Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa.

BACKGROUND: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change. METHODS: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm. RESULTS: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity. CONCLUSIONS: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

Hippocampal atrophy and altered brain responses to pleasant tastes among obese compared with healthy weight children.

OBJECTIVE: The hippocampus is a key structure implicated in food motivation and intake. Research has shown that the hippocampus is vulnerable to the consumption of a western diet (i.e., high saturated fat and simple carbohydrates). Studies of patients with obesity (OB), compared with healthy weight (HW), show changes in hippocampal volume and response to food cues. Moreover, evidence suggests that OB children, relative to HW, have greater hippocampal response to taste. However, no study has examined the association of hippocampal volume with taste functioning in children. We hypothesized that OB children, relative to HW, would show a significant reduction in hippocampal volume and that decreased volume would be significantly associated with greater activation to taste. Finally, we explored whether hippocampal activation would be associated with measures on eating and eating habits. SUBJECTS: Twenty-five 8-12-year-old children (i.e., 13 HW, 12 OB) completed a magnetic resonance imaging scan while participating in a taste paradigm (i.e., 1 ml of 10% sucrose or ionic water delivered pseudorandomly every 20 s). RESULTS: Children with OB, relative to HW, showed reduced left hippocampal volume (t=1.994, P=0.03, 95% confidence interval (CI)=-40.23, 755.42), and greater response to taste in three clusters within the left hippocampus (z=3.3, P=0.001, 95% CI=-0.241, -0.041; z=3.3, P=0.001, 95% CI=-0.2711, -0.0469; z=2.7, P=0.007, 95% CI=-0.6032, -0.0268). Activation within the hippocampus was associated with eating in the absence of hunger (EAH%; t=2.408, P=0.025, 95% CI= 1.751708, 23.94109) and two subscales on a measure of eating behaviors (Food responsiveness, t=2.572, P=0.017, 95% CI= 0.9565195, 9.043440; Food enjoyment, t=2.298, P=0.032, 95% CI=0.2256749, 4.531298). CONCLUSION: As hypothesized, OB children, relative to HW, had significantly reduced hippocampal volume, and greater hippocampal activation to taste. Moreover, hippocampal activation was associated with measures of eating. These results contribute to research on the relationship between OB, overeating and cognitive impairment.

Increased brain response to appetitive tastes in the insula and amygdala in obese compared with healthy weight children when sated.

OBJECTIVE: There is evidence of altered neural taste response in female adolescents who are obese (OB), and in adolescents who are at risk for obesity. To further understand risk factors for the development of overeating and obesity, we investigated response to tastes of sucrose and water in 23 OB and healthy weight (HW) children. METHODS AND DESIGN: Thirteen HW and 10 OB 8-12-year-old children underwent functional magnetic resonance imaging while tasting sucrose and water. Additionally, children completed an eating in the absence of hunger paradigm and a sucrose-liking task. RESULTS: A region of interest analysis revealed an elevated BOLD response to taste (sucrose and water) within the bilateral insula and amygdala in OB children relative to HW children. Whole-brain analyses revealed a group by condition interaction within the paracingulate, medial frontal, middle frontal gyri and right amygdala: post hoc analyses suggested an increased response to sucrose for OB relative to HW children, whereas HW children responded more strongly to water relative to sucrose. In addition, OB children, relative to HW, tended to recruit the right putamen as well as medial and lateral frontal and temporal regions bilaterally. CONCLUSION: This study showed increased reactivity in the amygdala and insula in the OB compared with HW children, but no functional differentiation in the striatum, despite differences in the striatum previously seen in older samples. These findings support the concept of the association between increased neural processing of food reward in the development of obesity, and raise the possibility that emotional and interoceptive sensitivity could be an early vulnerability in obesity.

Inhibitory synaptic plasticity: spike timing-dependence and putative network function.

While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

Elevated pulse pressure is associated with age-related decline in language ability.

Recent research suggests that pulse pressure (PP), a putative marker of vascular integrity, may be associated with brain microvascular damage and age-related cognitive decline. Thus, the present study examined the relationship between PP and cognition in a sample of healthy nondemented older adults. One hundred nine participants were administered neurological and neuropsychological evaluations and determined to be nondemented. Regression analyses were used to examine the relationships among pulse pressure (PP) [systolic blood pressure (SBP)--diastolic blood pressure (DBP)], age, and cognition. PP and related measures were inversely correlated with global cognitive functioning and scores on a composite measure of language function, even after adjusting for age, education, and relevant vascular risk factors. Results indicate that increases in the pulsatile component of blood pressure may convey added risk of global cognitive decline and specific impairment in language abilities.

Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis.

