Supported by the 2014-2015 Neurosurgery Research and Education Foundation (NREF) award and a 2014 Grant-In-Aid Award from Louisiana State University Shreveport School of Medicine (J.A.W.). We thank S. Harold and C.M. Keller for their invaluable technical assistance and teaching.

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The authors have no competing financial interests with regards to this methodology.

뇌 심부 자극술의 정확한 메커니즘이 완전히 특징되지 않지만, 모터와 정신 질환 모두 DBS의 효과는 전기 치료와 시간 6,22-26을 통해 다양한 피질과 대뇌 피질의 뇌 영역의 기능 사이의 역동적 인 상호 작용이 발생할 수 있습니다. 설치류에 필로폰 전달의 비 조건부 방법은 27,28 잘 설명되어 있지만,이 방법은 약물의 약물 동태 학 및 신경 화학적 효과 27 ~ 29의 개별 연구에 가장 적합합니다. 조작 적 IV 약물 자기 관리는 약물에 대한 동기 부여의 요소를 통합하여, 이상적으로 DBS와 같은 전기 치료는 시간이 지남에 병적 인 행동과 상호 작용하는 방법의 연구에 적합합니다. 우리가 설명하는 절차는 다른 환경에서 우발 메스 암페타민 사용에 대한 하나의 환경에서 DBS의 효과를 검사합니다. 우리의 IV의 필로폰 자기 administ의 세 가지 주요 단계가 있습니다배급 패러다임 : 긴 액세스 세션 동안 신속한 수집 및 약물 섭취의 상승 1) 유도, 이후 짧은 액세스 세션 동안 약물 섭취의 안정, 높은 비율의 2) 유지 관리 및 약물 복용의 전면 적재 패턴의 3) 개발. 비용 효율적이고 이상적 정신 자극제를 사용하여 설치류 헤드 캡의 잠재적으로 제한 수명 주어진 DBS의 효과를 테스트하기에 적합한 양이다 실험 당 12 래트 -이 패러다임은 10 2-3주 시간 내에 달성 될 수있다. 긴 19,30,31 액세스의 기간을 포함 다른 패러다임 등이 절차는 상당히 물질 사용 장애의 일부 측면을 시뮬레이션; 그것은 레크리에이션 사용 19,30 대 인간의 의존성의 중요한 측면이다 초기 세션 &quot;약물 로딩,&quot;로 약물을 얻기 위해 사용과 높은 동기 부여의 두 상승을 보여줍니다. IV의 필로폰 긴 액세스 노출이 설치류는인지 적자 (32)을 보여, 약물 치료 33, 약물 동태 학 (34)과 신경 화학적으로 별개의 응답은 짧은 액세스 노출 설치류보다 만성 메스 암페타민 사용 장애로 고통 인간에게 더 유사하다 (35)을 변경합니다. 마찬가지로 우리의 깊은 뇌 자극 절차의 세 가지 주요 단계가 있습니다 : 하나 또는 두 개의 &quot;모의&quot;세션의 머리 밧줄 연결을 포함 DBS 환경, 1) 요법 이니, 2) 매일, 상용 시스템을 사용하여 활성 자극의 간헐적 인 배달, 3) DBS의 분리 및 약물 설정 이후에 전송. 이 패러다임은 다소 전통적인 연속 DBS보다 TMS 같은 비 침습적 치료의 과정을 모방하도록 설계된다. 완전 이식, 일반적인 운동 장애 3에 사용되는 것과 같은 프로그램 DBS 시스템은 여러 가지 전술 한 이유로 정신 자극제 의존을 앓고있는 환자의 변두리에 가능한 것입니다. Intermitten더 나은이 환자 인구에 적용 할 수있다 TMS 같은 위험도가 높은 수술과 사후를 포함하지 않는 전기 치료 전략을, t. 우리가 기술 한 방법은 연구자가 개발하고 제한된 시간 내에 약물 환경 외부에서 전달되는 동안 마약 관련 동작을 수정할 수 있습니다 치료 전략을 구체화 할 수 있습니다. 축적 증거가 특정 신경 생리 학적 결손 (23) 후에 모방 또는 치료 중단 후 전신 약물 (36)을 발휘 몇 주 동안 정신 및 약물 관련 행동에 긍정적 인 효과를 오래 지속과 결합 과도 두개 전기 자극. 초기 우수한 수술 기법과 강렬한 약물 사용 중에 여러 수술 사이트의 지속적인 관리를위한 요구 사항은이 방법의 주요 제한 사항입니다. IV 카테터 또는 DBS 전극 중 하나가 비 작동 및 / 또는 감염 될 경우, 쥐해야연구를 종료합니다. 엄격한 무균 기술에서 경정맥 카테터 및 두개강 ​​내 전극 게재 위치를 가장 독립적으로이 절차를 시작하기 전에 경험이 풍부한 연구자에서 배운됩니다. . 자극 파형, 펄스 폭, 주파수, 진폭), 2) 다른 잠재적 인 치료 뇌 타겟 (예 - - 핵 중격 의지 1) 다른 자극 파라미터 (예 :.이 절차의 검토를 포함하여 여러 변형 및 미래 연구, 의무가있다 코어, 내측 전두엽 피질, 중뇌, habenula), 3) 다른 DBS 전달 패턴 (예를 들어, -. 매일 DBS 배달, 주간 DBS 배달, DBS 이전에 가장 흥미로운 아마도 조작 적 세션, DBS 인수 전), 그리고, 다양한 간격으로, 4) 짧은 기간 DBS의 조합과 선택적 경로의 optogenetic 자극을 모방 행동 수정 (36)을 지속 발휘 제약 에이전트.

