Editorial for "Altered Functional Connectivity of Hypothalamus in Lifelong Premature Ejaculation Patients".

LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2020;52:785-786.

Definition of the neurological phenotype associated with dup (X)(p11.22-p11.23).

The aim of this study was to describe in detail the neurological features of nine patients carrying the recently reported microduplication at Xp11.22-11.23. Clinical and neurological examination, brain magnetic resonance imaging (except for two patients), electroencephalography and a neuropsychological assessment specific for language disturbances were performed in nine patients with microduplication at Xp11.22-11.23, disclosed by comparative genomic hybridisation array. Six patients were familial cases belonging to three unrelated pedigrees and three were sporadic cases. The patients had the following characteristics: mild dysmorphic facial features (except for two patients), mental retardation with moderate to severe global language deterioration, electroencephalographic epileptiform discharges during wakefulness and especially during sleep or electrical status epilepticus during slow sleep in younger cases, and negative brain magnetic resonance imaging. The main clinical features of this new microduplication syndrome were mild facial dysmorphisms, from increased electroencephalogram abnormalities during sleep to electrical status epilepticus during slow sleep, and mental retardation mainly involving language function in the absence of detectable brain lesions. In the absence of detectable brain lesions, speech delay may be associated with electrical status epilepticus during slow sleep or, alternatively, related to abnormal brain expression of a dosage-sensitive gene contained within the duplication region.

Functional MRI (fMRI) Evaluation of Hyperbaric Oxygen Therapy (HBOT) Efficacy in Chronic Cerebral Stroke: A Small Retrospective Consecutive Case Series.

Topics: Functional Magnetic Resonance Imaging (fMRI) evaluation of HyberBaric Oxygen Therapy (HBOT) effects on chronic cerebral stroke Patients (Pts). Introduction: Our aim was to evaluate with fMRI, in a 3 Tesla system, the functional effects of HBOT on the Central Nervous System (CNS) in four Pts with established ischaemic and haemorrhagic cerebral strokes (2 Pts each). To our knowledge, no author used this Magnetic Resonance (MR) technique for this purpose, till now. Methods: All four Pts underwent a fMRI study before and after 40 HBOT sessions, with a time window of a few days. They carried out two language (text listening, silent word-verb generation) and two motor (hand and foot movements) tasks (30 s On-Off block paradigms). Results: After HBOT, all Pts reported a clinical improvement, mostly concerning language fluency and motor paresis. fMRI analysis demonstrated an increase in both the extent and the statistical significance of most of the examined eloquent areas. Conclusions: These changes were consistent with the clinical improvement in all Pts, suggesting a possible role of fMRI in revealing neuronal functional correlates of neuronal plasticity and HBOT-related neoangiogenesis. Although only four Pts were examined, fMRI proved to be a sensitive, non-invasive and reliable modality for monitoring neuronal functional changes before and after HBOT.

Brain and behaviour in post-acute stroke: Reduction in seeking and posterior cingulate neuronal variability.

INTRODUCTION: Stroke is a complex event on both behavioral and neuronal grounds. Recent investigations evidence the central role of subcortical damage on the post-stroke brain and behavior reorganization. We have conducted an exploratory study combining anatomical lesion analysis, functional analysis of resting state fMRI, and behavioral assessment with focus on exploration as represented by SEEKING. METHOD: 24 stroke inpatients were studied immediately after their clinical stabilization post-stroke; neuronal variability in fMRI along with behavioral outcomes were assessed. These outcomes were compared with a control group of 22 healthy subjects. RESULTS: First, we observed predominant subcortical lesions in our sample with all stroke patients showing subcortical lesions and only some exhibiting additional cortical lesions. Second, we observed significantly reduced neuronal variability in the posterior cingulate cortex (PCC) that did not show any structural damage. Third, our stroke subjects showed reduced SEEKING which was related to reduced PCC neuronal variability in an abnormal way (compared to healthy subjects). This last outcome was assessed by considering the subset of 11 stroke subjects for which fMRI and behavioral outcomes were jointly measured. CONCLUSIONS: Taken together, our findings suggest that damage in subcortical regions may play a central role in abnormalities in both cortical activity (PCC) and associated behavior of post-stroke reorganization. Accounting for these aspects may have significant implications to optimize multidisciplinary rehabilitation processes, particularly during the early steps of recovery, reducing the impact of stroke on the patient and caregiver quality of life.

Videopolygraphic and functional MRI study of musicogenic epilepsy. A case report and literature review.

A 36-year-old right-handed man, who had experienced partial seizures since the age of 24 every time he played or listened to music with a strong emotional charge, underwent videopolygraphic recording, including autonomic variables, and brain fMRI study during which he listened to both "neutral" and "emotionally charged" music. Three right temporal seizures recorded during videopolygraphic monitoring were elicited by listening to the triggering song. The fMRI study disclosed activation in right acoustic areas during "neutral music," whereas an "emotionally charged melody" provoked widespread activation over the right fronto-temporo-occipital area before seizure onset. The literature review disclosed 110 published cases of musicogenic epilepsy that seemed to suggest a right-sided predominance of the epileptogenic zone. Our results support the role of the right temporal lobe in musicogenic epilepsy and demonstrate that the cerebral areas activated during the period of strong emotion leading to the seizures encompass the auditory cortex activated by neutral music.

