Identification of the Neural Circuit Underlying Episodic Memory Deficit in Amnestic Mild Cognitive Impairment via Machine Learning on Gray Matter Volume

Based on whole-brain gray matter volume (GMV), we used relevance vector regression to predict the Rey’s Auditory Verbal Learning Test Delayed Recall (AVLT-DR) scores of individual amnestic mild cognitive impairment (aMCI) patient. The whole-brain GMV pattern could significantly predict the AVLT-DR scores (r = 0.54, p < 0.001). The most important GMV features mainly involved default-mode (e.g., posterior cingulate gyrus, angular gyrus, and middle temporal gyrus) and limbic systems (e.g., hippocampus and parahippocampal gyrus). Therefore, our results provide evidence supporting the idea that the episodic memory deficit in aMCI patients is associated with disruption of the default-mode and limbic systems.

Longitudinal Changes in Functional Connectivity in Antipsychotic-treated and Antipsychotic-naive Patients with First Episode Psychosis

BackgroundAltered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.MethodsSixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.ResultsAt baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.Conclusions and RelevanceAntipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

Hyperexcitability of the Nucleus Accumbens Is Involved in Noise-Induced Hyperacusis

Reduced tolerance to sound stimuli (hyperacusis) is commonly seen in tinnitus patients. Dysfunction of limbic systems, such as the nucleus accumbens (NAc), may be involved in emotional reactions to the sound stimuli in tinnitus patients. To study the functional changes in the NAc in hyperacusis, we have examined the neural activity changes of the NAc using c-Fos staining in an animal model of hyperacusis. The c-Fos staining was also examined in the medial geniculate nucleus (MGN), a central auditory pathway which has neural projections to the NAc. Postnatal rats (14 days) were exposed to loud noise (115 dB SPL, 4 hours for two consecutive days) to induce hyperacusis ( n = 4 ). Rats without noise exposure were used as the controls ( n = 4 ). After P35, rats in both groups were put in a behavioral training for sound detection. After they were trained to detect sound stimuli, their reaction time to noise bursts centered at 2 kHz (40-110 dB SPL) was measured. Rats in the noise group showed a significantly shorter reaction time than those in the control group to the noise bursts at high intensities, suggesting the noise exposure induced hyperacusis behavior. The c-Fos expressions in the NAc and the MGNs of the noise group were significantly higher than those of the control group. Our results suggested that early-age noise exposure caused hyperactivity in the NAc and the MGNs which may induce the loudness increase in these rats.

Predictions of Current and Future Episodic Memory Using Grey Matter Volume and Functional Connectome: A Longitudinal Study in Amnestic Mild Cognitive Impairment Patients

Background: Amnestic mild cognitive impairment (aMCI) patients are considered an at-risk group for progression to Alzheimer’s dementia and accurate prediction of aMCI progression could facilitate the optimal decision-making for both clinicians and patients. Based on the baseline whole-brain grey-matter volume (GMV) and resting-state functional connectivity (FC), we used relevance vector regression to predict the baseline and longitudinal Rey’s Auditory Verbal Learning Test Delayed Recall (AVLT-DR) scores of individual aMCI patients.Methods: Fifty aMCI patients completed baseline and 3-year follow-up visits. All patients underwent comprehensive neuropsychological assessments and multimodal brain MRI scans.Results: We found that the GMV pattern predicted the baseline AVLT-DR score, while the pattern of FC predicted the longitudinal AVLT-DR score. In particular, GMV predicted the baseline AVLT-DR score with an accuracy of r = 0.54 (P < 0.001); the regions that contributed the most were within the default mode (e.g., the posterior cingulate gyrus, angular gyrus and middle temporal gyrus) and limbic systems (e.g., the hippocampus and parahippocampal gyrus). The FC predicted the longitudinal AVLT-DR score with an accuracy of r = 0.50 (P < 0.001), and the connections that contributed the most were the within- and between-system connectivity of the default mode and limbic systems. As a complement, we demonstrated that the GMV and FC patterns could also effectively predict the baseline and longitudinal composite episodic memory scores (calculated by averaging three well-known episodic memory test scores).Conclusions: Our results demonstrated the multimodal brain features in the individualized prediction of aMCI patients’ current and future episodic memory performance. These “neural fingerprints” have the potential to be biomarkers for aMCI patients and can help medical professionals optimize individual patient management and longitudinal evaluation.

Predictions of Current and Future Episodic Memory Using Gay Matter Volume and Functional Connectome: A Longitudinal Study in Amnestic Mild Cognitive Impairment Patients

