Trevor Hurwitz

Human Medial Forebrain Bundle (MFB) and Anterior Thalamic Radiation (ATR): Imaging of Two Major Subcortical Pathways and the Dynamic Balance of Opposite Affects in Understanding Depression

The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

Olfactory deficits in neuroleptic naive patients with schizophrenia

Because previous studies have shown deficits in olfactory identification for male patients with schizophrenia, either withdrawn from or receiving neuroleptic medication, the purpose of the current study was to determine if such deficits occurred in male patients who had never received neuroleptics. A sample of male (n = 30) and female (n = 10) patients as well as age appropriate controls (males, n = 28, females, n = 30) was assessed in terms of olfactory acuity and identification ability. No differences were found in olfactory acuity, but an olfactory identification deficit was present in 31% of the male patients with schizophrenia. As the olfactory pathways project through the limbic system and to the orbitofrontal cortex, odour identification may be a measure of the functional integrity of these structures. Therefore, these results suggest that for a sub-sample of male patients, the functional integrity of these structures is compromised.

Medial forebrain bundle stimulation as a pathophysiological mechanism for hypomania in subthalamic nucleus deep brain stimulation for Parkinson's disease.

OBJECTIVEHypomania accounts for approximately 4% to 13% of psychotropic adverse events during subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinsons disease. Diffusion of current into the inferior and medial “limbic” STN is often reported to be the cause. We suggest a different explanation, in which the coactivation of the medial forebrain bundle (MFB), outside the STN, leads to hypomania during STN DBS. METHODSSix patients with advanced Parkinsons disease (age, 54 ± 11 years) underwent bilateral STN DBS surgery. Preoperative diffusion tensor imaging scans for fiber tracking of the MFB were conducted on a 3T magnetic resonance imaging scanner. After implantation, the electrode positions were determined with computed tomography and integrated in a diffusion tensor imaging software environment. RESULTSThe medial STN was shown to send tributaries to the MFB using it as a pathway to connect to the reward circuitry. One patient, who had a transient, stimulation-induced acute hypomanic episode, showed a direct contact between 1 active electrode contact and these putative limbic STN tributaries to the MFB unilaterally on the left. In 5 asymptomatic patients, the active contacts were between 2.9 and 7.5 mm distant from the MFB or its limbic STN tributaries. CONCLUSIONWe hypothesize that STN DBS-induced reversible acute hypomania might be elicited by inadvertent and unilateral coactivation of putative limbic STN tributaries to the MFB. These findings may provide insight into the neural pathways of hypomania and may facilitate future investigations of the pathophysiology of mood disorders.

REGIONAL CEREBRAL GLUCOSE METABOLISM IN MAJOR DEPRESSIVE DISORDER

Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. Significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.

Olfactory deficits in schizophrenia

Olfactory discrimination was measured in patients with schizophrenia who were on neuroleptic medication and was compared with other psychiatric patients receiving neuroleptics and normal controls. The performance of the patients with schizophrenia was significantly lower than the psychiatric and normal controls. The latter two groups performed at equivalent levels. The findings are discussed with respect to olfactory deficits found in patients with cerebral lesions and with abnormalities of specific neurotransmitter systems.

Tractographic Analysis of Historical Lesion Surgery for Depression

Various surgical brain ablation procedures for the treatment of refractory depression were developed in the twentieth century. Most notably, key target sites were (i) the anterior cingulum, (ii) the anterior limb of the internal capsule, and (iii) the subcaudate white matter, which were regarded as effective targets. Long-term symptom remissions were better following lesions of the anterior internal capsule and subcaudate white matter than of the cingulum. It is possible that the observed clinical improvements of these various surgical procedures may reflect shared influences on presently unspecified brain affect-regulating networks. Such possibilities can now be analyzed using modern brain connectivity procedures such as diffusion tensor imaging (DTI) tractography. We determined whether the shared connectivities of the above lesion sites in healthy volunteers might explain the therapeutic effects of the various surgical approaches. Accordingly, modestly sized historical lesions, especially of the anatomical overlap areas, were ‘implanted’ in brain-MRI scans of 53 healthy subjects. These were entered as seed regions for probabilistic DTI connectivity reconstructions. We analyzed for the shared connectivities of bilateral anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and stereotactic limbic leucotomy (a combination of the last two lesion sites). Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic ‘reward’ system in the midbrain ventral tegmental area. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB.

Clinical utility of three measures of frontal lobe dysfunction in neuropsychiatric samples

The utility of the Word Fluency Test, Wisconsin Card-Sorting Test, and a shorter form of the Categories Test as screening instruments for detecting frontal lobe dysfunction in a neuropsychiatric setting was examined. On the basis of clinical and neurological examination, patients were assigned to one of three groups: frontal lobe injured, brain impaired excluding the frontal areas, and psychiatric with no evidence of brain dysfunctioning. It was possible to assign correctly 66.3% of the patients to their respective groups. The Word Fluency Test made the strongest contribution to the prediction of the presence of frontal lobe pathology, even when the effects of age and postmorbid intellectual functioning were controlled. The results were consistent with the interpretation of lowered verbal fluency and deficits in the capacity to suppress habitual behaviour as a major feature of frontal lobe dysfunctioning.

Somatization and conversion disorder.

Somatization is the psychological mechanism whereby psychological distress is expressed in the form of physical symptoms. The psychological distress in somatization is most commonly caused by a mood disorder that threatens mental stability. Conversion disorder occurs when the somatic presentation involves any aspect of the central nervous system over which voluntary control is exercised. Conversion reactions represent fixed ideas about neurologic malfunction that are consciously enacted, resulting in psychogenic neurologic deficits. Treatment is complex and lengthy; it includes recovery of neurologic function aided by narcoanalysis and identification and treatment of the primary psychiatric disorder, usually a mood disorder.

Olfactory deficits in schizophrenia are not a function of task complexity.

The purpose of the current study was to determine if olfactory identification deficits in patients with schizophrenia were related to task complexity. Given that we had previously reported that male patients with schizophrenia are the most impaired on olfactory identification tests (the University of Pennsylvania Smell Identification Test, UPSIT), we wished to determine whether a similar deficit would exist for this group on a task of similar format and complexity, the Colour Identification Test (CIT). Sixty-five neuroleptically medicated patients with a DSM-III-R diagnosis of schizophrenia and 30 normal control subjects participated. The dependent measures were scores on the UPSIT and CIT. Overall, patients with schizophrenia had significantly lower USPIT scores than did the normal control subjects whereas no mean difference was observed for colour identification. Male patients with schizophrenia had olfactory identification deficits but performed comparably to all other groups on the CIT. Furthermore, microsmic patients with schizophrenia had CIT scores that did not differ from normal control subjects. Finally, CIT and UPSIT scores were not significantly correlated for the study sample as a whole. The results of this study suggest that the olfactory identification deficits observed in patients with schizophrenia likely reflect abnormalities of brain areas involved in olfactory pathways and are not a function of task complexity.

Regional metabolism in microsmic patients with schizophrenia.

The cerebral glucose metabolism of eight patients with schizophrenia and an olfactory agnosia was compared with that of eight normosmic patients with schizophrenia and eight normal controls. Since all patients were scanned while on their current medication regimen, the duration and dosage of the medication of the two patient groups were compared. Similarly, duration and dosage were correlated with absolute regional metabolic rates. No significant effects were found in these analyses. The patients with schizophrenia had significantly lower rates of frontal metabolism than the normal controls. However, the patients with schizophrenia and an olfactory agnosia had a lower right basal ganglia and thalamic metabolism than the normosmic patients with schizophrenia.