Implicit and Explicit Routes to Recognize the Own Body: Evidence from Brain Damaged Patients.

Much research suggested that recognizing our own body-parts and attributing a body-part to our physical self-likely involve distinct processes. Accordingly, facilitation for self-body-parts was found when an implicit, but not an explicit, self-recognition was required. Here, we assess whether implicit and explicit bodily self-recognition is mediated by different cerebral networks and can be selectively impaired after brain lesion. To this aim, right- (RBD) and left- (LBD) brain damaged patients and age-matched controls were presented with rotated pictures of either self- or other-people hands. In the Implicit task participants were submitted to hand laterality judgments. In the Explicit task they had to judge whether the hand belonged, or not, to them. In the Implicit task, controls and LBD patients, but not RBD patients, showed an advantage for self-body stimuli. In the Explicit task a disadvantage emerged for self-compared to others' body stimuli in controls as well as in patients. Moreover, when we directly compared the performance of patients and controls, we found RBD, but not LBD, patients to be impaired in both the implicit and explicit recognition of self-body-part stimuli. Conversely, no differences were found for others' body-part stimuli. Crucially, 40% RBD patients showed a selective deficit for implicit processing of self-body-part stimuli, whereas 27% of them showed a selective deficit in the explicit recognition of their own body. Additionally, we provide anatomical evidence revealing the neural basis of this dissociation. Based on both behavioral and anatomical data, we suggest that different areas of the right hemisphere underpin implicit and explicit self-body knowledge.

Do brain lesions in stroke affect basic emotions and attachment?

The aim of the current study was to investigate basic emotions and attachment in a sample of 86 stroke patients. We included a control group of 115 orthopedic patients (matched for age and cognitive status) without brain lesions to control for unspecific general illness effects of a traumatic recent event on basic emotions and attachment. In order to measure basic emotions and attachment style we applied the Affective Neuroscience Personality Scale (ANPS) and the Attachment Style Questionnaire (ASQ). The stroke patients showed significantly different scores in the SEEKING, SADNESS, and ANGER subscales of the ANPS as well as in the Relationship as Secondary Attachment dimension of the ASQ when compared to the control group. These differences show a pattern influenced by lesion location mainly as concerns basic emotions. Anterior, medial, left, and subcortical patients provide scores significantly lower in ANPS-SEEKING than the control group; ANPS-SADNESS scores in anterior, right, medial, and subcortical patients were significantly higher than those of the control group. ANPS-ANGER scores in posterior, right, and lateral patients were significantly higher than those in the control group; finally, the ANPS-FEAR showed slightly lower scores in posterior patients than in the control group. Minor effects on brain lesions were also individuated in the attachment style. Anterior lesion patients showed a significantly higher average score in the ASQ-Need for Approval subscale than the control group. ASQ-Confidence subscale scores differed significantly in stroke patients with lesions in medial brain regions when compared to control subjects. Scores at ANPS and ASQ subscales appear significantly more correlated in stroke patients than in the control group. Such finding of abnormalities, especially concerning basic emotions in stroke brain-lesioned patients, indicates that the effect of brain lesions may enhance the interrelation between basic emotions and attachment with respect to the control group.

Characterization and Regional Distribution of a Class of Synapses with Highly Concentrated cAMP Binding Sites in the Rat Brain.

A class of putative synaptic terminals with concentrated cAMP binding sites are labelled in unfixed sections of rat brain by means of the ligand 8-thioacetamido fluorescein cAMP (SAF-cAMP), a fluorescent analogue of cAMP. The labelled terminals appear as sharply delimited bouton-like structures in close proximity but external to the cell body of neurons. The SAF-cAMP binding, measured at equilibrium in competition with other nucleotides, indicates that the binding site recognizes the cAMP moiety of SAF-cAMP. In the labelled terminals of the frontal cortex the concentration of SAF-cAMP binding sites is estimated to be in the millimolar range (at least 2.1 +/- 1.0 mM). In a brain homogenate, labelled terminals are visualized only in the membrane fraction enriched in synaptosomes. The cAMP binding activity of the synaptosomes is insoluble in high and in low ionic strength solution and is only partially solubilized by detergents, suggesting that the binding sites are intrinsic membrane proteins and/or proteins associated with the cytoskeleton. There is the possibility that SAF-cAMP labels new cAMP binding sites highly concentrated in a class of synaptic terminals. SAF-cAMP labelling is prominent in well defined regions of the rat brain: (i) the frontal and entorhinal areas of the cortex; (ii) the field CA1 of the hippocampus; (iii) the olfactory system; (iv) the medial nuclei of the thalamus; (v) the parabrachial nuclei and other less defined regions of the reticular substance; (vi) the substantia gelatinosa of Rolando in the spinal cord; and (vii) the neo- and paleocerebellum in the Purkinje cell layer, the archicerebellum in the granular cell layer. SAF-cAMP labelling is absent in specific motor and sensory structures, with the exception of the olfactory system. It is proposed that SAF-cAMP binding sites single out a new type of synaptic terminals involved in complex nervous functions.

