Depth electrode recordings show double dissociation between pitch processing in lateral Heschl’s gyrus and sound onset processing in medial Heschl’s gyrus

Pitch is a fundamental perceptual attribute of sounds. Our ability to discriminate, separate, and identify sounds relies heavily on pitch. Recent neuroimaging studies in humans have provided converging evidence for the existence of a “pitch center”—a region on the superior temporal plane (STP) lateral to Heschl’s gyrus specialized in pitch extraction—but a direct confirmation is still missing. Intracerebral recordings in humans are ideally suited for such a confirmation. Here we report results from depth electrode recordings in a patient undergoing investigation for epilepsy. We demonstrate a double dissociation between responses from the medial and lateral STP around Heschl’s gyrus to the onset of sound energy and the onset of pitch. Three pieces of evidence support this finding: (1) the response to sounds that do not contain pitch is small in the lateral STP compared to the medial STP; (2) sounds that contain pitch evoke a strong response in the lateral STP; (3) at the transition from noise to a specialised noise-like, but tonal, sound referred to as iterated ripple noise, where the onset of pitch is the sole acoustic event, only the lateral contact showed a response. Our results provide direct evidence for a pitch-specific area on lateral STP with intracranial recordings from the human auditory cortex.     

Cholinergic cortical circuits in Parkinson’s disease and in progressive supranuclear palsy: a transcranial magnetic stimulation study

To investigate the involvement of the cortical cholinergic system in patients with Parkinsons disease (PD) and with progressive supranuclear palsy (PSP), we performed a comparative study of the short latency afferent inhibition (SAI) in ten patients with PD, in eight patients with PSP and in 15 healthy subjects. Six of the PD patients and four of the PSP patients had dementia. SAI was significantly increased in the PD patients, whereas it was not significantly different between PSP patients and the normal controls. Our findings demonstrate that the excitability of the motor cortex is differentially modulated by sensory afferents in PD and PSP and may indicate that the mechanisms of cholinergic dysfunction are different between the two diseases.     

Structure-function relationships in the context of reinforcement-related learning: a combined diffusion tensor imaging–functional magnetic resonance imaging study

In the context of probabilistic learning, previous functional magnetic resonance imaging studies have shown decreasing uncertainty accompanying decreasing neuronal activation in task-relevant networks. Moreover, initial evidence points to a relationship between white matter structure and cognitive performance. Little is known, however, about the structural correlates underlying individual differences in activation and performance in the context of probabilistic learning. This combined functional magnetic resonance imaging–diffusion tensor imaging study aimed at investigating the individual ability to reduce processing resources with decreasing uncertainty in direct relation to individual characteristics in white matter brain structure. Results showed that more successful learners, as compared with less successful learners, exhibited stronger activation decreases with decreasing uncertainty. An increased mean and axial diffusivity in, among others, the inferior and superior longitudinal fasciculus, the posterior part of the cingulum bundle, and the corpus callosum were detectable in less successful learners compared with more successful learners. Most importantly, there was a negative correlation between uncertainty-related activation and diffusivity in a fronto-parieto-striatal network in less successful learners only, indicating a direct relation between diffusivity and the ability to reduce processing resources with decreasing uncertainty. These findings indicate that interindividual variations in white matter characteristics within the normal population might be linked to neuronal activation and critically influence individual learning performance.     

High-field magnetic resonance imaging of brain iron: birth of a biomarker?

The brain has an unusually high concentration of iron, which is distributed in an unusual pattern unlike that in any other organ. The physiological role of this iron and the reasons for this pattern of distribution are not yet understood. There is increasing evidence that several neurodegenerative diseases are associated with altered brain iron metabolism. Understanding these dysmetabolic conditions may provide important information for their diagnosis and treatment. For many years the iron distribution in the human brain could be studied effectively only under postmortem conditions. This situation was changed dramatically by the finding that T2-weighted MR imaging at high field strength (initially 1.5 T) appears to demonstrate the pattern of iron distribution in normal brains and that this imaging technique can detect changes in brain iron concentrations associated with disease states. Up to the present time this imaging capability has been utilized in many research applications but it has not yet been widely applied in the routine diagnosis and management of neurodegenerative disorders. However, recent advances in the basic science of brain iron metabolism, the clinical understanding of neurodegenerative diseases and in MRI technology, particularly in the availability of clinical scanners operating at the higher field strength of 3 T, suggest that iron-dependent MR imaging may soon provide biomarkers capable of characterizing the presence and progression of important neurological disorders. Such biomarkers may be of crucial assistance in the development and utilization of effective new therapies for Alzheimer's and Parkinson's diseases, multiple sclerosis and other iron-related CNS disorders which are difficult to diagnose and treat.     

