Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings

Abstract Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.

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Electroconvulsive Therapy: The Role of Hippocampal Neurogenesis

European Psychiatry ◽

10.1016/s0924-9338(09)70308-6 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

T. Bolwig

Keyword(s):

Severe Depression ◽

Hippocampal Volume ◽

Structure And Function ◽

Hippocampal Neurogenesis ◽

Actual Number ◽

Before And After ◽

And Function ◽

Hippocampal Structure ◽

Electroconvulsive Seizures

During recent years magnetic (MRI) studies have pointed to a reduction in hippocampal volume in patients with severe depression. Volumetric changes reflect the actual number of days that individuals have been depressed (1). These findings have heightened interest in studying hippocampal structure and function in experimental animals, especially during and after electroconvulsive seizures -the most powerful of antidepressant therapies (2). Both before and after 2000, with the earliest report on hippocampal neurogenesis following seizures, findings of gliogenesis and synaptogenesis have been reported (3). During the last decade further studies of neurotropic factors have supported ideas of the role of neuroplasticity related to ECT in humans (4). All antidepressant medications, but not antipsychotics, have a similar, but weaker effect on hippocampal neurogenesis. We hypothesize that an induction of neurotropic factors leading to hippocampal neurogenesis may play a major role for the action of ECT (5).

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The effects of regular aerobic exercise on hippocampal structure and function

10.1101/2020.08.14.250688 ◽

2020 ◽

Author(s):

Joshua Hendrikse ◽

Yann Chye ◽

Sarah Thompson ◽

Nigel C. Rogasch ◽

Chao Suo ◽

...

Keyword(s):

Magnetic Resonance ◽

Associative Memory ◽

Hippocampal Volume ◽

Structure And Function ◽

Pattern Separation ◽

Regular Exercise ◽

Middle Aged ◽

And Function ◽

Middle Aged Adults ◽

Hippocampal Structure

AbstractEngaging in regular exercise has numerous benefits for brain health. In particular, a number of studies have associated exercise with improvements to the structure and function of the hippocampus, especially in older adults. This region plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g. depression and schizophrenia), as well as healthy ageing. Thus, exercise may provide an effective method of enhancing / ameliorating hippocampal integrity; however, an improved understanding of exercise-related effects in young to middle-aged adults is required. We assessed the effects of regular exercise and cardiorespiratory fitness on hippocampal structure and function in young to middle-aged adults. We recruited a sample of 40 healthy adults, comprised of individuals who self-reported as engaging in high (regular exercisers) or low (sedentary) levels of physical activity (PA) according to World Health Organisation guidelines (high PA n=20; low PA n=20). A multi-modal assessment of hippocampal structure and function was conducted using structural magnetic resonance imaging (sMRI), magnetic resonance (MR) spectroscopy, and hippocampal-dependent memory tasks. We observed evidence of increased N-acetyl-aspartate (NAA) concentration and associative memory performance in high PA individuals. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. We found that cardiorespiratory fitness was positively associated with (left, right, and bilateral) hippocampal volume, NAA concentration, and pattern separation, but not associative memory. Therefore, we provide evidence that engaging in higher levels of exercise has demonstrable benefits for hippocampal integrity and function. Given that young and middle-aged adults are overrepresented in the diagnosis of psychiatric illnesses which affect hippocampal integrity (e.g. depression and schizophrenia), it is possible that exercise may provide a low-risk, effective method of remediating this dysfunction.

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