Impulsivity Relates to Relative Preservation of Mesolimbic Connectivity in Patients with Parkinson Disease.

IntroductionThe relationship between Parkinson Disease (PD) pathology, dopamine replacement therapy (DRT), and impulse control disorder (ICD) development is still incompletely understood. Given the sensorimotor-lateral substantia nigra (SN) selective degeneration associated with PD, we posit that a relative sparing of the limbic-medial SN in the context of DRT drives impulsive, reward-seeking behavior in PD patients with recent history of severe impulsivity.MethodsImpulsive and control participants were selected from a consecutive list of PD patients receiving pre-operative deep brain stimulation (DBS) planning scans including 3T structural MRI and 64 direction diffusion tensor imaging (DTI). Using previously identified substantia nigra (SN) subsegment network connectivity profiles to develop classification targets, split-hemisphere target-based SN segmentation with probabilistic tractography was performed. The relative subsegment volumes and strength of connectivity between the SN and the limbic, associative, and motor network targets were compared.ResultsOur results show that there is greater probability of connectivity between the SN and limbic network targets relative to motor and associative network targets in PD patients with recent history of severe impulsivity as compared to PD patients without impulsivity (P = 0.0075). We did not observe relative volumetric subsegment differences across groups.ConclusionFirstly, our results suggest that fine-grained, atlas-derived classification targets may be used in PD to parcellate and classify functionally distinct subsegments of the SN, with the apparent preservation of previously reported topographical limbic-medial SN, associative-ventral SN, and sensorimotor-lateral SN orientation. We suggest that relative, as opposed to absolute, degeneration amongst SN-associated dopaminergic networks relates to the impulsivity phenotype in PD

Acute Effects and the Dreamy State Evoked by Deep Brain Electrical Stimulation of the Amygdala: Associations of the Amygdala in Human Dreaming, Consciousness, Emotions, and Creativity.

Accurate localization of complex human experiences such as emotions, dreaming, creativity, and consciousness to specific cerebral structures or neural networks has remained elusive despite technological advances. We report the use of acute deep brain stimulation (DBS) to evoke behavioral and emotional effects by applying electrical stimulation (ES) at various voltage strengths to the basolateral and central subnuclei of the amygdala in addition to the head of hippocampus (HC) for two subjects with medically refractory post-traumatic stress disorder (PTSD). Our results suggest that the amygdala could be a node in a neural network responsible for the generation of complex vivid mental imagery and integrated sensory experiences similar to John Hughlings Jackson's "dreamy state" and "double consciousness," which have been classically associated with temporal lobe epilepsy during uncinate seizures. That we were able to elicit similar vivid, dynamic, complex, bizarre, and original mental imagery with ES in non-epileptic subjects suggests that Jackson's seizure related "dreamy state" and "double consciousness" may arise from heightened innate brain mechanisms with the amygdala acting as a node in the neural network responsible for physiologic dreaming and creative functions. Furthermore, our subjects experienced different emotions with different stimulation strengths at various electrode contacts. Our results suggest that higher voltage stimulation of the amygdala and HC at 4-5 V leads to predominantly negative responses and 2-4 V stimulation showed inversely coupled positive and negative responses of the amygdala in either hemisphere which may imply hemispheric dominance of emotional valences without relation to handedness. Due to the unique and complex responses dependent on location and strength of stimulation, we advise that all patients receiving DBS of the amygdala undergo acute stimulation mapping in a monitored setting before selecting therapeutic parameters for chronic stimulation

White matter tracts characteristics in habitual decision-making circuit underlie ritual behaviors in anorexia nervosa

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships

Sequential multi-locus transcranial magnetic stimulation for treatment of obsessive-compulsive disorder with comorbid major depression: A case series

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are highly comorbid [1], with depressive symptoms amplifying the chronicity and severity of OCD symptoms. Comorbid illness decreases quality of life and daily functioning [2] and is associated with greater suicidality and more frequent inpatient hospitalizations [3]. Furthermore, comorbid OCD/depression is associated with poorer response to OCD-focused psychological and pharmacological treatments [4]. Epidemiologic studies have shown that OCD symptoms generally precedes the occurrence of depression, suggesting a causal interacting model in which OCD predisposes to development of depressive symptoms [5]. In line with that causal model, Tadayonnejad et al. showed aberrant effective (directional) connectivity between OCD and MDD circuits may be a potential network mechanism of depressive symptom genesis or worsening in OCD-MDD [6]. The challenging nature of this comorbidity necessitates the development of novel, more effective treatments

Sequential multi-locus transcranial magnetic stimulation for treatment of obsessive-compulsive disorder with comorbid major depression: A case series

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are highly comorbid [1], with depressive symptoms amplifying the chronicity and severity of OCD symptoms. Comorbid illness decreases quality of life and daily functioning [2] and is associated with greater suicidality and more frequent inpatient hospitalizations [3]. Furthermore, comorbid OCD/depression is associated with poorer response to OCD-focused psychological and pharmacological treatments [4]. Epidemiologic studies have shown that OCD symptoms generally precedes the occurrence of depression, suggesting a causal interacting model in which OCD predisposes to development of depressive symptoms [5]. In line with that causal model, Tadayonnejad et al. showed aberrant effective (directional) connectivity between OCD and MDD circuits may be a potential network mechanism of depressive symptom genesis or worsening in OCD-MDD [6]. The challenging nature of this comorbidity necessitates the development of novel, more effective treatments

The rationale for deep brain stimulation in Alzheimer\u27s disease

Alzheimer\u27s disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer\u27s disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer\u27s disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer\u27s disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials