Loss of memory for auditory-spatial associations following unilateral medial temporal-lobe damage

The goal of the present experiment was to determine the role of medial temporal-lobe structures in episodic memory of auditory-spatial associations. By using a two-alternative forced choice paradigm in which an association between eight different sounds and their spatial location must be recognized, learning abilities over 10 learning sessions were tested in 19 patients who had undergone a right or a left medial temporal-lobe resection for the relief of intractable seizures as well as in nine normal control participants. The data demonstrated that significant learning took place over the successive sessions for all the participants. In addition, the results showed that patients with left but not right medial temporal-lobe lesion were impaired in this learning task as compared to normal participants, suggesting the predominant implication of left medial temporal-lobe structures in auditory-spatial associative learning. The predominant role of left hemisphere structures in this memory task could be explained by a spatial categorical coding, which was enhanced by the use of eight loud-speakers. This result also suggests that the ability to store an episodic event associated with a rich spatial (or temporal) context depends on the left medial temporal-lobe structures. Thus, this finding provides an interesting parallel with data obtained in the visual modality by documenting for the first time the role of the left medial temporal-lobe in episodic learning of auditory-spatial associations

The effects of railway noise on sleep medication intake: results from the ALPNAP-study

In the 1980s/90s, a number of socio-acoustic surveys and laboratory studies on railway noise effects have observed less reported disturbance/interference with sleep at the same exposure level compared with other modes of transportation. This lower grade of disturbance has received the label "railway bonus", was implemented in noise legislation in a number of European countries and was applied in planning and environmental impact assessments. However, majority of the studies investigating physiological outcomes did not find the bespoke difference. In a telephone survey (N=1643) we investigated the relationship between railway noise and sleep medication intake and the impact of railway noise events on motility parameters during night was assessed with contact-free high resolution actimetry devices. Multiple logistic regression analysis with cubic splines was applied to assess the probability of sleep medication use based on railway sound level and nine covariates. The non-linear exposure-response curve showed a statistically significant leveling off around 60 dB (A), Lden. Age, health status and trauma history were the most important covariates. The results were supported also by a similar analysis based on the indicator "night time noise annoyance". No railway bonus could be observed above 55 dB(A), Lden. In the actimetry study, the slope of rise of train noise events proved to be almost as important a predictor for motility reactions as was the maximum sound pressure level - an observation which confirms similar findings from laboratory experiments and field studies on aircraft noise and sleep disturbance. Legislation using a railway bonus will underestimate the noise impact by about 10 dB (A), Lden under the conditions comparable with those in the survey study. The choice of the noise calculation method may influence the threshold for guideline setting

Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in organization and quality across European countries, translating into huge societal cost (0.2% GDP) and stressing the need for cost-effective programs of harmonization and optimization of epilepsy care throughout Europe. There is currently no cure or prevention for epilepsy, and 30% of affected persons are not controlled by current treatments, stressing the need for pursuing research efforts in the field within Horizon 2020. Priorities should include (1) development of innovative biomarkers and therapeutic targets and strategies, from gene and cell-based therapies to technologically advanced surgical treatment; (2) addressing issues raised by pediatric and aging populations, as well as by specific etiologies and comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction, toward more personalized medicine and prevention; and (3) translational studies and clinical trials built upon well-established European consortia

Effect of unilateral temporal lobe resection on short-term memory for auditory object and sound location

To investigate auditory spatial and nonspatial short-term memory, a sound location discrimination task and an auditory object discrimination task were used in patients with medial temporal lobe resection. The results showed a double dissociation between the side of the medial temporal lobe lesion and the nature of the auditory discrimination deficits, suggesting that right and left temporal lobe structures are differently involved in auditory spatial and nonspatial short-term memory

Spatial and non-spatial auditory short-term memory in patients with temporal-lobe lesion

Primate auditory systems are divided into at least two different pathways. One refers to objects and the other deals with localization. To investigate auditory spatial and non-spatial short-term memory, we tested patients with unilateral medial temporal lobe lesions including the pole in two tasks involving either sound localization discrimination or auditory object discrimination. The results showed that both left and right temporal lobe lesions impaired spatial short-term memory whereas only lesions on the right affected non-spatial short-term memory. By contrast, the same patients were able to perform the tasks when short interstimulus intervals were used suggesting that short-term memory deficits can not be ascribed to difficulties in perception. These findings document, for the first time, in a neurological population, the functional dissociation between spatial and non-spatial auditory short-term memory that seem to depend on separate neural circuits within the medial temporal lobe

Mild malformations of cortical development in sleep-related hypermotor epilepsy due to KCNT1 mutations

open14siMutations in the sodium-activated potassium channel gene KCNT1 have been associated with nonlesional sleep-related hypermotor epilepsy (SHE). We report the co-occurrence of mild malformation of cortical development (mMCD) and KCNT1 mutations in four patients with SHE. Focal cortical dysplasia type I was neuropathologically diagnosed after epilepsy surgery in three unrelated MRI-negative patients, periventricular nodular heterotopia was detected in one patient by MRI. Our findings suggest that KCNT1 epileptogenicity may result not only from dysregulated excitability by controlling Na+K+ transport, but also from mMCD. Therefore, pathogenic variants in KCNT1 may encompass both lesional and nonlesional epilepsies.openRubboli G.; Plazzi G.; Picard F.; Nobili L.; Hirsch E.; Chelly J.; Prayson R.A.; Boutonnat J.; Bramerio M.; Kahane P.; Dibbens L.M.; Gardella E.; Baulac S.; Moller R.S.Rubboli, G.; Plazzi, G.; Picard, F.; Nobili, L.; Hirsch, E.; Chelly, J.; Prayson, R. A.; Boutonnat, J.; Bramerio, M.; Kahane, P.; Dibbens, L. M.; Gardella, E.; Baulac, S.; Moller, R. S

Cardiac investigations in sudden unexpected death in DEPDC5-related epilepsy

Objective: Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP. Methods: Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5c/−), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures. Results: Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic–ECG records on Depdc5c/− mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event are not preceded by cardiac arrhythmia. Interpretation: Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. ANN NEUROL 2022;91:101–11