Value of magnetic resonance enterography in diagnosis and treatment follow up in Crohn’s disease in children

PurposeCrohn’s disease (CD) is a chronic inflammatory disease which can affect all parts of the gastrointestinal tract. Magnetic resonance enterography (MRE) enables detection of pathologic changes in the small intestine, which are not accessible by conventional endoscopy. The aim of the study was to assess the value of MRE in imaging of small bowel lesions, their location and extent, in CD patients and its correlation with clinical and endoscopic activity.Materials and methodsMRE was performed in 108 children with CD, aged 5.5 to 18 years. The diagnosis was based on the Porto criteria. Location and clinical manifestation was evaluated according to the Paris classification. Clinical CD activity was assessed with PCDAI and endoscopic activity with SES-CD. In 36 children, control MRE was performed.ResultsThe most common endoscopic location of the disease was the colon (41.7%), terminal ileum and colon (24.1%). Inflammation as the main clinical manifestation was dominant (81.5%). In MRE, inflammatory changes were found in 40.8% of children, strictures in 11.1%. The EIA value (activity in MRE) increased along with PCDAI score and SES-CD. MRE performed during follow up, showed transmural healing in 16.7% of patients and improvement in 55.5%.ConclusionsMRE is an efficient diagnostic tool in proper characterization of disease location in pediatric CD. As positive correlation of the results of MRE with the endoscopic and clinical activity has been found, taking into account good tolerance and non-invasiveness of the procedure it can be recommended to be used in reassessment.     

Muscle abnormalities of the chest in Poland’s syndrome: variations and proposal for a classification

Purposes  

Poland’s syndrome (PS) is a rare congenital malformation, which combines anomalies of the chest and the homolateral upper limb. The purposes of the paper are to study the chest musculoskeletal malformations of the syndrome and propose a classification for the thoracic anomalies through our experience and taking into account the literature.     

Discrete functional contributions of cerebral cortical foci in voluntary swallowing: a functional magnetic resonance imaging (fMRI) “Go,No-Go” study

Brain-imaging studies have shown that visually-cued, voluntary swallowing activates a distributed network of cortical regions including the precentral and postcentral gyri, anterior cingulate cortex (ACC), insula, frontoparietal operculum, cuneus and precuneus. To elucidate the functional contributions of these discrete activation foci for swallowing, a Go, No-Go functional magnetic resonance imaging (fMRI) paradigm was designed. Brain activation associated with visually-cued swallowing was compared with brain activation evoked by a comparable visual cue instructing the subject not to swallow. Region-of-interest analyses performed on data from eight healthy subjects showed a significantly greater number of activated voxels within the precentral gyrus, postcentral gyrus, and ACC during the Go condition compared to the No-Go condition. This finding suggests that the precentral gyrus, postcentral gyrus, and ACC contribute primarily to the act of swallowing. In contrast, the numbers of activated voxels within the cuneus and precuneus were not significantly different for the Go and No-Go conditions, suggesting that these regions mediate processing of the cue to swallow. Together these findings support the view that the discrete cortical foci previously implicated in swallowing mediate functionally distinct components of the swallowing act.     

Stereological evaluation of the volume and volume fraction of newborns’ brain compartment and brain in magnetic resonance images

Purpose

Brain development in early life is thought to be critical period in neurodevelopmental disorder. Knowledge relating to this period is currently quite limited. This study aimed to evaluate the volume relation of total brain (TB), cerebrum, cerebellum and bulbus+pons by the use of Archimedes’ principle and stereological (point-counting) method and after that to compare these approaches with each other in newborns.

Methods

This study was carried out on five newborn cadavers mean weighing 2.220?±?1.056?g with no signs of neuropathology. The mean (±SD) age of the subjects was 39.7 (±1.5) weeks. The volume and volume fraction of the total brain, cerebrum, cerebellum and bulbus+pons were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods and by the use of fluid displacement technique.

Results

The mean (±SD) TB, cerebrum, cerebellum and bulbus+pons volumes by fluid displacement were 271.48?±?78.3, 256.6?±?71.8, 12.16?±?6.1 and 2.72?±?1.6?cm³, respectively. By the Cavalieri principle (point-counting) using sagittal MRIs, they were 262.01?±?74.9, 248.11?±?68.03, 11.68?±?6.1 and 2.21?±?1.13?cm³, respectively. The mean (±?SD) volumes by point-counting technique using axial MR images were 288.06?±?88.5, 275.2?±?83.1, 19.75?±?5.3 and 2.11?±?0.7?cm³, respectively. There were no differences between the fluid displacement and point-counting (using axial and sagittal images) for all structures (p?>?0.05).