Results of long-term experimental studies on the carcinogenicity of methyl alcohol and ethyl alcohol in rats.

Methyl alcohol was administered in drinking water supplied ad libitum at doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female Sprague-Dawley rats 8 weeks old at the start of the experiment. Animals were kept under observation until spontaneous death. Ethyl alcohol was administered by ingestion in drinking water at a concentration of 10% or 0% supplied ad libitum to groups of male and female Sprague-Dawley rats; breeders and offspring were included in the experiment. Treatment started at 39 weeks of age (breeders), 7 days before mating, or from embryo life (offspring) and lasted until their spontaneous death. Under tested experimental conditions, methyl alcohol and ethyl alcohol were demonstrated to be carcinogenic for various organs and tissues. They must also be considered multipotential carcinogenic agents. In addition to causing other tumors, ethyl alcohol induced malignant tumors of the oral cavity, tongue, and lips. These sites have been shown to be target organs in man by epidemiologic studies.

Results of long-term experimental studies on the carcinogenicity of ethylene-bis-dithiocarbamate (Mancozeb) in rats.

Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation. Groups of 150 male and female Sprague-Dawley rats, 8 weeks old at the start of the treatment, were administered Mancozeb at the concentration of 1000, 500, 100, 10, and 0 ppm in feed supplied ad libitum for 104 weeks. At the end of the treatment, animals were kept under controlled conditions until spontaneous death. Mancozeb caused an increase in (1) total malignant tumors, (2) malignant mammary tumors, (3) Zymbal gland and ear duct carcinomas, (4) hepatocarcinomas, (5) malignant tumors of the pancreas, (6) malignant tumors of the thyroid gland, (7) osteosarcomas of the bones of the head, and (8) hemolymphoreticular neoplasias. On the basis of these data, Mancozeb must be considered a multipotent carcinogenic agent.

Amygdala responses to masked and low spatial frequency fearful faces: a preliminary fMRI study in panic disorder.

Previous studies have demonstrated amygdala activation in response to fearful faces even if presented below the threshold of conscious visual perception. It has also been proposed that subcortical regions are selectively sensitive to low spatial frequency (LSF) information. However, chronic hyperarousal may reduce amygdala activation in panic disorder (PD). Our aim was to establish whether the amygdala is engaged by masked and LSF fearful faces in PD as compared to healthy subjects. Neutral faces were used as the mask stimulus. Thirteen PD patients (seven females, six males; mean age=29.1 (S.D: 5.9)) and 15 healthy volunteers (seven females, eight males; mean age=27.9 (S.D. 4.5)) underwent two passive viewing tasks during a 3T functional magnetic resonance imaging (fMRI) as follows: 1) presentation of faces with fearful versus neutral expressions (17ms) using a backward masking procedure and 2) presentation of the same faces whose spatial frequency contents had been manipulated by low-pass filtering. Level of awareness was confirmed by a forced choice fear-detection task. Whereas controls showed bilateral activation to fearful masked faces versus neutral faces, patients failed to show activation within the amygdala. LSF stimuli did not elicit amygdala response in either group, contrary to the view that LSF information plays a crucial role in the processing of facial expressions in the amygdala. Findings suggest maladaptive amygdala responses to potentially threatening visual stimuli in PD patients.

Brain functional changes in patients with ulcerative colitis: a functional magnetic resonance imaging study on emotional processing.

BACKGROUND: Ulcerative colitis (UC) is associated with psychological stress and poor emotional functioning. The neural emotional processing involves the complex integration of several cortical and subcortical brain structures. The amygdala plays a fundamental role in the neural processing of emotional stimuli and is a core structure of the brain-gut axis (BGA) that represents the anatomo-functional substrate for the bidirectional influences between emotions and gastrointestinal functions. The aim of this study was to investigate the brain emotional processing in UC patients compared to healthy people. METHODS: Ten UC patients in remission and 10 matched healthy controls underwent a functional magnetic resonance imaging (fMRI) scan while performing a task involving emotional visual stimuli. A set of negative, positive, and neutral pictures were used to study brain-related emotional responses. RESULTS: A significantly reduced blood oxygen level-dependent (BOLD) signal in UC patients relative to controls was found in the amygdala, thalamic regions, and cerebellar areas (P < 0.05 corrected for multiple comparisons). The group-related differences were detected in the brain activity in response to positive emotional stimuli. CONCLUSIONS: UC is associated with an emotional dysfunction characterized by decreased sensitivity to emotions with a positive content. The previous intestinal inflammatory activity in UC patients might have contributed to determine the functional changes of the amygdala that we found. On the other hand, the dysfunction of the amygdala may influence the course of the disease.