필로폰 인해 시냅스 모노 아민의 급성 증가, 특히 도파민에 강렬하고 장기간의 행복감을 생산하는 정신 자극제입니다. 필로폰 의존은 전 세계적으로 약 25-34000000 사용자와 전혀 입증 된 치료 1, 2와 전염병의 건강 문제입니다. 메탐페타민에 대한 의존성 신규 한 치료 전략의 개발이 상당히 요구되고있다. 깊은 뇌 자극 (DBS)은 두뇌 &quot;심장 박동&quot;파킨슨 병, 근육 긴장 이상, 그리고 3 태성 진전 비롯한 특정 질환에서 발생하는 신경 세포 파괴 소성 패턴을 정상화를 사용하여 신경 외과 절차이다. 최근 인간의 경우 보고서는 DBS는 알코올 및 약물 의존에 대한 효과적인 치료가 될 수 있지만, 정신 자극제에 대한 임상 증거 (예 :., 코카인, 필로폰)이 4-8을 제한하는 것이 좋습니다. 연속 깊은 뇌 자극이 currentl 그대로Y는 연습 환자와 그 / 그녀의 가족에서 예외적 인 협력이 필요합니다. 꼼꼼한 상처 치료 및 개인 위생에도 결과 균혈증과 정맥 약물을 사용하지 않는 환자에서 감염에 취약 기본 맥박 조정기 하드웨어를 보호해야합니다. DBS 장치의 정기적 추적 시스템의 개방 루프 설계 주어진 필요가있다; 경험이 풍부한 의사 일상 클리닉 약속 3시 대상의 증상을 감소시키는 현대 DBS의 설정을 변경합니다. 이 치료의 패러다임은 그들의 도전 정신 사회적 상황에 코카인과 암페타민 사용자로 제한됩니다. 여러 설치류 연구는 치료가 약물 사용 환경 9-11에서 코카인 자기 관리 절차 중에 연속적으로 전달 될 ​​때 DBS의 효과를 검토하여이 비현실적 패러다임을 모방했다. 두개 같이 내주 하드웨어를 필요로하지 않는 불연속 기법 비 침습적자기 자극 (TMS)은, 물질 사용 장애 (12)의 치료를위한 더 나은 옵션이 될 수 있습니다. TMS는 비 침습적 하루 동안 특정 뇌 대상 전기 필드, 간헐적 인 치료를 생성하는 외부 headcoil를 사용하여 제공됩니다. H 코일 또는 &quot;깊은&quot;은 TMS가 잠재적 인 사용을 확대 13,14, 피질 부위에 추가로, 깊은 뇌 자극 구조가되도록 최근 출현. 두 치료법은 기본 약물 사용의 경우보다 다른 환경에서 세션 동안 연속적으로 일련의 전달 및 약물 의존 13,15-17 인간과 쥐 실험 모두에서 약속을 보여 주었다. 그들이 폭력적이거나 산만 한 행동 (18)을 체험 할 수있는 경우 필로폰 의존 환자를 치료하는 창 가능성이 거리 binges 동안하지, 같은 법원이 의무적으로 재활 등의 금주 기간 동안있을 것입니다. 따라서,이 문서의 목적은 일시적이다 전기 자극의 전달을 설명하는 것입니다공간적으로 더 밀접 IV의 암페타민 의존의 치료를위한 인간에서 무엇이 가능한지에 근사 약물 사용 환경으로부터 분리한다.