Conclusion

This study presents the basic data for studies relative to newborn’s brain volume fractions according to two methods. Stereological (point-counting) estimation may be accepted a beneficial and new tool for neurological evaluation in vivo research of the brain. Based on these techniques we introduce here, the clinician may evaluate the growth of the brain in a more efficient and precise manner.     

Ofatumumab in the treatment of low-grade non-Hodgkin’s lymphomas and chronic lymphocytic leukemia

Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved for the treatment of chronic lymphocytic leukemia refractory to alemtuzumab and fludarabine. Ofatumumab has also demonstrated activity in other low-grade non-Hodgkin’s lymphomas. However, the optimal time to use ofatumumab and in what patient population is debatable. This article will review some of the key clinical studies that led to the drug’s approval, current recommended usage of the drug and significant future directions.     

Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn’s disease versus healthy controls

In patients with Crohn’s disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD.     

Cortical excitability and plasticity in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies

BackgroundTranscranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with electromyography measures, TMS can probe functions of cortical excitability and plasticity in vivo. The purpose of this meta-analysis is to evaluate the utility of TMS-derived measures for differentiating patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults (CN).MethodsDatabases searched included PubMed, Embase, APA PsycInfo, Medline, and CINAHL Plus from inception to July 2021.ResultsSixty-one studies with a total of 2728 participants (1454 patients with AD, 163 patients with MCI, and 1111 CN) were included. Patients with AD showed significantly higher cortical excitability, lower cortical inhibition, and impaired cortical plasticity compared to the CN cohorts. Patients with MCI exhibited increased cortical excitability and reduced plasticity compared to the CN cohort. Additionally, lower cognitive performance was significantly associated with higher cortical excitability and lower inhibition. No seizure events due to TMS were reported, and the mild adverse response rate is approximately 3/1000 (i.e., 9/2728).ConclusionsFindings of our meta-analysis demonstrate the potential of using TMS-derived cortical excitability and plasticity measures as diagnostic biomarkers and therapeutic targets for AD and MCI.     

Interval timing and Parkinson’s disease: heterogeneity in temporal performance

Interval timing deficiencies in Parkinson’s disease (PD) patients have been a matter of debate. Here we test the possibility of PD heterogeneity as a source for this discrepancy. Temporal performance of PD patients and control subjects was assessed during two interval tapping tasks and during a categorization task of time intervals. These tasks involved temporal processing of intervals in the hundreds of milliseconds range; however, they also covered a wide range of behavioral contexts, differing in their perceptual, decision-making, memory, and execution requirements. The results showed the following significant findings. First, there were two clearly segregated subgroups of PD patients: one with high temporal variability in the three timing tasks, and another with a temporal variability that did not differ substantially from control subjects. In contrast, PD patients with high and low temporal variability showed similar perceptual, decision-making, memory, and execution performance in a set of control tasks. Second, a slope analysis, designed to dissociate time-dependent from time-independent sources of variation, revealed that the increase in variability in this group of PD patients was mainly due to an increment in the variability associated with the timing mechanism. Third, while the control subjects showed significant correlations in performance variability across tasks, PD patients, and particularly those with high temporal variability, did not show such task correlations. Finally, the results showed that dopaminergic treatment restored the correlation effect in PD patients, producing a highly significant correlation between the inter-task variability. Altogether, these results indicate that a subpopulation of PD patients shows a strong disruption in temporal processing in the hundreds of milliseconds range. These findings are discussed in terms of the role of dopamine as a tuning element for the synchronization of temporal processing across different behavioral contexts in PD patients.     

Mitochondrial dysfunction,oxidative stress,neuroinflammation, and metabolic alterations in the progression of Alzheimer’s disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies

Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the neural signatures associated with these metabolic alterations and underlying molecular mechanisms are still elusive. Accordingly, we reviewed the literature on in vivo human brain ¹H and ³¹P-MRS studies and use meta-analyses to identify patterns of brain metabolic alterations in MCI and AD. 40 and 39 studies on MCI and AD, respectively, were classified according to brain regions. Our results indicate decreased N-acetyl aspartate and creatine but increased myo-inositol levels in both MCI and AD, decreased glutathione level in MCI as well as disrupted energy metabolism in AD. In addition, the hippocampus shows the strongest alterations in most of these metabolites. This meta-analysis also illustrates progressive metabolite alterations from MCI to AD. Taken together, it suggests that 1) neuroinflammation and oxidative stress may occur in the early stages of AD, and likely precede neuron loss in its progression; 2) the hippocampus is a sensitive region of interest for early diagnosis and monitoring the response of interventions; 3) targeting bioenergetics associated with neuroinflammation/oxidative stress is a promising approach for treating AD.     

