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Biomedical subjects

Brian Martis

Publications and source records attributed to Brian Martis.

16 recordsLinked to original sources

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.

Adolescent↗

Medial frontal cortex activity and loss-related responses to errors.

Making an error elicits activity from brain regions that monitor performance, especially the medial frontal cortex (MFC). However, uncertainty exists about whether the posterior or anterior/rostral MFC processes errors and to what degree affective responses to errors are mediated in the MFC, specifically the rostral anterior cingulate cortex (rACC). To test the hypothesis that rACC mediates a type of affective response, we conceptualized affect in response to an error as a reaction to loss and amplified this response with a monetary penalty. While subjects performed a cognitive interference task during functional magnetic resonance imaging, hemodynamic activity in the rACC was significantly greater when subjects lost money as a result of an error compared with errors that did not lead to monetary loss. A significant interaction between the incentive conditions and error events demonstrated that the effect was not merely attributable to working harder to win (or not lose) money, although an effect of motivation was noted in the mid-MFC. Activation foci also occurred in similar regions of the posterior MFC for error and interference processing, which were not modulated by the incentive conditions. However, at the level of the individual subject, substantial functional variability occurred along the MFC during error processing, including foci in the rostral/anterior extent of the MFC not appearing in the group analysis. The findings support the hypothesis that the rostral extent of the MFC (rACC) processes loss-related responses to errors, and individual differences may account for some of the reported variation of error-related foci in the MFC.

Adult↗

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

Adult↗

Neuroimaging studies of emotional responses in PTSD.

Neuroimaging research offers a powerful and noninvasive means to understand healthy as well as dysregulated emotional processing in healthy subjects and PTSD patients. Functional neuroimaging findings suggest specific roles for subregions of the medial prefrontal (mPFC), orbito frontal (OFC), anterior cingulate (ACC), and insular cortices as well as the sublenticular extended amygdala (SLEA) and hippocampus in various components of emotional processing. Some of the same regions appear to be associated with emotional response to trauma, and with symptom formation in PTSD. Neuroimaging findings of emotional processing in healthy subjects and PTSD patients are discussed, addressing the specific roles of cortical regions like mPFC, ACC, and insula, and their potential contribution to PTSD pathophysiology. Processes of cognitive-emotional interactions and social emotions are discussed in an attempt to synthesize the prefrontal findings in healthy subjects and PTSD patients. Further links between functional neuroanatomy of emotional responses and neuroendocrine stress regulation are proposed.

Brain↗

Brain correlates of negative and positive visuospatial priming in adults.

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.

Adolescent↗

Brain correlates of negative visuospatial priming in healthy children.

Inhibitory mechanisms that begin to develop in childhood are essential for efficient and goal-directed behaviors. These inhibitory mechanisms may go awry in several childhood-onset neuropsychiatric disorders, such as Tourette syndrome, obsessive-compulsive disorder and attention deficit hyperactivity disorder. Negative visuospatial priming is a well-established behavioral probe of inhibition that has been used to demonstrate deficits in children with neuropsychiatric disorders of inhibition, but the brain correlates of negative visuospatial priming have not previously been well delineated. In the present study, we use a visuospatial priming paradigm and event-related functional magnetic resonance imaging (fMRI) to probe inhibitory brain mechanisms in healthy children. When subjects performed the control (i.e. neutral) motor task, a network of cortical and subcortical sensorimotor regions was activated. In contrast, during performance of the negative priming (i.e. inhibitory) task, several regions of the prefrontal cortex were selectively engaged. These results support the notion that the prefrontal cortex is involved in inhibitory processing in healthy children and demonstrate that negative visuospatial priming shares brain correlates with other inhibitory tasks. In conjunction with fMRI, the visuospatial priming task described in the current study may be useful for studying the pathophysiology of childhood-onset neuropsychiatric disorders characterized by deficient inhibitory processing.

Adolescent↗

Deep brain stimulation for refractory obsessive-compulsive disorder.