<table>
	<tbody>
		<tr>
			<td>Rodent operant chambers</td>
			<td>Med Associates, Inc</td>
			<td>ENV-008CT</td>
			<td>Med Associates Inc. PO Box 319 St. Albans, Vermont 05478 USA Phone: (802) 527-2343</td>
		</tr>
		<tr>
			<td>Kopf Small Animal Stereotaxic Instrument with Digital Display Console</td>
			<td>Kopf Instruments</td>
			<td>Model 940</td>
			<td>Kopf Phone: 1-877-352-3275 Fax: 1-818-352-3275 Email: sales@kopfinstruments.net</td>
		</tr>
		<tr>
			<td>Z-Series 3-DSP Bioamp Processor</td>
			<td>Tucker Davis Technologies</td>
			<td>RZ5D</td>
			<td>Tucker-Davis Technologies&#160;11930 Research Circle Alachua, FL 32615&#160;USA Ph: 386-462-9622&#160;www.tdt.com</td>
		</tr>
		<tr>
			<td>Z-Series 32-Channel Stimulator</td>
			<td>Tucker Davis Technologies</td>
			<td>IZ2-32</td>
			<td>Software is accompanied by a manual that discusses how to program experiments using the OpenEx platform, which can be accessed here: http://www.tdt.com/files/manuals/OpenEx_User_Guide.pdf</td>
		</tr>
		<tr>
			<td>48 Volt LI-ION Battery Pack for IZ2 Stimulator</td>
			<td>Tucker Davis Technologies</td>
			<td>LZ48-200</td>
			<td></td>
		</tr>
		<tr>
			<td>32-Channel Splitter Box for PZ5</td>
			<td>Tucker Davis Technologies</td>
			<td>S-BOX_PZ5</td>
			<td></td>
		</tr>
		<tr>
			<td>OpenEx Ext Software Package for Multi-Channel Neural Recording</td>
			<td>Tucker Davis Technologies</td>
			<td>OpenEx</td>
			<td></td>
		</tr>
		<tr>
			<td>Platinum-iridium stimulating electrodes</td>
			<td>Plastics One Inc</td>
			<td>MS303/8-B/SPC ELECT PT 2C TW .005&#34;</td>
			<td>Plastics One Inc P.O.Box 21465, S.W. Roanoke, VA 24018, PH 540-772-7950</td>
		</tr>
		<tr>
			<td>2-channel cables between stimulator and commutator</td>
			<td>Plastics One Inc</td>
			<td>305-441/2 W/ Spring</td>
			<td></td>
		</tr>
		<tr>
			<td>2-channel cables between commutator and electrode pedestal</td>
			<td>Plastics One Inc</td>
			<td>305-305 W/ Spring</td>
			<td></td>
		</tr>
		<tr>
			<td>4-channel commutators</td>
			<td>Plastics One Inc</td>
			<td>SL2+2C and SL2+SC/SB</td>
			<td></td>
		</tr>
	</tbody>
</table>

a general method for evaluating deep brain stimulation effects on intravenous methamphetamine self-administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

