Volume 33, Issue 8

There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a time scale of tens of ms. If such assemblies form an odor representation, then a fundamental question is how each assembly then induces neuronal activity in downstream structures. We have addressed this question in a detailed model of superficial layers of lateral entorhinal cortex, a recipient of input from olfactory cortex and olfactory bulb. Our results predict that the response of the fan cell subpopulation can be approximated by a relatively simple Boolean process, somewhat along the lines of the McCulloch/Pitts scheme; this is the case because of the sparsity of recurrent excitation amongst fan cells. However, because of recurrent excitatory connections between layer 2 and layer 3 pyramidal cells, synaptic and probably also gap junctional, the response of pyramidal cell subnetworks cannot be so approximated. Because of the highly structured anatomy of entorhinal output projections, our model suggests that downstream targets of entorhinal cortex (dentate gyrus, hippocampal CA3, CA1, piriform cortex, olfactory bulb) receive differentially processed information.

Posterior cortical atrophy (PCA) is a neurodegenerative disorder characterized by an early prominent deficit of visual functions associated with signs and symptoms that are the expression of dysfunction of posterior brain regions. Although PCA is commonly associated with Alzheimer’s disease (AD), in recent years new pathological substrates have emerged. Among them, frontotemporal lobar degeneration (FTLD) is the most commonly reported but, to date, little is known about the clinical features of PCA due to FTLD. We conducted a systematic search in the main biomedical database MEDLINE. We searched for all clinical PCA reports that assessed the pathological basis of such syndrome with at least one of the following: (1) neuropathological examination, (2) cerebrospinal fluid biomarkers, (3) amyloid-PET imaging and (4) genetic testing. Of 369 potentially eligible studies, 40 fulfilled the inclusion criteria with an overall number of 144 patients (127 PCA-AD vs. 17 PCA-FTD/non-AD). We found that hallucinations/illusions were present in none of the probable PCA-FTD/non-AD subjects while were reported in 15 out of 97 PCA-AD individuals. Optic ataxia and Parkinsonism showed a significantly greater prevalence in probable PCA FTD/non-AD than in PCA-AD whereas myoclonus and disorientation in time and space were significantly more frequent in PCA-AD than in probable PCA FTD/non-AD. We also found a predominance of a left-side pattern of atrophy/hypometabolism in the probable PCA FTD/non-AD. Clinical features such as optic ataxia, Parkinsonism, myoclonus, hallucinations and disorientation in time and space suggest the underlying pathological basis of PCA and help in leading the diagnostic protocol consequently.

The precise cortical and subcortical mechanisms of Tourette syndrome (TS) are still not fully understood. In the present retrospective analysis, adolescent and adult medication-naïve patients showed increased DA transporter (DAT) binding in nucleus caudate (CAUD), putamen (PUT) and/or whole neostriatum (NSTR). D 2 receptor (R) binding and DA release were not different from controls throughout the nigrostriatal and mesolimbocortical system. When patients were medication-free (either medication-naïve or under withdrawal), DAT was still increased in PUT, but not different from controls in CAUD, NSTR and ventral striatum (VSTR). SERT was unaltered in midbrain/pons (MP), but decreased in PUT, thalamus (THAL) and hypothalamus. D 2 R was unaltered throughout the nigrostriatal and mesolimbocortical system, while DA release was not different from controls in PUT, CAUD and NSTR, but elevated in VSTR. 5-HT 2A R binding was unaltered in neocortex and cingulate. In acutely medicated adults, DAT was unaltered in PUT, but still increased in CAUD, whereas DA release remained unaltered throughout the nigrostriatal and mesolimbocortical system. When part of the patients was acutely medicated, vesicular monoamine transporter (VMAT2), DAT, SERT and DA synthesis were not different from controls in striatal regions, whereas D 2 R was decreased in NSTR, THAL, frontal cortex and limbic regions. Conversely, 5-HT 2A R binding was unaltered in striatal regions and THAL, but increased in neocortical and limbic areas. It may be hypothesized that both the DA surplus and the 5-HT shortage in key regions of the nigrostriatal and mesolimbic system are relevant for the bouts of motor activity and the deficiencies in inpulse control.

Sudden unexpected death in epilepsy (SUDEP) is a devastating yet overlooked complication of epilepsy. The rare and complex nature of SUDEP makes it challenging to study. No prediction or prevention of SUDEP is currently available in a clinical setting. In the past decade, significant advances have been made in our knowledge of the pathophysiologic cascades that lead to SUDEP. In particular, studies of brain, heart, and respiratory functions in both human patients at the epilepsy monitoring unit and animal models during fatal seizures provide critical information to integrate computational tools for SUDEP prediction. The rapid advances in automated seizure detection and prediction algorithms provide a fundamental framework for their adaption in predicting SUDEP. If a SUDEP can be predicted, then there will be a potential for medical intervention to be administered, either by their caregivers or via an implanted device automatically delivering electrical stimulation or medication, and finally save lives from fatal seizures. This article presents recent developments of SUDEP studies focusing on the pathophysiologic basis of SUDEP and computational implications of machine learning techniques that can be adapted and extended for SUDEP prediction. This article also discusses some novel ideas for SUDEP prediction and rescue including principal component analysis and closed-loop intervention.

Sustained performance of cognitive tasks could lead to the development of state mental fatigue characterized by subjective sensation of mental weariness and decrease in cognitive performance. In addition to the occupational hazards associated with mental fatigue, it can also affect physical performance reducing endurance, balance, and sport-specific technical skills. Similarly, mental fatigue is a common symptom in certain chronic health conditions such as multiple sclerosis affecting quality of life of the patients. Despite its widely acknowledged negative impact, the neural mechanisms underlining this phenomenon are still not fully understood. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies investigating the effect of mental fatigue due to time-on-task (TOT) on brain activity to elucidate the possible underlying mechanisms. Studies were included if they examined change in brain activity induced by experimental mental fatigue (TOT effect) or investigated the relationship between brain activity and subjective mental fatigue due to TOT. A total of 33 studies met the review’s inclusion criteria, 13 of which were included in meta-analyses. Results of the meta-analyses revealed a decrease in activity with TOT in brain areas that constitute the cognitive control network. Additionally, an increased activity with TOT, as well as negative relationship with subjective mental fatigue was found in parts of the default mode network of the brain. The changes in cognitive control and the default mode networks of the brain due to state mental fatigue observed in this study were discussed in relation to the existing theories of mental fatigue.

The ability to produce high movement speeds is a crucial factor in human motor performance, from the skilled athlete to someone avoiding a fall. Despite this relevance, there remains a lack of both an integrative brain-to-behavior analysis of these movements and applied studies linking the known dependence on open-loop, central control mechanisms of these movements to their real-world implications, whether in the sports, performance arts, or occupational setting. In this review, we cover factors associated with the planning and performance of fast limb movements, from the generation of the motor command in the brain to the observed motor output. At each level (supraspinal, peripheral, and motor output), the influencing factors are presented and the changes brought by training and fatigue are discussed. The existing evidence of more applied studies relevant to practical aspects of human performance is also discussed. Inconsistencies in the existing literature both in the definitions and findings are highlighted, along with suggestions for further studies on the topic of fast limb movement control. The current heterogeneity in what is considered a fast movement and in experimental protocols makes it difficult to compare findings in the existing literature. We identified the role of the cerebellum in movement prediction and of surround inhibition in motor slowing, as well as the effects of fatigue and training on central motor control, as possible avenues for further research, especially in performance-driven populations.