggressive behavior. They are also consistent with the hypothesis that a functional alteration of this cortical region may be present in individuals with pathological aggressive behavior.

Purpose: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla (T). Materials and Methods:Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T 1 relaxation, T 2 relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations.Results: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate. Conclusion:In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T. PROTON MR SPECTROSCOPY (MRS) of the brain is a useful technique for evaluating several neurological and psychiatric diseases (1). For clinicians interpreting spectra from individual patients, it is important to have knowledge of the normal range of spectral patterns from different brain regions, including how the spectra may depend on the patient's age, and on the spectroscopic technique used. While normal regional and age-related spectral variations have been reported previously at field strengths of 1T (2-5), 2T (6 -8), and 4T (9,10), to the best of our knowledge, there have been no reports using 3T scanners. Because use of 3T scanners is increasing for neuroimaging and spectroscopy in clinical practice, there is, therefore, a need for normative 3T data for comparison with patient studies. Also, even when results from all field strengths are taken together, there have been relatively few quantitative reports of normal values; therefore, expansion of coverage of different brain regions and confirmation of previously reported values is desirable.The purpose of this study was to establish normative spectroscopic data at 3T, from a variety of regions often involved in brain pathology, using commonly available methodology (single voxel PRESS localization at short echo time, with analysis using the LCModel software (11)). Because MRS-measurable metabolic asymmetry in the human brain is minimal (12), unilateral measurements from multiple different anatomical regions were measured, rather than bilateral measurements in fewer structures. Quantitative ...