IV의 경정맥 카테터 및 두개 내 DBS 전극의 배치에 따라, 설치류가 성공적으로 짧은 회복 기간 후 자기 관리] 4의 필로폰을 훈련 할 수있다. 쥐를 획득하고 확장 된 액세스 2 일 이후 필로폰 자기 관리를 확대 할 3은 그림 4 일에 의해 세션 당 168 ± 12 주입의 평균 약물. 1) 필로폰 독성 및 영구, 장기간 액세스 할 수있는 심각한 행동 변화를 방지하고 2) 그 응답의 상대적으로 안정적인 속도를 설정하기 위해 다양한 조작 할 수 있습니다 쥐 다음 두 가지 이유에 대한 조작 적 훈련을 매일 2 시간 일정으로 이동 치료 적 개입. 그림 4는 두 번째 주에 걸쳐 짧은 액세스 세션 당 총 주입의 평균 수는 75 ± 8임을 보여줍니다 일반적으로 10 % 이하로 일상을 변화한다. 그림 5는 쥐 (STABLE)를 보여줍니다OP 일에 비해 훈련 6 일째에 의한 섭취 &quot;프런트 로딩」패턴의 출현에 의해 나타낸 바와 같이 약물을 취할 증가 동기 1.이 개발되면, 효과는 크게 후속 세션 동안 유지된다 (데이터는 미도시) . 그림 6은 양자 DBS는 가짜 자극 군에 비해 3 ~ 5의 일에 대한 조작 적 IV의 필로폰 자기 관리의 현저한 감소의 결과 비 약물 환경에서 전달되는 것을 알 수있다. (- 8.5, ML은 2.4 ± AP + 1.6, DV)의 핵은 쉘은 브레 그마를 기준으로 좌표를 다음 정위를 사용하여 약물 consummatory 동작을 8 년에 알려진 참여를 목표로하는 소정했다 중격 의지. 자극 파라미터 및 지속 시간은 느슨하게 정신과 8,20,21 질병의 치료 용 DBS와 이전 경험에 기초하여 게시 되었으나 실험자의 요구에 따라 조정될 수있다. 오차 막대는 온건하고 모든 일 것이란 있습니다명확한 치료 효과의 평가에도 불구하고, 행동에서 볼 수있는 응답의 범위를 나타내는 의미 CH. 실험 당 쥐의 수를 늘리면이 자연의 변화를 보상 할 수 있습니다. 11 동물은 초기 실험에 사용 하였다. 하나의 동물에 의한 발작에 수유 수술 후, 하나의 동물이 제외 된 대한 안락사하고, 하나의 동물 (8) 동물의 총을 우리에게 남겨 인해 DBS 전극 고장 제외되었다 (; N = 4 활성 DBS를 N = 4 샴). 성공적인 완료를 허용 각 실험 (12) 쥐 - 일반적으로 약 10부터 시작. <img alt="그림 1" src="/files/ftp_upload/53266/53266fig1.jpg" /> 그림 1. 비주얼 프로그래밍 언어. 조사는 여러 애니에 뇌 자극을 제공 할 수있는 프로그램을 설계, 여기의 예처럼, 비주얼 프로그래밍 언어를 사용LS 동시에 사용자가 입력 매개 변수에. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig1large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 2" src="/files/ftp_upload/53266/53266fig2.jpg" /> 도 2 카메라 제어판. 실험의 개시에 앞서, 조사관 시각적 컨트롤 패널의 왼쪽에 원하는 주파수, 펄스 폭과 진폭을 지정한다. 여기에 자극 매개 변수는 다음과 같습니다 현재 강도 200 μA; 펄스는 61 밀리 폭; 펄스 주파수 130 Hz에서. 자극이 활성 전류 전달을위한 파형이 오른쪽에 표시됩니다 시작되면. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig2large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> IV 필로폰 자기 관리 그림 3. 취득. 응답 전체 조건화는 (360 분) 데이터는 반복 측정으로 정의 매일 세션과 반복 - 측정 ANOVA를 이용하여 분석 하였다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 조작 적 훈련 첫 4 일 동안 매일 6 시간 조작 적 세션 동안 총 필로폰 주입. + P &lt;0.05 세션 1에 비교 2. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig3large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 4" src="/files/ftp_upload/53266/53266fig4.jpg" /> 그림 4.IV 필로폰 자기 관리의 유지 보수. 총 조작 적 응답 (120 분) 데이터는 반복 측정으로 정의 매일 세션과 반복 - 측정 ANOVA를 이용하여 분석 하였다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 안정된하지만 강렬한 약물 복용 행동을 보여주는 조작 적 훈련, 둘째 주에 걸쳐 매일 2 시간의 조작 적 세션 동안 총 필로폰 주입. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig4large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 5" src="/files/ftp_upload/53266/53266fig5.jpg" /> 그림 동기 부여의 5 개발은 약을 복용합니다. 조작 적 첫 번째 시간 동안 매 15 분을 합계 한이 응답하고 데이터를 분석 하였다 사용하여 반복-날ANOVA는 반복 측정으로 정의 된 각 15 분 사분면으로 asures. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. &quot;프런트 로딩&quot;패턴은 조작 적 훈련의 1 일에 존재하는 것이 아니라 약을 복용하는 강한 의욕을 나타내는 두 번째 주에 의해 개발. + P &lt;0.05에 비해 60 분에 비해 45 ~ 60 분, + + + P &lt;0.05에 비해 30, 45, 60 분, + + P &lt;0.05. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig5large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 6" src="/files/ftp_upload/53266/53266fig6.jpg" /> 그림 6. IV 필로폰 자기 관리에 DBS 효과. 제 시간에 응답 총 조건화는 (60 분) 데이터는 betwe와 혼합 ANOVA를 이용하여 분석 하였다치료의 대상 변수 (가짜 대 DBS) 매일 세션의 반복 측정 갖추고 있습니다. 페이지를 한 모든 분석은 &lt;0.05으로 유의하다고 하였다. 데이터는 평균 ± 표준 오차이다. 양자 미리 조건화 깊은 뇌 자극이 크게 치료 일 3, 4에 대응 조건화의 제 60 분에 걸쳐 주입 메탐페타민의 수를 감소하고, 모의 그룹과 기준선 응답에 비해 7 + P &lt;0.05. 종료 매일 치료 후베이스 라인 수준으로 돌아 응답. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig6large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a>