Visual and somatosensory processing in the macaque temporal cortex: the role of ‘expectation’

Summary The somatosensory and visual properties of cells in a polymodal region of temporal cortex were studied in 4 awake behaving macaque monkeys. When stimulated passively and out of sight, cells with tactile responses were found to have very large receptive fields covering most of the body surface and an apparent lack of selectivity for size, shape or texture of the tactile stimulus. These properties are equivalent to those described for the anaesthetized preparation (Bruce et al. 1981). Our study revealed that tactile responses were influenced by the degree to which stimuli could be expected. Tactile stimulation arising from active exploration of novel surfaces produced vigourous neuronal responses but equivalent stimulation of the skin arising when the monkey contacted expected surfaces such as itself or items with which it had become familiar produced no responses. The responses of cells to active or passive tactile stimulation were attenuated when the monkey could see the objects causing the stimulation. For cells responsive to more than one sensory modality, visual and somatosensory responses were associated in a compatible manner. Cells responsive to the onset of touch were selective for the sight of objects moving towards the monkey, whereas cells selective for the offset of touch were responsive to the sight of movements away from the monkey.     

The role of the right dorsolateral prefrontal cortex in the Tower of London task performance: repetitive transcranial magnetic stimulation study in patients with Parkinson’s disease

We studied whether one session of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over either the right or left dorsolateral prefrontal cortex would induce any measurable changes in the Tower of London spatial planning task performance in patients with Parkinson’s disease (PD). Ten patients with PD (with no dementia and/or depression) entered the randomized, sham-stimulation-controlled study with a crossover design. Active and placebo rTMS were applied over either the left or the right dorsolateral prefrontal cortex (in four separate sessions) in each patient. The order of sessions was randomized. The Tower of London task was performed prior to and immediately after each appropriate session. The “total problem-solving time” was our outcome measure. Only active rTMS of the right dorsolateral prefrontal cortex induced significant enhancement of the total problem-solving time, p = 0.038. Stimulation of the left prefrontal cortex or sham stimulations induced no significant effects. Only rTMS applied over the right dorsolateral prefrontal cortex induced positive changes in the spatial planning task performance in PD, which further supports the results of functional imaging studies indicating the causal engagement of the right-sided hemispheric structures in solving the task in this patient population.     

Abnormal resonance behavior of the postural control loop in Parkinson’s disease

Human postural control of upright stance sporadically can show an oscillatory behavior. Based on previous work, we assessed whether an abnormal tendency for such oscillations might contribute to the motor impairments in patients with basal ganglia dysfunction such as Parkinsons disease (PD). We investigated postural control during unperturbed stance in normal control subjects and in PD patients off and under treatment, focusing on stabilogram diffusion analysis (SDA) of the foot center of pressure (COP) excursions and conventional measures of the sway amplitude and velocity. We found abnormal 1 Hz body sway oscillation in the SDA curves of PD patients that differed significantly from the body sway typically observed in control subjects during quiet stance. The 1 Hz body sway oscillation was associated with abnormally large and fast sway in the patients off treatment. Under treatment with levodopa, with deep brain stimulation (subthalamic nucleus) and even more so with combined treatment, the oscillations in the SDA curves vanished and the sway became slower. The loss of oscillation and reduction of sway velocity were highly correlated with the improvements of patients clinical motor assessment score. However, sway amplitude was not correlated with the patients motor assessment score and patients reported clinical improvement under therapy even though sway amplitude increased on average. A simple feedback model of the postural control system with abnormally large internal noise could predict experimental measures both on and off treatment. The off treatment condition was consistent with a high motor gain in the feedback loop, and the on treatment condition with a reduced motor gain.     

New method for quantification of Trypanosoma cruzi in animal’s tissue in the chronic phase of experimental Chagas' disease

We developed a new method for the quantification of parasites in tissue. Trypanosoma cruzi strain CL parasites were genetically engineered to express the Escherichia coli β-galactosidase gene, lacZ and this enzyme is able to catalyze a colorimetric reaction with chlorophenol red β-d galactopyranoside (CPRG) as the substrate. The animals were infected with clone CL Brener strain B5 of T. cruzi and treated with benznidazole in order to verify the reduction in the number of parasites in tissue study by quantifying the enzyme β-galactosidase. The assay demonstrates a reduction in the number of parasites in the groups treated. Thus, this test can be used to test other substances with the aim of verifying the effectiveness in the chronic phase of experimental Chagas' disease.