Background: Amnestic mild cognitive impairment (aMCI) patients are considered an at-risk group for progression to Alzheimer’s dementia and accurate prediction of aMCI progression could facilitate the optimal decision-making for both clinicians and patients. Based on the baseline whole-brain grey-matter volume (GMV) and resting-state functional connectivity (FC), we used relevance vector regression to predict the baseline and longitudinal Rey’s Auditory Verbal Learning Test Delayed Recall (AVLT-DR) scores of individual aMCI patients.Methods: Fifty aMCI patients completed baseline and 3-year follow-up visits. All patients underwent comprehensive neuropsychological assessments and multimodal brain MRI scans.Results: We found that the GMV pattern predicted the baseline AVLT-DR score, while the pattern of FC predicted the longitudinal AVLT-DR score. In particular, GMV predicted the baseline AVLT-DR score with an accuracy of r = 0.54 (P < 0.001); the regions that contributed the most were within the default mode (e.g., the posterior cingulate gyrus, angular gyrus and middle temporal gyrus) and limbic systems (e.g., the hippocampus and parahippocampal gyrus). The FC predicted the longitudinal AVLT-DR score with an accuracy of r = 0.50 (P < 0.001), and the connections that contributed the most were the within- and between-system connectivity of the default mode and limbic systems. As a complement, we demonstrated that the GMV and FC patterns could also effectively predict the baseline and longitudinal composite episodic memory scores (calculated by averaging three well-known episodic memory test scores).Conclusions: Our results demonstrated the multimodal brain features in the individualized prediction of aMCI patients’ current and future episodic memory performance. These “neural fingerprints” have the potential to be biomarkers for aMCI patients and can help medical professionals optimize individual patient management and longitudinal evaluation.

Substance use disorders and the mechanisms of drug addiction

The understanding of drug addiction has gained much from a neuroscientific approach, reflected by changing approaches in diagnosis. The two main psychological accounts of addiction to substances, ranging from alcohol and nicotine to opioids and stimulant drugs, are opponent motivational processing, emphasizing the importance of withdrawal symptoms, and aberrant learning from positive reinforcement. The neural and neurochemical systems implicated have been identified on the basis of animal studies, using especially the self-administration paradigm, and human investigations employing a range of brain imaging modalities. These neural substrates include dopamine-dependent functions of the ventral and dorsal striatum, as well as regulatory influences of fronto-limbic systems. The chapter considers the critical issue of cause and effect, and whether brain changes reflect neurotoxic effects of abuse or whether there are predisposing neurobehavioural factors. It also outlines the current situation and future prospects for treatment by medication, possibly in association with psychological approaches.

The Pathophysiology of Tinnitus: Involvement of the Somatosensory, Brain, and Limbic Systems

This study reviewed the pathophysiology of tinnitus. Tinnitus is a symptom that a subject perceives sound regardless of external stimuli. Tinnitus sufferers have reported varying sound types, loudness, and duration of tinnitus. Also, the pathophysiology of tinnitus is also reported to be varied. We searched a web database and found 2,545 articles related to tinnitus. The selection criteria for articles to be reviewed was the year of publication, research category, participant characteristic, publication type, and area of study. Thirty-three studies on the pathophysiology of tinnitus were finally selected and reviewed. Tinnitus pathophysiology was reviewed in relation to the somatosensory, brain, and limbic systems. Fourteen sub-regions were identified to be associated with tinnitus. The data on each sub-region was also reviewed, including its primary role and the tinnitus trigger mechanism. The results of this study can be used as baseline data for studies attempting to understand the mechanism of tinnitus and develop intervention methods.

Emotional Interference in Early Adolescence: Positive Reinforcement Modulates the Behavioral and Neural Effects of Negative Emotional Distracters

Limited research has examined functioning within fronto-limbic systems subserving the resistance to emotional interference in adolescence despite evidence indicating that alterations in these systems are implicated in the developmental trajectories of affective disorders. This study examined the functioning of fronto-limbic systems subserving emotional interference in early adolescence and whether positive reinforcement could modulate these systems to promote resistance to emotional distraction. Fifty healthy early adolescents (10–13 years old) completed an emotional delayed working memory (WM) paradigm in which no distractors (fixation crosshair) and emotional distracters (neutral and negative images) were presented with and without positive reinforcement for correct responses. WM accuracy decreased with negative distracters relative to neutral distracters and no distracters, and activation increased in amygdala and prefrontal cortical (PFC) regions (ventrolateral, dorsomedial, ventromedial, and subgenual anterior cingulate) with negative distracters compared with those with no distracters. Reinforcement improved performance and reduced activation in the amygdala, dorsomedial PFC, and ventrolateral PFC. Decreases in amygdala activation to negative distracters due to reinforcement mediated observed decreases in reaction times. These findings demonstrate that healthy adolescents recruit similar fronto-limbic systems subserving emotional interference as adults and that positive reinforcement can modulate fronto-limbic systems to promote resistance to emotional distraction.

Feasibility of intravenous ketamine infusion for refractory headache

Background: Ketamine intravenous infusion has been used safely to several chronic pains and it is a good option to refractory chronic headaches. It is a noncompetitive NMDA receptor antagonist that blocks glutamate, responsible for the dissociation between thalamus-neocortical and limbic systems, leading to changes in patients’ pain perception. Due to this theorical mechanism and results in reducing cortical spreading depression, Ketamine has been proposed as a treatment for migraine. Methods: We conducted a retrospective medical chart review study at Hospital Israelita Albert Einstein including three patients. All of them were diagnosed previosly with refractory chronic headache. Results: Of participants included (n = 3), two were woman. The median duration of the disease was 21 years and 12 previous treatment’s failures. All the patients were currently in use of more than 4 preventive drugs. Treatment-emergent response was seen in all patients, requiring 1, 3 and 4 sessions to complete plain remission. They presented good tolerability to the treatment. One patient complained of tinnitus and mild dizziness at the end of the last session, which lasted less than 30 minutes. Conclusion: Ketamine is well tolerated and an effective treatment for patients with refractory chronic headache.