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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

정맥 필로폰 자기 관리에 깊은 뇌 자극의 효과를 평가하기위한 일반적인 방법

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

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15.1K 조회수.  Louisiana State University. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

비디오: A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

실험실 쥐에 Tastants의 강화 속성을 평가하기위한 새로운 방법 : 조작 적 구강 자기 관리

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

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행동분석학

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

원인이되는 뇌 - 행동의 관계와 자신의 시간 과정을 조사하기위한 경 두개 자기 자극

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

인식 및 학습을 연구하는 도구로 전기 생리 텍스 녹화 및 자극과 셔틀 박스 교육을 결합

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

도구로 미주 신경 자극은 멸종 학습을위한 관련 진학 가소성을 유도

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

물 박탈, 사카린 페이딩 또는 확장 액세스 교육을받지 않은 쥐에 에탄올의 강화 속성을 평가하는 방법

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

계단 및 실린더 테스트 : 소설 접근은 Hemiparkinsonian 쥐에 깊은 뇌 자극 효과의 모터 결과를 평가하는

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

Visualization Method for Proprioceptive Drift on a 2D Plane Using Support Vector Machine

Proprioceptive drift, which is a perceptual shift in body-part position from the unseen real body to a visible body-like image, has been measured as the behavioral correlate for the sense of ownership. Previously, the estimation of proprioceptive drift was limited to one spatial dimension, such as height, width, or depth. As the hand can move freely in 3D, measuring proprioceptive drift in only one dimension is not sufficient for the estimation of the drift in real life situations. In this article, we provide a novel method to estimate proprioceptive drift on a 2D plane using the mirror illusion by combining an objective behavioral measurement (hand position tracking) and subjective, phenomenological assessment (subjective assessment of hand position and questionnaire) with a sophisticated machine learning approach. This technique permits not only an investigation of the underlying mechanisms of the sense of ownership and agency but also assists in the rehabilitation of a missing or paralyzed limb and in the design rules of real-time control systems with a self-body-like usability, in which the operator controls the system as if it were part of his/her own body.

This article describes a novel method to estimate proprioceptive drift on a 2D plane using the mirror illusion and combining a psychophysical procedure with an analysis using machine learning.

Proprioceptive drift, which is a perceptual shift in body-part position from the unseen real body to a visible body-like image, has been measured as the ...

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

어떻게 우울증 이외의 조건에 대한 H1 깊은 경 두개 자기 자극 코일을 사용하는

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

This novel protocol is designed to assess the neural bases of social interaction in infants. The paradigm is designed to tease apart how various social inputs such as language, joint attention, and face-to-face interaction relate to infant neural activation. Infant EEG power is recorded during both social and nonsocial conditions.

A는 내 - 과목 실험 프로토콜 유아 EEG에 대한 사회 입력의 효과를 평가하기 위해

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants ...

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations. TACS employs frequency-specific stimulation of the human brain through current applied to the scalp with surface electrodes. Most current knowledge of the technique is based on behavioral studies; thus, combining the method with brain imaging holds potential to better understand the mechanisms of tACS. Because of electrical and susceptibility artifacts, combining tACS with brain imaging can be challenging, however, one brain imaging technique that is well suited to be applied simultaneously with tACS is functional magnetic resonance imaging (fMRI). In our lab, we have successfully combined tACS with simultaneous fMRI measurements to show that tACS effects are state, current, and frequency dependent, and that modulation of brain activity is not limited to the area directly below the electrodes. This article describes a safe and reliable setup for applying tACS simultaneously with visual task fMRI studies, which can lend to understanding oscillatory brain function as well as the effects of tACS on the brain.

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations, though its effects are not completely understood. This article describes a safe and reliable setup for applying tACS simultaneously with functional magnetic resonance imaging, which can increase understanding oscillatory brain function and effects of tACS.