Episodic autobiographical memory is associated with variation in the size of hippocampal subregions

Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA_2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high‐resolution MRI of the hippocampal subfields and measures of real‐world (autobiographical) episodic memory. In addition to the association with DG/CA_2/3, we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA₁ or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real‐world episodic remembering in humans.     

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward‐driven behaviors, which can result in life‐altering morbidity. The mesocorticolimbic dopamine network guides reward‐motivated behavior; however, its role in this treatment‐related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward‐learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD‐fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex‐matched PD patients with (n = 19) or without (n = 18) ICB. An incentive‐based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole‐brain voxelwise analyses and region‐of‐interest‐based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala‐to‐midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum‐to‐subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment‐avoidance learning. These data indicate that PD‐ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward‐based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509–521, 2018. © 2017 Wiley Periodicals, Inc.     

Effects of molsidomine on global and regional left ventricular function at rest and during exercise in patients with angina pectoris

Although the antianginal properties of molsidomine are well-established, little is known about its effects on global and regional left ventricular dysfunction secondary to myocardial ischemia. In the present study, left ventricular performance was assessed by radionuclide ventriculography at rest and during exercise in 15 patients with coronary artery disease (CAD) and angina pectoris before and after the administration of 2 mg molsidomine sublingually. Gated blood pool studies were performed for evaluation of left ventricular ejection fraction (LVEF) and regional wall motion by analyzing amplitudes and phases of the first Fourier coefficient of regional time–activity curves. In contrast to normal subjects, during the control study period LVEF in patients with CAD decreased from 50.9% at rest to 42.7% during exercise (p<0.01). After molsidomine the resting values of LVEF increased slightly from 50.9% to 55.7% (p<0.05). Exercise values of LVEF increased from 42.7% to 51.3% (p<0.01). This is usually associated with amelioration of anginal pain and ischemic ST depression in the precordial ECG (0.15 mV vs. 0.09 mV; p<0.01). Before molsidomine, regional wall motion deteriorated from rest to exercise in 11 of 15 patients. These wall motion abnormalities usually expressed themselves as newly developed regions of left ventricular dysfunction (8 patients) or as accentuation of pre-existing contraction disturbances (3 patients). After molsidomine, regional wall motion did not show consistent changes at rest. Comparison during exercise showed enhanced regional function in 10 of the 15 patients after administration of the drug. At rest a slight but significant increase in heart rate was measured following molsidomine, whereas exercise heart rate remained unchanged. Only minor changes in systolic blood pressure occurred after molsidomine (rest, 143 mmHg vs. 134 mmHg; p<0.05; exercise, 177 mmHg vs. 174 mmHg; p>0.10). In conclusion, assessment of left ventricular performance at rest and during exercise in patients with CAD revealed significant improvement of global and regional left ventricular function, indicating reduction of myocardial ischemia. These effects may result primarily from reduction of left ventricular wall tension.     

Diffusion tensor imaging can localize the epileptogenic zone in nonlesional extra-temporal refractory epilepsies when [(18)F]FDG-PET is not contributive

Surgical outcome in patients with nonlesional refractory partial epilepsies could be improved by a more precise definition of the epileptogenic zone (EZ). The value of interictal FDG-PET hypometabolism, voxel-based-morphometry (VBM) and diffusion tensor imaging (DTI) is still debated. We compared the sensitivity and specificity of these noninvasive techniques in localizing the EZ with stereo-electroencephalography (SEEG) results. Twenty patients with nonlesional partial epilepsy (13 temporal lobe epilepsy (TLE) and 7 extra-temporal (extra-TLE)) underwent structural MRI, DTI and FDG-PET. FDG-PET was analyzed visually (vPET) blinded and unblinded and by statistical parametric mapping (SPM) (sPET). Individual modifications of grey matter volume and mean diffusivity increase were compared to a control group with SPM. The best sensitivity was provided by vPET unblinded (75%) and the best specificity (60%) by DTI. The sensitivity of vPET blinded (55%) was lower and those of sPET (40%) and VBM (35%) were still lower. In TLE, vPET analyzed either blinded or unblinded, performed the best and additional use of the other tools improved slightly the sensitivity. For extra-TLE, combining vPET and DTI results increased the number of pertinent abnormalities detected especially for circumscribed changes in frontal lobe epilepsy (FLE). Combining vPET and DTI was the more efficient strategy for extra-TLE, allowing the detection of pertinent abnormalities in FLE when FDG-PET alone was not contributive. Combining sPET or VBM with vPET was less useful.     

Subcellular synaptic connectivity of layer 2 pyramidal neurons in the medial prefrontal cortex

Pyramidal neurons in the prefrontal cortex (PFC) are important for the control of cognitive and emotional behavior. The medial PFC (mPFC) receives diverse long-range excitatory inputs from the midline thalamus, contralateral mPFC, basolateral amygdala, and ventral hippocampus. While axons from these different regions have distinct distributions in the mPFC, their functional connections at the cellular and subcellular levels remain unknown. Here, we use optogenetics to show that layer 2 pyramidal neurons in acute slices of the mouse mPFC receive excitatory inputs from each of these regions. Using a combination of optogenetics and two-photon microscopy, we then determine the subcellular properties of these inputs. We find that different types of inputs make selective contacts at the levels of both dendrites and spines. Using two-photon uncaging, we show that this subcellular targeting strongly influences synaptic efficacy in these neurons. Together, our results show that functional connectivity is finely tuned, with important implications for signal processing in the mPFC.     

Genetic differences in emotionally enhanced memory

Understanding genetic contributions to individual differences in the capacity for emotional memory has tremendous implications for understanding normal human memory as well as pathological reactions to traumatic stress. Research in the last decade has identified genetic polymorphisms thought to influence cognitive/affective processes that may contribute to emotional memory capacity. In this paper, we review key polymorphisms linked to emotional and mnemonic processing and their influence on neuromodulator activity in the amygdala and other emotion-related structures. We discuss their potential roles in specific cognitive processes involved in memory formation, and review links between these genetic variants, brain activation, and specific patterns of attention, perception, and memory consolidation that may be linked to individual differences in memory vividness. Finally we propose a model predicting an influence of noradrenergic, serotonergic, and dopaminergic processes on emotional perception, as well as on memory consolidation and self-regulation. Outside of the laboratory, it is likely that real-life effects of arousal operate along a continuum that incorporates other “non-emotional” aspects of memory. For this reason we further discuss additional literature on genetic variations that influence general episodic memory processes, rather than being specific to emotional enhancement of memory. We conclude that specific neuromodulators contribute to an amygdala-driven memory system that is relatively involuntary, embodied, and sensorily vivid.