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Functional relation between interneuron input and population activity in the rat hippocampal cornu ammonis 1 area.

Inhibitory interneurons are important components of the cornu ammonis 1 (CA1) network, as they are strategically positioned to control network information transfer. We investigated in detail synaptic input to individual CA1 interneurons (mainly basket and bistratified cells) after the local circuit was activated through the Schaffer-Commissural pathway and related this input to the population activity of the pyramidal cells. Synaptic responses were measured under whole-cell voltage clamp and population activity was determined from local field potentials. The synaptic input that was evoked in CA1 interneurons fell into two distinct groups. Disynaptic input with a long latency always started after the population spike with a mean latency of 3.0+/-0.3 ms (n=22) in respect to the peak of the population spike. This type of synaptic input to the interneurons was causally linked to the occurrence and amplitude of the population spike and most likely driven by CA1 pyramidal cells. Short-latency monosynaptic input occurred 0.8+/-0.2 ms (n=18) before the peak of the population spike. Its timing was strictly linked to the stimulus and showed significantly less jitter than long-latency input. In the absence of a population spike only short-latency input could be observed. Whether an interneuron receives direct monosynaptic Schaffer input or disynaptic input from the pyramidal cell population determines when that interneuron will be recruited in the network after Schaffer collateral stimulation. In addition, we found that the relation between the strength of the synaptic input and the population activity was different for the two types of input. Short-latency monosynaptic input showed large sensitivity to input changes at stimulus intensities that evoked little activity in the pyramidal cell population. In contrast, the amplitude of the long-latency disynaptic input to the interneurons closely reflected the population activity and increased gradually with stimulus intensity. Interneurons receiving the first type of input may expand the input sensitivity of the network, while interneurons receiving the second type could be involved in overall normalization of the output of the CA1 network. Our results underscore the importance of knowledge of the input to an interneuron for the understanding of its inhibitory role in the network.

Miniature inhibitory postsynaptic currents in CA1 pyramidal neurons after kindling epileptogenesis.

Miniature inhibitory postsynaptic currents (mIPSCs) were measured in CA1 pyramidal neurons from long-term kindled rats (>6 weeks after they reached the stage of generalized seizures) and compared with controls. A large reduction in the number of mIPSCs was observed in a special group of large mIPSCs (amplitude >75 pA). The frequency of mIPSCs in this group was reduced from 0.042 Hz in controls to 0.027 Hz in the kindled animals. The reduction in this group resulted in a highly significant difference in the amplitude distributions. A distinction was made between fast mIPSCs (rise time <2.8 ms) and slow mIPSCs. Fast mIPSCs, which could originate from synapses onto the soma and proximal dendrites, had significantly larger amplitudes than slow mIPSCs, which could originate from more distal synapses (35.4 +/- 1.1 vs. 26.2 +/- 0.4 pA in the kindled group; means +/- SE). The difference in the value of the mean of all amplitudes and frequency of fast and slow mIPSCs did not reach significance when the kindled group was compared with controls. The mIPSC kinetics were not different after kindling, from which we conclude that the receptor properties had not changed. Nonstationary noise analysis of the largest mIPSCs suggested that the single-channel conductance and the number of postsynaptic receptors was similar in the kindled and control groups. Our results suggest a 40-50% reduction in a small fraction of (peri-) somatic synapses with large or complex postsynaptic structure after kindling. This functionally relevant reduction may be related to previously observed loss of a specific class of interneurons. Our findings are consistent with a reduction in inhibitory drive in the CA1 area. Such a reduction could underlie the enhanced seizure susceptibility after kindling epileptogenesis.

Wada difference a day makes: interpretive cautions regarding same-day injections.

OBJECTIVE: To determine whether memory scores after second intracarotid amobarbital procedure (IAP) injections are affected by the time between the first and second injections. METHODS: Sixty-two patients received their second IAP injection on the day after the first injection. Forty-three other patients received the second injection on the same day as the first injection. Both groups underwent similar IAP protocols and memory assessments, except for the timing of the second injection. RESULTS: The second IAP memory scores in the two-day group were significantly higher (p < 0.05) than those in the one-day group. Timing of second injection was a significant correlate of second memory scores, but amobarbital dosage, first IAP memory score, and pre-IAP measures of memory and intelligence were not significant correlates. CONCLUSION: One-day and two-day IAP protocols do not result in similar memory scores after the second injection. Nineteen percent of a subset of patients in the one-day protocol were misclassified, in terms of IAP memory ratings, because of the deleterious effect of having both injections on the same day. It is recommended that correction scores be considered, for some patients who receive two IAP injections on one day, to approximate what the second IAP memory score would have been had the second injection occurred on a second day.