BACKGROUND: Neurosurgery (anterior capsulotomy) has been beneficial to many patients with debilitating, refractory obsessive-compulsive disorder (OCD), but the irreversibility of the procedure is an important limitation to its use. Nondestructive, electrical stimulation (deep brain stimulation; DBS) has proven an effective alternative to ablative surgery for neurological indications, suggesting potential utility in place of capsulotomy for OCD. METHODS: The effects of DBS for OCD were examined in four patients in a short-term, blinded, on-off design and long-term, open follow-up. The patients had incapacitating illness, refractory to standard treatments. Hardware developed for movement disorder treatment was surgically implanted, with leads placed bilaterally in the anterior limbs of their internal capsules. Patients received stimulation in a randomized "on-off" sequence of four 3-week blocks. Ongoing, open stimulation was continued in consenting patients after the controlled trial. RESULTS: Patients tolerated DBS well. Dramatic benefits to mood, anxiety, and OCD symptoms were seen in one patient during blinded study and open, long-term follow-up. A second patient showed moderate benefit during open follow-up. CONCLUSIONS: It appears that DBS has potential value for treating refractory psychiatric disorders, but additional development work is needed before the procedure is utilized outside of carefully controlled research protocols.

Adult↗

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

BACKGROUND: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). OBJECTIVES: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions. RESULTS: The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. CONCLUSIONS: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.

Amygdala↗

Amygdala responses to human faces in obsessive-compulsive disorder.

BACKGROUND: To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI). METHODS: Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross. RESULTS: Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed. CONCLUSIONS: Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders.

Adult↗

A magnetic resonance imaging study of cortical thickness in animal phobia.

BACKGROUND: Despite the high prevalence of specific phobia (SP), its neural substrates remain undetermined. Although an initial series of functional neuroimaging studies have implicated paralimbic and sensory cortical regions in the pathophysiology of SP, to date contemporary morphometric neuroimaging methods have not been applied to test specific hypotheses regarding structural abnormalities. METHODS: Morphometric magnetic resonance imaging (MRI) methods were used to measure regional cortical thickness in 10 subjects with SP (animal type) and 20 healthy comparison (HC) subjects. RESULTS: Consistent with a priori hypotheses, between-group differences in cortical thickness were found within paralimbic and sensory cortical regions. Specifically, in comparison with the HC group, the SP group exhibited increased cortical thickness in bilateral insular, bilateral pregenual anterior cingulate, and bilateral posterior cingulate cortex as well as left visual cortical regions. CONCLUSIONS: Taken together, these structural findings parallel results from initial functional imaging studies that implicate paralimbic and sensory cortical regions in the mediating anatomy of SP symptoms. Further research will be necessary to replicate these findings and to determine their specificity as well as their pathophysiologic significance.

Adult↗

Functional magnetic resonance imaging evidence for a lack of striatal dysfunction during implicit sequence learning in individuals with animal phobia.

OBJECTIVE: This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia, in a follow-up to analogous studies of obsessive-compulsive disorder (OCD). METHOD: Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging. RESULTS: A main effect of condition (implicit sequence learning versus random sequence) was observed across diagnostic groups in the right striatum, as well as in other regions. In the striatum, the a priori region of interest, there were no significant effects of diagnosis or the interaction of diagnosis and condition. CONCLUSIONS: Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning. This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD, in which deficient striatal recruitment has been reproducibly found with this paradigm. This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation.

Adult↗

Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia.

BACKGROUND: Contemporary neurobiological models suggest that the amygdala plays an important role in the pathophysiology of anxiety disorders. However, it is not clear to what extent this concept applies across anxiety disorders. Several studies have examined brain function in specific phobias but did not demonstrate amygdala responses or use specific probes of the amygdala. METHODS: Ten subjects with specific small animal phobia and 10 matched control subjects were studied with functional magnetic resonance imaging. Subjects viewed emotionally expressive and neutral faces, and amygdala blood oxygenation level dependent responses from each group were compared. RESULTS: There was a significant response to the fearful versus neutral faces in the amygdala across both groups but no diagnosis x condition interaction. Post hoc analysis of the whole brain revealed a significantly greater response to the fearful versus neutral faces in the right insular cortex of the specific phobia group than in the control group. CONCLUSIONS: Amygdala hyperresponsivity to emotional faces was not observed in subjects with small animal specific phobia, in contrast to findings in other anxiety disorders (e.g., posttraumatic stress disorder). This suggests a restricted role for the amygdala in specific phobia. The insular hyperresponsivity to fearful versus neutral faces in the subjects with specific phobias warrants further study.

Adult↗

Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex.

Recent studies of amygdala function have focused on examining responses to emotionally valenced versus neutral stimuli. However, electrophysiologic and neuroimaging studies also suggest that novel neutral faces activate the amygdala, though few investigations have examined the effects of novelty and its relation to changes in stimulus condition. To further investigate how the human amygdala and related structures react to novel neutral faces and to stimulus condition changes, we evaluated human brain responses to blocks containing multiple novel and single repeated face stimuli, presented in two different orders, using functional magnetic resonance imaging (fMRI). Significantly increased signal was present in the amygdala, substantia innominata (SI), and inferior temporal cortex (ITC) to the contrast of multiple novel versus single faces. However, these regions differed in their responses based on whether a stimulus condition was presented 1st or 2nd, with the amygdala and SI having significantly different response profiles than the ITC. Specifically, greater responses to stimuli presented 2nd (i.e., after a condition change) were found in the amygdala and SI, but not in the ITC. Furthermore, the response difference to the Multiple versus Single contrast was greatest in the amygdala and SI, when single faces were presented 1st, and multiple faces presented 2nd, but this pattern was the reverse in the ITC. We speculate that the signal changes to neutral faces in the amygdala and SI with respect to condition (multiple or single faces) and stimulus order may relate to the involvement of these structures in novelty detection and the orienting response.

Adult↗

Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is being investigated as a potential treatment for depression. Few studies have addressed the neurocognitive effects of a course of rTMS in severely depressed patients. We evaluated neurocognitive effects of a 1-4 week course (mean 3 weeks) of rTMS using an aggressive set of parameters, in 15 severely depressed subjects. METHODS: A battery of neurocognitive tests relevant to attention, working memory-executive function, objective memory and motor speed were administered to 15 subjects with treatment-resistant major depression (unipolar and bipolar), before and after a course of rTMS. Mean z scores were computed for each of 4 cognitive domains and analyzed using repeated measures multivariate analysis of covariance. Significant interactions were further clarified using univariate analysis of variance. RESULTS: There was no worsening of performance on any of the cognitive domains over the baseline-post rTMS period. On the contrary, evidence of modest but statistically significant improvement in performance was noted in working memory-executive function, objective memory and fine motor speed domains over the rTMS treatment period. CONCLUSIONS: There was no evidence of adverse neurocognitive changes over the baseline-post rTMS period in 15 treatment-resistant depressed subjects undergoing a 3 week (mean) trial of rTMS. Significant improvements in several domains observed over the rTMS treatment period could not be explained by improved mood. Practice effects as well as other factors potentially contributing to these findings are discussed. SIGNIFICANCE: rTMS is being increasingly studied as a neurophysiological probe as well as for its potential antidepressive effects. The effects on neuronal function raise appropriate questions of safety of its use at varying stimulus parameters and durations. This study contributes to the small body of evidence of the cognitive effects of rTMS in severely depressed patients.

Adult↗

Enhanced amygdala responses to emotional versus neutral schematic facial expressions.

Human facial emotional expressions are complex. This may confound studies examining brain responses to these stimuli in control and clinical populations. However, several lines of evidence suggest that a few elementary facial features convey the gist of emotional expressions. Using fMRI, we assessed brain responses to line drawings of emotionally valenced (i.e. angry and happy) and neutral faces in healthy human subjects. Significantly increased fMRI signal was found in the amygdala, hippocampus and prefrontal cortex in response to emotional vs neutral schematic faces. Although direct comparisons of schematic and human faces will be needed, these initial results suggest that schematic faces may be useful for studying brain responses to emotional stimuli because of their simplicity relative to human faces.

Adult↗

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial.

BACKGROUND: Many severely depressed patients do not benefit from or tolerate existing treatments. Repetitive transcranial magnetic stimulation (rTMS) has been reported to benefit depression. We compared rTMS to electroconvulsive therapy (ECT) in severely ill, depressed patients. METHODS: Twenty-five patients with a major depression (unipolar or bipolar) deemed clinically appropriate for ECT were randomly assigned to rTMS (10-20 treatments, 10 Hz, 110% motor threshold applied to the left dorsolateral prefrontal cortex for a total of 10,000-20,000 stimulations) or a course of bitemporal ECT (4-12 treatments). The primary outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue medications were utilized. RESULTS: Mean percent improvement on the baseline HDRS score did not significantly differ between the two treatments (i.e., 55% for the rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50% reduction from baseline and a final score < or = 8 on the HDRS, there was also no significant difference between the two groups. We did not observe any differences between groups on the secondary measures. CONCLUSIONS: A 2-4 week randomized, prospective trial comparing rTMS to ECT produced comparable therapeutic effects in severely depressed patients.

Adolescent↗